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  • 1
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    Online Resource
    Serum Ethylamine Levels as an Indicator of l -Theanine Consumption and the Risk of Type 2 Diabetes in a General Japanese Population: The Hisayama Study
    American Diabetes Association ; 2019
    In:  Diabetes Care Vol. 42, No. 7 ( 2019-07-01), p. 1234-1240
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 7 ( 2019-07-01), p. 1234-1240
    Abstract: This study investigated the association between serum ethylamine levels as an indicator of l-theanine consumption and the development of type 2 diabetes in a Japanese community. RESEARCH DESIGN AND METHODS A total of 2,253 community-dwelling Japanese individuals aged 40–79 years without diabetes were monitored for 7 years. Serum ethylamine levels were divided into quartiles: ≤0.86, 0.87–2.10, 2.11–5.28, and ≥5.29 ng/mL. Kinetic analysis of serum ethylamine concentrations was performed after ingestion of l-theanine–rich green tea products containing 8 mg of l-theanine by 12 healthy volunteers. RESULTS During follow-up, 282 subjects developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes decreased significantly with elevating levels of serum ethylamine (P for trend = 0.04). This association remained unchanged after adjusting for potential confounding factors. The multivariable-adjusted hazard ratio (HR) for type 2 diabetes was significantly lower in the fourth quartile of serum ethylamine than in the first quartile (HR 0.69, 95% CI 0.49–0.98). This trend of decrease in diabetic risk across serum ethylamine levels was more prominent in middle-aged subjects and in subjects with prediabetes, obesity, or insulin resistance. Kinetic analysis estimated that the minimum concentration at the steady state was & gt;5.90 ng/mL in the case of twice-daily ingestion with an interval of 12 h. CONCLUSIONS Higher serum ethylamine was significantly associated with lower risk of the development of type 2 diabetes in a general Japanese population. The measurement of serum ethylamine concentration would be a useful biomarker for the objective estimation of l-theanine consumption.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc18-2655
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 2
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    Impact of Sleep Duration on Obesity and the Glycemic Level in Patients With Type 2 Diabetes
    American Diabetes Association ; 2013
    In:  Diabetes Care Vol. 36, No. 3 ( 2013-03-01), p. 611-617
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 36, No. 3 ( 2013-03-01), p. 611-617
    Abstract: 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 HbA1c levels were examined in a cross-sectional manner. RESULTS The HbA1c 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 & lt;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-HbA1c association. A significant interaction between sleep duration and age or the use of insulin was observed for the HbA1c levels. CONCLUSIONS Sleep duration was shown to have U-shaped associations with obesity and the HbA1c 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.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc12-0904
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2013
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  • 3
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    Impact of Body Weight Loss From Maximum Weight on Fragility Bone Fractures in Japanese Patients With Type 2 Diabetes: The Fukuoka Diabetes Registry
    American Diabetes Association ; 2018
    In:  Diabetes Care Vol. 41, No. 5 ( 2018-05-01), p. 1061-1067
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 41, No. 5 ( 2018-05-01), p. 1061-1067
    Abstract: 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: & lt;10%, 10% to & lt;20%, 20% to & lt;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 ( & lt;10% weight loss from maximum body weight), 7.8 (10% to & lt;20%), 11.7 (20% to & lt;30%), and 19.2 (≥30%) (P for trend & lt;0.001). Multivariate-adjusted hazard ratios for fragility fractures compared with reference ( & lt;10% weight loss) were 1.48 (95% CI 0.79–2.77) in the 10% to & lt;20% group, 2.23 (1.08–4.64) in 20% to & lt;30%, and 5.20 (2.15–12.57) in ≥30% in men, and 1.19 (0.78–1.82) in 10% to & lt;20%, 1.62 (0.96–2.73) in 20% to & lt;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.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc17-2004
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 4
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    Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study
    American Diabetes Association ; 2018
    In:  Diabetes Care Vol. 41, No. 6 ( 2018-06-01), p. 1275-1284
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 41, No. 6 ( 2018-06-01), p. 1275-1284
    Abstract: Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach). RESEARCH DESIGN AND METHODS In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) & lt;70 mg/dL (n = 2,518) or standard statin therapy targeting LDL-C 100–120 mg/dL (n = 2,524). RESULTS Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group (P & lt; 0.001). The primary end point events occurred in 129 intensive group patients and 153 standard group patients (hazard ratio [HR] 0.84 [95% CI 0.67–1.07] ; P = 0.15). The relationship between the LDL-C difference in the two groups and the event reduction rate was consistent with primary prevention studies in patients with diabetes. Exploratory findings showed significantly fewer cerebral events in the intensive group (HR 0.52 [95% CI 0.31–0.88]; P = 0.01). Safety did not differ significantly between the two groups. CONCLUSIONS We found no significant decrease in CV events or CV-associated deaths with intensive therapy, possibly because our between-group difference of LDL-C was lower than expected (27.7 mg/dL at 36 months of treatment). The potential benefit of achieving LDL-C & lt;70 mg/dL in a treat-to-target strategy in high-risk patients deserves further investigation.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc17-2224
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
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  • 5
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    Association Between Diabetes and Hippocampal Atrophy in Elderly Japanese: The Hisayama Study
    American Diabetes Association ; 2016
    In:  Diabetes Care Vol. 39, No. 9 ( 2016-09-01), p. 1543-1549
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 39, No. 9 ( 2016-09-01), p. 1543-1549
    Abstract: To investigate the association between diabetes and brain or hippocampal atrophy in an elderly population. RESEARCH DESIGN AND METHODS A total of 1,238 community-dwelling Japanese subjects aged ≥65 years underwent brain MRI scans and a comprehensive health examination in 2012. Total brain volume (TBV), intracranial volume (ICV), and hippocampal volume (HV) were measured using MRI scans for each subject. We examined the associations between diabetes-related parameters and the ratios of TBV to ICV (an indicator of global brain atrophy), HV to ICV (an indicator of hippocampal atrophy), and HV to TBV (an indicator of hippocampal atrophy beyond global brain atrophy) after adjustment for other potential confounders. RESULTS The multivariable-adjusted mean values of the TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios were significantly lower in the subjects with diabetes compared with those without diabetes (77.6% vs. 78.2% for the TBV-to-ICV ratio, 0.513% vs. 0.529% for the HV-to-ICV ratio, and 0.660% vs. 0.676% for the HV-to-TBV ratio; all P & lt; 0.01). These three ratios decreased significantly with elevated 2-h postload glucose (PG) levels (all P for trend & lt;0.05) but not fasting plasma glucose levels. Longer duration of diabetes was significantly associated with lower TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios. The subjects with diabetes diagnosed in midlife had significantly lower HV-to-ICV and HV-to-TBV ratios than those without and those diagnosed in late life. CONCLUSIONS Our data suggest that a longer duration of diabetes and elevated 2-h PG levels, a marker of postprandial hyperglycemia, are risk factors for brain atrophy, particularly hippocampal atrophy.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc15-2800
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2016
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  • 6
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    2456-PUB: Cholesterol Uptake Capacity of High-Density Lipoprotein Predicts the Risk of Future Diabetes: The Hisayama Study
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Background: Cholesterol uptake capacity (CUC) is a novel index of the functionality of serum high-density lipoprotein (HDL), which has been reported to be associated with insulin resistance and the cardiovascular risk. However, only a few studies investigated the association of CUC with the development of diabetes. Herein, we assessed the association of CUC with incident type 2 diabetes in a general Japanese population. Methods: A total of 2,162 subjects aged 40-79 years without diabetes underwent comprehensive health examination including 75g OGTT and were followed-up prospectively for a median of 6.0 years. The amount of HDL-contained cholesterol per apolipoprotein A1 levels after incubating the participants’ HDL with cholesterol as CUC were measured at baseline. CUC levels were categorized into quartiles (Q1: & lt;0.303, Q2:0.303-0.325, Q3:0.326-0.351, Q4:≥0.352 a.u.). The hazard ratios (HRs) and their 95% confidence intervals (CIs) of CUC levels on the incident diabetes were estimated by using a Cox’s proportional hazard model with adjustment for confounding factors. Results: During the follow-up period, 219 subjects experienced diabetes. The multivariable-adjusted HR (95% CI) was significantly decreased with elevating levels of CUC: 1.00 (reference) in Q1, 0.83 (0.57, 1.20) in Q2, 0.77 (0.52, 1.14) in Q3 and 0.64 (0.42, 0.98) in Q4 (p=0.04 for trend). In the analysis combined serum HDL cholesterol level (≤50mg/dl [25 percentile value] vs. & gt;51 mg/dl) and CUC (Q1-Q3 vs. Q4), HRs (95% CIs) for the incident diabetes compared to both low group were 0.72 (0.36, 1.45) in isolated high CUC group, 0.73 (0.50, 1.06) in isolated high HDL cholesterol group, and 0.56 (0.34, 0.93) in both high group (p=0.88 for interaction). Conclusion: Our findings suggest that the risk of diabetes decreased with elevating CUC levels independent of HDL cholesterol levels in the general Japanese population. Disclosure Y. Hirakawa: None. R. Toh: Other Relationship; Self; Sysmex Corporation. M. Higashioka: None. M. Yoshinari: None. T. Honda: None. D. Yoshida: None. J. Hata: None. U. Nakamura: None. T. Kitazono: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation. Funding Japan Ministry of Education, Culture, Sports, Science and Technology; Japan Ministry of Health, Labour and Welfare; Japan Agency for Medical Research and Development
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-2456-PUB
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 7
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    Angiopoietin-Like Protein 2 and Risk of Type 2 Diabetes in a General Japanese Population
    American Diabetes Association ; 2013
    In:  Diabetes Care Vol. 36, No. 1 ( 2013-01-01), p. 98-100
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 36, No. 1 ( 2013-01-01), p. 98-100
    Abstract: To examine, for the first time, the association between a novel inflammatory cytokine, angiopoietin-like protein (ANGPTL) 2, and the development of type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS A total of 2,164 community-dwelling Japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years. Serum ANGPTL2 levels were divided into quartile categories at baseline: & lt;2.15, 2.16–2.71, 2.72–3.40, and ≥3.41 ng/mL. During follow-up, 221 participants developed T2DM. RESULTS In multivariate analyses, after adjusting for comprehensive risk factors and high-sensitivity C-reactive protein (hs-CRP) levels, the risk of developing T2DM was significantly higher in the highest ANGPTL2 quartile than in the lowest quartile (hazard ratio, 1.80; 95% CI, 1.14–2.85; P = 0.01). CONCLUSIONS Elevated serum ANGPTL2 levels were positively associated with the development of T2DM in a general population, independent of other risk factors including hs-CRP levels.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc12-0166
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2013
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  • 8
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    1522-P: Serum Mac-2 Binding Protein Glycosylation Isomer Level and the Risk of Type 2 Diabetes in a Japanese Community: The Hisayama Study
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Background: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker of chronic liver disease including liver fibrosis. Chronic liver disease has been acknowledged to cause glucose intolerance. However, few studies have addressed the association between serum M2BPGi levels and the risk of type 2 diabetes (T2D). Methods: A total of 2,143 participants aged 40-79 years without diabetes were followed-up for a median of 7.0 years. Serum M2BPGi levels were measured at baseline and were categorized into quartiles: ≤ 0.40; 0.41-0.55; 0.56-0.75; and ≥0.76 (cut-off index). A Cox’s proportional hazards model was used to estimate hazard ratios (HRs) and their 95% CIs for the incident T2D with the adjustment for confounders-namely age, sex, family history of diabetes, systolic blood pressure, use of antihypertensive agents, serum total and HDL cholesterol, serum triglyceride, use of lipid-modifying agents, BMI, smoking, drinking, regular exercise, and fasting plasma glucose. The impact of serum M2BPGi levels on the predictive ability of incident T2D was evaluated with Harrell’s C statistics, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI). Results: During follow-up periods, 219 subjects developed T2D. The multivariable-adjusted HR (95% CI) of developing T2D increased significantly with higher serum M2BPGi levels (p for trend=0.03), being 1.00 (reference) in Q1, 1.38 (0.89-2.15) in Q2, 1.51 (0.95-2.39) in Q3, 1.70 (1.07-2.70) in Q4. The predictive ability of incident T2D was improved by adding serum M2BPGi level to the model comprising aforementioned confounders: Harrell’s c-statistics from 0.787 to 0.795 (p=0.03), cNRI 0.19 (p=0.03), and IDI 0.004 (p=0.07). Conclusion: Our findings suggest that higher serum M2BPGi level was a significant risk factor for T2D in the general Japanese population. Measuring serum M2BPGi level may be effective to detect the high-risk population of T2D. Disclosure M. Higashioka: None. Y. Hirakawa: None. M. Yoshinari: None. T. Honda: None. S. Sakata: None. M. Shibata: None. D. Yoshida: None. J. Hata: None. T. Kitazono: None. H. Osawa: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1522-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 9
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    Online Resource
    1516-P: A Comparison of the Contributions of Impaired Insulin Secretion and Insulin Resistance to the Development of Type 2 Diabetes in a Japanese Community: The Hisayama Study
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Objective: Impaired insulin secretion (IIS) and insulin resistance (IR) are the two main mechanisms for type 2 diabetes (T2D), but IIS has been reported to contribute to incident T2D more than IR in Asian populations. However, we assumed that the impact of IR on the incident T2D was being greater in the recent Japanese population, because the burden of obesity increased. Herein, we addressed the magnitude of the contribution of IIS and IR to the development of T2D in a Japanese community. Methods: In 2007, a total of 2,108 residents aged 40-79 years (participation rate 77.1%) without diabetes at baseline underwent health examination including 75g OGTT, insulinogenic index (IGI), and HOMA-IR. Subjects were divided into 4 groups according to the presence or absence of IIS (IGI ≤ 0.4) and IR (1.6 ≤ HOMA-IR) and were followed-up prospectively for a median of 6.9 years. A Cox’s proportional hazards model was used to estimate the hazard ratios and 95% confidential intervals (CIs) for incident T2D with adjustment for confounders. The population attributable fraction (PAF) for the development of diabetes due to IS, IR and their combination were calculated. Result: At baseline, the proportions of subjects with neither of IIS nor IR, isolated IIS, isolated IR, and both IIS and IR were 45.5%, 21.0%, 28.7%, and 4.8%, respectively. During follow-up period, 273 subjects developed T2D. The risk of incident T2D was 5.3 (95% CI 3.6-7.9) times higher in subjects with isolated IIS, 4.1 (2.8-6.2) times higher in subjects with isolated IR, and 13.5 (8.5-21.5) times higher in subjects with both IIS and IR than subjects with neither of IIS nor IR. The PAFs on the excess risk of T2D among subjects with isolated IIS, isolated IR and both IIS and IR were 25.8%, 29.1%, and 15.9%, respectively. Conclusion: Our finding suggests that IIS and IR contributed equally to the development of T2D in the recent general Japanese population. Disclosure M. Yoshinari: None. Y. Hirakawa: None. J. Hata: None. M. Higashioka: None. T. Honda: None. D. Yoshida: None. N. Mukai: None. U. Nakamura: None. T. Kitazono: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1516-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 10
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    Association Between Diabetes and Gray Matter Atrophy Patterns in a General Older Japanese Population: The Hisayama Study
    American Diabetes Association ; 2022
    In:  Diabetes Care Vol. 45, No. 6 ( 2022-06-02), p. 1364-1371
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 45, No. 6 ( 2022-06-02), p. 1364-1371
    Abstract: To examine the association between diabetes and gray matter atrophy patterns in a general older Japanese population. RESEARCH DESIGN AND METHODS In 2012, a total of 1,189 community-dwelling Japanese aged ≥65 years underwent brain MRI scans. Regional gray matter volumes (GMV) and intracranial volume (ICV) were measured by applying voxel-based morphometry (VBM) methods. The associations of diabetes and related parameters with the regional GMV/ICV were examined using an ANCOVA. The regional gray matter atrophy patterns in the subjects with diabetes or elevated fasting plasma glucose (FPG) or 2-h postload glucose (2hPG) levels were investigated using VBM. RESULTS Subjects with diabetes had significantly lower mean values of GMV/ICV in the frontal lobe, temporal lobe, insula, deep gray matter structures, and cerebellum than subjects without diabetes after adjusting for potential confounders. A longer duration of diabetes was also significantly associated with lower mean values of GMV/ICV in these brain regions. The multivariable-adjusted mean values of the temporal, insular, and deep GMV/ICV decreased significantly with elevating 2hPG levels, whereas higher FPG levels were not significantly associated with GMV/ICV of any brain regions. In the VBM analysis, diabetes was associated with gray matter atrophy in the bilateral superior temporal gyri, right middle temporal gyrus, left inferior temporal gyrus, right middle frontal gyrus, bilateral thalami, right caudate, and right cerebellum. CONCLUSIONS The current study suggests that a longer duration of diabetes and elevated 2hPG levels are significant risk factors for gray matter atrophy in various brain regions.
    Type of Medium: Online Resource
    ISSN: 0149-5992
    URL: Article
    DOI: 10.2337/dc21-1911
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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