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Background: The purpose of this study was to describe changes in physical activity volumes and sedentary time over 3 years in the middle-aged and older Japanese population. Methods: Study participants included 1151 Japanese community-dwelling residents aged ≥40 years in 2009 who underwent 2 sets of health examinations (2009 and 2012). Using a triaxial accelerometer, longitudinal changes in sedentary time, light physical activity volume, moderate to vigorous physical activity volume, number of steps, and total physical activity volume were evaluated according to sex, age (40–49, 50–59, 60–69, 70–79, and ≥80 y), and obese (nonobese and obese) categories. Results: Sedentary time significantly increased, and all physical activity volumes significantly decreased among all participants. Although most variables did not change significantly in the 40–49 and 50–59 year age categories, similar changes as all participants were observed across all other categories. In the correlation analyses, changes in sedentary time correlated, at most, only modestly for each change in physical activity volumes, indicating that increased physical activity volume does not always lead to decreased sedentary time, and vice versa. Conclusions: Strategies to reduce sedentary time and promote physical activity are needed in Japan, particularly for people aged ≥60 years. [ABSTRACT FROM AUTHOR]

The real-world effectiveness of the coronavirus disease 2019 (COVID-19) vaccines in Japan remains unclear. This case–control study evaluated the vaccine effectiveness (VE) of two doses of mRNA vaccine, BNT162b2 or mRNA-1273, against the delta (B.1.617.2) variant in the Japanese general population in the period June–September 2021. Individuals in close contact with COVID-19 patients were tested using polymerase chain reaction (PCR). A self-administered questionnaire evaluated vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, and living environment. Two vaccine doses were reported by 11.6% of cases (n = 389) and 35.2% of controls (n = 179). Compared with controls, cases were younger and had a lower proportion who always performed handwashing for ≥20 s, a higher proportion of alcohol consumers, and a lower proportion of individuals living in single-family homes or with commuting family members. After adjusting for these confounding factors and day of PCR testing by multivariate logistic regression analysis, the VE in the period June–July (delta variant proportion 45%) was 92% and 79% in the period August–September (delta variant proportion 89%). The adjusted VE for homestay, hotel-based isolation and quarantine, and hospitalization was 78%, 77%, and 97%, respectively. Despite declining slightly, VE against hospitalization remained robust for ~3 months after the second dose. Vaccination policymaking will require longer-term monitoring of VE against new variants. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Changes in histologically quantified β‐ and α‐cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in β‐ and α‐cell mass according to the glucose tolerance status. Materials and Methods: Autopsy samples from a total of 103 individuals (40 with normal glucose tolerance, 31 with prediabetes and 32 with type 2 diabetes mellitus) who underwent a 75‐g oral glucose tolerance test within 5 years before death were selected from 643 community‐based autopsy samples collected from 2002 to 2016. Fractional β‐cell area (BCA) and α‐cell area were quantified with Image Pro Plus software. Associations of BCA and α‐cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman's correlation coefficients between glycemic markers and β‐cell function were estimated. Results: The mean values of BCA decreased significantly with worsening glucose tolerance status (mean ± standard error 1.85 ± 0.10% in normal glucose tolerance, 1.59 ± 0.11% in prediabetes and 1.17 ± 0.11% in type 2 diabetes mellitus, P for trend < 0.001), whereas there was no significant association between α‐cell area and glucose tolerance status. BCA was inversely correlated with fasting and 2‐h plasma glucose levels during oral glucose tolerance test and glycated hemoglobin measurement, and positively correlated with disposition index (all P < 0.01). Conclusions: β‐Cell mass decreased significantly with worsening glucose tolerance, from the stage of prediabetes, in the Japanese population. Prevention of declining β‐cell mass before the onset of glucose intolerance is important to reduce the burden of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Purpose: In assisted reproductive technology, normal zygotes are bipronuclear (2PN) during fertilization confirmation; however, sometimes, nonpronuclear zygotes (0PN) and monopronuclear zygotes (1PN) are found during routine observations. Methods: To elucidate the clinical usefulness of in vitro‐fertilized embryos, we investigated the rates of clinical pregnancy, live birth, miscarriage, and congenital abnormality after transfer of frozen‐thawed 1PN‐ and 0PN‐derived single blastocysts at Denentoshi Ladies Clinic, Kanagawa, Japan. Results: The rates of pregnancy and live birth for 1PN‐derived blastocysts obtained by conventional in vitro fertilization were 37.5% and 27.1%, respectively, which was not significantly different from those for 2PN‐derived blastocysts; however, the rates for 0PN‐derived blastocysts were significantly lower. The pregnancy and live birth rates for 0PN‐derived embryos obtained by intracytoplasmic sperm injection (ICSI) were 45.7% and 34.8%, respectively, which was not significantly different from those for 2PN‐derived blastocysts; however, the rates for 1PN‐derived blastocysts were significantly lower (4.0% for both) than those for 2PN‐ and 0PN‐derived blastocysts. No congenital abnormalities were found in infants resulting from transfer of 0PN‐ or 1PN‐derived blastocysts. Conclusions: Both 1PN‐ and 0PN‐derived blastocysts can be used for embryo transfer; however, care should be taken in making decisions about 1PN‐derived blastocysts, especially if they are obtained by ICSI. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The present study aimed to examine cross‐sectional associations between objectively measured sedentary time and the prevalence of diabetes mellitus in a general Japanese population, and to elucidate possible mediating roles of diet, obesity and insulin resistance in this relationship. Materials and Methods: A total of 1,758 community‐dwelling individuals aged 40–79 years wore an accelerometer for ≥7 days and underwent a comprehensive health examination in 2012. Diabetes mellitus was diagnosed by a 75‐g oral glucose tolerance test. The associations of sedentary time with the presence of diabetes mellitus and the levels of the homeostasis model assessment of insulin resistance were estimated by logistic and linear regression models. Results: After adjustment for demographic and lifestyle factors including moderate‐to‐vigorous physical activity, participants who spent ≥10 h in sedentary time had a significantly higher odds ratio of the presence of diabetes than those who spent <6 h in sedentary time (odds ratio 1.84, 95% confidence interval 1.02–3.31). This significant association remained after adjusting for overall and central obesity (as measured by body mass index and waist circumference), but weakened after adjusting for dietary energy intake or homeostasis model assessment of insulin resistance. Sedentary time was positively associated with homeostasis model assessment of insulin resistance levels among non‐diabetic participants after adjusted for obesity or energy intake (P for trend <0.01). Conclusions: Longer sedentary time was associated with a higher prevalence of diabetes mellitus in a general Japanese population. Insulin resistance appeared to be mainly involved in this association. These results highlight the importance of public health strategies targeting reductions in sedentary time for the primary prevention of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Summary: The aim of the present study was to examine the prevalence and causes of adult epilepsy in a general Japanese population. We examined a total of 3333 Japanese residents in the town of Hisayama aged ≥40 years in 2012‐2013. The examination was performed mainly at the municipal center for health promotion, but some subjects were examined in their homes, hospitals, or nursing homes. Twenty‐three subjects had a diagnosis of epilepsy. The prevalence (95% confidence interval [CI]) of epilepsy per 1000 was 6.9 (4.1‐9.7) in total, 4.9 (1.3‐8.5) in men, and 8.4 (4.3‐12.5) in women (P = 0.23 between sexes). The prevalence of epilepsy was significantly higher in the elderly (aged ≥65 years; 10.3 per 1000 [95% CI 5.4‐15.1]) than in the middle‐aged (aged 40‐64 years; 3.6 per 1000 [95% CI 0.7‐6.4]; P = 0.02). The major cause of epilepsy was cerebrovascular diseases (n = 11; 48% of the epilepsy patients). More than half of the epilepsy patients experienced the first episode of seizure in older age (≥65 years; n = 13; 57%). The findings of this study suggest the clinical importance of the prevention of cerebrovascular diseases to reduce the burden of epilepsy in the future. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between daily sleep duration and risk of dementia and death in a Japanese elderly population. Design: Prospective cohort study. Setting: The Hisayama Study, Japan. Participants: Community‐dwelling Japanese individuals aged 60 and older without dementia. Measurements: Self‐reported daily sleep duration was grouped into 5 categories (<5.0, 5.0–6.9, 7.0–7.9, 8.0–9.9, ≥10.0 hours). The association between daily sleep duration and risk of dementia and death was determined using a Cox proportional hazards models. Results: During follow‐up, 294 participants developed dementia, and 282 died. Age‐ and sex‐adjusted incidence rates of dementia and all‐cause mortality were significantly greater in subjects with daily sleep duration of less than 5.0 hours and 10.0 hours and more than in those with daily sleep duration of 5.0 to 6.9 hours. These associations remained unchanged after adjustment for potential confounding factors (<5.0 hours: hazard ratio (HR)=2.64, 95% confidence interval (CI)=1.38–5.05 for dementia; HR=2.29, 95% CI=1.15–4.56 for death; ≥10.0 hours: HR=2.23, 95% CI=1.42–3.49 for dementia; HR=1.67, 95% CI=1.07–2.60 for death). Similar U‐shaped associations were observed for Alzheimer's disease and vascular dementia. With regard to the influence of hypnotic use on risk of dementia and death, subjects who used hypnotics and had any sleep duration had a risk of dementia that was 1.66 times as great and a risk of death that was 1.83 times as great as those who did not use hypnotics and had a daily sleep duration of 5.0 to 6.9 hours. Conclusion: Short and long daily sleep duration and hypnotic use are risk factors for dementia and death in Japanese elderly adults. [ABSTRACT FROM AUTHOR]

Objective: 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 < 0.01). These three ratios decreased significantly with elevated 2-h postload glucose (PG) levels (all P for trend <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. [ABSTRACT FROM AUTHOR]

Aims/Introduction We examined secular trends in the prevalence of type 2 diabetes and prediabetes in community-dwelling Japanese subjects. Materials and Methods A total of 2,490 subjects in 1988 and 2,852 subjects in 2002 aged 40-79 years underwent a 75-g oral glucose tolerance test, and their glucose tolerance status was defined by the 1998 World Health Organization criteria. Results The age-adjusted prevalence of type 2 diabetes increased significantly from 1988 to 2002 in men (14.6% in 1988 to 20.8% in 2002, P < 0.001) and women (9.1% in 1988 to 11.2% in 2002, P = 0.002). A significant rise in the age-adjusted prevalence of prediabetes was also observed in both sexes (26.2% in 1988 to 35.3% in 2002, P < 0.001 for men; 22.5% in 1988 to 25.1% in 2002, P = 0.04 for women). In age-stratified analysis, the prevalence of type 2 diabetes increased markedly over time in men aged 60-69 and 70-79 years (both P < 0.001) and women aged 70-79 years ( P = 0.02). The prevalence of overall and central obesity increased significantly in men aged 60-69 and 70-79 years, and women aged 70-79 years from 1988 to 2002, whereas the frequency of regular exercise decreased significantly in men aged 70-79 years between the surveys. Conclusions Our findings suggest that the prevalence of type 2 diabetes and prediabetes increased significantly in both sexes from the 1980s to the 2000s in a general Japanese population, and that the increasing prevalence of obesity and the decline in physical activity exerted an influence on this rising trend. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan. Methods: A total of 2452 community-dwelling Japanese subjects aged ≥40 years were followed prospectively for 24 years. Results: The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend < 0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend < 0.01), and such tendency was seen for atherothrombotic infarction (P for trend = 0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend = 0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations = 1.17, 95% confidence interval (CI) = 1.02 to 1.35], atherothrombotic infarction (adjusted HR = 1.39, 95% CI = 1.09 to 1.79), and cardioembolic infarction (adjusted HR = 0.64, 95% CI = 0.47 to 0.85). Conclusions: Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population. [Copyright &y& Elsevier]

Abstract: Objective: We examined the association between the ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) or the docosahexaenoic acid (DHA)/AA and the development of cardiovascular disease in a general Japanese population. Methods: A total of 3103 community-dwelling Japanese individuals aged ≥40 years were followed up for an average of 5.1 years. Serum EPA/AA ratios were categorized into quartiles. The risk estimates were computed using a Cox proportional hazards model. Results: During the follow-up period, 127 subjects experienced cardiovascular events. Age- and sex-adjusted incidence rates of cardiovascular disease increased with lower serum EPA/AA ratios in individuals with high-sensitivity C-reactive protein (HS-CRP) of ≥1.0 mg/L (p for trend = 0.006), whereas no clear association was observed in those with HS-CRP of <1.0 mg/L (p for trend = 0.27). The multivariable-adjusted risk of cardiovascular disease increased significantly, by 1.52 times (95% confidence interval 1.12–2.04) per 0.20 decrement in serum EPA/AA ratio in subjects with HS-CRP of ≥1.0 mg/L. A lower serum EPA/AA ratio was significantly associated with an increased risk of coronary heart disease, but there was no evidence of an association with stroke. The magnitude of the influence of the serum EPA/AA ratio on the cardiovascular risk increased significantly with elevating HS-CRP levels taken as a continuous variable (p for heterogeneity = 0.007). However, no such association was observed for DHA/AA ratio. Conclusion: Our findings suggest that a lower serum EPA/AA ratio is associated with a greater risk of cardiovascular disease, especially coronary heart disease, among subjects with higher HS-CRP levels in the general Japanese population. [Copyright &y& Elsevier]

Context: Although recent genetic studies have identified many susceptibility loci associated with type 2 diabetes (T2D), the usefulness of such loci for precision medicine remains uncertain., Objective: This study investigated the impact of genetic risk score (GRS) on the development of T2D in a general Japanese population., Participants: The current study consists of 1465 subjects aged 40 to 79 years without diabetes who underwent a health examination in 2002., Design: The GRS was generated using the literature-based effect size for T2D of 84 susceptibility loci for the Japanese population, and the risk estimates of GRS on the incidence of T2D were computed by using a Cox proportional hazard model in a 10-year follow-up study. The influence of GRS on the predictive ability was estimated with Harrell C statistics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI)., Results: During the 10-year follow-up, 199 subjects experienced T2D. The risk of developing T2D increased significantly with elevating quintiles of GRS (multivariable-adjusted hazard ratio for the fifth vs first quintile, 2.85; 95% CI, 1.83 to 4.44). When incorporating GRS into the multivariable model comprising environmental risk factors, the Harrell C statistics (95% CI) increased from 0.681 (0.645 to 0.717) to 0.707 (0.672 to 0.742) and the predictive ability of T2D was significantly improved (IDI, 0.0376; 95% CI, 0.0284 to 0.0494; cNRI, 0.3565; 95% CI, 0.1278 to 0.5829). GRS was also associated with the risk of T2D independently of environmental risk factors., Conclusions: These findings suggest the usefulness of GRS for identifying a high-risk population together with environmental risk factors in the Japanese population., (Copyright © 2019 Endocrine Society.)

Objective: We estimated secular trends in the prevalence of type 2 diabetes (T2DM) and prediabetes, and examined potential explanatory factors for these trends in a Japanese community., Methods: 4 cross-sectional examinations were conducted among subjects aged 40-79 years in 1988 ( n  = 2,490), 2002 ( n  = 2,856), 2007 ( n  = 2,761), and 2012 ( n  = 2,644). Glucose tolerance status was defined by a 75g oral glucose tolerance test., Results: The age-standardized prevalence of T2DM increased significantly in both sexes from 1988 to 2002, and thereafter it remained stable in men, and decreased nonsignificantly in women from 2002 to 2012. The age-standardized prevalence of prediabetes in men increased significantly between 1988 and 2002, but then decreased significantly. A similar trend was observed in women. The age-specific prevalence of T2DM increased greatly in men aged 60-79 years and women aged 70-79 years from 1988 to 2002, and then plateaued at a high level, while a significant decreasing trend was observed in women aged 40-49 years. The mean values of body mass index (BMI) increased steeply in these elderly subjects from 1988 to 2002, and remained at a high level, whereas those in middle-aged women decreased appreciably over the study period., Conclusions: Our findings suggest that in Japanese, there was no further increase in the prevalence of T2DM or prediabetes in either men or women in the 2000s. Secular change in the BMI level was likely to contribute to trends in the prevalence of T2DM, and thus the management of obesity may be important to reduce the prevalence of T2DM., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest associated with this manuscript.

Background: The purpose of this cross-sectional study was to describe the patterns and levels of sedentary time and physical activity (PA) in a general Japanese population., Methods: A total of 1,740 community-dwelling Japanese adults aged ≥40 years participated in this study. Sedentary time and PA were assessed for 7 consecutive days using a tri-axial accelerometer. Daily patterns and levels of sedentary time and PA were calculated by sex, age group (40-64, 65-74, and ≥75 years), and body mass index (BMI; <25 and ≥25 kg/m 2 )., Results: Participants spent half of their waking time being sedentary, 32.7% of which was accumulated in prolonged bouts ≥30 minutes, versus only 54.4 minutes/day (7% of waking time) as moderate-to-vigorous PA (MVPA) (11.8 minutes/day in bouts ≥10 minutes). In addition to total sedentary time, men had longer prolonged sedentary bouts and fewer breaks per sedentary hour than women. Similar trends were observed in participants aged ≥75 years and those with a higher BMI (≥25 kg/m 2 ) compared to those with a younger age and lower BMI. Moreover, participants aged ≥75 years and those with a higher BMI accumulated fewer MVPA minutes in bouts ≥10 minutes. Only 34.8% of the population met the recommended level of ≥150 minutes/week MVPA in bouts ≥10 minutes., Conclusion: Japanese adults accumulated a large proportion of total sedentary time in prolonged bouts but few minutes in sustained bouts of MVPA, and few of them met the current PA guideline.

Background: The association of morning and evening home blood pressures (HBPs) with carotid atherosclerosis has been uncertain in general populations, so we aimed to investigate it in a general Japanese population.Methods and Results:We performed a cross-sectional survey of 2,856 community-dwelling individuals aged ≥40 years to examine the association of morning and evening HBPs with carotid mean intima-media thickness (IMT). The age- and sex-adjusted geometric averages of carotid mean IMT increased significantly with increasing morning HBP (optimal: 0.67 mm; normal: 0.69 mm; high normal: 0.72 mm; grade 1 hypertension: 0.74 mm; and grade 2+3 hypertension: 0.76 mm) and with increasing evening HBP (0.68 mm, 0.71 mm, 0.73 mm, 0.76 mm, and 0.78 mm, respectively) (both P for trend <0.001). These associations remained significant even after adjusting for potential confounding factors. Likewise, both isolated morning hypertension (morning HBP ≥135/85 mmHg and evening HBP <135/85 mmHg) and isolated evening hypertension (evening HBP ≥135/85 mmHg and morning HBP <135/85 mmHg) as well as sustained hypertension (both morning and evening HBP ≥135/85 mmHg) were significantly associated with thicker mean IMT., Conclusions: Our findings suggested that both morning and evening HBPs were significantly associated with carotid atherosclerosis in this general Japanese population.

Background: Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations.Methods and Results:We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002-2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH) 2 D levels (HR 1.54 [95% confidence interval, 1.18-2.01] for the lowest quartile, 1.31 [0.99-1.73] for the 2nd quartile, 0.94 [0.70-1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend <0.001). A similar association was observed for cardiovascular and respiratory infection death (both P for trend <0.01), but not for cancer death or death from other causes. In the stratified analysis, the association between lower serum 1,25(OH) 2 D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 than in those with eGFR ≥60 mL/min/1.73 m 2 ; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04)., Conclusions: The findings suggested that a lower serum 1,25(OH) 2 D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH) 2 D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.

Context and Objective: We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer's disease (AD)., Design and Participants: A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years., Results: The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third [HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82] and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status., Conclusions: Our findings suggest that elevated GA/HbA1c ratio-but not HbA1c, GA, or 1,5-AG level-is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD., (Copyright © 2017 Endocrine Society)

Aim: It is not clear whether elevated serum non-high-density lipoprotein cholesterol (non-HDL-C) levels are a risk factor for cardiovascular disease (CVD) in subjects with chronic kidney disease (CKD) in the general population., Methods: A total of 2,630 community-dwelling Japanese subjects (1,107 men and 1,523 women) without history of CVD and aged ≥40 years were prospectively followed up for an average of 19 years, and the association between serum non-HDL-C levels and the incidence of type-specific CVD was estimated using a Cox proportional hazards model. CKD was defined as estimated glomerular filtration rate ＜60 mL/min/1.73 m 2 or proteinuria (≥1＋ on dipstick)., Results: At baseline, 357 subjects had CKD. During the follow up, 186 coronary heart disease (CHD) and 277 stroke events occurred. The age- and sex-adjusted incidence of CHD was significantly higher in subjects with higher non-HDL-C levels, both in those with and without CKD. In the CKD group, the risk of CHD was significantly higher in those with non-HDL-C levels of 150- 189 mg/dL [adjusted hazard ratio (HR), 2.23; 95% confidence interval (CI), 1.04-4.77] and those with levels ≥190 mg/dL (adjusted HR, 3.20; 95% CI, 1.46-7.03) than in those with levels ＜150 mg/dL. In the non-CKD group, the risk of CHD was significantly higher only in those with nonHDL-C levels ≥190 mg/dL (adjusted HR, 2.12; 95% CI, 1.33-3.38). However, no such association was observed for the risk of stroke., Conclusions: Our findings suggest that higher serum non-HDL-C levels are associated with greater risk of CHD in subjects with and without CKD and that this association is greater in subjects with CKD than in those without CKD.