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The pathophysiology of type 2 diabetes is characterized by variable degrees of insulin resistance and impaired insulin secretion. Both genetic and environmental factors serve as etiologic factors. Recent genetic studies have identified at least 83 variants associated with diabetes. A significant number of these loci are thought to be involved in insulin secretion, either through ß-cell development or ß-cell dysfunction. Environmental factors have changed rapidly during the past half century, and the increased prevalence of obesity and diabetes can be attributed to these changes. Environmental factors may affect epigenetic changes and alter susceptibility to diabetes. A recent epidemiologic study revealed that Korean patients with type 2 diabetes already had impaired insulin secretion and insulin resistance 10 years before the onset of diabetes. Those who developed diabetes showed impaired ß-cell compensation with an abrupt decrease in insulin secretion during the last 2 years before diabetes developed. The retrograde trajectory of the disposition index differed according to the baseline subgroups of insulin secretion and insulin sensitivity. We hope that obtaining a more detailed understanding of the perturbations in the major pathophysiologic process of diabetes on the individual level will eventually lead to the implementation of precision medicine and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Recent improvements in sequencing technology have enabled the investigation of so-called missing heritability, and a large number of affected subjects have been sequenced in order to detect significant associations between human diseases and rare variants. However, the cost of genome sequencing is still high, and a statistically powerful strategy for selecting informative subjects would be useful. Therefore, in this report, we propose a new statistical method for selecting cases and controls for sequencing studies based on family history. We assume that disease status is determined by unobserved liability scores. Our method consists of two steps: first, the conditional means of liability are estimated with the liability threshold model given the individual's disease status and those of their relatives. Second, the informative subjects are selected with the estimated conditional means. Our simulation studies showed that statistical power is substantially affected by the subject selection strategy chosen, and power is maximized when affected (unaffected) subjects with high (low) risks are selected as cases (controls). The proposed method was successfully applied to genome-wide association studies for type 2 diabetes, and our analysis results reveal the practical value of the proposed methods. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To evaluate plasma apolipoprotein B (ApoB)-48 concentrations among Korean diabetic subjects with normal to moderately high levels of low-density-lipoprotein cholesterol (LDL-C). Methods This multicenter, cross-sectional study included subjects with LDL-C levels between 100 and 160 mg/dL who had not been treated with a lipid-lowering agent for over 6 weeks prior to baseline. Blood tests to assess lipid-profile parameters were conducted in both fasting and postprandial states. This study compared ApoB-48 and other lipid-profile parameters in diabetic and nondiabetic subjects. Results Of the 93 subjects enrolled, 88 (42 diabetic; 46 nondiabetic) completed the study. Significantly higher mean incremental area under curve (0–6 h; iAUC 0–6h ) of postprandial ApoB-48 levels was noted among diabetic subjects than nondiabetic subjects ( p = 0.0078). The mean postprandial ApoB-48 peak level was higher in diabetic subjects; however, the difference was not statistically significant. The fasting ApoB-48 level was similar in both groups: 5.9 (3.5) in diabetics and 7.3 (5.8) in nondiabetics ( p = 0.18). The iAUC 0–6h of postprandial total cholesterol (TC), triglyceride (TG), LDL-C, non–high-density-lipoprotein cholesterol (non-HDL-C), ApoB-100, and remnant cholesterol was similar in both groups. The ApoB-48 level was moderately correlated with TG and non-HDL-C for both groups ( p < 0.05). Conclusion Without lipid-lowering treatment, the postprandial increment in ApoB-48 level was significantly higher in Korean diabetic subjects compared with nondiabetic subjects, irrespective of similar LDL-C levels. [ABSTRACT FROM AUTHOR]

Objectives: The relationship between the renin-angiotensin system (RAS) and diabetes has been studied for many years. However, studies that assessed RAS components comprehensively were limited. We hypothesized that serum RAS components, especially the effector peptide angiotensin-II, might be closely associated with glucose metabolism status and diabetic complications.Methods: We investigated the association of individual RAS component with albuminuria in 407 subjects with normal glucose metabolism (NGM), prediabetes, or type 2 diabetes mellitus (T2DM). Anthropometric and biochemical parameters, including glucose homeostasis, albuminuria, and RAS-related parameters such as plasma renin activity (PRA), aldosterone, angiotensin-converting enzyme (ACE), and angiotensin-II levels, were measured.Results: The mean±standard deviation (SD) age and body mass index were 57.1±11.1years and 24.7±3.3kg/m2, respectively. There were 54 subjects with NGM, 102 with prediabetes, and 251 with T2DM. The mean±SD angiotensin-II levels in these groups were 9.32±6.89, 12.89±10.39, and 17.00±15.28pg/mL, and the respective urinary albumin-to-creatinine ratios (ACRs) were 8.1±5.3, 13.3±17.3, and 30.7±51.9mg/g, which were significantly different among the groups. The serum angiotensin-II levels were correlated with levels of PRA, insulin resistance, C-reactive protein, and urinary ACR. Among RAS-related parameters, only the angiotensin-II level was significantly associated with urinary ACR after adjusting for relevant risk factors.Conclusions: Angiotensin-II may play an important role in the development of albuminuria, particularly in subjects with impaired glucose metabolism. [ABSTRACT FROM AUTHOR]

Aims: There could be an overlap of monogenic diabetes and early onset type 2 diabetes in those who are diagnosed before age of 30years. Genetic diagnosis in these patients might improve the quality of care. A limited number of studies have used whole exome sequencing (WES) in Asian patients with early onset diabetes, and the clinical utility of WES is largely unknown.Methods: We performed whole exome capture and massive parallel sequencing in 28 patients with early onset diabetes. Those who had a strong family history of diabetes were preferentially enrolled. Rare and non-silent variants in 29 genes known to cause monogenic diabetes, including 12 maturity-onset diabetes of the young (MODY) genes, were investigated for pathogenicity.Results: The average depth of on-target WES reads was 97 X. A total of four pathogenic or likely pathogenic rare missense variants (p.Leu319Pro in HNF4A, p.His103Tyr and p.Arg74Gln in ABCC8, and p.Leu139Val in HNF1A) in MODY genes were identified in three patients. Although four rare non-silent variants in MODY genes (p.Arg183Cys in PAX4, p.Val139Ile and p.Pro740fs in CEL, and p.Val147Ile in HNF4A) and two rare non-silent variants in monogenic diabetes genes (p.Glu169Lys in WFS1, and p.Pro407Gln in GATA4) were identified, their pathogenicity was uncertain or likely benign.Conclusions: WES could be an initial option for genetic testing in patients with early onset diabetes. However, sufficient and universal coverage of genes of interest is required. In addition, it could be difficult to interpret variant pathogenicity, and these cases might require further validation. [ABSTRACT FROM AUTHOR]

Abstract: It is crucial to investigate age-related body composition changes in geriatric medicine. Bioelectrical impedance analysis (BIA) is easy to perform, non-invasive, relatively inexpensive, and portable. However, the accuracy of measurement by BIA is questionable. To develop and cross-validate the predictive equation for estimated appendicular skeletal muscle mass (ASM) using BIA in older community-dwelling Korean adults, we include two cohorts: study participants aged 65–80 years in the Ansung cohort for the Korean Health and Genome Study (men, n =285; women, n =435) used as equation-generating group, and Korean Longitudinal Study of Health Aging (KLoSHA) as cross-validation group (men, n =202; women, n =208). Dual energy X-ray absorptiometry (DXA) and BIA were performed in both cohorts. Using multiple linear regression analysis, we drew a predictive equation for DXA-measured ASM by BIA resistance. From DXA and BIA measurements in the Ansung cohort, we generated the estimated equation ASM (kg)=[(Ht2/R ×0.104)+(age×−0.050)+(gender×2.954)+(weight×0.055)]+5.663 where Ht is height in centimeters; R is BIA resistance in 250Ω; for gender, men=1 and women=0; and age is in years. We validated this equation in the KLoSHA. The r 2 of the estimated ASM was 0.890. This BIA equation provides valid estimates of ASM in older Korean adults. [Copyright &y& Elsevier]