Updated on 2024/10/01

Information

 

写真a

 
OKUMA TOSHIAKI
 
Organization
Kyushu University Hospital Department of Nephrology,Hypertension,and Strokology Assistant Professor
School of Medicine Department of Medicine(Concurrent)
Title
Assistant Professor
Tel
0926425256
Profile
研究 九州大学および関連施設と共同で行っている大規模ゲノムコホート研究、福岡県糖尿病患者データベース研究(Fukuoka Diabetes Registry; FDR)に従事している。 臨床 九州⼤学病院における糖尿病の診療を⾏っている.対象となる疾患は、1型糖尿病、2型糖尿病、遺伝⼦異常による糖尿病や薬剤による糖尿病、妊娠糖尿病、移植後糖尿病、インスリノーマ等の低⾎糖症など。特に⽣体腎移植や膵腎同時移植の周術期の⾎糖管理に関わることが多い。 教育 医学部学生に対する講義、ベッドサイド実習、クリニカルクラークシップでの指導を行っている。 大学院生に対して臨床疫学研究、論文作成について指導している。
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Degree

  • 医学博士

Research Interests・Research Keywords

  • Research theme: The Fukuoka Diabetes Registry: a multicenter prospective study designed to investigate the influence of the modern treatments on the prognoses of patients with diabetes mellitus

    Keyword: Diabetes Mellitus、Clinical epidemiology

    Research period: 2009.4 - 2025.5

Awards

  • 九州大学第二内科 尾前賞

    2023.11  

  • 牛乳乳製品健康科学 2021年度研究 最優秀賞

    2022.8  

  • 2021 AJKD Editors’ Choice Award

    2021.11  

  • 九州大学第二内科同門会賞奨励賞

    2019.11  

  • The John Chalmers Post-Doctoral Award 2018

    2018.12  

  • 日本高血圧学会 Hypertension Research Award 優秀賞

    2017.10  

  • 日本糖尿病学会九州支部賞

    2014.11  

  • 九州大学第二内科同門会賞奨励賞

    2013.11  

  • Kyushu Diabetes Research Conference 最優秀奨励賞

    2012.6  

  • 福岡県医学会総会 ポスター優秀賞

    2012.1  

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Papers

  • Sleep duration and its association with constipation in patients with diabetes: The fukuoka diabetes registry. International journal

    Toshiaki Ohkuma, Masanori Iwase, Takanari Kitazono

    PloS one   19 ( 5 )   e0302430   2024

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    AIMS: Shorter and longer sleep durations are associated with adverse health consequences. However, available evidence on the association of sleep duration with constipation is limited, especially in patients with diabetes, who are at a high risk of both conditions. This study aimed to examine the association between sleep duration and constipation in patients with type 2 diabetes. METHODS: A total of 4,826 patients with type 2 diabetes were classified into six groups according to sleep duration: <4.5, 4.5-5.4, 5.5-6.4, 6.5-7.4, 7.5-8.4, and ≥8.5 hours/day. The odds ratios for the presence of constipation, defined as a defecation frequency <3 times/week and/or laxative use, were calculated using a logistic regression model. RESULTS: Shorter and longer sleep durations were associated with a higher likelihood of constipation than an intermediate duration (6.5-7.4 hours/day). This U-shaped association persisted after adjusting for confounding factors, including lifestyle behavior, measures of obesity and glycemic control, and comorbidities. Broadly identical findings were observed when decreased defecation frequency and laxative use were individually assessed. CONCLUSIONS: This study shows a U-shaped association between sleep duration and constipation in patients with type 2 diabetes, and highlights the importance of assessing sleep duration in daily clinical practice.

    DOI: 10.1371/journal.pone.0302430

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  • ASL灌流像が診断に有用であった可逆性後頭葉白質脳症(PRES)合併2型糖尿病の1例

    牟田 大毅, 岩瀬 正典, 井手 均, 青谷 領一郎, 平田 詩乃, 高木 可南子, 酒匂 哲平, 由比 智裕, 宇都宮 英綱, 大隈 俊明, 北園 孝成

    糖尿病   66 ( 9 )   697 - 704   2023.9

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    症例は56歳の男性で頭痛,嘔吐,意識障害のため救急搬送された.血圧192/100mmHg,血糖233mg/dL,HbA1c 10.8&#37;,蛋白尿12.0g/gCr,血清アルブミン2.1g/dL,eGFR 41mL/min/1.73m2,右下1/4盲を認めた.頭部MRIのFLAIR,T2強調画像で両側側脳室周囲白質に慢性虚血性変化が認められたが,その他には異常信号域は認められなかった.arterial spin labeling(ASL)では左側頭葉から後頭葉にかけて過灌流状態であった.Posterior Reversible Encephalopathy Syndrome(PRES)と診断し,降圧治療とインスリン治療を施行した.経過中,無症候性の微小脳梗塞を発症したが,過灌流は改善し,右下1/4盲は改善した.ASLはPRESの診断に有用である.(著者抄録)

  • Sex differences in cardiovascular risk, lifestyle, and psychological factors in patients with type 2 diabetes: the Fukuoka Diabetes Registry. International journal

    Toshiaki Ohkuma, Masanori Iwase, Hiroki Fujii, Takanari Kitazono

    Biology of sex differences   14 ( 1 )   32 - 32   2023.5

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    BACKGROUND: The excess risk of cardiovascular diseases associated with diabetes is greater in women than in men. The present study aimed to examine sex differences in the control of cardiovascular risk factors, as well as lifestyle and psychological factors, in patients with type 2 diabetes. METHODS: A total of 4923 Japanese patients with type 2 diabetes were included in this cross-sectional study. Female/male differences in cardiovascular risk factor levels, and corresponding odds ratios for achieving recommended ranges for preventing cardiovascular diseases and having unhealthy lifestyle and psychological factors were computed by linear and logistic regression models. RESULTS: Women were less likely than men to achieve recommended ranges for glycated hemoglobin, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and obesity-related anthropometric indices such as body mass index and waist circumference, but were more likely than men to be on target for high-density lipoprotein cholesterol and triglycerides. Women were also more likely than men to have an unhealthy lifestyle and psychological factors, including less dietary fiber intake, less leisure-time physical activity, shorter sleep duration, more constipation, and more depressive symptoms. Similar findings were observed when the participants were subgrouped by age (< 65 and ≥ 65 years) and past history of cardiovascular disease. CONCLUSIONS: We observed significant sex differences for a range of cardiovascular risk factors, as well as lifestyle and psychological factors, suggesting the importance of adopting a sex-specific approach for the daily clinical management of diabetes.

    DOI: 10.1186/s13293-023-00517-8

  • Incidence and risks of coronary heart disease and heart failure in Japanese patients with type 2 diabetes mellitus: The Fukuoka diabetes registry. International journal

    Masanori Iwase, Toshiaki Ohkuma, Hiroki Fujii, Yutaro Oku, Taiki Higashi, Ayaka Oshiro, Hitoshi Ide, Udai Nakamura, Takanari Kitazono

    Diabetes research and clinical practice   201   110732 - 110732   2023.5

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    AIMS: We prospectively investigated the incidence of coronary heart disease (CHD) and heart failure (HF), risk factors and prognosis in Japanese patients with type 2 diabetes. METHODS: A total of 4,874 outpatients with type 2 diabetes (mean age 65 years, male 57&#37;, previous CHD 14&#37;) were registered at multicenter diabetes clinics of a prefecture in 2008-2010 and followed for the development of CHD and HF requiring hospitalization for a median of 5.3 years (follow-up rate 98&#37;). Risk factors were evaluated using multivariable adjusted Cox proportional models. RESULTS: The incidence rates per 1,000 person-years were 12.3 for CHD (silent myocardial ischemia 5.8, angina pectoris 4.3, myocardial infarction 2.1) and 3.1 for hospitalized HF, respectively. New-onset CHD was significantly associated with higher serum adiponectin [the highest quartile vs. the lowest quartile HR 1.6 (95&#37;CI 1.0-2.6)]. HF was significantly associated with higher serum adiponectin [the highest quartile vs. the lowest quartile HR 2.4 (95&#37;CI 1.1-5.2)], and lower serum creatinine/cystatin C ratio, a surrogate marker for sarcopenia [lowest quartile vs. the highest quartile HR 4.6 (95&#37;CI 1.9-11.1)]. CONCLUSIONS: The incidence of heart disease was low and circulating adiponectin and sarcopenia may predict the development of heart disease in Japanese patients with type 2 diabetes.

    DOI: 10.1016/j.diabres.2023.110732

  • Design and methods of an open-label, randomized controlled trial to evaluate the effect of pemafibrate on proteinuria in CKD patients (PROFIT-CKD).

    Mai Seki, Toshiaki Nakano, Shigeru Tanaka, Yuta Matsukuma, Kouta Funakoshi, Toshiaki Ohkuma, Takanari Kitazono

    Clinical and experimental nephrology   27 ( 4 )   358 - 364   2023.2

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    BACKGROUND: Hypertriglyceridemia is increasingly considered a residual risk of cardiovascular disease in patients with chronic kidney disease (CKD). Pemafibrate-a novel selective peroxisome proliferator-activated receptor alpha modulator and a new treatment for hypertriglyceridemia in CKD patients-is reported to have fewer side effects in CKD patients than other fibrates. Appropriate control of hypertriglyceridemia can be expected to improve renal prognosis. However, data on the renal protective effect of pemafibrate are limited. This study aims to evaluate the effectiveness of pemafibrate on urinary protein excretion in CKD patients. METHODS: The Pemafibrate, open-label, Randomized cOntrolled study to evaluate the renal protective eFfect In hyperTriglyceridemia patients with Chronic Kidney Disease (PROFIT-CKD) study is an investigator-initiated, multi-center, open-label, parallel-group, randomized controlled trial. Participants are outpatients with hypertriglyceridemia aged 20 years and over, who have received the care of a nephrologist or a diabetologist for more than 3 months. Inclusion criteria include the following: proteinuria (urine protein/creatinine ratio of ≥ 0.15 g/gCr) within three months before allocation, and hypertriglyceridemia (triglycerides ≥ 150 mg/dL and < 1,000 mg/dL) at allocation. In the treatment group, pemafibrate is added to conventional treatment, while conventional treatment is continued with no additional treatment in the control group. Target patient enrollment is 140 patients. The primary endpoint is the change from baseline in the logarithmic urine protein/creatinine ratio at 12 months after study start. CONCLUSION: This study will provide new findings on the renal protective effect of pemafibrate in CKD patients. CLINICAL TRIAL REGISTRATION: This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN-CTR: UMIN000042284).

    DOI: 10.1007/s10157-023-02322-4

  • Onset of type 1 diabetes during bone growth period is associated with increased prevalence of bone fracture: A post-hoc analysis of a cross-sectional study.

    Yuji Komorita, Masae Minami, Yasutaka Maeda, Rie Kishita, Toshiaki Ohkuma, Takanari Kitazono

    Journal of diabetes investigation   2022.9

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    In this single-center, cross-sectional study, we demonstrated that the prevalence of fracture was significantly higher in patients who onset type 1 diabetes during 0-4 years, and 10-14 years compared with adult-onset type 1 diabetes. We are aware that this study contains a lot of limitations including non-prospective study design and a small number of participants. However, the results of this study, if followed by a larger cohort study, could provide important insights into the increased risk of fracture in patients with type 1 diabetes, and suggest the need for attention and perhaps early intervention for patients with type 1 diabetes who developed during these periods.

    DOI: 10.1111/jdi.13898

  • Short-Term Changes in Serum Potassium and the Risk of Subsequent Vascular Events and Mortality: Results from a Randomized Controlled Trial of ACE Inhibitors. International journal

    Toshiaki Ohkuma, Katie Harris, Mark Cooper, Diederick E Grobbee, Pavel Hamet, Stephen Harrap, Giuseppe Mancia, Michel Marre, Anushka Patel, Anthony Rodgers, Bryan Williams, Mark Woodward, John Chalmers

    Clinical journal of the American Society of Nephrology : CJASN   17 ( 8 )   1139 - 1149   2022.8

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    BACKGROUND AND OBJECTIVES: Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes. However, whether to continue or discontinue the drug after hyperkalemia remains unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data came from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, which included a run-in period where all participants initiated angiotensin-converting enzyme inhibitor-based therapy (a fixed combination of perindopril and indapamide). The study population was taken as patients with type 2 diabetes with normokalemia (serum potassium of 3.5 to <5.0 mEq/L) at the start of run-in. Potassium was remeasured 3 weeks later when a total of 9694 participants were classified into hyperkalemia (≥5.0 mEq/L), normokalemia, and hypokalemia (<3.5 mEq/L) groups. After run-in, patients were randomized to continuation of the angiotensin-converting enzyme inhibitor-based therapy or placebo; major macrovascular, microvascular, and mortality outcomes were analyzed using Cox regression during the following 4.4 years (median). RESULTS: During active run-in, 556 (6%) participants experienced hyperkalemia. During follow-up, 1505 participants experienced the primary composite outcome of major macrovascular and microvascular events. Randomized treatment of angiotensin-converting enzyme inhibitor-based therapy significantly decreased the risk of the primary outcome (38.1 versus 42.0 per 1000 person-years; hazard ratio, 0.91; 95% confidence interval, 0.83 to 1.00; P=0.04) compared with placebo. The magnitude of effects did not differ across subgroups defined by short-term changes in serum potassium during run-in (P for heterogeneity =0.66). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, major coronary events, major cerebrovascular events, and new or worsening nephropathy (P for heterogeneity ≥0.27). CONCLUSIONS: Continuation of angiotensin-converting enzyme inhibitor-based therapy consistently decreased the subsequent risk of clinical outcomes, including cardiovascular and kidney outcomes and death, regardless of short-term changes in serum potassium. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), NCT00145925.

    DOI: 10.2215/CJN.00180122

  • HLA-DRB1*04:04を有した高齢インスリン自己免疫症候群(平田病)の1例

    原 規子, 平田 詩乃, 高木 可南子, 於久 祐太郎, 牟田 大毅, 井手 均, 岩瀬 正典, 大隈 俊明, 北園 孝成

    糖尿病   65 ( 6 )   312 - 318   2022.6

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    我が国は超高齢化社会を迎え,低血糖を呈する非糖尿病の高齢者を診療する機会が増加している.今回,88歳男性で認知機能低下,不穏で救急搬送され,血糖38mg/dLの症例を経験した.高インスリン血症を認め(349μU/mL),インスリン抗体高値,Scatchard解析で低親和性高結合能のインスリン抗体を認めた.インスリン自己免疫症候群と関連するHLAを有さず,DRB1*04:04を認めた.インスリン自己免疫症候群を誘発することが知られているクロピドグレルを含む常用薬をすべて中止し,分割食,間食,さらに,ボグリボースを追加したが低血糖は改善しなかった.そのためプレドニゾロン30mg/日から開始したところ低血糖は消失し,血中インスリンやインスリン抗体も徐々に減少した.既知のHLA遺伝要因を有さない高齢者でインスリン自己免疫症候群を発症することがあり,臨床上注意が必要である.(著者抄録)

  • Usefulness of urinary tubule injury markers for predicting progression of renal dysfunction in patients with type 2 diabetes and albuminuria: The Fukuoka Diabetes Registry. International journal

    Hitoshi Ide, Masanori Iwase, Toshiaki Ohkuma, Hiroki Fujii, Yuji Komorita, Yutaro Oku, Taiki Higashi, Masahito Yoshinari, Udai Nakamura, Takanari Kitazono

    Diabetes research and clinical practice   186   109840 - 109840   2022.3

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    AIMS: We prospectively investigated the association of urinary tubule injury markers with estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes. METHODS: Urinary kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty-acid-binding protein (L-FABP), and urinary albumin-to creatinine ratio (UACR) were measured in 2,685 participants with type 2 diabetes. Renal outcomes were ≥ 30% decline in eGFR from the baseline and annual eGFR decline for 5 years. RESULTS: In normoalbuminuric participants, no tubular markers were associated with ≥ 30% decline in eGFR or annual eGFR changes. In those with UACR ≥ 30 mg/gCr, hazard ratios for ≥ 30% eGFR decline were 1.37 (95% confident interval (CI) 1.07-1.75) for urinary KIM-1 (>1.5 µg/gCr), 1.46 (95% CI 1.13-1.66) for urinary NGAL (>16.4 µg/gCr), and 1.26 (95% CI 0.94-1.66) for urinary L-FABP (>12.5 µg/gCr), 2.61 (95% CI 1.64-4.17) for the combination of 3 tubular markers above the cutoff after multivariable adjustments including UACR and eGFR. CONCLUSIONS: The current study demonstrated that urinary tubule injury markers and their combination were significant predictors for the future eGFR decline in those with type 2 diabetes and albuminuria independently of UACR and eGFR. Urinary tubular markers may be useful to identify high-risk patients with albuminuria.

    DOI: 10.1016/j.diabres.2022.109840

  • Relationship of coffee consumption with a decline in kidney function among patients with type 2 diabetes: The Fukuoka Diabetes Registry.

    Yuji Komorita, Toshiaki Ohkuma, Masanori Iwase, Hiroki Fujii, Hitoshi Ide, Yutaro Oku, Taiki Higashi, Ayaka Oshiro, Wakako Sakamoto, Masahito Yoshinari, Udai Nakamura, Takanari Kitazono

    Journal of diabetes investigation   2022.2

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    AIMS/INTRODUCTION: The evidence regarding the effects of coffee consumption on incident chronic kidney disease is inconclusive, and no studies have investigated the relationship in patients with diabetes. We aimed to prospectively investigate the relationship between coffee consumption and the decline in estimated glomerular function rate (eGFR) in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 3,805 patients (2,112 men, 1,693 women) with type 2 diabetes (mean age 64.2 years) and eGFR ≥60 mL/min/1.73 m2 were followed (completion of follow up, 97.6%; median 5.3 years). Coffee consumption was assessed at baseline. The end-point was a decline in eGFR to <60 mL/min/1.73 m2 during the follow-up period. RESULTS: During follow up, 840 participants experienced a decline in eGFR to <60 mL/min/1.73 m2 . Higher coffee consumption reduced the risk of decline in eGFR. Compared with no coffee consumption, the multivariate-adjusted hazard ratios (95% confidence intervals) were 0.77 (0.63-0.93) for less than one cup per day, 0.77 (0.62-0.95) for one cup per day and 0.75 (0.62-0.91) for two or more cups per day (P for trend 0.01). This trend was unaffected by further adjustment for baseline eGFR and albuminuria. The mean eGFR change per year was -2.16 mL/min/1.73 m2 with no coffee consumption, -1.89 mL/min/1.73 m2 with less than one cup per day, -1.80 mL/min/1.73 m2 with one cup per day and -1.78 mL/min/1.73 m2 with two or more cups per day (P for trend 0.03). CONCLUSIONS: Coffee consumption is significantly associated with a lower risk of decline in eGFR in patients with type 2 diabetes.

    DOI: 10.1111/jdi.13769

  • Constipation and diabetic kidney disease: The Fukuoka Diabetes Registry.

    Toshiaki Ohkuma, Masanori Iwase, Hiroki Fujii, Hitoshi Ide, Yuji Komorita, Masahito Yoshinari, Yutaro Oku, Taiki Higashi, Ayaka Oshiro, Udai Nakamura, Takanari Kitazono

    Clinical and experimental nephrology   25 ( 11 )   1247 - 1254   2021.11

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    BACKGROUND: Constipation was shown to be associated with higher risk of end-stage kidney disease or incident chronic kidney disease, although evidence in diabetic patients is lacking. The objective of the present study was to examine the association between constipation and diabetic kidney disease (DKD). METHODS: In total, 4826 Japanese outpatients with type 2 diabetes were classified according to presence or absence of constipation (defecation frequency < 3 times/week and/or taking laxative medication). DKD was defined as presence of decreased estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2), and/or albuminuria (urinary albumin-to-creatinine ratio ≥ 30 mg/g). Odds ratios for the presence of DKD were computed by a logistic regression model. RESULTS: Compared with participants without constipation, the age- and sex-adjusted odds ratio for presence of DKD was 1.58 (95% confidence interval 1.38-1.82) for those with constipation. This association persisted following adjustment for potential confounding factors. Decreased defecation frequency and laxative use were also significantly associated with higher prevalence of DKD. Overall, these findings were identical even when decreased eGFR and albuminuria were separately analyzed. CONCLUSIONS: Constipation was associated with higher likelihood of DKD in patients with diabetes, suggesting the importance of clinical assessment of constipation to identify patients at high risk of progression of kidney disease.

    DOI: 10.1007/s10157-021-02105-9

  • Safety and Efficacy of Sodium-glucose Cotransporter 2 Inhibitors in Kidney Transplant Recipients With Pretransplant Type 2 Diabetes Mellitus: A Retrospective, Single-center, Inverse Probability of Treatment Weighting Analysis of 85 Transplant Patients. International journal

    Yu Hisadome, Takanori Mei, Hiroshi Noguchi, Toshiaki Ohkuma, Yu Sato, Keizo Kaku, Yasuhiro Okabe, Masafumi Nakamura

    Transplantation direct   7 ( 11 )   e772   2021.11

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    Whether sodium-glucose cotransporter 2 (SGLT2) inhibitors can be used effectively and safely in kidney transplant (KT) recipients with pretransplant type 2 diabetes as the primary cause of end-stage renal disease (ESRD) remains unclear. In this study, we retrospectively analyzed the efficacy and safety of SGLT2 inhibitors compared with other oral hypoglycemic agents (OHAs) in KT recipients with pretransplant type 2 diabetes as the primary cause of ESRD. Methods: In this retrospective, observational, single-center, inverse probability of treatment weighting (IPTW) analysis study, we compared the outcomes of SGLT2 inhibitors (SGLT2 group) and other OHAs (control group) following KT. A total of 85 recipients with type 2 diabetic nephropathy as the major cause of ESRD before KT who were treated at our institute between October 2003 and October 2019 were screened and included. The variables considered for IPTW were recipient age, sex, body mass index, history of cardiovascular disease, ABO incompatibility, insulin therapy, estimated glomerular filtration rate (eGFR), and hemoglobin A1c (HbA1c) at the initiation of additional OHAs. Primary endpoints were changes in HbA1c, body weight, and eGFR 1 y after the initiation of additional OHAs. Results: After IPTW analysis, there were 26 patients in the SGLT2 group and 59 patients in the control group (n = 85 overall). The body weights were significantly reduced in the SGLT2 group. There was no statistical difference in changes in HbA1c and eGFR. Similarly, there was no significant difference in the incidence of urinary infection, acute rejection, or other side effects between the groups. Conclusions: Our findings suggested that SGLT2 inhibitors reduced the body weight of KT recipients and were used safely without increasing side effects.

    DOI: 10.1097/TXD.0000000000001228

  • Polypharmacy and bone fracture risk in patients with type 2 diabetes: The Fukuoka Diabetes Registry. International journal

    Yuji Komorita, Toshiaki Ohkuma, Masanori Iwase, Hiroki Fujii, Yutaro Oku, Taiki Higashi, Ayaka Oshiro, Wakako Sakamoto, Masahito Yoshinari, Udai Nakamura, Takanari Kitazono

    Diabetes research and clinical practice   181   109097 - 109097   2021.11

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    AIMS: To prospectively investigate the association between the number of prescribed drugs and the fracture risk in patients with type 2 diabetes. METHODS: Japanese participants with type 2 diabetes (n = 4,706; 2,755 men, 1,951 postmenopausal women; mean age, 66 years) were followed for a median of 5.3 years and grouped on the basis of the number of prescribed drugs at baseline. The main outcomes were fractures at any anatomic site and fragility fractures (fractures at hip and spine sites). RESULTS: During follow-up, any fracture occurred in 662 participants. The overall age- and sex-adjusted fracture incidence rates per 1,000 person-years were 21.2 (0-2 drugs), 28.1 (3-5 drugs), 37.7 (6-8 drugs), and 44.0 (≥9 drugs) (p for trend < 0.001). Compared with 0-2 drugs, the multivariate-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for fractures were 1.34 (1.07-1.68) for 3-5 drugs, 1.76 (1.37-2.26) for 6-8 drugs, and 1.71 (1.27-2.31) in ≥ 9 drugs. The multivariate-adjusted HR (95% CI) per increment in drugs was 1.05 (1.02-1.08) (p < 0.001). Similar tendencies were observed for fragility fractures. CONCLUSIONS: A greater number of prescribed drugs is associated with an increased bone fracture risk in patients with type 2 diabetes.

    DOI: 10.1016/j.diabres.2021.109097

  • Changes in GFR and Albuminuria in Routine Clinical Practice and the Risk of Kidney Disease Progression. International journal

    Brendon L Neuen, Misghina Weldegiorgis, William G Herrington, Toshiaki Ohkuma, Margaret Smith, Mark Woodward

    American journal of kidney diseases : the official journal of the National Kidney Foundation   78 ( 3 )   350 - 360   2021.9

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    RATIONALE & OBJECTIVE: Changes in urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used separately as alternative kidney disease outcomes in randomized trials. We tested the hypothesis that combined changes in UACR and eGFR predict advanced kidney disease better than either alone. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 91,319 primary care patients assembled from the Clinical Practice Research Datalink in the United Kingdom between 2000 and 2015. EXPOSURES: Changes in UACR and eGFR (categorized as ≥30% increase, stable, or ≥30% decrease), alone and in combination, over a 3-year period. OUTCOMES: The primary outcome was advanced CKD (sustained eGFR <30 mL/min/1.73 m2); secondary outcomes included kidney failure, cardiovascular disease, and all-cause mortality. ANALYTICAL APPROACH: Multivariable Cox regression with bias from missing values assessed using multiple imputation; discrimination statistics compared across exposure groups. RESULTS: 91,319 individuals were studied, with a mean eGFR of 72.6 mL/min/1.73 m2 and median UACR of 9.7 mg/g; 70,957 (77.7%) had diabetes. During a median follow-up of 2.9 years, 2,541 people progressed to advanced CKD. Compared with stable values, hazard ratios for a ≥30% increase in UACR and ≥30% decrease in eGFR were 1.78 (95% CI, 1.59-1.98) and 7.53 (95% CI, 6.70-8.45), respectively, for the outcome of advanced CKD. Compared with stable values of both, the hazard ratio for the combination of an increase in UACR and a decrease in eGFR was 15.15 (95% CI, 12.43-18.46) for the outcome of advanced CKD. The combination of changes in UACR and eGFR predicted kidney outcomes better than either alone. LIMITATIONS: Selection bias, relatively small proportion of individuals without diabetes, and very few kidney failure events. CONCLUSIONS: In a large-scale general population, the combination of an increase in UACR and a decrease in eGFR was strongly associated with the risk of advanced CKD. Further assessment of combined changes in UACR and eGFR as an alternative outcome for kidney failure in trials of CKD progression is warranted.

    DOI: 10.1053/j.ajkd.2021.02.335

  • Incidence of end-stage renal disease and risk factors for progression of renal dysfunction in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry.

    Masanori Iwase, Hitoshi Ide, Toshiaki Ohkuma, Hiroki Fujii, Yuji Komorita, Masahito Yoshinari, Yutaro Oku, Taiki Higashi, Udai Nakamura, Takanari Kitazono

    Clinical and experimental nephrology   26 ( 2 )   122 - 131   2021.9

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    BACKGROUND: Epidemiological data regarding diabetic kidney disease are accumulated insufficiently in Japan. We prospectively investigated the incidence of end-stage renal disease (ESRD) and risk factors for progression of renal dysfunction in Japanese patients with type 2 diabetes. METHODS: 4904 participants with type 2 diabetes (mean age 65 years, mean estimated glomerular filtration rate (eGFR) 75 mL/min/1.73 m2, proportion of eGFR  < 60 mL/min/1.73 m2 21%) were investigated for the progression to ESRD requiring dialysis in multicenter outpatients registry for 5 years. Risk factors for progression of renal dysfunction (≥ 30% decline in eGFR from the baseline and annual eGFR decline rates) were evaluated. RESULTS: The incidence rates of ESRD and all-cause mortality were 4.1/1000 person-years and 12.3/1000 person-years, respectively, and increased according to stages of chronic kidney disease (eGFR  < 30 mL/min/1.73 m2, incidence of ESRD 176.6/1000 person-years, all-cause mortality 57.4/1000 person-years). Incidence of  ≥ 30% decline in eGFR from the baseline was 16.4% at 5 years, and the mean annual decline rate was -1.84 mL/min/1.73 m2/year. The progression of renal dysfunction was significantly associated with older age, poor glycemic control, blood pressure, albuminuria, eGFR, previous cardiovascular disease, lifestyle factors (body mass index, reduced intake of dietary fiber, increased intake of sodium, no regular exercise), and depressive symptoms. CONCLUSIONS: This prospective study has emphasized the importance of multifactorial interventions on risk factors to suppress the high incidence of ESRD in Japanese patients with type 2 diabetes.

    DOI: 10.1007/s10157-021-02136-2

  • The comparative effects of intensive glucose lowering in diabetes patients aged below or above 65 years: Results from the ADVANCE trial. International journal

    Toshiaki Ohkuma, John Chalmers, Mark Cooper, Pavel Hamet, Stephen Harrap, Michel Marre, Giuseppe Mancia, Neil Poulter, Mark Woodward

    Diabetes, obesity & metabolism   23 ( 6 )   1292 - 1300   2021.6

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    AIMS: For relatively old patients with diabetes, current guidelines recommend adjustment of glycaemic goals based on patients' cognitive function, or coexisting chronic illnesses. However, the evidence which supports the efficacy and safety of intensive glucose lowering in older patients with diabetes is scarce. The objective of the present study was to compare the efficacy and safety of intensive glucose lowering in patients with type 2 diabetes stratified by age (<65 and ≥ 65 years), and examine whether the effects differ according to patients' characteristics in the older patient group. MATERIALS AND METHODS: The effects of intensive glucose lowering (to a target glycated haemoglobin [HbA1c] concentration of ≤48 mmol/mol [6.5%]) on major clinical outcomes were evaluated by Cox regression models according to subgroups defined by baseline age of <65 or ≥ 65 years in the ADVANCE trial (n = 11 140). RESULTS: Over a median follow-up of 5 years, intensive glucose lowering significantly decreased the risk of the composite of major macrovascular and microvascular events (hazard ratio 0.90, 95% confidence interval 0.82-0.98), with no heterogeneity in the effects across age subgroups (p for heterogeneity = 0.44). Relative effects on all-cause death, cardiovascular death, and components of major vascular events were also similar (P for heterogeneity ≥0.06), except for severe hypoglycaemia, which was of greater risk for patients aged <65 years. Absolute benefits and harms were broadly consistent across subgroups. Among patients aged ≥65 years, randomized treatment effects did not differ significantly across different levels of cognitive function or coexisting chronic illnesses. CONCLUSIONS: Our results suggest that an intensive glycaemic control strategy to reduce HbA1c to 48 mmol/mol (6.5%) provided broadly similar benefits and harms and may be recommended for older, as well as younger, patients.

    DOI: 10.1111/dom.14339

  • An adult patient with permanent neonatal diabetes successfully discontinued insulin therapy after initiating sitagliptin added to sulphonylurea. International journal

    Ayaka Oshiro, Toshiaki Ohkuma, Wakako Sakamoto, Yuji Komorita, Yutaro Oku, Yoichiro Hirakawa, Takanari Kitazono

    Diabetes, obesity & metabolism   23 ( 5 )   1213 - 1214   2021.5

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    DOI: 10.1111/dom.14318

  • Prevalence of bone fracture and its association with severe hypoglycemia in Japanese patients with type 1 diabetes. International journal

    Yuji Komorita, Masae Minami, Yasutaka Maeda, Rie Yoshioka, Toshiaki Ohkuma, Takanari Kitazono

    BMJ open diabetes research & care   9 ( 1 )   2021.4

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    INTRODUCTION: Type 1 diabetes (T1D) is associated with higher fracture risk. However, few studies have investigated the relationship between severe hypoglycemia and fracture risk in patients with T1D, and the results are controversial. Besides, none has investigated the risk factors for fracture in Asian patients with T1D. The aim of the present study was to investigate the prevalence of bone fracture and its relationship between severe hypoglycemia and other risk factors in Japanese patients with T1D. RESEARCH DESIGN AND METHODS: The single-center cross-sectional study enrolled 388 Japanese patients with T1D (mean age, 45.2 years; women, 60.4%; mean duration of diabetes, 16.6 years) between October 2019 and April 2020. The occurrence and circumstances of any fracture after the diagnosis of T1D were identified using a self-administered questionnaire. The main outcomes were any anatomic site of fracture and fall-related fracture. Severe hypoglycemia was defined as an episode of hypoglycemia that required the assistance of others to achieve recovery. RESULTS: A total of 92 fractures occurred in 64 patients, and 59 fractures (64%) were fall-related. Only one participant experienced fracture within the 10 years following their diagnosis of diabetes. In logistic regression analysis, the multivariate-adjusted ORs (95% CIs) of a history of severe hypoglycemia were 2.11 (1.11 to 4.09) for any fracture and 1.91 (0.93 to 4.02) for fall-related fracture. Fourteen of 18 participants with multiple episodes of any type of fracture had a history of severe hypoglycemia (p<0.001 vs no fracture). CONCLUSIONS: We have shown that a history of severe hypoglycemia is significantly associated with a higher risk of bone fracture in Japanese patients with T1D.

    DOI: 10.1136/bmjdrc-2020-002099

  • Defecation frequency and glycemic control in patients with diabetes: The Fukuoka Diabetes Registry. International journal

    Toshiaki Ohkuma, Masanori Iwase, Hiroki Fujii, Hitoshi Ide, Yuji Komorita, Masahito Yoshinari, Yutaro Oku, Taiki Higashi, Udai Nakamura, Takanari Kitazono

    Journal of diabetes and its complications   35 ( 2 )   107751 - 107751   2021.2

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    AIMS: Constipation has been shown to be associated with a higher risk of diabetes. However, few studies have evaluated the relationship between defecation frequency, one of the major symptoms of constipation, and glycemic control in patients with diabetes. The aim of the present study was to determine the relationship between defecation frequency and HbA1c in patients with diabetes. METHODS: We determined the relationship between defecation frequency and HbA1c in 5029 patients with diabetes in the Fukuoka Diabetes Registry, a multi-center prospective cohort study conducted in diabetes specialist outpatient clinic (mean age 64.9 years, men 55%). Participants were classified according to their defecation frequency: ≥7, 3-<7 and <3 times/week. RESULTS: Low defecation frequency was linearly associated with high HbA1c, with mean levels of 7.41% (95% confidence interval, 7.37-7.44%), 7.54% (7.49-7.60%) and 7.63% (7.52-7.74%) for patients with defecation frequencies of ≥7 times/week, 3-<7 times/week and <3 times/week (p for trend <0.001). This association remained after multivariable adjustment for confounding factors. There was no evidence of heterogeneity in the association between defecation frequency and HbA1c level according to age, sex, type of diabetes, or laxative use. CONCLUSIONS: The present study suggests the importance of assessing defecation frequency in the management of diabetes.

    DOI: 10.1016/j.jdiacomp.2020.107751

  • Incidence of stroke and its association with glycemic control and lifestyle in Japanese patients with type 2 diabetes mellitus: The Fukuoka diabetes registry. International journal

    Masanori Iwase, Yuji Komorita, Toshiaki Ohkuma, Hiroki Fujii, Hitoshi Ide, Masahito Yoshinari, Yutaro Oku, Taiki Higashi, Udai Nakamura, Takanari Kitazono

    Diabetes research and clinical practice   172   108518 - 108518   2021.2

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    AIMS: We prospectively investigated the incidence of stroke and its subtypes, risk factors and prognosis in Japanese patients with type 2 diabetes. METHODS: A total of 4,875 participants with type 2 diabetes (mean age 65.4 years, male 57%, previous stroke 10%) were investigated for the development of stroke for 5 years. Risk factors were evaluated using multivariable adjusted Cox proportional models. RESULTS: The incidence rates per 1,000 person-years were 6.7 for new-onset stroke (ischemic 5.5, hemorrhagic 1.2) and 22.7 for recurrent stroke (ischemic 18.8, hemorrhagic 3.8), respectively. Ischemic stroke was significantly associated with age, male, reduced regular physical activity, HbA1c, diabetic kidney disease and previous stroke. Lacunar infarction was significantly associated with obesity, reduced regular physical activity, HbA1c and diabetic kidney disease, whereas atherothrombotic stroke was significantly associated with age, reduced intake of dietary fiber, reduced regular physical activity, HbA1c and previous stroke. Recurrent stroke was significantly associated with depressive symptom. Thirty-day and one-year survival was 76% and 64% for hemorrhagic stroke, and 96% and 91% for ischemic stroke, respectively. CONCLUSIONS: The current study reemphasized the importance of glycemic control and lifestyle modification such as regular physical exercise for stroke prevention in patients with type 2 diabetes.

    DOI: 10.1016/j.diabres.2020.108518

  • Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. International journal

    Brendon L Neuen, Toshiaki Ohkuma, Bruce Neal, David R Matthews, Dick de Zeeuw, Kenneth W Mahaffey, Greg Fulcher, Jaime Blais, Qiang Li, Meg J Jardine, Vlado Perkovic, David C Wheeler

    American journal of kidney diseases : the official journal of the National Kidney Foundation   77 ( 1 )   23 - 34   2021.1

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    RATIONALE & OBJECTIVE: Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio. STUDY DESIGN: Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. SETTINGS & PARTICIPANTS: The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR≥30mL/min/1.73m2 to treatment with canagliflozin or placebo. INTERVENTION(S): Canagliflozin or matching placebo. OUTCOMES: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes. RESULTS: Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (P trend=0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greater within higher KDIGO risk categories (P trend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend=0.06) and for chronic eGFR slope (P trend = 0.04). LIMITATIONS: Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR<30mL/min/1.73m2. CONCLUSIONS: Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin. FUNDING: This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical. TRIAL REGISTRATION: The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754.

    DOI: 10.1053/j.ajkd.2020.06.018

  • Usefulness of the SAGE score to predict elevated values of brachial-ankle pulse wave velocity in Japanese subjects with hypertension. International journal

    Hirofumi Tomiyama, Charalambos Vlachopoulos, Panagiotis Xaplanteris, Hiroki Nakano, Kazuki Shiina, Tomoko Ishizu, Takahide Kohro, Yukihito Higashi, Bonpei Takase, Toru Suzuki, Tsutomu Yamazaki, Tomoo Furumoto, Kazuomi Kario, Teruo Inoue, Shinji Koba, Yasuhiko Takemoto, Takuzo Hano, Masataka Sata, Yutaka Ishibashi, Koichi Node, Atsushi Tanaka, Koji Maemura, Yusuke Ohya, Taiji Furukawa, Hiroshi Ito, Toshiaki Ohkuma, Toshiharu Ninomiya, Taishiro Chikamori, Akira Yamashina, Shin-Ichiro Ueda

    Hypertension research : official journal of the Japanese Society of Hypertension   43 ( 11 )   1284 - 1292   2020.11

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    The score based on the office systolic blood pressure, age, fasting blood glucose level, and estimated glomerular filtration rate (SAGE score) has been proposed as a useful marker to identify elevated values of carotid-femoral pulse wave velocity (PWV). The present cross-sectional study was conducted to examine whether the SAGE score is also a useful marker to identify subjects with elevated brachial-ankle PWV values in Japanese subjects with hypertension. We measured the brachial-ankle PWV and calculated the SAGE score in a total of 1019 employees of a Japanese company with hypertension and 817 subjects with hypertension derived from a multicenter study cohort. The analyses in this study were based on data from these two study groups as well as on a composite population of the two (n = 1836). The receiver operating characteristic curve analysis showed that the area under the curve to identify subjects with brachial-ankle PWV values of ≥1800 cm/s was over 0.70 in each of the three study groups. Even after adjustments, a SAGE score ≥7 had a significant odds ratio for identifying subjects with brachial-ankle PWV values ≥1800 cm/s in the 1836 study subjects from the composite occupational and multicenter study cohort (odds ratio = 2.1, 95% confidence interval = 1.4-3.0, P < 0.01). Thus, in Japanese subjects with hypertension, the SAGE score may be a useful marker for identifying subjects with elevated brachial-ankle PWV values.

    DOI: 10.1038/s41440-020-0472-7

  • Additive effects of green tea and coffee on all-cause mortality in patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry. International journal

    Yuji Komorita, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Masahito Yoshinari, Yutaro Oku, Taiki Higashi, Udai Nakamura, Takanari Kitazono

    BMJ open diabetes research & care   8 ( 1 )   2020.10

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    INTRODUCTION: The impact of consuming green tea or coffee on mortality in patients with diabetes is controversial. We prospectively investigated the impact of each beverage and their combination on mortality among Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In all, 4923 patients (2790 men, 2133 women) with type 2 diabetes (mean age, 66 years) were followed prospectively (median, 5.3 years; follow-up rate, 99.5%). We evaluated the amount of green tea and coffee consumed using self-administered questionnaires. RESULTS: During the follow-up period, 309 participants died. The consumption of green tea, coffee, and a combination of the beverages was associated with reduced all-cause mortality. Multivariable-adjusted hazard ratios (95% CIs) for green tea were as follows: none 1.0 (referent); 0.85 (0.60-1.22) for ≤1 cup/day; 0.73 (0.51-1.03) for 2-3 cups/day; 0.60 (0.42-0.85) for ≥4 cups/day; and P for trend, 0.002. For coffee, they were: none 1.0 (referent); 0.88 (0.66-1.18) for <1 cup/day; 0.81 (0.58-1.13) for 1 cup/day; 0.59 (0.42-0.82) for ≥2 cups/day; P for trend, 0.002. With the combination they were 1.0 (referent) for no consumption of green tea and coffee; 0.49 (0.24-0.99) for 2-3 cups/day of green tea with ≥2 cups/day of coffee; 0.42 (0.20-0.88) for ≥4 cups/day of green tea with 1 cup/day of coffee; and 0.37 (0.18-0.77) for ≥4 cups/day of green tea with ≥2 cups/day of coffee. CONCLUSIONS: Higher consumption of green tea and coffee was associated with reduced all-cause mortality: their combined effect appeared to be additive in patients with type 2 diabetes.

    DOI: 10.1136/bmjdrc-2020-001252

  • Sex-specific associations between cardiovascular risk factors and myocardial infarction in patients with type 2 diabetes: The ADVANCE-ON study. International journal

    Toshiaki Ohkuma, Sanne A E Peters, Min Jun, Stephen Harrap, Mark Cooper, Pavel Hamet, Neil Poulter, John Chalmers, Mark Woodward

    Diabetes, obesity & metabolism   22 ( 10 )   1818 - 1826   2020.10

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    AIM: To examine possible sex differences in the excess risk of myocardial infarction (MI) consequent to a range of conventional risk factors in a large-scale international cohort of patients with diabetes, and to quantify these potential differences both on the relative and absolute scales. MATERIALS AND METHODS: Eleven thousand and sixty-five participants (42% women) with type 2 diabetes in the ADVANCE trial and its post-trial follow-up study, ADVANCE-ON, were included. Cox regression models were used to estimate hazard ratios (HRs) for associations between risk factors and MI (fatal and non-fatal) by sex, and the women-to-men ratio of HRs (RHR). RESULTS: Over a median of 9.6 years of follow-up, 719 patients experienced MI. Smoking status, smoking intensity, higher systolic blood pressure (SBP), HbA1c, total and LDL cholesterol, duration of diabetes, triglycerides, body mass index (BMI) and lower HDL cholesterol were associated with an increased risk of MI in both sexes. Furthermore, some variables were associated with a greater relative risk of MI in women than men: RHRs were 1.75 (95% CI: 1.05-2.91) for current smoking, 1.53 (1.00-2.32) for former smoking, 1.18 (1.02-1.37) for SBP, and 1.13 (95% CI, 1.003-1.26) for duration of diabetes. Although incidence rates of MI were higher in men (9.3 per 1000 person-years) compared with women (5.8 per 1000 person-years), rate differences associated with risk factors were greater in women than men, except for HDL cholesterol and BMI. CONCLUSIONS: In patients with type 2 diabetes, smoking, higher SBP and longer duration of diabetes had a greater relative and absolute effect in women than men, highlighting the importance of routine sex-specific approaches and early interventions in women with diabetes.

    DOI: 10.1111/dom.14103

  • Home monitoring with technology-supported management in chronic heart failure: a randomised trial. International journal

    Kazem Rahimi, Milad Nazarzadeh, Ana-Catarina Pinho-Gomes, Mark Woodward, Gholamreza Salimi-Khorshidi, Toshiaki Ohkuma, Raymond Fitzpatrick, Lionel Tarassenko, Mike Denis, John Cleland

    Heart (British Cardiac Society)   106 ( 20 )   1573 - 1578   2020.10

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    OBJECTIVES: We aimed to investigate whether digital home monitoring with centralised specialist support for remote management of heart failure (HF) is more effective in improving medical therapy and patients' quality of life than digital home monitoring alone. METHODS: In a two-armed partially blinded parallel randomised controlled trial, seven sites in the UK recruited a total of 202 high-risk patients with HF (71.3 years SD 11.1; left ventricular ejection fraction 32.9% SD 15.4). Participants in both study arms were given a tablet computer, Bluetooth-enabled blood pressure monitor and weighing scales for health monitoring. Participants randomised to intervention received additional regular feedback to support self-management and their primary care doctors received instructions on blood investigations and pharmacological treatment. The primary outcome was the use of guideline-recommended medical therapy for chronic HF and major comorbidities, measured as a composite opportunity score (total number of recommended treatment given divided by the total number of opportunities the treatment should have been given, with a score 1 indicating 100% adherence to recommendations). Co-primary outcome was change in physical score of Minnesota Living with Heart Failure questionnaire. RESULTS: 101 patients were randomised to 'enhanced self-management' and 101 to 'supported medical management'. At the end of follow-up, the opportunity score was 0.54 (95% CI 0.46 to 0.62) in the control arm and 0.61 (95% CI 0.52 to 0.70) in the intervention arm (p=0.25). Physical well-being of participants also did not differ significantly between the groups (17.4 (12.4) mean (SD) for control arm vs 16.5 (12.1) in treatment arm; p for change=0.84). CONCLUSIONS: Central provision of tailored specialist management in a multi-morbid HF population was feasible. However, there was no strong evidence for improvement in use of evidence-based treatment nor health-related quality of life. TRIAL REGISTRATION NUMBER: ISRCTN86212709.

    DOI: 10.1136/heartjnl-2020-316773

  • Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program. International journal

    Megumi Oshima, Bruce Neal, Tadashi Toyama, Toshiaki Ohkuma, Qiang Li, Dick de Zeeuw, Hiddo J L Heerspink, Kenneth W Mahaffey, Gregory Fulcher, William Canovatchel, David R Matthews, Vlado Perkovic

    Journal of the American Society of Nephrology : JASN   31 ( 10 )   2446 - 2456   2020.10

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    BACKGROUND: Traditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes. METHODS: To assess whether eGFR declines <57% could detect canagliflozin's effects on renal outcomes, we conducted a post hoc study comparing effects of canagliflozin versus placebo on composite renal outcomes using sustained 57%, 50%, 40%, or 30% eGFR reductions in conjunction with ESKD and renal death. Because canagliflozin causes an acute reversible hemodynamic decline in eGFR, we made estimates using all eGFR values as well as estimates that excluded early measures of eGFR influenced by the acute hemodynamic effect. RESULTS: Among the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect. CONCLUSIONS: Declines in eGFR <57% may provide robust estimates of canagliflozin's effects on renal outcomes if the analysis controls for the drug's acute hemodynamic effect. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754.

    DOI: 10.1681/ASN.2019121312

  • Incidence of severe hypoglycemia and its association with serum adiponectin in Japanese patients with type 1 and insulin-treated type 2 diabetes: The Fukuoka Diabetes Registry.

    Masanori Iwase, Yuji Komorita, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Masahito Yoshinari, Yutaro Oku, Taiki Higashi, Udai Nakamura, Takanari Kitazono

    Journal of diabetes investigation   11 ( 5 )   1258 - 1264   2020.9

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    AIMS/INTRODUCTION: The incidence of severe hypoglycemia and its risk factors including an insulin-sensitizing adipokine, adiponectin, were prospectively investigated in Japanese patients with type 1 or insulin-treated type 2 diabetes. MATERIALS AND METHODS: A total of 207 participants with type 1 diabetes (mean age 55 years) and 1,396 with insulin-treated type 2 diabetes (mean age 65 years) from the local diabetes registry were followed for 5 years (follow-up rate 99%). Severe hypoglycemia was defined as events requiring the assistance of others for recovery from hypoglycemia. RESULTS: The incidence of severe hypoglycemia was 9.2 per 100 person-years in those with type 1 diabetes, and 2.3 per 100 person-years in those with insulin-treated type 2 diabetes, respectively. For type 1 diabetes, the risk was significant in those with a history of severe hypoglycemia within the previous year, slow eating and higher serum adiponectin (the highest vs the lowest in quartile hazard ratio 2.36, 95% confidence interval 1.22-4.69). For insulin-treated type 2 diabetes, the risk included age ≥65 years, history of severe hypoglycemia within the previous year, alcohol consumption ≥60 g/day, larger insulin dose and higher serum adiponectin (the highest vs the lowest in quartile, hazard ratio 2.95, 95% confidence interval 1.22-4.69). For all participants, the incidence of severe hypoglycemia increased along with serum adiponectin (age- and sex-adjusted hazard ratio 1.65 per 1 standard deviation increase of log serum adiponectin, 95% confidence interval 1.45-1.87). CONCLUSIONS: The incidence of severe hypoglycemia was prospectively determined, and the association between severe hypoglycemia and higher serum adiponectin was observed in Japanese patients with type 1 and insulin-treated type 2 diabetes.

    DOI: 10.1111/jdi.13253

  • Effects of Intensive Glycemic Control on Clinical Outcomes Among Patients With Type 2 Diabetes With Different Levels of Cardiovascular Risk and Hemoglobin A1c in the ADVANCE Trial. International journal

    Jingyan Tian, Toshiaki Ohkuma, Mark Cooper, Stephen Harrap, Giuseppe Mancia, Neil Poulter, Ji-Guang Wang, Sophia Zoungas, Mark Woodward, John Chalmers

    Diabetes care   43 ( 6 )   1293 - 1299   2020.6

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    OBJECTIVE: To study whether the effects of intensive glycemic control on major vascular outcomes (a composite of major macrovascular and major microvascular events), all-cause mortality, and severe hypoglycemia events differ among participants with different levels of 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and hemoglobin A1c (HbA1c) at baseline. RESEARCH DESIGN AND METHODS: We studied the effects of more intensive glycemic control in 11,071 patients with type 2 diabetes (T2D), without missing values, in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, using Cox models. RESULTS: During 5 years' follow-up, intensive glycemic control reduced major vascular events (hazard ratio [HR] 0.90 [95% CI 0.83-0.98]), with the major driver being a reduction in the development of macroalbuminuria. There was no evidence of differences in the effect, regardless of baseline ASCVD risk or HbA1c level (P for interaction = 0.29 and 0.94, respectively). Similarly, the beneficial effects of intensive glycemic control on all-cause mortality were not significantly different across baseline ASCVD risk (P = 0.15) or HbA1c levels (P = 0.87). The risks of severe hypoglycemic events were higher in the intensive glycemic control group compared with the standard glycemic control group (HR 1.85 [1.41-2.42]), with no significant heterogeneity across subgroups defined by ASCVD risk or HbA1c at baseline (P = 0.09 and 0.18, respectively). CONCLUSIONS: The major benefits for patients with T2D in ADVANCE did not substantially differ across levels of baseline ASCVD risk and HbA1c.

    DOI: 10.2337/dc19-1817

  • Association of anthropometry and weight change with risk of dementia and its major subtypes: A meta-analysis consisting 2.8 million adults with 57 294 cases of dementia. International journal

    Crystal ManYing Lee, Mark Woodward, G David Batty, Alexa S Beiser, Steven Bell, Claudine Berr, Espen Bjertness, John Chalmers, Robert Clarke, Jean-Francois Dartigues, Kendra Davis-Plourde, Stéphanie Debette, Emanuele Di Angelantonio, Catherine Feart, Ruth Frikke-Schmidt, John Gregson, Mary N Haan, Linda B Hassing, Kathleen M Hayden, Marieke P Hoevenaar-Blom, Jaakko Kaprio, Mika Kivimaki, Georgios Lappas, Eric B Larson, Erin S LeBlanc, Anne Lee, Li-Yung Lui, Eric P Moll van Charante, Toshiharu Ninomiya, Liv Tybjaerg Nordestgaard, Tomoyuki Ohara, Toshiaki Ohkuma, Teemu Palviainen, Karine Peres, Ruth Peters, Nawab Qizilbash, Edo Richard, Annika Rosengren, Sudha Seshadri, Martin Shipley, Archana Singh-Manoux, Bjorn Heine Strand, Willem A van Gool, Eero Vuoksimaa, Kristine Yaffe, Rachel R Huxley

    Obesity reviews : an official journal of the International Association for the Study of Obesity   21 ( 4 )   e12989   2020.4

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    Uncertainty exists regarding the relation of body size and weight change with dementia risk. As populations continue to age and the global obesity epidemic shows no sign of waning, reliable quantification of such associations is important. We examined the relationship of body mass index, waist circumference, and annual percent weight change with risk of dementia and its subtypes by pooling data from 19 prospective cohort studies and four clinical trials using meta-analysis. Compared with body mass index-defined lower-normal weight (18.5-22.4 kg/m2 ), the risk of all-cause dementia was higher among underweight individuals but lower among those with upper-normal (22.5-24.9 kg/m2 ) levels. Obesity was associated with higher risk in vascular dementia. Similarly, relative to the lowest fifth of waist circumference, those in the highest fifth had nonsignificant higher vascular dementia risk. Weight loss was associated with higher all-cause dementia risk relative to weight maintenance. Weight gain was weakly associated with higher vascular dementia risk. The relationship between body size, weight change, and dementia is complex and exhibits non-linear associations depending on dementia subtype under scrutiny. Weight loss was associated with an elevated risk most likely due to reverse causality and/or pathophysiological changes in the brain, although the latter remains speculative.

    DOI: 10.1111/obr.12989

  • Clinical outcomes with canagliflozin according to baseline body mass index: results from post hoc analyses of the CANVAS Program. International journal

    Toshiaki Ohkuma, Luc Van Gaal, Wayne Shaw, Kenneth W Mahaffey, Dick de Zeeuw, David R Matthews, Vlado Perkovic, Bruce Neal

    Diabetes, obesity & metabolism   22 ( 4 )   530 - 539   2020.4

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    AIMS: Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce several cardiovascular risk factors, including plasma glucose, blood pressure, albuminuria and body weight. Long-term treatment lowers risks of cardiovascular and renal events. The objective of this post hoc analysis was to determine the effects of canagliflozin treatment versus placebo on clinical outcomes in relation to body mass index (BMI). MATERIALS AND METHODS: The CANVAS Program randomized 10 142 participants with type 2 diabetes to canagliflozin or placebo. These analyses tested the consistency of canagliflozin treatment effects across BMI levels for cardiovascular, renal, safety and body weight outcomes in three groups defined by baseline BMI: <25, 25-<30 and ≥30 kg/m2 . RESULTS: In total, 10 128 participants with baseline BMI measurements were included. There were 966 participants with BMI <25 kg/m2 , 3153 with BMI 25-<30 kg/m2 and 6009 with BMI ≥30 kg/m2 . Mean percent body weight reduction with canagliflozin compared with placebo was greater at 12 months [-2.77%  (95% confidence interval (CI): -2.95, -2.59)] than at 3 months [-1.72%  (95% CI: -1.83, -1.62)]. The hazard ratios (HRs) for canagliflozin compared with placebo control for the composite outcome of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke were 1.03 (95% CI: 0.66, 1.59) in participants with BMI <25 kg/m2 , 0.97 (0.76, 1.23) with BMI 25-<30 kg/m2 and 0.79 (0.67, 0.93) with BMI ≥30 kg/m2 (P for heterogeneity = 0.55). The effects of canagliflozin on each component of the composite were also similar across BMI subgroups, as were effects on heart failure and renal outcomes (P for heterogeneity ≥0.19). The effects on safety outcomes were also broadly similar. CONCLUSIONS: Canagliflozin improved cardiovascular and renal outcomes consistently across patients with a broad range of BMI levels.

    DOI: 10.1111/dom.13920

  • Intensive glucose-lowering and the risk of vascular events and premature death in patients with decreased kidney function: The ADVANCE trial. International journal

    Toshiaki Ohkuma, Sophia Zoungas, Min Jun, Liu Lisheng, Giuseppe Mancia, Michel Marre, Anthony Rodgers, Bryan Williams, Mark Woodward, John Chalmers

    Diabetes, obesity & metabolism   22 ( 3 )   452 - 457   2020.3

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    To assess the effects of intensive glucose control on the risk of major clinical outcomes according to estimated glomerular filtration rate (eGFR) levels in people with type 2 diabetes. Of 11 140 ADVANCE trial participants, 11 096 with baseline eGFR measurements were included, and classified into three eGFR groups: ≥90 mL/min/1.73 m2 ; 60 to 89 mL/min/1.73 m2 ; and < 60 mL/min/1.73 m2 . Relative risk reduction of randomized intensive glucose control with regard to the composite outcome of major macro- and microvascular events, all-cause death and cardiovascular death did not significantly vary by eGFR level (P for heterogeneity ≥0.49). The risk of severe hypoglycaemia increased with intensive glucose control; however, this risk did not vary across eGFR groups (P for heterogeneity = 0.83). The risk-benefit profile of intensive glucose control in patients with type 2 diabetes and impaired kidney function appears similar to that observed in those with preserved kidney function.

    DOI: 10.1111/dom.13878

  • Impact of hip fracture on all-cause mortality in Japanese patients with type 2 diabetes mellitus: The Fukuoka Diabetes Registry.

    Yuji Komorita, Masanori Iwase, Yasuhiro Idewaki, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Masahito Yoshinari, Ai Murao-Kimura, Yutaro Oku, Udai Nakamura, Takanari Kitazono

    Journal of diabetes investigation   11 ( 1 )   62 - 69   2020.1

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    AIMS/INTRODUCTION: Patients with type 2 diabetes mellitus have an increased hip fracture risk. We investigated the relationship between hip fracture and all-cause death in patients with type 2 diabetes in comparison with cardiovascular disease (CVD) or end-stage renal disease (ERSD). MATERIALS AND METHODS: In total, 4,923 Japanese participants with type 2 diabetes (mean age 65 years, 2,790 men, 2,133 women) were followed for a median of 5.3 years (follow-up rate 99.5%). We evaluated the associations between the presence of hip fracture (n = 110), upper limb fracture (n = 801), CVD (n = 1,344), ESRD (n = 104) and all-cause death by logistic regression analysis. RESULTS: A total of 309 participants died during follow up. Multivariate-adjusted odds ratios (ORs) for all-cause mortality were significantly higher in participants with hip fractures than those without hip fractures (OR 2.67, 95% confidence interval [CI] 1.54-4.41), whereas the ORs for upper limb fracture were not significant. The ORs for all-cause mortality were significantly higher in participants with CVD than those without CVD (OR 1.78, 95% CI, 1.39-2.70) and ESRD (OR 2.36, 95% CI 1.32-4.05). The ORs for all-cause mortality of hip fracture were not affected by further adjustment for CVD and ESRD (OR 2.74, 95% CI 1.58-4.54). The cause of death was infection (40.0%), malignant neoplasm (25.0%) and CVD (15.0%) among participants with hip fracture. CONCLUSIONS: Hip fractures were associated with an increased risk of death among Japanese patients with type 2 diabetes, independently of CVD and ESRD.

    DOI: 10.1111/jdi.13076

  • The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE. International journal

    Alexandra K Lee, Mark Woodward, Dan Wang, Toshiaki Ohkuma, Bethany Warren, A Richey Sharrett, Bryan Williams, Michel Marre, Pavel Hamet, Stephen Harrap, John W Mcevoy, John Chalmers, Elizabeth Selvin

    The Journal of clinical endocrinology and metabolism   105 ( 1 )   2020.1

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    CONTEXT: Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. OBJECTIVE: To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. DESIGN AND SETTING: The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. RESULTS: Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. CONCLUSIONS: In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.

    DOI: 10.1210/clinem/dgz045

  • Brachial-Ankle Pulse Wave Velocity Versus Its Stiffness Index β-Transformed Value as Risk Marker for Cardiovascular Disease. International journal

    Hirofumi Tomiyama, Toshiaki Ohkuma, Toshiharu Ninomiya, Hiroki Nakano, Chisa Matsumoto, Alberto Avolio, Takahide Kohro, Yukihito Higashi, Tatsuya Maruhashi, Bonpei Takase, Toru Suzuki, Tomoko Ishizu, Shinichiro Ueda, Tsutomu Yamazaki, Tomoo Furumoto, Kazuomi Kario, Teruo Inoue, Shinji Koba, Yasuhiko Takemoto, Takuzo Hano, Masataka Sata, Yutaka Ishibashi, Koichi Node, Koji Maemura, Yusuke Ohya, Taiji Furukawa, Hiroshi Ito, Taishiro Chikamori, Akira Yamashina

    Journal of the American Heart Association   8 ( 24 )   e013004   2019.12

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    Background The difference in the predictive ability of the brachial-ankle pulse wave velocity (baPWV) and its stiffness index β-transformed value (β-baPWV, ie, baPWV adjusted for the pulse pressure) for the development of pathophysiological abnormalities related to cardiovascular disease or future occurrence of cardiovascular disease was examined. Methods and Results In study 1, a 7-year prospective observational study in cohorts of 3274 men and 3490 men, the area under the curve in the receiver operator characteristic curve analysis was higher for baPWV than for β-baPWV for predicting the development of hypertension (0.73, 95% CI=0.70 to 0.75 versus 0.59, 95% CI=0.56 to 0.62; P<0.01) and/or the development of retinopathy (0.78, 95% CI=0.73 to 0.82 versus 0.66, 95% CI=0.60 to 0.71; P<0.01) by the end of the study period. During study 2, a 3-year observation period on 511 patients with coronary artery disease, 72 cardiovascular events were confirmed. The C statistics of both markers for predicting the development of cardiovascular events were similar. Conclusions Stiffness index β transformation of the baPWV may attenuate the significance of the baPWV as a risk marker for development of pathophysiological abnormalities related to cardiovascular disease in male subjects.

    DOI: 10.1161/JAHA.119.013004

  • Effect of Canagliflozin on Renal and Cardiovascular Outcomes across Different Levels of Albuminuria: Data from the CANVAS Program. International journal

    Brendon L Neuen, Toshiaki Ohkuma, Bruce Neal, David R Matthews, Dick de Zeeuw, Kenneth W Mahaffey, Greg Fulcher, Qiang Li, Meg Jardine, Richard Oh, Hiddo L Heerspink, Vlado Perkovic

    Journal of the American Society of Nephrology : JASN   30 ( 11 )   2229 - 2242   2019.11

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    BACKGROUND: If SGLT2 inhibitors protect the kidneys by reducing albuminuria as hypothesized, people with type 2 diabetes mellitus (T2DM) with higher albuminuria should benefit more. METHODS: We conducted a post-hoc analysis of data from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, which randomized 10,142 participants with T2DM and high cardiovascular risk to canagliflozin or placebo. We assessed effects of canagliflozin on renal, cardiovascular, and safety outcomes by baseline albuminuria. The trial included 2266 participants (22.3%) with moderately increased albuminuria (urinary albumin/creatinine ratio [UACR] 30-300 mg/g) and 760 (7.5%) with severely increased albuminuria (UACR >300 mg/g) at baseline. RESULTS: Canagliflozin lowered albuminuria with greater proportional reductions in those with moderately and severely increased albuminuria (P heterogeneity<0.001). After week 13, canagliflozin slowed the annual loss of kidney function across albuminuria subgroups, with greater absolute reductions in participants with severely increased albuminuria (placebo-subtracted difference 3.01 ml/min per 1.73 m2 per year; P heterogeneity<0.001). Heterogeneity for the renal composite outcome of 40% reduction in eGFR, ESKD, or renal-related death was driven by lesser effects in participants with moderately increased albuminuria (P heterogeneity=0.03), but no effect modification was observed when albuminuria was fitted as a continuous variable (P heterogeneity=0.94). Cardiovascular and safety outcomes were mostly consistent across albuminuria levels including increased risks for amputation across albuminuria subgroups (P heterogeneity=0.66). Greater absolute risk reductions in the renal composite outcome were observed in participants with severely increased albuminuria (P heterogeneity=0.004). CONCLUSIONS: The proportional effects of canagliflozin on renal and cardiovascular outcomes are mostly consistent across patients with different levels of albuminuria, but absolute benefits are greatest among those with severely increased albuminuria.

    DOI: 10.1681/ASN.2019010064

  • The relationship between eGFR slope and subsequent risk of vascular outcomes and all-cause mortality in type 2 diabetes: the ADVANCE-ON study. International journal

    Megumi Oshima, Min Jun, Toshiaki Ohkuma, Tadashi Toyama, Takashi Wada, Mark E Cooper, Samy Hadjadj, Pavel Hamet, Stephen Harrap, Giuseppe Mancia, Michel Marre, Bryan Williams, John Chalmers, Mark Woodward, Vlado Perkovic

    Diabetologia   62 ( 11 )   1988 - 1997   2019.11

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    AIMS/HYPOTHESIS: Some studies have reported that annual change in eGFR (eGFR slope) is associated with the future risk of end-stage kidney disease, cardiovascular disease and death in general or chronic kidney disease cohorts. However, the benefits of using eGFR slopes for prediction of major clinical outcomes in diabetes are unclear. METHODS: We used data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial and the ADVANCE Post-Trial Observational Study (ADVANCE-ON). After excluding the first 4 months during which an acute fall in eGFR was induced by the initiation of an ACE inhibitor and diuretic combination agent, eGFR slopes were estimated by linear mixed models, using three measurements of eGFR at 4, 12 and 24 months after randomisation over 20 months, and categorised according to quartiles. Cox regression models were used to evaluate adjusted HRs for the study's primary outcome, a composite of major renal events, major macrovascular events and all-cause mortality during the subsequent follow-up from 24 months after randomisation. RESULTS: A total of 8,879 participants (80%) were included in this cohort. The mean age was 65.6 years (SD 6.3), the mean eGFR was 75 ml min-1 (1.73 m)-2 (SD 17) and the median urinary albumin/creatinine ratio was 14 μg/mg (interquartile range 7-38). The mean eGFR slope was -0.63 ml min-1 (1.73 m)-2 year-1 (SD 1.75). Over a median follow-up of 7.6 years following the 20-month eGFR slope ascertainment period, 2,221 participants (25%) met the primary outcome. An annual substantial decrease in eGFR (lowest 25%, <-1.63 ml min-1 [1.73 m]-2 year-1) was significantly associated with the subsequent risk of the primary outcome (HR 1.30 [95% CI 1.17, 1.43]) compared with a stable change in eGFR (middle 50%, -1.63 to 0.33). An annual substantial increase in eGFR (highest 25%, >0.33) had no significant association with the risk of the primary outcome (HR 0.96 [95% CI 0.86, 1.07]). CONCLUSIONS/INTERPRETATION: Our study supports the utility of eGFR slope in type 2 diabetes as a surrogate endpoint for renal outcomes, as well as a prognostic factor for identifying individuals at high risk of cardiovascular disease and all-cause mortality. TRIAL REGISTRY NUMBER: ClinicalTrials.gov registration no. NCT00145925 and no. NCT00949286.

    DOI: 10.1007/s00125-019-4948-4

  • Associations of Impaired Renal Function With Declines in Muscle Strength and Muscle Function in Older Men: Findings From the CHAMP Study. International journal

    Tadashi Toyama, Oliver van den Broek-Best, Toshiaki Ohkuma, David Handelsman, Louise M Waite, Markus J Seibel, Robert Cumming, Vasi Naganathan, Cathie Sherrington, Vasant Hirani, Amanda Y Wang

    The journals of gerontology. Series A, Biological sciences and medical sciences   74 ( 11 )   1812 - 1820   2019.10

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    BACKGROUND: Advanced kidney disease is associated with reduced muscle strength and physical performance. However, associations between early stages of renal impairment and physical outcomes are unclear. METHODS: The Concord Health and Ageing in Men Project is a prospective study of 1,705 community-dwelling men aged 70 years and older. Participants with estimated glomerular filtration rate (eGFR) more than 30 mL/min/1.73 m2 were included and further divided into four eGFR categories. Physical parameters including grip strength, gait speed, appendicular lean mass (ALM, a sum of skeletal mass of arms and legs), ALM adjusted for body mass index (ALMBMI), and muscle function (measured using grip strength divided by arm lean mass) were assessed at both baseline and 5-year follow-up. Associations between kidney function and changes in physical parameters were analyzed using linear and logistic regression models. RESULTS: Our study included 789 men with a median age of 75 years and median eGFR of 72 mL/min/1.73 m2 at baseline. Over 5 years, grip strength, gait speed, ALMBMI, and muscle function all declined in the whole cohort, compared with baseline. The multivariable analyses showed that poorer renal function was associated with more rapid declines in grip strength, gait speed, and muscle function in participants with mild-to-moderate renal impairment (GFR category stage G3, eGFR < 60 mL/min/1.73 m2) (p = .01, p < .01, p = .02, respectively) but less so in those with eGFR more than 60 mL/min/1.73 m2, whereas eGFR category did not have a significant impact on declines in ALMBMI. These results remained unchanged with or without adjustment for age. CONCLUSIONS: In community-dwelling older men, mild-to-moderate renal impairment at baseline was associated with declines in grip strength, gait speed, and muscle function over time despite preservation of muscle mass.

    DOI: 10.1093/gerona/glz100

  • Prospective study of cancer in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry.

    Masanori Iwase, Hiroki Fujii, Yasuhiro Idewaki, Udai Nakamura, Toshiaki Ohkuma, Hitoshi Ide, Yuji Komorita, Tamaki Jodai-Kitamura, Masahito Yoshinari, Takanari Kitazono

    Diabetology international   10 ( 4 )   260 - 267   2019.10

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    Background: Although the association between type 2 diabetes and cancer has been reported, few epidemiological studies have been conducted in Japanese patients whose leading cause of death is cancer. We prospectively studied the incidence of site-specific cancer, risk factors for developing cancer, cancer death, and survival in Japanese patients with type 2 diabetes. Methods: We followed 4923 participants (mean age, 65 years) with type 2 diabetes attending an outpatient diabetes clinic for a median of 5.3 years (follow-up rate, 99.0%). Results: During the follow-up period, cancer occurred in 450 participants (incidence rate, 22.3/1000 person-years in men and 12.2/1000 person-years in women). In men, prostate cancer was the most common cancer (4.3/1000 person-years), colorectal cancer was the second (3.6/1000 person-years), and gastric cancer was the third (3.3/1000 person-years). In women, colorectal cancer was the most common cancer (2.6/1000 person-years), gastric cancer was the second (2.0/1000 person-years), and breast cancer was the third (1.4/1000 person-years). Smoking, male sex, low-density lipoprotein cholesterol, family history of cancer, and reduced intake of isoflavone daidzein were significant risk factors for developing cancer using multivariable Cox proportional hazards models. The leading cancer death was lung cancer in men and pancreatic cancer in women. The survival was the best for prostate cancer and the worst for pancreatic cancer (2-year cancer-specific survival 95.4%, 30.0%, respectively). Conclusions: Since the leading cause of death in patients with type 2 diabetes is cancer in Japan, clinicians should be aware of epidemiological data regarding cancer besides diabetic complications.

    DOI: 10.1007/s13340-019-00390-0

  • Diabetes as a risk factor for heart failure in women and men: a systematic review and meta-analysis of 47 cohorts including 12 million individuals. International journal

    Toshiaki Ohkuma, Yuji Komorita, Sanne A E Peters, Mark Woodward

    Diabetologia   62 ( 9 )   1550 - 1560   2019.9

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    AIMS/HYPOTHESIS: The prevalence of diabetes and heart failure is increasing, and diabetes has been associated with an increased risk of heart failure. However, whether diabetes confers the same excess risk of heart failure in women and men is unknown. The aim of this study was to conduct a comprehensive systematic review with meta-analysis of possible sex differences in the excess risk of heart failure consequent to diabetes. Our null hypothesis was that there is no such sex difference. METHODS: A systematic search was conducted in PubMed for population-based cohort studies published between January 1966 and November 2018. Studies were selected if they reported sex-specific estimates of RRs for heart failure associated with diabetes, and its associated variability, which were adjusted at least for age. Random-effects meta-analyses with inverse variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratio of RRs (RRRs) for heart failure associated with diabetes. RESULTS: Data from 47 cohorts, involving 12,142,998 individuals and 253,260 heart failure events, were included. The pooled multiple-adjusted RR for heart failure associated with type 1 diabetes was 5.15 (95% CI 3.43, 7.74) in women and 3.47 (2.57, 4.69) in men, leading to an RRR of 1.47 (1.44, 1.90). Corresponding pooled RRs for heart failure associated with type 2 diabetes were 1.95 (1.70, 2.22) in women and 1.74 (1.55, 1.95) in men, with a pooled RRR of 1.09 (1.05, 1.13). CONCLUSIONS/INTERPRETATION: The excess risk of heart failure associated with diabetes is significantly greater in women with diabetes than in men with diabetes. PROSPERO registration: CRD42019135246.

    DOI: 10.1007/s00125-019-4926-x

  • Combination of Changes in Estimated GFR and Albuminuria and the Risk of Major Clinical Outcomes. International journal

    Toshiaki Ohkuma, Min Jun, John Chalmers, Mark E Cooper, Pavel Hamet, Stephen Harrap, Sophia Zoungas, Vlado Perkovic, Mark Woodward

    Clinical journal of the American Society of Nephrology : CJASN   14 ( 6 )   862 - 872   2019.6

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    BACKGROUND AND OBJECTIVES: Whether combining changes in eGFR and urine albumin-to-creatinine ratio (UACR) is more strongly associated with outcomes compared with either change alone is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed 8766 patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation Observational (ADVANCE-ON) study. Changes in eGFR and UACR (baseline to 2 years) were defined as ≥40% decrease, minor change, and ≥40% increase. The primary outcome was the composite of major macrovascular (nonfatal or fatal myocardial infarction, nonfatal or fatal stroke, or cardiovascular death), major kidney events (requirement for kidney replacement therapy or kidney death), and all-cause mortality. RESULTS: Over a median of 7.7 years of follow-up, 2191 primary outcomes were recorded. Strong linear associations between eGFR and UACR changes and subsequent risk of the outcome were observed. For eGFR, the hazard ratios were 1.58 (95% confidence interval [95% CI], 1.27 to 1.95) for a decrease ≥40% and 0.82 for an increase ≥40% (95% CI, 0.64 to 1.04) compared with minor change. For UACR, the hazard ratios were 0.96 (95% CI, 0.85 to 1.07) for a decrease ≥40% and 1.32 (95% CI, 1.19 to 1.46) for ≥40% increase compared with minor change. Compared with dual minor changes, both an eGFR decrease ≥40% and a UACR increase ≥40% had 2.31 (95% CI, 1.67 to 3.18) times the risk of the outcome, with evidence of interaction between the two markers. CONCLUSIONS: Clinically meaningful decreases in eGFR and increases in UACR over 2 years, independently and in combination, were significantly associated with higher risk of major clinical outcomes.

    DOI: 10.2215/CJN.13391118

  • Effects of Blood Pressure Lowering on Clinical Outcomes According to Baseline Blood Pressure and Cardiovascular Risk in Patients With Type 2 Diabetes Mellitus. International journal

    Faisal Rahman, John W McEvoy, Toshiaki Ohkuma, Michel Marre, Pavel Hamet, Stephen Harrap, Giuseppe Mancia, Anthony Rodgers, Elizabeth Selvin, Bryan Williams, Paul Muntner, John Chalmers, Mark Woodward

    Hypertension (Dallas, Tex. : 1979)   73 ( 6 )   1291 - 1299   2019.6

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    The optimal blood pressure (BP) goal in patients with diabetes mellitus remains controversial. We examined whether benefits and risks of intensified antihypertensive therapy in diabetes mellitus are influenced by either baseline BP or cardiovascular disease (CVD) risk. We studied 10 948 people with diabetes mellitus, at moderate-to-high risk, in the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation). Cox models were used to determine whether baseline BP category or CVD risk modified the outcomes of combination perindopril-indapamide treatment, compared with placebo. During 4.3 years of follow-up, treatment with perindopril-indapamide versus placebo reduced mortality and major vascular (macrovascular or microvascular) events. There was no evidence of differences in these effects, regardless of baseline systolic BP (evaluated down to <120 mm Hg; P for heterogeneity, 0.85), diastolic BP (evaluated down to <70 mm Hg; P=0.49), or whether 10-year CVD risk was ≥20% or <20% ( P=0.08). The effects of randomized treatment on discontinuation of treatment because of cough or hypotension/dizziness were also statistically consistent across subgroups defined by baseline BP and CVD risk (all P ≥0.08). Adults with diabetes mellitus appear to benefit from more intensive BP treatment even at levels of BP and CVD risk that some guidelines do not currently recommend for intervention. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00751972.

    DOI: 10.1161/HYPERTENSIONAHA.118.12414

  • Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta-analysis. International journal

    Tadashi Toyama, Brendon L Neuen, Min Jun, Toshiaki Ohkuma, Bruce Neal, Meg J Jardine, Hiddo L Heerspink, Muh Geot Wong, Toshiharu Ninomiya, Takashi Wada, Vlado Perkovic

    Diabetes, obesity & metabolism   21 ( 5 )   1237 - 1250   2019.5

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    AIM: The use of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycaemic efficacy is dependent on kidney function. We performed a systematic review and meta-analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 . MATERIALS AND METHODS: We searched MEDLINE, EMBASE and the Cochrane Library until 7 August 2018 and websites of the US, European and Japanese regulatory authorities until 27 July 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals. RESULTS: Data were obtained from 27 studies with up to 7363 participants involved. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated haemoglobin (-0.29%; 95% CI, -0.39 to -0.19) as well as blood pressure, body weight and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR, 0.81; 95% CI, 0.70-0.94) and heart failure (RR, 0.61; 95% CI, 0.48-0.78), without a clear effect on all-cause mortality (HR, 0.86; 95% CI, 0.73-1.01). These agents also attenuated the annual decline in eGFR slope (placebo-subtracted difference of 1.35 mL/1.73 m2 /y; 95% CI, 0.78-1.93) and reduced the risk of the composite renal outcome (HR, 0.71; 95% CI, 0.53-0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. CONCLUSION: Currently available data suggest that, despite only modest reductions in glycated haemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.

    DOI: 10.1111/dom.13648

  • Steno-Stiffness Approach for Cardiovascular Disease Risk Assessment in Primary Prevention. International journal

    Hirofumi Tomiyama, Toshiaki Ohkuma, Toshiharu Ninomiya, Chisa Mastumoto, Kazuomi Kario, Satoshi Hoshide, Yoshikuni Kita, Toyoshi Inoguchi, Yasutaka Maeda, Katsuhiko Kohara, Yasuharu Tabara, Motoyuki Nakamura, Takayoshi Ohkubo, Hirotaka Watada, Masanori Munakata, Mitsuru Ohishi, Norihisa Ito, Michinari Nakamura, Tetsuo Shoji, Charalambos Vlachopoulos, Victor Aboyans, Akira Yamashina

    Hypertension (Dallas, Tex. : 1979)   73 ( 3 )   508 - 513   2019.3

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    DOI: 10.1161/HYPERTENSIONAHA.118.12110

  • Acute Increases in Serum Creatinine After Starting Angiotensin-Converting Enzyme Inhibitor-Based Therapy and Effects of its Continuation on Major Clinical Outcomes in Type 2 Diabetes Mellitus. International journal

    Toshiaki Ohkuma, Min Jun, Anthony Rodgers, Mark E Cooper, Paul Glasziou, Pavel Hamet, Stephen Harrap, Giuseppe Mancia, Michel Marre, Bruce Neal, Vlado Perkovic, Neil Poulter, Bryan Williams, Sophia Zoungas, John Chalmers, Mark Woodward

    Hypertension (Dallas, Tex. : 1979)   73 ( 1 )   84 - 91   2019.1

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    Discontinuation of angiotensin-converting enzyme (ACE) inhibitor is recommended if patients experience ≥30% acute increase in serum creatinine after starting this therapy. However, the long-term effects of its continuation or discontinuation on major clinical outcomes after increases in serum creatinine are unclear. In the ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation), 11 140 diabetes mellitus patients were randomly assigned to perindopril-indapamide or placebo after a 6-week active run-in period. The current study included 11 066 participants with 2 serum creatinine measurements recorded before and during the active run-in period (3 weeks apart). Acute increase in creatinine was determined using these 2 measurements and classified into 4 groups: increases in serum creatinine of <10%, 10% to 19%, 20% to 29%, and ≥30%. The primary study outcome was the composite of major macrovascular events, new or worsening nephropathy, and all-cause mortality. An acute increase in serum creatinine was associated with an elevated risk of the primary outcome ( P for trend <0.001). The hazard ratios were 1.11 (95% CI, 0.97-1.28) for those with an increase of 10% to 19%, 1.34 (1.07-1.66) for 20% to 29%, and 1.44 (1.15-1.81) for ≥30%, compared with <10%. However, there was no evidence of heterogeneity in the benefit of randomized treatment effects on the outcome across subgroups defined by acute serum creatinine increase ( P for heterogeneity=0.94). Acute increases in serum creatinine after starting perindopril-indapamide were associated with greater risks of subsequent major clinical outcomes. However, the continuation of angiotensin-converting enzyme inhibitor-based therapy reduced the long-term risk of major clinical outcomes, irrespective of acute increase in creatinine. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00145925.

    DOI: 10.1161/HYPERTENSIONAHA.118.12060

  • Is there evidence for sex differences in the association between diabetes and cancer? Reply to Dankner R, Boker LK, Freedman LS [letter]. International journal

    Toshiaki Ohkuma, Sanne A E Peters, Mark Woodward

    Diabetologia   62 ( 1 )   201 - 201   2019.1

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    DOI: 10.1007/s00125-018-4761-5

  • The serum creatinine to cystatin C ratio predicts bone fracture in patients with type 2 diabetes: The Fukuoka Diabetes Registry. International journal

    Yuji Komorita, Masanori Iwase, Hiroki Fujii, Hitoshi Ide, Toshiaki Ohkuma, Tamaki Jodai-Kitamura, Akiko Sumi, Masahito Yoshinari, Udai Nakamura, Takanari Kitazono

    Diabetes research and clinical practice   146   202 - 210   2018.12

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    AIMS: Sarcopenia is involved in the pathogenesis of increased fracture risk associated with diabetes. The serum creatinine to cystatin C (Cr/CysC) ratio has been reported as a surrogate marker for muscle mass. We aimed to prospectively investigate the relationship between the Cr/CysC ratio and fracture risk. METHODS: We followed 1911 postmenopausal women and 2689 men with type 2 diabetes (mean age, 66 years) for a median of 5.3 years, and divided into Cr/CysC ratio quartiles by sex. The primary outcome was fragility fractures and the secondary outcome was any fracture. RESULTS: Fragility fractures occurred in 192 participants, and any fracture occurred in 645 participants. Multivariate-adjusted hazard ratios (95% CI) for fragility fractures were 2.15 (1.19-3.88) (Q1), 1.63 (0.89-2.98) (Q2), 1.34 (0.72-2.51) (Q3) and 1.0 (ref.) (Q4) in postmenopausal women, and 1.75 (0.64-4.50) (Q1), 2.09 (0.83-5.26) (Q2), 1.56 (0.58-4.18) (Q3) and 1.0 (ref.) (Q4) in men. Those for any fracture were 1.46 (1.07-1.98) (Q1), 1.33 (0.98-1.81) (Q2), 1.40 (1.03-1.88) (Q3) and 1.0 (ref.) (Q4) in postmenopausal women, and 2.33 (1.54-3.54) (Q1), 2.02 (1.54-3.04) (Q2), 1.13 (0.71-1.78) (Q3) and 1.0 (ref.) (Q4) in men. CONCLUSIONS: A lower Cr/CysC ratio is a significant risk factor for fractures in patients with type 2 diabetes.

    DOI: 10.1016/j.diabres.2018.10.021

  • Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function. International journal

    Brendon L Neuen, Toshiaki Ohkuma, Bruce Neal, David R Matthews, Dick de Zeeuw, Kenneth W Mahaffey, Greg Fulcher, Mehul Desai, Qiang Li, Hsiaowei Deng, Norm Rosenthal, Meg J Jardine, George Bakris, Vlado Perkovic

    Circulation   138 ( 15 )   1537 - 1550   2018.10

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    BACKGROUND: Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease, including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. METHODS: The CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without chronic kidney disease, defined as eGFR <60 and ≥60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ≥90 mL/min/1.73 m2). RESULTS: At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55-0.90) and those with preserved kidney function (hazard ratio, 0.92; 95% CI, 0.79-1.07; P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. CONCLUSIONS: The effects of canagliflozin on cardiovascular and renal outcomes were not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2. Reassessing current limitations on the use of canagliflozin in chronic kidney disease may allow additional individuals to benefit from this therapy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629, NCT01989754.

    DOI: 10.1161/CIRCULATIONAHA.118.035901

  • Sex differences in the association between diabetes and cancer: a systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events. International journal

    Toshiaki Ohkuma, Sanne A E Peters, Mark Woodward

    Diabetologia   61 ( 10 )   2140 - 2154   2018.10

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    AIMS/HYPOTHESIS: Diabetes has been shown to be a risk factor for some cancers. Whether diabetes confers the same excess risk of cancer, overall and by site, in women and men is unknown. METHODS: A systematic search was performed in PubMed for cohort studies published up to December 2016. Selected studies reported sex-specific relative risk (RR) estimates for the association between diabetes and cancer adjusted at least for age in both sexes. Random-effects meta-analyses with inverse-variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratios of RRs (RRRs) for all-site and site-specific cancers. RESULTS: Data on all-site cancer events (incident or fatal only) were available from 121 cohorts (19,239,302 individuals; 1,082,592 events). The pooled adjusted RR for all-site cancer associated with diabetes was 1.27 (95% CI 1.21, 1.32) in women and 1.19 (1.13, 1.25) in men. Women with diabetes had ~6% greater risk compared with men with diabetes (the pooled RRR was 1.06, 95% CI 1.03, 1.09). Corresponding pooled RRRs were 1.10 (1.07, 1.13) for all-site cancer incidence and 1.03 (0.99, 1.06) for all-site cancer mortality. Diabetes also conferred a significantly greater RR in women than men for oral, stomach and kidney cancer, and for leukaemia, but a lower RR for liver cancer. CONCLUSIONS/INTERPRETATION: Diabetes is a risk factor for all-site cancer for both women and men, but the excess risk of cancer associated with diabetes is slightly greater for women than men. The direction and magnitude of sex differences varies by location of the cancer.

    DOI: 10.1007/s00125-018-4664-5

  • Impact of age at menarche on obesity and glycemic control in Japanese patients with type 2 diabetes: Fukuoka Diabetes Registry.

    Akiko Sumi, Masanori Iwase, Udai Nakamura, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Yuji Komorita, Masahito Yoshinari, Takanari Kitazono

    Journal of diabetes investigation   9 ( 5 )   1216 - 1223   2018.9

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    AIMS/INTRODUCTION: A younger age at menarche is associated with obesity and type 2 diabetes in adult life. The impact of early-onset menarche on obesity and glycemic control in type 2 diabetes has not been investigated. The present study examined the relationship between age at menarche and obesity and glycemic control in type 2 diabetes. MATERIALS AND METHODS: A total of 2,133 patients with type 2 diabetes aged ≥20 years were divided into groups according to age at menarche (≤11, 12, 13, 14 and ≥15 years). A retrospective cohort study examined the association of menarcheal age with adiposity and hemoglobin A1c . RESULTS: Age at menarche was inversely associated with body mass index (BMI) and abdominal circumference (P < 0.001). Each 1-year decrease in age at menarche was associated with a 0.25-kg/m2 and 0.6-cm increase in BMI and abdominal circumference, respectively, using a multivariate-adjusted model. Odds ratios for obesity and abdominal obesity significantly increased in participants with age at menarche ≤11 years after multivariable adjustments when age at menarche of 13 years was used as the reference (odds ratio 1.95, 95% CI 1.33-2.88, odds ratio 1.95, 95% CI 1.32-2.87, respectively). Younger age at menarche was significantly associated with higher hemoglobin A1c (P < 0.001); however, the association was not statistically significant after adjusting for BMI. CONCLUSIONS: Age at menarche of ≤11 years was associated with obesity after adjusting for confounding factors, and poor glycemic control associated with high BMI in type 2 diabetes. Age at menarche should be considered during clinical assessments.

    DOI: 10.1111/jdi.12839

  • Ankle-brachial index measured by oscillometry is predictive for cardiovascular disease and premature death in the Japanese population: An individual participant data meta-analysis. International journal

    Toshiaki Ohkuma, Toshiharu Ninomiya, Hirofumi Tomiyama, Kazuomi Kario, Satoshi Hoshide, Yoshikuni Kita, Toyoshi Inoguchi, Yasutaka Maeda, Katsuhiko Kohara, Yasuharu Tabara, Motoyuki Nakamura, Takayoshi Ohkubo, Hirotaka Watada, Masanori Munakata, Mitsuru Ohishi, Norihisa Ito, Michinari Nakamura, Tetsuo Shoji, Charalambos Vlachopoulos, Victor Aboyans, Akira Yamashina

    Atherosclerosis   275   141 - 148   2018.8

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    BACKGROUND AND AIMS: The ankle-brachial index (ABI) is a predictor of cardiovascular disease (CVD) and premature death. However, few studies on this marker are available in the general Asian populations. This study aimed to investigate the association between ABI measured with oscillometry and the risk of these outcomes. METHODS: We conducted an individual participant data meta-analysis in 10,679 community-dwelling Japanese individuals without a history of CVD. The primary outcome was a composite of CVD events and all-cause mortality. RESULTS: During an average of 7.8 years of follow-up, 720 participants experienced the primary outcome. The multivariable-adjusted hazard ratios (HRs) of the primary outcome significantly increased with a lower ABI. The HRs were 1.07 (95% confidence interval [CI] 0.91-1.27) for ABI of 1.00-1.09, HR 1.37 (95% CI 1.04-1.81) for ABI of 0.91-0.99, and HR 1.60 (95% CI 1.06-2.41) for ABI of ≤0.90, compared with ABI of 1.10-1.19. Furthermore, a high ABI (≥1.30) was associated with a greater risk of outcome (HR 2.42 [95% CI 1.14-5.13]). Similar tendencies were observed for CVD events alone and all-cause mortality alone. Addition of ABI to a model with the Framingham risk score marginally improved the c-statistics (p = 0.08) and integrated discrimination improvement (p < 0.05) for the primary outcome. CONCLUSIONS: The present study suggests that lower and higher ABI are significantly associated with an increased risk of CVD and all-cause mortality in the Japanese population. The ABI, which is easily measured by oscillometry, may be incorporated into daily clinical practice to identify high-risk populations.

    DOI: 10.1016/j.atherosclerosis.2018.05.048

  • Use of the waist-to-height ratio to predict cardiovascular risk in patients with diabetes: Results from the ADVANCE-ON study. International journal

    Karin Rådholm, John Chalmers, Toshiaki Ohkuma, Sanne Peters, Neil Poulter, Pavel Hamet, Stephen Harrap, Mark Woodward

    Diabetes, obesity & metabolism   20 ( 8 )   1903 - 1910   2018.8

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    AIMS: Patients with type 2 diabetes have a high risk of cardiovascular disease (CVD). Central obesity has been particularly associated with this risk relationship. We aimed to evaluate waist to height ratio (WHtR) as a predictor of risk in such patients. METHODS: WHtR was evaluated as a predictor of the risk of CVD and mortality amongst 11 125 participants with type 2 diabetes in the ADVANCE and ADVANCE-ON studies, and was compared with body mass index (BMI), waist circumference and waist hip ratio (WHR). Primary outcome was a composite of death from CVD, non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes were myocardial infarction, stroke, cardiovascular death and death from any cause. Cox models were used, with bootstrapping to compare associations between anthropometric measures for the primary outcome. RESULTS: Median follow-up time was 9.0 years. There was a positive association between WHtR and adverse outcomes. The hazard ratio (HR) (confidence interval), per SD higher WHtR, was 1.16 (1.11-1.22) for the primary endpoint, with no heterogeneity by sex or region, but a stronger effect in individuals aged 66 years or older. The other 3 anthropometric measurements showed similar associations, although there was evidence that WHtR marginally outperformed BMI and WHR. Based on commonly used BMI cut-points, the equivalent WHtR cut-points were estimated to be 0.55 and 0.6, with no evidence of a difference across subgroups. CONCLUSIONS: In patients with diabetes, WHtR is a useful indicator of future adverse risk, with similar effects in different population subgroups.

    DOI: 10.1111/dom.13311

  • Simultaneously Measured Interarm Blood Pressure Difference and Stroke: An Individual Participants Data Meta-Analysis. International journal

    Hirofumi Tomiyama, Toshiaki Ohkuma, Toshiharu Ninomiya, Chisa Mastumoto, Kazuomi Kario, Satoshi Hoshide, Yoshikuni Kita, Toyoshi Inoguchi, Yasutaka Maeda, Katsuhiko Kohara, Yasuharu Tabara, Motoyuki Nakamura, Takayoshi Ohkubo, Hirotaka Watada, Masanori Munakata, Mitsuru Ohishi, Norihisa Ito, Michinari Nakamura, Tetsuo Shoji, Charalambos Vlachopoulos, Akira Yamashina

    Hypertension (Dallas, Tex. : 1979)   71 ( 6 )   1030 - 1038   2018.6

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    We conducted individual participant data meta-analysis to examine the validity of interarm blood pressure difference in simultaneous measurement as a marker to identify subjects with ankle-brachial pressure index <0.90 and to predict future cardiovascular events. We collected individual participant data on 13 317 Japanese subjects from 10 cohorts (general population-based cohorts, cohorts of patients with past history of cardiovascular events, and those with cardiovascular risk factors). Binary logistic regression analysis with adjustments identified interarm blood pressure difference >5 mm Hg as being associated with a significant odds ratio for the presence of ankle-brachial pressure index <0.90 (odds ratio, 2.19; 95% confidence interval, 1.60-3.03; P<0.01). Among 11 726 subjects without a past history of cardiovascular disease, 249 developed stroke during the average follow-up period of 7.4 years. Interarm blood pressure difference >15 mm Hg was associated with a significant Cox stratified adjusted hazard ratio for subsequent stroke (hazard ratio, 2.42; 95% confidence interval, 1.27-4.60; P<0.01). Therefore, interarm blood pressure differences, measured simultaneously in both arms, may be associated with vascular damage in the systemic arterial tree. These differences may be useful for identifying subjects with an ankle-brachial pressure index of <0.90 in the overall study population, and also a reliable predictor of future stroke in subjects without a past history of cardiovascular disease. These findings support the recommendation to measure blood pressure in both arms at the first visit.

    DOI: 10.1161/HYPERTENSIONAHA.118.10923

  • Impact of Body Weight Loss From Maximum Weight on Fragility Bone Fractures in Japanese Patients With Type 2 Diabetes: The Fukuoka Diabetes Registry. International journal

    Yuji Komorita, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Akiko Sumi, Masahito Yoshinari, Udai Nakamura, Dongchon Kang, Takanari Kitazono

    Diabetes care   41 ( 5 )   1061 - 1067   2018.5

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    OBJECTIVE: There is growing evidence that weight loss is associated with increased fracture risk in the general population. As patients with diabetes often lose weight intentionally or unintentionally, we aimed to investigate prospectively the relationship between weight loss from maximum body weight and fracture risk. RESEARCH DESIGN AND METHODS: A total of 4,706 Japanese participants with type 2 diabetes (mean age 66 years), including 2,755 men and 1,951 postmenopausal women, were followed for a median of 5.3 years and were divided according to weight loss from maximum weight: <10%, 10% to <20%, 20% to <30%, and ≥30%. The primary outcomes were fragility fractures defined as fractures at sites of hip and spine. RESULTS: During the follow-up period, fragility fractures occurred in 198 participants. The age- and sex-adjusted incidence rates per 1,000 person-years in all participants were 6.4 (<10% weight loss from maximum body weight), 7.8 (10% to <20%), 11.7 (20% to <30%), and 19.2 (≥30%) (P for trend <0.001). Multivariate-adjusted hazard ratios for fragility fractures compared with reference (<10% weight loss) were 1.48 (95% CI 0.79-2.77) in the 10% to <20% group, 2.23 (1.08-4.64) in 20% to <30%, and 5.20 (2.15-12.57) in ≥30% in men, and 1.19 (0.78-1.82) in 10% to <20%, 1.62 (0.96-2.73) in 20% to <30%, and 1.97 (0.84-4.62) in ≥30% in postmenopausal women. CONCLUSIONS: The current study demonstrates that ≥20% body weight loss from maximum weight is a significant risk factor for fragility fractures in patients with type 2 diabetes, especially in men.

    DOI: 10.2337/dc17-2004

  • Incidence of diabetic foot ulcer in Japanese patients with type 2 diabetes mellitus: The Fukuoka diabetes registry. International journal

    Masanori Iwase, Hiroki Fujii, Udai Nakamura, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Akiko Sumi, Yuji Komorita, Masahito Yoshinari, Takanari Kitazono

    Diabetes research and clinical practice   137   183 - 189   2018.3

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    AIMS: Although diabetic foot ulcer (DFU) is a serious diabetic complication, there have been no large-scale epidemiological studies of DFU in Japan. We prospectively investigated the incidences of DFU and limb amputation, the risk for developing DFU, and mortality in Japanese patients with type 2 diabetes. METHODS: We followed 4870 participants (mean age, 65 years) with type 2 diabetes attending an outpatient diabetes clinic for a median of 5.3 years (follow-up rate, 97.7%). The primary outcome was the development of DFU. RESULTS: During the follow-up period, DFU occurred in 74 participants (incidence rate, 2.9/1000 person-years) and limb amputation in 12 (incidence rate, 0.47/1000 person-years). DFU recurrence was observed in 21.4% of participants with history of DFU. History of DFU, chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2), depressive symptoms, and poor glycemic control were significant risk factors for developing DFU. Survival was significantly lower in participants with DFU and/or history of DFU compared with those without (5-year survival rates: with DFU, 87.7%, without DFU, 95.3%; P < .0001). The hazard ratio for death was 1.80 (95% confidence interval, 1.13-2.73, P = .014) in those with DFU and/or history of DFU in a multi-adjusted model. The most common cause of death was cardiovascular disease among participants with DFU, whereas it was malignant neoplasm among those without. CONCLUSIONS: Incidences of DFU and limb amputation were 0.3% and 0.05% per year in this Japanese cohort, respectively. Mortality significantly increased approximately 2-fold in those with DFU and/or history of DFU compared with those without.

    DOI: 10.1016/j.diabres.2018.01.020

  • Response to Comment on Ohkuma et al. Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial. Diabetes Care 2017;40:1203-1209. International journal

    Toshiaki Ohkuma, Mark Woodward, John Chalmers

    Diabetes care   41 ( 3 )   e39   2018.3

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    DOI: 10.2337/dci17-0060

  • Changes in Albuminuria and the Risk of Major Clinical Outcomes in Diabetes: Results From ADVANCE-ON. International journal

    Min Jun, Toshiaki Ohkuma, Sophia Zoungas, Stephen Colagiuri, Giuseppe Mancia, Michel Marre, David Matthews, Neil Poulter, Bryan Williams, Anthony Rodgers, Vlado Perkovic, John Chalmers, Mark Woodward

    Diabetes care   41 ( 1 )   163 - 170   2018.1

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    OBJECTIVE: To assess the association between 2-year changes in urine albumin-to-creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from 8,766 participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post-Trial Observational Study (ADVANCE-ON). Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds, we repeated these analyses accounting for regression to the mean (RtM). The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality; secondary outcomes were these components. Cox regression models were used to estimate hazard ratios (HRs). RESULTS: Over a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome (HR for ≥30% UACR increase vs. minor change: 1.26; 95% CI 1.13-1.41), whereas a decrease in UACR was not significantly associated with lower risk (HR 0.93; 95% CI 0.83-1.04). However, after allowing for RtM, the effect of "real" decrease in UACR on the primary outcome was found to be significant (HR 0.84; 95% CI 0.75-0.94), whereas the estimated effect on an increase was unchanged. CONCLUSIONS: Changes in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.

    DOI: 10.2337/dc17-1467

  • The gene-treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registry. International journal

    Akiko Sumi, Udai Nakamura, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Yuji Komorita, Masahito Yoshinari, Yoichiro Hirakawa, Atsushi Hirano, Michiaki Kubo, Takanari Kitazono

    BMC medical genetics   18 ( 1 )   146 - 146   2017.12

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    BACKGROUND: Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins' interaction with paraoxonase (PON)1 enzyme polymorphism. METHODS: Adult Japanese type 2 diabetes patients (n = 3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA1c, C-peptide, HOMA2-%β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups. RESULTS: Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA1c, and with increased serum C peptide and HOMA2-%β (all P < 0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-%β (P < 0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations. CONCLUSIONS: Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.

    DOI: 10.1186/s12881-017-0509-1

  • Serum adiponectin predicts fracture risk in individuals with type 2 diabetes: the Fukuoka Diabetes Registry. International journal

    Yuji Komorita, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai-Kitamura, Akiko Sumi, Masahito Yoshinari, Udai Nakamura, Dongchon Kang, Takanari Kitazono

    Diabetologia   60 ( 10 )   1922 - 1930   2017.10

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    AIMS/HYPOTHESIS: Serum adiponectin has been reported to impact upon fracture risk in the general population. Although type 2 diabetes is associated with increased fracture risk, it is unclear whether serum adiponectin predicts fractures in individuals with type 2 diabetes. The aim of the study was to prospectively investigate the relationship between serum adiponectin and fracture risk in individuals with type 2 diabetes. METHODS: In this study, data was obtained from The Fukuoka Diabetes Registry, a multicentre prospective study designed to investigate the influence of modern treatments on the prognoses of patients with diabetes mellitus. We followed 4869 participants with type 2 diabetes (mean age, 65 years), including 1951 postmenopausal women (defined as self-reported amenorrhea for >1 year) and 2754 men, for a median of 5.3 years. The primary outcomes were fractures at any site and major osteoporotic fractures (MOFs). RESULTS: During the follow-up period, fractures at any site occurred in 682 participants, while MOFs occurred in 277 participants. Age-adjusted HRs (95% CIs) of any fracture and MOFs for 1 SD increment in log e -transformed serum adiponectin were 1.27 (1.15, 1.40) and 1.35 (1.17, 1.55) in postmenopausal women and 1.22 (1.08, 1.38) and 1.40 (1.15, 1.71) in men, respectively. HRs (95% CIs) of MOFs for hyperadiponectinaemia (≥ 20 μg/ml) were 1.72 (1.19, 2.50) in postmenopausal women and 2.19 (1.23, 3.90) in men. The per cent attributable risk of hyperadiponectinaemia for MOFs was as high as being age ≥70 years or female sex. CONCLUSIONS/INTERPRETATION: Higher serum adiponectin levels were significantly associated with an increased risk of fractures at any site and with an increased risk of MOFs in individuals with type 2 diabetes, including postmenopausal women.

    DOI: 10.1007/s00125-017-4369-1

  • Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial. International journal

    Toshiaki Ohkuma, Min Jun, Mark Woodward, Sophia Zoungas, Mark E Cooper, Diederick E Grobbee, Pavel Hamet, Giuseppe Mancia, Bryan Williams, Paul Welsh, Naveed Sattar, Jonathan E Shaw, Kazem Rahimi, John Chalmers

    Diabetes care   40 ( 9 )   1203 - 1209   2017.9

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    OBJECTIVE: This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A nested case-cohort study was conducted in 3,098 participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. RESULTS: A higher value of each biomarker was significantly associated with a higher risk of heart failure incidence or progression, after adjustment for major risk factors. The hazard ratios per 1-SD increase were 3.06 (95% CI 2.37, 3.96) for NT-proBNP, 1.50 (1.27, 1.77) for hs-cTnT, 1.48 (1.27, 1.72) for IL-6, and 1.32 (1.12, 1.55) for hs-CRP. The addition of NT-proBNP to the model including conventional risk factors meaningfully improved 5-year risk-predictive performance (C statistic 0.8162 to 0.8800; continuous net reclassification improvement [NRI] 73.1%; categorical NRI [<5%, 5-10%, >10% 5-year risk] 24.2%). In contrast, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP. CONCLUSIONS: Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers.

    DOI: 10.2337/dc17-0509

  • Proposed Cutoff Value of Brachial-Ankle Pulse Wave Velocity for the Management of Hypertension.

    Toshiaki Ohkuma, Hirofumi Tomiyama, Toshiharu Ninomiya, Kazuomi Kario, Satoshi Hoshide, Yoshikuni Kita, Toyoshi Inoguchi, Yasutaka Maeda, Katsuhiko Kohara, Yasuharu Tabara, Motoyuki Nakamura, Takayoshi Ohkubo, Hirotaka Watada, Masanori Munakata, Mitsuru Ohishi, Norihisa Ito, Michinari Nakamura, Tetsuo Shoji, Charalambos Vlachopoulos, Akira Yamashina

    Circulation journal : official journal of the Japanese Circulation Society   81 ( 10 )   1540 - 1542   2017.9

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    BACKGROUND: The optimal cutoff values of the brachial-ankle pulse wave velocity (baPWV) for predicting cardiovascular disease (CVD) were examined in patients with hypertension.Methods and Results:A total of 7,656 participants were followed prospectively. The hazard ratio for the development of CVD increased significantly as the baPWV increased, independent of conventional risk factors. The receiver-operating characteristic curve analysis showed that the optimal cutoff values for predicting CVD was 18.3 m/s. This cutoff value significantly predicted THE incidence of CVD. CONCLUSIONS: The present analysis suggests that the optimal cutoff value for CVD in patients with hypertension is 18.3 m/s.

    DOI: 10.1253/circj.CJ-17-0636

  • Prognostic Value of Variability in Systolic Blood Pressure Related to Vascular Events and Premature Death in Type 2 Diabetes Mellitus: The ADVANCE-ON Study. International journal

    Toshiaki Ohkuma, Mark Woodward, Min Jun, Paul Muntner, Jun Hata, Stephen Colagiuri, Stephen Harrap, Giuseppe Mancia, Neil Poulter, Bryan Williams, Peter Rothwell, John Chalmers

    Hypertension (Dallas, Tex. : 1979)   70 ( 2 )   461 - 468   2017.8

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    Visit-to-visit variability in systolic blood pressure (SBP) is a risk factor for cardiovascular events. However, whether it provides additional predictive information beyond traditional risk factors, including mean SBP, in the long term is unclear. The ADVANCE trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) was a randomized controlled trial in patients with type 2 diabetes mellitus; ADVANCE-ON (ADVANCE-Observational) followed-up patients subsequently. In these analyses, 9114 patients without major macrovascular or renal events or death during the first 24 months were included. Data on SBP from 6 visits during the first 24 months after randomization were used to estimate visit-to-visit variability in several ways: the primary measure was the standard deviation. Events accrued during the following 7.6 years. The primary outcome was a composite of major macrovascular and renal events and all-cause mortality. Standard deviation of SBP was log-linearly associated with an increased risk of the primary outcome (P<0.001) after adjustment for mean SBP and other cardiovascular risk factors. The hazard ratio (HR; 95% confidence interval [CI]) in the highest, compared with the lowest, tenth of the standard deviation was 1.39 (1.15-1.69). Results were similar for major macrovascular events alone and all-cause mortality alone (both P<0.01). Addition of standard deviation of SBP significantly improved 8-year risk classification (continuous net reclassification improvement, 5.3%). Results were similar for other measures of visit-to-visit variability, except maximum SBP. Visit-to-visit variability in SBP is an independent predictor of vascular complications and death, which improves risk prediction beyond that provided by traditional risk factors, including mean SBP.

    DOI: 10.1161/HYPERTENSIONAHA.117.09359

  • Joint impact of modifiable lifestyle behaviors on glycemic control and insulin resistance in patients with type 2 diabetes: the Fukuoka Diabetes Registry.

    Toshiaki Ohkuma, Masanori Iwase, Hiroki Fujii, Hitoshi Ide, Shinako Kaizu, Tamaki Jodai, Yohei Kikuchi, Yasuhiro Idewaki, Akiko Sumi, Udai Nakamura, Takanari Kitazono

    Diabetology international   8 ( 3 )   296 - 305   2017.8

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    Aims: Little is known about the combined effects of unhealthy lifestyle behaviors on glycemia. The objective of this study was to examine the association between combined modifiable lifestyle and glycemic control, as well as markers of insulin resistance and secretion. Patients and methods: In total, 4,870 patients with type 2 diabetes were sorted by lifestyle scores. Scores were determined by summing the number of unhealthy lifestyle factors that showed a significant association with hemoglobin A1c (HbA1c) (current smoking, decreased dietary fiber intake, eating quickly, inadequate sleep duration, and obesity). The associations between lifestyle score and hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA2-IR), and β-cell function (HOMA2-%B) were cross-sectionally analyzed. Results: HbA1c increased progressively with increases in lifestyle score (p for trend <0.001). Mean HbA1c was 0.48% (95% confidence intervals 0.34-0.63) higher in patients with scores of four to five than in those with zero scores. HOMA2-IR and high-sensitivity C-reactive protein also revealed a similar tendency, but adiponectin showed an inverse association. However, these graded tendencies were not observed for HOMA2-%B. Additionally, lower HOMA2-%B levels enhanced the effects of lifestyle score on glycemia. Increases in HbA1c per point in the lifestyle score in patients with the lowest and highest quartiles of HOMA2-%B were 0.25% (0.18-0.32) and 0.10% (0.06-0.15), respectively (p for interaction <0.001). Conclusions: Accumulation of unhealthy lifestyle factors was dose-dependently associated with poor glycemic control, which may be modified by insulin secretory capacity.

    DOI: 10.1007/s13340-017-0310-6

  • Brachial-Ankle Pulse Wave Velocity and the Risk Prediction of Cardiovascular Disease: An Individual Participant Data Meta-Analysis. International journal

    Toshiaki Ohkuma, Toshiharu Ninomiya, Hirofumi Tomiyama, Kazuomi Kario, Satoshi Hoshide, Yoshikuni Kita, Toyoshi Inoguchi, Yasutaka Maeda, Katsuhiko Kohara, Yasuharu Tabara, Motoyuki Nakamura, Takayoshi Ohkubo, Hirotaka Watada, Masanori Munakata, Mitsuru Ohishi, Norihisa Ito, Michinari Nakamura, Tetsuo Shoji, Charalambos Vlachopoulos, Akira Yamashina

    Hypertension (Dallas, Tex. : 1979)   69 ( 6 )   1045 - 1052   2017.6

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    An individual participant data meta-analysis was conducted in the data of 14 673 Japanese participants without a history of cardiovascular disease (CVD) to examine the association of the brachial-ankle pulse wave velocity (baPWV) with the risk of development of CVD. During the average 6.4-year follow-up period, 687 participants died and 735 developed cardiovascular events. A higher baPWV was significantly associated with a higher risk of CVD, even after adjustments for conventional risk factors (P for trend <0.001). When the baPWV values were classified into quintiles, the multivariable-adjusted hazard ratio for CVD increased significantly as the baPWV quintile increased. The hazard ratio in the subjects with baPWV values in quintile 5 versus that in those with the values in quintile 1 was 3.50 (2.14-5.74; P<0.001). Every 1 SD increase of the baPWV was associated with a 1.19-fold (1.10-1.29; P<0.001) increase in the risk of CVD. Moreover, addition of baPWV to a model incorporating the Framingham risk score significantly increased the C statistics from 0.8026 to 0.8131 (P<0.001) and also improved the category-free net reclassification (0.247; P<0.001). The present meta-analysis clearly established baPWV as an independent predictor of the risk of development of CVD in Japanese subjects without preexisting CVD. Thus, measurement of the baPWV could enhance the efficacy of prediction of the risk of development of CVD over that of the Framingham risk score, which is based on the traditional cardiovascular risk factors.

    DOI: 10.1161/HYPERTENSIONAHA.117.09097

  • Comparison of cystatin C- and creatinine-based estimated glomerular filtration rates for predicting all-cause mortality in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry.

    Hitoshi Ide, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Shinako Kaizu, Tamaki Jodai, Yohei Kikuchi, Yasuhiro Idewaki, Akiko Sumi, Udai Nakamura, Takanari Kitazono

    Clinical and experimental nephrology   21 ( 3 )   383 - 390   2017.6

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    BACKGROUND: There is little information about the predictive ability of cystatin C-based estimated glomerular filtration rates (eGFRCys) for all-cause mortality in Asian populations. We compared the discriminatory ability of eGFRCys for all-cause mortality with that of creatinine-based estimated glomerular filtration rates (eGFRCr) in Japanese patients with type 2 diabetes. METHODS: A total of 4869 participants were classified into four categories (eGFR ≤29, 30-59, 60-89, and ≥90 ml/min/1.73 m2) by eGFRCr and eGFRCys, and followed up for a median of 3.3 years. RESULTS: 150 deaths were identified. The multivariable-adjusted risk of all-cause mortality was significantly increased in eGFRCr ≤29 ml/min/1.73 m2 compared with eGFRCr ≥90 ml/min/1.73 m2 [hazard ratio (HR) 2.4 (95 % confidence interval (95 % CI) 1.2-5.0)], whereas it was significantly increased in eGFRCys 59 ml/min/1.73 m2 or lower [30-59 ml/min/1.73 m2, HR 1.9 (95 % CI 1.1-3.5); ≤29 ml/min/1.73 m2, HR 5.8 (95 % CI 2.8-12.0)]. Comparing eGFRCys with eGFRCr, the proportions of participants reclassified to lower and higher eGFR stages were 6.3 and 28.8 %, respectively. The multivariable-adjusted HRs for all-cause mortality were 1.8 (95 % CI 1.1-2.9) and 0.7 (95 % CI 0.4-1.1), respectively. The C statistic of the model including eGFRCys and other risk factors was significantly increased compared with the model including eGFRCr. The net reclassification improvement and the integrated discrimination improvement were significantly positive. CONCLUSIONS: Our findings suggest that eGFRCys has a stronger association with all-cause mortality and is superior to eGFRCr for predicting all-cause mortality in Japanese patients with type 2 diabetes.

    DOI: 10.1007/s10157-016-1296-2

  • Effects of smoking and its cessation on creatinine- and cystatin C-based estimated glomerular filtration rates and albuminuria in male patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry. International journal

    Toshiaki Ohkuma, Udai Nakamura, Masanori Iwase, Hitoshi Ide, Hiroki Fujii, Tamaki Jodai, Shinako Kaizu, Yohei Kikuchi, Yasuhiro Idewaki, Akiko Sumi, Yoichiro Hirakawa, Takanari Kitazono

    Hypertension research : official journal of the Japanese Society of Hypertension   39 ( 10 )   744 - 751   2016.10

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    Cigarette smoking is an important modifiable risk factor for lifestyle diseases. The smoking rate remains high, and the prevalence of diabetes mellitus is increasing in Asian countries; however, few studies have examined the effects of smoking on chronic kidney disease (CKD) in Asian diabetic patients. The aim of the present study was to investigate the association between smoking and its cessation with CKD and its components in patients with type 2 diabetes. A total of 2770 Japanese male patients with type 2 diabetes aged ⩾20 years were divided according to the amount of cigarette smoking and the years since cessation. The associations with CKD, the urinary albumin-creatinine ratio (UACR) and the estimated glomerular filtration rate (eGFR) were cross-sectionally examined. The proportions of CKD and the mean UACR dose-dependently increased with increases in both the number of cigarettes per day and the Brinkman index compared with the never smokers. The creatinine-based eGFR also increased with increases in the amount of smoking, whereas the cystatin C-based eGFR decreased, and their average did not significantly change. These parameters exhibited inverse associations with the years after smoking cessation compared with the association with the amount of smoking. A dose-dependent association of active smoking and a graded inverse association of the years since quitting with CKD enhance the merit of smoking cessation in patients with type 2 diabetes.

    DOI: 10.1038/hr.2016.51

  • Association of Genetically Determined Aldehyde Dehydrogenase 2 Activity with Diabetic Complications in Relation to Alcohol Consumption in Japanese Patients with Type 2 Diabetes Mellitus: The Fukuoka Diabetes Registry. International journal

    Yasuhiro Idewaki, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Shinako Kaizu, Tamaki Jodai, Yohei Kikuchi, Atsushi Hirano, Udai Nakamura, Michiaki Kubo, Takanari Kitazono

    PloS one   10 ( 11 )   e0143288   2015.10

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    Aldehyde dehydrogenase 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. A genetic defect in this enzyme is common in East Asians and determines alcohol consumption behaviors. We investigated the impact of genetically determined ALDH2 activity on diabetic microvascular and macrovascular complications in relation to drinking habits in Japanese patients with type 2 diabetes mellitus. An ALDH2 single-nucleotide polymorphism (rs671) was genotyped in 4,400 patients. Additionally, the relationship of clinical characteristics with ALDH2 activity (ALDH2 *1/*1 active enzyme activity vs. *1/*2 or *2/*2 inactive enzyme activity) and drinking habits (lifetime abstainers vs. former or current drinkers) was investigated cross-sectionally (n = 691 in *1/*1 abstainers, n = 1,315 in abstainers with *2, n = 1,711 in *1/*1 drinkers, n = 683 in drinkers with *2). The multiple logistic regression analysis for diabetic complications was adjusted for age, sex, current smoking habits, leisure-time physical activity, depressive symptoms, diabetes duration, body mass index, hemoglobin A1c, insulin use, high-density lipoprotein cholesterol, systolic blood pressure and renin-angiotensin system inhibitors use. Albuminuria prevalence was significantly lower in the drinkers with *2 than that of other groups (odds ratio [95% confidence interval (CI)]: *1/*1 abstainers as the referent, 0.94 [0.76-1.16] in abstainers with *2, 1.00 [0.80-1.26] in *1/*1 drinkers, 0.71 [0.54-0.93] in drinkers with *2). Retinal photocoagulation prevalence was also lower in drinkers with ALDH2 *2 than that of other groups. In contrast, myocardial infarction was significantly increased in ALDH2 *2 carriers compared with that in ALDH2 *1/*1 abstainers (odds ratio [95% CI]: *1/*1 abstainers as the referent, 2.63 [1.28-6.13] in abstainers with *2, 1.89 [0.89-4.51] in *1/*1 drinkers, 2.35 [1.06-5.79] in drinkers with *2). In summary, patients with type 2 diabetes and ALDH2 *2 displayed a lower microvascular complication prevalence associated with alcohol consumption but a higher macrovascular complication prevalence irrespective of alcohol consumption.

    DOI: 10.1371/journal.pone.0143288

  • Dose- and time-dependent association of smoking and its cessation with glycemic control and insulin resistance in male patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry. International journal

    Toshiaki Ohkuma, Masanori Iwase, Hiroki Fujii, Shinako Kaizu, Hitoshi Ide, Tamaki Jodai, Yohei Kikuchi, Yasuhiro Idewaki, Yoichiro Hirakawa, Udai Nakamura, Takanari Kitazono

    PloS one   10 ( 3 )   e0122023   2015.10

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    OBJECTIVE: Cigarette smoking is an important modifiable risk factor for cardiovascular diseases. However, the effect of smoking and its cessation on glycemic control in diabetic patients has not been fully examined yet. The aim of the present study was to examine the association of smoking status with glycemic level and markers of insulin resistance and secretion in patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: A total of 2,490 Japanese male patients with type 2 diabetes mellitus aged ≥20 years were divided according to smoking status, amount of cigarettes smoked and years since quitting. The associations with glycemic level and markers of insulin resistance and secretion were examined cross-sectionally. RESULTS: HbA1c levels increased progressively with increases in both number of cigarettes per day and pack-years of cigarette smoking compared with never smokers (P for trend = 0.001 and <0.001, respectively), whereas fasting plasma glucose did not. On the other hand, HbA1c, but not fasting plasma glucose, decreased linearly with increase in years after smoking cessation (P for trend <0.001). These graded relationships persisted significantly after controlling for the confounders, including total energy intake, current drinking, regular exercise, depressive symptoms, and BMI. In addition, a homeostasis model assessment of insulin resistance and high-sensitivity C-reactive protein also showed similar trends. CONCLUSIONS: Smoking and its cessation showed dose- and time-dependent relationship with glycemic control and insulin resistance in patients with type 2 diabetes mellitus. These findings may highlight the importance of smoking cessation in the clinical management of diabetes mellitus.

    DOI: 10.1371/journal.pone.0122023

  • Association of severe hypoglycemia with depressive symptoms in patients with type 2 diabetes: the Fukuoka Diabetes Registry. International journal

    Yohei Kikuchi, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Shinako Kaizu, Hitoshi Ide, Tamaki Jodai, Yasuhiro Idewaki, Udai Nakamura, Takanari Kitazono

    BMJ open diabetes research & care   3 ( 1 )   e000063   2015.3

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    OBJECTIVE: Although many studies have investigated the clinical characteristics of patients with diabetes with depression in Western populations, there is a lack of information regarding other ethnicities. We studied the association between clinical characteristics and depressive symptoms in Japanese patients with type 2 diabetes. METHODS: A total of 4218 Japanese patients with type 2 diabetes who were not taking antidepressants were divided into four groups according to the Center for Epidemiologic Studies Depression Scale (CES-D) score. The relationship between the severity of depressive symptoms and clinical parameters was examined cross-sectionally. RESULTS: After multivariate adjustments, the severity of depressive symptoms was significantly associated with body mass index, leisure-time physical activity, current smoking, sleep duration, sucrose intake, skipping breakfast, insulin use, severe hypoglycemia, dysesthesia of both feet, history of foot ulcer, photocoagulation, ischemic heart disease, and stroke. ORs for severe hypoglycemia increased significantly with the CES-D score in 2756 sulfonylurea and/or insulin-treated patients after multivariate adjustment including age, sex, duration of diabetes, glycated hemoglobin, insulin use, self-monitoring of blood glucose, leisure-time physical activity, skipping breakfast, dysesthesia of both feet, ischemic heart disease, and stroke (CES-D score ≤9, referent; 10-15, OR 1.64; 16-23, OR 2.09; ≥24, OR 3.66; p for trend <0.01). CONCLUSIONS: Severe hypoglycemia was positively associated with the severity of depressive symptoms in Japanese patients with type 2 diabetes independent of glycemic control, insulin therapy, lifestyle factors, and diabetic complications. As both severe hypoglycemia and depression are known risk factors for morbidity and mortality in patients with diabetes, clinicians should be aware of this association. UMIN CLINICAL TRIAL REGISTRY: 000002627.

    DOI: 10.1136/bmjdrc-2014-000063

  • Impact of leisure-time physical activity on glycemic control and cardiovascular risk factors in Japanese patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry. International journal

    Shinako Kaizu, Hiro Kishimoto, Masanori Iwase, Hiroki Fujii, Toshiaki Ohkuma, Hitoshi Ide, Tamaki Jodai, Yohei Kikuchi, Yasuhiro Idewaki, Yoichiro Hirakawa, Udai Nakamura, Takanari Kitazono

    PloS one   9 ( 6 )   e98768   2014.9

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    AIMS/HYPOTHESIS: The effects of leisure-time physical activity (LTPA) on glycemia and cardiovascular risk factors are not fully understood in Asian type 2 diabetic patients, who are typically non-obese. We studied associations between LTPA and glycemia and cardiovascular risk factors in Japanese type 2 diabetic patients. METHODS: A total of 4,870 Japanese type 2 diabetic patients aged ≥ 20 years were divided into eight groups according to their LTPA. We investigated associations between the amount and intensity levels of physical activity (PA) and glycemic control, insulin sensitivity, cardiovascular risk factors, and low-grade systemic inflammation in a cross-sectional study. RESULTS: LTPA was dose-dependently associated with body mass index (BMI), waist circumference, hemoglobin A1c (HbA1c), fasting plasma glucose, homeostasis model assessment of insulin resistance, triglyceride, high density lipoprotein cholesterol, high sensitivity C-reactive protein, and prevalence of metabolic syndrome, but not with blood pressure, low density lipoprotein cholesterol or adiponectin. The amount of PA required to lower HbA1c was greater than that required to improve cardiovascular risk factors. LTPA was inversely associated with HbA1c in non-obese participants but not in obese participants after multivariate adjustments for age, sex, duration of diabetes, current smoking, current drinking, energy intake, cardiovascular diseases, depressive symptoms, and treatment of diabetes. Higher-intensity LTPA, not lower-intensity LTPA was associated with HbA1c after multivariate adjustments with further adjustment including BMI. CONCLUSIONS/INTERPRETATION: LTPA was dose-dependently associated with better glycemic control and amelioration of some cardiovascular risk factors in Japanese type 2 diabetic patients. In addition, increased higher-intensity LTPA may be appropriate for glycemic control.

    DOI: 10.1371/journal.pone.0098768

  • U-shaped association of sleep duration with metabolic syndrome and insulin resistance in patients with type 2 diabetes: the Fukuoka Diabetes Registry. International journal

    Toshiaki Ohkuma, Hiroki Fujii, Masanori Iwase, Shinako Ogata-Kaizu, Hitoshi Ide, Yohei Kikuchi, Yasuhiro Idewaki, Tamaki Jodai, Yoichiro Hirakawa, Udai Nakamura, Takanari Kitazono

    Metabolism: clinical and experimental   63 ( 4 )   484 - 91   2014.4

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    OBJECTIVE: Sleep duration is suggested to be associated with adverse health outcomes. However, few studies are available on the impact of sleep duration on metabolic syndrome in patients with diabetes, who were at high risk for cardiovascular diseases (CVD). The objective of the present study was to examine the associations of sleep duration with metabolic syndrome and insulin resistance, a major pathophysiologic feature of metabolic syndrome, in patients with type 2 diabetes. MATERIALS/METHODS: A total of 4402 Japanese patients with type 2 diabetes aged ≥20years were divided into 5 groups according to self-reported sleep duration: less than 5.5h, 5.5-6.4h, 6.5-7.4h, 7.5-8.4h, and more than 8.5h. The associations of sleep duration with metabolic syndrome and other cardiovascular risk factors were examined cross-sectionally. RESULTS: The proportions of patients who had metabolic syndrome increased significantly in both patients with shorter and longer sleep duration compared with those with 6.5-7.4h of sleep (P for quadratic trend <0.001). This U-shaped association remained significant after adjustment for potential confounders, including total energy intake, current smoking, current drinking and depressive symptoms. Each component of metabolic syndrome also showed similar trends. Furthermore, sleep duration had a quadratic association with homeostasis model assessment of insulin resistance and high sensitivity C-reactive protein. CONCLUSIONS: Sleep duration was shown to have a U-shaped relationship with metabolic syndrome and insulin resistance, independent of potential confounders, and therefore may be an important modifiable risk factor for CVD prevention in patients with type 2 diabetes.

    DOI: 10.1016/j.metabol.2013.12.001

  • Impact of dietary fiber intake on glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry. International journal

    Hiroki Fujii, Masanori Iwase, Toshiaki Ohkuma, Shinako Ogata-Kaizu, Hitoshi Ide, Yohei Kikuchi, Yasuhiro Idewaki, Tamaki Joudai, Yoichiro Hirakawa, Kazuhiro Uchida, Satoshi Sasaki, Udai Nakamura, Takanari Kitazono

    Nutrition journal   12   159 - 159   2013.12

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    BACKGROUND: Dietary fiber is beneficial for the treatment of type 2 diabetes mellitus, although it is consumed differently in ethnic foods around the world. We investigated the association between dietary fiber intake and obesity, glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese type 2 diabetic patients. METHODS: A total of 4,399 patients were assessed for dietary fiber intake using a brief self-administered diet history questionnaire. The associations between dietary fiber intake and various cardiovascular risk factors were investigated cross-sectionally. RESULTS: Body mass index, fasting plasma glucose, HbA1c, triglyceride and high-sensitivity C-reactive protein negatively associated with dietary fiber intake after adjusting for age, sex, duration of diabetes, current smoking, current drinking, total energy intake, fat intake, saturated fatty acid intake, leisure-time physical activity and use of oral hypoglycemic agents or insulin. The homeostasis model assessment insulin sensitivity and HDL cholesterol positively associated with dietary fiber intake. Dietary fiber intake was associated with reduced prevalence of abdominal obesity, hypertension and metabolic syndrome after multivariate adjustments including obesity. Furthermore, dietary fiber intake was associated with lower prevalence of albuminuria, low estimated glomerular filtration rate and chronic kidney disease after multivariate adjustments including protein intake. Additional adjustments for obesity, hypertension or metabolic syndrome did not change these associations. CONCLUSION: We demonstrated that increased dietary fiber intake was associated with better glycemic control and more favorable cardiovascular disease risk factors including chronic kidney disease in Japanese type 2 diabetic patients. Diabetic patients should be encouraged to consume more dietary fiber in daily life.

    DOI: 10.1186/1475-2891-12-159

  • Association between sleep duration and urinary albumin excretion in patients with type 2 diabetes: the Fukuoka diabetes registry. International journal

    Toshiaki Ohkuma, Hiroki Fujii, Masanori Iwase, Shinako Ogata-Kaizu, Hitoshi Ide, Yohei Kikuchi, Yasuhiro Idewaki, Tamaki Jodai, Yoichiro Hirakawa, Udai Nakamura, Takanari Kitazono

    PloS one   8 ( 11 )   e78968   2013.8

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    OBJECTIVE: Few studies have so far investigated the impact of sleep duration on chronic kidney disease in diabetic patients. The objective of the present study was to examine the relationship between sleep duration and albuminuria in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 4,870 Japanese type 2 diabetic patients ≥20 years of age were divided into six groups according to self-reported sleep duration: less than 4.5 hours, 4.5-5.4 hours, 5.5-6.4 hours, 6.5-7.4 hours, 7.5-8.4 hours and more than 8.5 hours. The association between sleep duration and urinary albumin-creatinine ratio (UACR) was examined cross-sectionally. RESULTS: Both short and long sleep durations were significantly associated with higher UACR levels and higher proportions of patients with albuminuria (≥30 mg/g) and macroalbuminuria (≥300 mg/g) compared with a sleep duration of 6.5-7.4 hours (P for quadratic trend <0.001). A U-shaped association between sleep duration and UACR remained significant even after adjustment for potential confounders, including age, sex, duration of diabetes, current smoking habits, former smoking habits, current drinking habits, regular exercise habits, total energy intake, total protein intake, hypnotic use and estimated glomerular filtration rate. Furthermore, the association remained substantially unchanged after additional adjustment for body mass index, hemoglobin A1c, systolic blood pressure, renin-angiotensin system inhibitor use and depressive symptoms. CONCLUSIONS: Our findings suggest that sleep duration has a U-shaped association with the UACR levels in type 2 diabetic patients, independent of potential confounders.

    DOI: 10.1371/journal.pone.0078968

  • Slowly progressive and painless thoracic aortic dissection presenting with a persistent Fever in an elderly patient: the usefulness of combined measurement of biochemical parameters. International journal

    Shunsuke Yamada, Masanori Tokumoto, Toshiaki Ohkuma, Yasuo Kansui, Yoshinobu Wakisaka, Yuji Uchizono, Kazuhiko Tsuruya, Takanari Kitazono, Hiroaki Ooboshi

    Case reports in medicine   2013   498129 - 498129   2013.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    Aortic dissection is a fatal medical condition that requires urgent diagnosis and appropriate intervention. Because acute aortic dissection often manifests as sudden onset excruciating chest pain, physicians can easily reach a proper diagnosis. However, some patients with aortic dissection present with varied clinical manifestations without exhibiting typical chest pain, leading to a delayed diagnosis and possible fatality. We herein present the case of an elderly subject with a fever of unknown origin who was ultimately diagnosed with aortic dissection. In the present case, a negative procalcitonin test, increased D-dimer and serum creatinine phosphokinase-BB levels, and reelevation of the CPR level led us to the correct diagnosis.

    DOI: 10.1155/2013/498129

  • Impact of sleep duration on obesity and the glycemic level in patients with type 2 diabetes: the Fukuoka Diabetes Registry. International journal

    Toshiaki Ohkuma, Hiroki Fujii, Masanori Iwase, Yohei Kikuchi, Shinako Ogata, Yasuhiro Idewaki, Hitoshi Ide, Yasufumi Doi, Yoichiro Hirakawa, Udai Nakamura, Takanari Kitazono

    Diabetes care   36 ( 3 )   611 - 7   2013.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: Few studies are currently available regarding the influence of sleep duration on glycemic control in diabetic patients. The objective of the current study was to examine the relationship between sleep duration, obesity, and the glycemic level in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 4,870 Japanese type 2 diabetic patients aged ≥20 years were divided into six groups according to their self-reported sleep duration: less than 4.5 h, 4.5-5.4 h, 5.5-6.4 h, 6.5-7.4 h, 7.5-8.4 h, and more than 8.5 h. The associations of sleep duration with obesity and the HbA(1c) levels were examined in a cross-sectional manner. RESULTS: The HbA(1c) levels showed a quadratic association with sleep duration; namely, a shorter or longer sleep duration was associated with a higher level compared with a sleep duration of 6.5-7.4 h (P for quadratic trend <0.001). This association remained significant after adjusting for potential confounders, including the total energy intake and depressive symptoms. Furthermore, additional adjustments for obesity, which also showed a U-shaped relationship with sleep duration, did not attenuate the U-shaped sleep-HbA(1c) association. A significant interaction between sleep duration and age or the use of insulin was observed for the HbA(1c) levels. CONCLUSIONS: Sleep duration was shown to have U-shaped associations with obesity and the HbA(1c) levels in type 2 diabetic patients, independent of potential confounders, and therefore may be an important modifiable factor for the clinical management of patients with type 2 diabetes.

    DOI: 10.2337/dc12-0904

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Presentations

  • Combination of changes in estimated GFR and albuminuria and the risk of major clinical outcomes in patients with type 2 diabetes: the ADVANCE-ON study International conference

    Toshiaki Ohkuma, Min Jun, John Chalmers, Sophia Zoungas, Vlado Perkovic, Mark Woodward

    Australasian Diabetes Congress 2018  2018.9 

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    Event date: 2022.4

    Language:Japanese  

    Country:Japan  

  • Sex-specific associations of conventional risk factors and duration of diabetes with myocardial infarction in type 2 diabetes: the ADVANCE-ON study International conference

    Toshiaki Ohkuma, Min Jun, John Chalmers, Mark Woodward

    Australasian Diabetes Congress 2019  2019.8 

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    Event date: 2019.8

    Language:Japanese  

    Country:Australia  

  • 2 型糖尿病患者におけるeGFR、アルブミン尿の変化が糖尿病合併症発症に及ぼす影響: ADVANCE-ON 研究

    大隈 俊明, Min Jun, John Chalmers, Sophia Zoungas, Vlado Perkovic, Mark Woodward

    日本臨床疫学会第2回年次学術大会  2018.9 

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    Event date: 2018.9

    Language:Japanese  

    Country:Japan  

  • Acute Increase in Creatinine after Starting ACE Inhibitor and Vascular Events and Premature Death in Patients with Type 2 Diabetes: the ADVANCE trial

    Toshiaki Ohkuma, Min Jun, Mark Woodward, John Chalmers, Vlado Perkovic, Anthony Rodgers

    American Diabetes Association 78th Scientific Sessions  2018.6 

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    Event date: 2018.6

    Language:English  

    Country:United States  

  • 2型糖尿病患者におけるACE阻害薬投与後早期のCr上昇と心血管病、腎症、総死亡との関連: ADVANCE試験

    大隈 俊明, Min Jun, Mark Woodward, John Chalmers, Vlado Perkovic, Anthony Rodgers

    第61 回日本糖尿病学会年次学術集会  2018.5 

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    Event date: 2018.5

    Language:Japanese  

    Country:Japan  

  • Cardiac stress and inflammatory markers as predictors of heart failure in patients with type 2 diabetes: the ADVANCE trial International conference

    Toshiaki Ohkuma , Min Jun , Sophia Zoungas , Paul Welsh , Naveed Sattar , Mark E. Cooper , Jonathan E. Shaw , John Chalmers , Mark Woodward

    2017 ADS/ADEA Annual Scientific Meeting  2017.8 

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    Event date: 2017.8

    Language:English  

    Country:Australia  

  • <シンポジウム: 本邦のリアルワールド研究からみる糖尿病患者の心・腎合併症> Fukuoka Diabetes Registry (FDR)

    大隈俊明, 岩瀬正典, 藤井裕樹, 北園孝成

    第57回 糖尿病学の進歩  2023.2 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 血清アディポネクチン高値は1型および2型糖尿病患者の重症低血糖のリスクである:福岡糖尿病患者 データベース研究(FDR)

    岩瀬正典,藤井裕樹,小森田佑二,大隈俊明,井手均,吉成匡人,村尾 愛,於久祐太郎,井手脇康裕, 佐々木伸浩,布井清秀,佐藤雄一, 五島大祐,井元博文, 野原栄,南昌江,和田美也,横溝由史,菊池正統,野見山理久,中村晋,田代憲司,吉成元孝,市川晃治郎,中村宇大,北園孝成

    第62回日本糖尿病学会年次学術集会  2019.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • クレアチニン-/シスタチンC-推算糸球体濾過量比による糖尿病性腎臓病の進展予測:the Fukuoka Diabetes Registry

    井手均,岩瀬正典,藤井裕樹,大隈俊明,小森田祐二,吉成匡人,於久祐太郎,村尾愛,井手脇康裕,佐々木伸浩,布井清秀,佐藤雄一,五島大祐,井元博文,野原 栄,南昌江,和田美也,横溝由史,菊池正統,野見山理久,中村晋,田代憲司,吉成元孝,市川晃治郎,中村宇大,北園孝成

    第62回日本糖尿病学会年次学術集会  2019.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 大腿骨骨折合併2型糖尿病患者の死亡リスクの検討:福岡県糖尿病患者データベース研究(Fukuoka Diabetes Registry)

    小森田祐二,岩瀬正典,藤井裕樹,大隈俊明,井手均,吉成匡人,村尾愛,於久祐太郎,井手脇康裕,佐々木伸浩,布井清秀,五島大祐,井元博文,野原栄,南昌江,和田美也,横溝由史,菊池正統,野見山理久,中村晋,田代憲司,吉成元孝,市川晃治郎,大星博明,中村宇大,北園孝成

    第62回日本糖尿病学会年次学術集会  2019.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 2型糖尿病患者におけるBMIの変動性と死亡の関係:福岡県糖尿病患者データベース研究(Fukuoka Diabetes Registry)

    藤井裕樹,岩瀬正典,中村宇大,大隈俊明,井手均,小森田祐二,吉成匡人,村尾 愛,於久祐太郎,佐々木伸浩,佐藤雄一,布井清秀,五島大祐,井元博文,野原 栄,南昌江,和田美也,横溝由史,菊池正統,野見山理久,中村晋,田代憲司,吉成元孝,市川晃治郎,北園孝成

    第62回日本糖尿病学会年次学術集会  2019.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • DPP-4阻害薬服用中に発症した水疱性類天疱瘡の1例

    守谷聡一朗,大城彩香,冬野洋子,東大樹,於久祐太郎,吉成匡人,大隈俊明,中村宇大,北園孝成

    第326回日本内科学会九州地方会  2019.8 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 歌舞伎症候群に併発した1型糖尿病の一例

    大城彩香,東大樹,於久祐太郎,吉成匡人,平川洋一郎,大隈俊明,中村宇大, 北園孝成

    第57回日本糖尿病学会九州地方会  2019.10 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 抗PD-L1抗体デュルバルマブ投与後に発症した劇症1型糖尿病の1例

    東大樹,中尾晶子,大城彩香,於久祐太郎,吉成匡人,平川洋一郎,大隈俊明, 中村宇大,北園孝成

    第57回日本糖尿病学会九州地方会  2019.10 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 糖尿病性ケトアシドーシスに十二指腸炎を合併した2型糖尿病の一例

    坂本和可子, 大城彩香, 大隈俊明,於久祐太郎,吉成匡人、平川洋一郎,北園孝成

    第332回日本内科学会九州地方会  2021.1 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 2型糖尿病患者における骨折のリスク因子と予後に関する疫学研究: 福岡県糖尿病患者データベース研究 (Fukuoka Diabetes Registry)

    小森田祐二,岩瀬正典,大隈俊明, 藤井裕樹,中村宇大, 北園孝成

    第64回日本糖尿病学会年次学術集会  2021.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 2型糖尿病患者においてポリファーマシーは骨折リスク上昇と関連する:Fukuoka Diabetes Registry (FDR)

    小森田祐二,岩瀬正典,大隈俊明, 藤井裕樹,於久祐太郎,東大樹,大城彩香, 井手均,吉成匡人,佐々木伸浩,佐藤雄一,五島大祐,野原栄,南昌江,和田美也,横溝由史,菊池正統,野見山理久,中村晋,田代憲司,吉成元孝,市川晃治郎,中村宇大, 北園孝成

    第64回日本糖尿病学会年次学術集会  2021.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • タクロリムス内服により糖尿病性ケトアシドーシスを発症した一例

    坂本知子,高野瑛子, 大隈俊明, 坂本和可子, 東大樹, 大城彩香, 小森田祐二, 平川洋一郎, 北園孝成

    第334回日本内科学会九州地方会  2021.8 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 糖尿病教室後の患者への振り返りを行った看護師の実態調査

    前田英子,岩本夏美,豊福由香里,梅津人美,久冨清美,坂本和可子,大城彩香,大隈俊明.

    第59回日本糖尿病学会 九州地方会  2021.11 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • DPP4阻害薬の追加によりインスリン離脱が可能となった永続型新生児糖尿病の一例

    大城彩香,大隈俊明,坂本和可子,高野瑛子,坂本知子,東大樹,小森田祐二,平川洋一郎,北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • コーヒー摂取とCKD発症の関連:Fukuoka Diabetes Registry

    小森田祐二,大隈俊明,岩瀬正典,藤井裕樹,中村宇大,於久祐太郎,東大樹,大城彩香,坂本和可子,吉成匡人,北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 前立腺肥大症治療薬が糖尿病の発症・悪化に寄与したと考えられた一例

    坂本和可子, 大隈俊明, 東大樹、於久祐太郎、大城彩香、小森田祐二、平川洋一郎、北園孝成

    第336回日本内科学会九州地方会  2022.1 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 今、改めて見直す糖尿病の治療 ~食事・運動・薬物療法~

    大隈俊明

    第95回日本薬理学会年会  2022.3 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 糖尿病合併症の性差を規定する環境・遺伝要因の解明: 大規模ゲノムコホート研究

    大隈俊明, 岩瀬正典, 藤井裕樹, 小森田祐二, 中村宇大, 北園孝成

    第9回日本糖尿病協会年次学術集会  2022.7 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 生物学的製剤やCOVID-19ワクチン接種後に続発性アミロイドーシスによる亜急性甲状腺炎様症候群(STLS)を繰り返したクローン病の1例

    大村一華, 大隈俊明, 大城彩香, 岩武史朗, 川崎啓祐, 梅野淳嗣, 岡村建, 北園孝成

    第340回日本内科学会九州地方会  2022.8 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • ボノプラザンが低Ca, Mg血症の一因と考えられた1例

    大村一華, 大隈俊明, 於久祐太郎, 藤平美佳, 大城彩香, 東大樹, 坂本和可子, 高波百合那, 恒吉章治, 北園孝成

    第340回日本内科学会九州地方会  2023.1 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 前立腺肥大症の治療開始後に耐糖能が悪化した一例

    坂本和可子,於久祐太郎,大城彩香,東大樹,小森田祐二,平川洋一郎,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 2型糖尿病患者における乳製品摂取量とメタボリックシンドローム、慢性腎臓病の関連:Fukuoka Diabetes Registry(FDR)

    吉成匡人, 大隈俊明, 岩瀬正典,藤井裕樹,小森田祐二,東大樹, 大城彩香, 坂本和可子,佐々木伸浩,佐藤雄一,中村宇大, 五島大祐,野原栄,井手均, 南昌江,和田美也,横溝由史,菊池正統,野見山理久,中村晋,田代憲司,吉成元孝,市川晃治郎,北園 孝成

    第66回 日本糖尿病学会年次学術集会  2023.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 2型糖尿病患者におけるACE阻害薬投与後の血清K上昇と生命予後や血管合併症との関連: ADVANCE試験

    大隈俊明, Katie Harris, Mark Woodward, John Chalmers

    第66回 日本糖尿病学会年次学術集会  2023.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • <シンポジウム: Big data, Real World研究が帰る糖尿病臨床> 福岡県糖尿病患者データベース研究 Fukuoka Diabetes Registry (FDR) Invited

    岩瀬正典, 中村宇大, 大隈俊明

    第66回 日本糖尿病学会年次学術集会  2023.5 

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    Event date: 2023.5

    Language:Japanese  

    Country:Japan  

  • 手術予定患者に対する糖尿病治療介入必要度トリアージの試み

    梶野美保,淀川千穂,坂本竜一,松田やよい,大隈俊明,佐藤直市,勝田仁,小川佳宏

    第60回日本糖尿病学会九州地方会  2022.10 

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    Event date: 2022.10 - 2023.5

    Language:Japanese  

    Country:Japan  

  • <シンポジウム: 予防に活かす 最新の大規模臨床研究の成果> 糖尿病診療におけるクリニカルクエスチョンと大規模臨床研究のエビデンス Invited

    大隈俊明, 岩瀬正典, 藤井裕樹, 北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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    Event date: 2022.10

    Language:Japanese  

    Country:Japan  

  • 糖尿病合併症および危険因子における性差の解明:福岡県糖尿病患者データベース研究:Fukuoka Diabetes Registry(FDR)

    大隈俊明,岩瀬正典,藤井裕樹,小森田祐二,中村宇大,北園孝成

    第65回日本糖尿病学会年次学術集会  2022.5 

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    Event date: 2022.5 - 2023.5

    Language:Japanese  

    Country:Japan  

  • 糖尿病患者において便秘は慢性腎臓病と関連する: Fukuoka Diabetes Registry (FDR)

    大隈俊明, 岩瀬正典, 中村宇大, 藤井裕樹, 井手均, 小森田祐二, 吉成匡人, 於久祐太郎, 東大樹, 大城彩香, 佐々木伸浩, 佐藤雄一, 五島大祐, 野原栄, 南昌江, 和田美也, 横溝由史, 菊池正統, 野見山理久, 中村晋, 田代憲司, 吉成元孝, 市川晃治郎, 北園孝成

    第64回日本糖尿病学会年次学術集会  2021.5 

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    Event date: 2021.5

    Language:Japanese  

    Country:Japan  

  • 当院における膵臓移植登録と周術期の血糖管理

    大城彩香, 大隈俊明,坂本和可子,東大樹,於久祐太郎,小森田祐二、平川洋一郎,加来啓三,北園孝成

    第48回日本膵・膵島移植研究会  2021.3 

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    Event date: 2021.3

    Language:Japanese  

    Country:Japan  

  • 腎移植患者におけるSGLT2阻害薬の安全性と有効性の検討

    久留裕, 野口浩司, 佐藤優, 目井孝典, 加来啓三, 岡部安博, 大隈俊明, 中村雅史

    第54回日本臨床腎移植学会  2021.2 

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    Event date: 2021.2

    Language:Japanese  

    Country:Japan  

  • 喫煙習慣は2型糖尿病患者の血糖コントロールに関連する:Fukuoka Diabetes Registry (FDR12)

    大隈 俊明

    第57回日本糖尿病学会年次学術集会 

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  • 生活習慣が2型糖尿病の病態や血管合併症に及ぼす影響: 福岡県糖尿病患者データベー ス研究 Invited

    大隈 俊明

    第52回日本糖尿病学会九州地方会 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  • 脂肪萎縮性糖尿病の一例

    原 功哉, 堤 礼子, 野原 栄, 大隈 俊明, 北園 孝成

    第58回日本糖尿病学会九州地方会  2020.10 

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    Language:Japanese  

    Country:Japan  

  • 当院外来における糖尿病神経障害に関する意識調査

    五島大祐, 坂本典彦, 中尾晶子, 松尾美奈, 大隈俊明, 北園孝成

    第58回日本糖尿病学会九州地方会  2020.10 

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  • 虚血性胃十二指腸炎から腹部アンギーナの診断に至った 2 型糖尿病の1例

    坂本典彦, 中尾晶子, 松尾美奈, 五島大祐, 大隈俊明, 北園孝成

    第58回日本糖尿病学会九州地方会  2020.10 

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  • 頭部 CT・MRI で典型的な所見を示さなかった糖尿病性舞踏病疑いの1例

    舟越弘樹, 五島大祐, 坂本典彦, 中尾晶子, 大隈俊明, 北園孝成

    第58回日本糖尿病学会九州地方会  2020.10 

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  • 炭酸水素Na 大量投与により意識障害が増悪した糖尿病ケトアシドーシス(DKA)の一例

    高野瑛子,眞田智慧,海津梓奈子,井元博文,中村宇大,大隈俊明,北園孝成

    第58回日本糖尿病学会九州地方会  2020.10 

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  • 胃切除後の膵外分泌機能低下に対する膵酵素補充により血糖管理が悪化した一例

    坂本和可子,大隈俊明,橋本千明,於久祐太郎,大城彩香,小森田祐二,平川洋一郎,北園孝成

    第58回日本糖尿病学会九州地方会  2020.10 

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  • 1型糖尿病患者における骨折頻度,特徴,リスク因子の検討

    小森田祐二,南昌江,前田泰孝,吉岡利絵,大隈俊明,北園孝成

    第58回日本糖尿病学会九州地方会  2020.10 

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  • 2型糖尿病患者においてコーヒーや緑茶の摂取は死亡リスクの低下と関連する:福岡県糖尿病患者データベース研究

    小森田祐二,岩瀬正典,藤井裕樹,大隈俊明,井手均,吉成匡人,於久祐太郎,東大樹,北村環,佐々木伸浩,佐藤雄一,五島大祐,井元博文,野原栄,南昌江,和田美也,横溝由史,菊池正統,野見山理久,中村晋,田代憲司,吉成元孝,市川晃治郎,大星博明,中村宇大,北園孝成

    第63回日本糖尿病学会年次学術集会  2020.10 

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  • 診断に苦慮した化膿性門脈血栓症の1例

    落合由佳,坂本典彦,中尾晶子,松尾美奈,五島大祐,大隈俊明,北園孝成

    第333回日本内科学会九州地方会  2021.6 

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  • 視床下部性副腎機能低下を合併したと考えられるインスリン自己免疫症候群の 1 例

    小林和貴,原規子,中尾晶子,五島大祐,大隈俊明,北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 膵頭十二指腸切除後に気腫肝膿瘍を発症した 2 型糖尿病の 1 例

    中村捷太郎,中尾晶子,原規子,五島大祐,大隈俊明,北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 糖尿病合併COVID-19患者における重症化リスクの検討

    池内 千明、堤 礼子、野原 栄、肥山 和俊、大隈 俊明、北園 孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 当院における糖尿病合併COVID-19患者の酸素投与期間に関わる因子の検討

    野原 栄、池内 千明、堤 礼子、肥山 和俊、大隈 俊明、北園 孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 持続皮下インスリン注入療法における基礎分泌補充調整強化による効果

    井元博文、堀内俊輔、藤平美佳、於久真由美、川本徹、佐々木伸浩、大隈俊明、北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • HbA1c と血糖値に顕著な乖離を認めた肥満合併 2 型糖尿病患者の 1 例

    佐々木伸浩、堀内俊輔、藤平美佳、於久真由美、川本徹、井元博文、大隈俊明、北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 重度の起立性低血圧とインスリン分泌能低下のため筋肉量増加に難渋した 2 型糖尿病の 1 例

    藤平美佳、堀内俊輔、於久真由美、川本徹、井元博文、佐々木伸浩、大隈俊明、北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 当院での糖尿病合併高度肥満患者におけるスリーブ状胃切除術前後の体重変化について

    落合弘貴、佐々木伸浩、堀内俊輔、藤平美佳、於久真由美、川本徹、井元博文、 安井隆晴、永井英司、大隈俊明、北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 当院における COVID-19 の診療経験

    川本徹、堀内俊輔、藤平美佳、於久真由美、井元博文、佐々木伸浩、石丸敏之、吉成匡人、小森田祐二、大隈俊明、北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 2型糖尿病患者における肝線維化スコアリングシステムFIB-4 indexの検討

    坂本典彦,原功哉,眞田知慧,高野瑛子,大隈俊明,中村宇大,北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • HLA-DRB1*0404を有した超高齢インスリン自己免疫症候群(IAS)の1例

    原規子, 平田詩乃, 髙木可南子, 於久祐太郎, 井手均, 岩瀬正典, 五島大祐, 大隈俊明, 北園孝成

    第59回日本糖尿病学会 九州地方会  2021.11 

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  • 糖尿病教室を受講した患者の退院後のセルフケア能力および療養行動

    鳥越 夏美, 梅津 人美, 豊福 由香里, 前田 英子, 久冨 清美, 坂本 和可子, 大城 彩香, 大隈 俊明

    糖尿病  2022.4 

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  • 糖尿病合併症および危険因子における性差の解明 福岡県糖尿病患者データベース研究(Fukuoka Diabetes Registry:FDR)

    大隈 俊明, 岩瀬 正典, 藤井 裕樹, 小森田 祐二, 中村 宇大, 北園 孝成

    糖尿病  2022.4 

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  • 女性の生殖関連因子は糖尿病患者の死亡や心血管病リスクと関連する Fukuoka Diabetes Registry(FDR)

    大城 彩香, 大隈 俊明, 岩瀬 正典, 中村 宇大, 藤井 裕樹, 小森田 祐二, 吉成 匡人, 於久 祐太郎, 東 大樹, 坂本 和可子, 佐々木 伸浩, 佐藤 雄一, 五島 大祐, 野原 栄, 井手 均, 南 昌江, 和田 美也, 横溝 由史, 菊池 正統, 野見山 理久, 中村 晋, 田代 憲司, 吉成 元孝, 市川 晃治郎, 北園 孝成

    糖尿病  2022.5 

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  • SAP療法における基礎分泌補充調整強化の重要性

    井元 博文, 堀内 俊輔, 藤平 美佳, 於久 真由美, 川本 徹, 佐々木 伸浩, 大隈 俊明, 北園 孝成

    第65回日本糖尿病学会年次学術集会  2022.5 

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  • 2型糖尿病患者における脳血管障害の発症頻度と血糖コントロールや生活習慣との関連 福岡県糖尿病患者データベース研究(FDR)

    岩瀬 正典, 大隈 俊明, 小森田 祐二, 藤井 裕樹, 井手 均, 吉成 匡人, 於久 祐太郎, 東 大樹, 大城 彩香, 中村 宇大, 佐々木 伸浩, 布井 清秀, 佐藤 雄一, 五島 大祐, 野原 栄, 南 昌江, 和田 美也, 横溝 由史, 菊池 正統, 野見山 理久, 中村 晋, 田代 憲司, 吉成 元孝, 市川 晃治郎, 北園 孝成

    第65回日本糖尿病学会年次学術集会  2022.5 

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  • 2型糖尿病患者においてポリファーマシーは重症低血糖リスク上昇と関連する Fukuoka Diabetes Registry(FDR)

    小森田 祐二, 大隈 俊明, 岩瀬 正典, 中村 宇大, 藤井 裕樹, 吉成 匡人, 於久 祐太郎, 東 大樹, 大城 彩香, 坂本 和可子, 佐々木 伸浩, 佐藤 雄一, 五島 大祐, 野原 栄, 井手 均, 南 昌江, 和田 美也, 横溝 由史, 菊池 正純, 野見山 理久, 中村 晋, 田代 憲司, 吉成 元孝, 市川 晃治郎, 北園 孝成

    第65回日本糖尿病学会年次学術集会  2022.5 

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  • 2型糖尿病における2年間のルセオグリフロジン投与の肝機能に対する影響

    堀内 俊輔, 佐々木 伸浩, 井元 博文, 川本 徹, 於久 真由美, 藤平 美佳, 大隈 俊明, 北園 孝成

    第65回日本糖尿病学会年次学術集会  2022.5 

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  • 高齢糖尿病患者12例におけるフレイルチェックでの検討 Invited

    内薗祐二,武石千鶴子,本田美貴,濱砂麻美,中島康浩,田平泰徳,岩屋祐子,佐藤雄一,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • デュラグルチドが奏効した抗GAD抗体陽性の糖尿病の一例 Invited

    高野瑛子,川野聡子,眞田知慧,中村宇大,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • SGLT2阻害薬内服中に高度脱水を伴うケトアシドーシスを来した2型糖尿病の2例 Invited

    東木孝太,佐々木伸浩,原功哉,於久真由美,川本徹,井元博文,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • 当科における経口GLP-1受容体作動薬・セマグルチドの使用経験 Invited

    横溝舞子,濵小路美貴,納富威充,井手誠,内薗祐二,佐藤雄一,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • SGLT2阻害薬により著明な高血糖が顕在化せず発見が遅れた1型糖尿病ケトアシドーシス Invited

    土師晶子,知識裕喜,原規子,五島大祐,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • Posterior reversible encephalopathy syndrome(PRES)を合併した2型糖尿病の1例 Invited

    牟田大毅,井手均,於久祐太郎,髙木可南子,平田詩乃,青谷領一郎,岩瀬正典,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • 約束処方中のロキソプロフェンが誘因と疑われたインスリン自己免疫症候群の1例 Invited

    川野聡子,高野瑛子,眞田知慧,中村宇大,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • SAP療法における基礎分泌補充調整強化の重要性(第2報):MiniMed770Gによる影響 Invited

    井元博文,東木孝太,原功哉,於久真由美,川本徹,佐々木伸浩,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • 糖尿病性ケトアシドーシス(DKA)の契機が急性壊死性食道炎(ANE)であった一例 Invited

    徳田信二,佐藤雄一,内薗祐二,井手誠,納富威充,横溝舞子,濵小路美貴,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • 維持透析中に糖尿病ケトアシドーシスを発症し救命し得なかった一例 Invited

    西崎愛佳,井手誠,濵小路美貴,横溝舞子,納富威充,内薗祐二,佐藤雄一,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • アテゾリズマブによるirAEとして発症した急性発症1B型糖尿病の一例 Invited

    古賀淳也,知識裕喜,原規子,土師晶子,五島大祐,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • <シンポジウム: IoT/AI診療 すべての患者さんに最適な治療を> 共有意思決定のためのツールとしてCGMを活用する Invited

    野原栄, 坂本知子,堤礼子,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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  • <シンポジウム: ゼロ感染症 糖尿病患者を守る> 福岡における COVID19 の現状 Invited

    佐々木伸浩,大隈俊明,北園孝成

    第60回日本糖尿病学会九州地方会  2022.10 

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Committee Memberships

  • 福岡糖尿病療養指導士認定会   研修試験委員会 委員長   Domestic

    2024.3 - 2024.4   

  • 福岡県糖尿病協会   Vice-chairman  

    2022.7 - 2024.6   

  • 日本糖尿病・生活習慣病ヒューマンデータ学会   Councilor   Domestic

    2020.10 - Present   

  • 日本糖尿病協会   代議員  

    2020.4 - Present   

  • 福岡糖尿病療養指導士認定会   研修試験委員会 委員   Domestic

    2020.4 - Present   

  • 日本臨床疫学会   専門家制度委員会 委員   Domestic

    2020.4 - 2024.4   

  • 福岡県糖尿病協会   Executive   Domestic

    2020.4 - 2022.5   

  • 日本糖尿病学会   Councilor  

    2019.5 - 2027.5   

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Academic Activities

  • Screening of academic papers

    Role(s): Peer review

    2023

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:9

    Proceedings of domestic conference Number of peer-reviewed papers:15

  • Screening of academic papers

    Role(s): Peer review

    2022

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:4

    Proceedings of domestic conference Number of peer-reviewed papers:15

  • Screening of academic papers

    Role(s): Peer review

    2021

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:7

    Proceedings of domestic conference Number of peer-reviewed papers:15

  • Screening of academic papers

    Role(s): Peer review

    2020

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:4

  • Screening of academic papers

    Role(s): Peer review

    2019

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:7

    Proceedings of domestic conference Number of peer-reviewed papers:18

  • Screening of academic papers

    Role(s): Peer review

    2018

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:4

  • Screening of academic papers

    Role(s): Peer review

    2017

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:3

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Research Projects

  • 糖尿病合併症に対する環境・遺伝要因の性特異的影響の解明:大規模ゲノムコホート研究

    Grant number:24K14678  2024 - 2026

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

  • 性差を考慮した糖尿病合併症の遺伝的、環境的因子の解明: 大規模ゲノムコホート研究

    Grant number:21K11700  2021 - 2024

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 大規模ゲノムコホートによる糖尿病合併症の性特異的遺伝・環境要因の同定

    Grant number:19K24229  2019 - 2020

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity start-up

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 大規模臨床試験に基づく糖尿病合併症の発症予測モデルの構築と血糖・血圧目標値の検討

    2016 - 2017

    Japan Society for the Promotion of Science  Postdoctoral Fellowships for Research Abroad

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    Grant type:Joint research

  • 一般地域住民を含む糖尿病患者データベース構築による前向きゲノムコホート研究

    Grant number:23249037  2011 - 2015

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

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    Grant type:Scientific research funding

Educational Activities

  • ・医学部4年⽣および医⻭薬合同講義で糖尿病に関する講義を担当する。
    ・医学部5年⽣のベッドサイド実習、および医学部6年⽣のクリニカルクラークシップで実習指導を⾏う。
    ・⼤学院博⼠課程学⽣に対して、臨床疫学研究、論⽂作成について指導する。

Class subject

  • 系統医学III (内分泌・代謝)

    2024.4 - 2024.9   First semester

  • 臨床医学II (内分泌・代謝・⽼化概論)

    2024.4 - 2024.9   First semester

  • 臨床医学II (内分泌・代謝・⽼化概論)

    2023.4 - 2023.9   First semester

  • 系統医学III (内分泌・代謝)

    2023.4 - 2023.9   First semester

  • 臨床医学II (内分泌・代謝・⽼化概論)

    2022.4 - 2022.9   First semester

  • 系統医学III (内分泌・代謝)

    2022.4 - 2022.9   First semester

  • 臨床医学II (内分泌・代謝・⽼化概論)

    2021.4 - 2021.9   First semester

  • 系統医学III (内分泌・代謝)

    2021.4 - 2021.9   First semester

  • 臨床医学II (内分泌・代謝・⽼化概論)

    2020.4 - 2020.9   First semester

  • 系統医学III (内分泌・代謝)

    2020.4 - 2020.9   First semester

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Outline of Social Contribution and International Cooperation activities

  • 市民を対象とした公開講座、糖尿病教室への参加

Social Activities

  • 今、改めて見直す糖尿病の治療

    第44回ふくおか市民糖尿病教室  2023.11

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    Audience:General, Scientific, Company, Civic organization, Governmental agency

    Type:Lecture

  • 危険な合併症を発症する前に正しく知って、正しく管理を「糖尿病」

    朝日新聞  2023.11

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    Audience:General, Scientific, Company, Civic organization, Governmental agency

    Type:Newspaper, magazine

  • この機会に正しく知ろう!糖尿病

    朝日新聞  2022.11

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    Audience:General, Scientific, Company, Civic organization, Governmental agency

    Type:Newspaper, magazine

  • 今、改めて見直す糖尿病の治療~食事・運動・薬物療法~

    第95回日本薬理学会年会 市民公開講座  福岡市  2022.3

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    Audience:General, Scientific, Company, Civic organization, Governmental agency

    Type:Lecture

  • 糖尿病の正しい理解普及のために~間違った認識と偏見をなくそう~

    朝日新聞  2021.11

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    Audience:General, Scientific, Company, Civic organization, Governmental agency

    Type:Newspaper, magazine

  • 筋肉量 コツコツ積み上げ 健康長寿

    朝日新聞  2020.11

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    Audience:General, Scientific, Company, Civic organization, Governmental agency

    Type:Newspaper, magazine

  • 令和時代の生活習慣改善法~改めて見直そう! 食事・運動・睡眠~

    第3回 九州大学病院 糖尿病市民公開講座  福岡市  2019.9

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    Audience:General, Scientific, Company, Civic organization, Governmental agency

    Type:Lecture

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Travel Abroad

  • 2016.7 - 2019.3

    Staying countory name 1:Australia   Staying institution name 1:The George Institute for Global Health

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Internal Medicine / Metabolism

Clinician qualification

  • Preceptor

    The Japan Diabetes Society(JDS)

  • Specialist

    The Japan Diabetes Society(JDS)

  • Specialist

    The Japanese Society of Internal Medicine(JSIM)

  • Certifying physician

    The Japanese Society of Internal Medicine(JSIM)

Year of medical license acquisition

  • 2005

Notable Clinical Activities

  • 糖尿病・内分泌代謝疾患を中心に、腎疾患、高血圧・心疾患、脳血管疾患などの血管合併症の診療、腎移植や膵腎同時移植における血糖管理を行っている。 ⽇本糖尿病協会 代議員、福岡県糖尿病協会 副会長・常任理事として協会が⾏う糖尿病の社会啓発活動に参加している。