To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS) including 26,488 cases and 83,964 controls of European, East Asian, South Asian, and Mexican and Mexican American ancestry. We observed significant excess in directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven novel T2D susceptibility loci. Furthermore, we observed considerable improvements in fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterisation of complex trait loci, and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in East Asian populations. The first stage meta-analysis of eight T2D genome-wide association studies (6,952 cases and 11,865 controls) was followed by a second stage in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which were mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, involved in pancreatic beta cell development and insulin gene expression1,2, is known for its association with fasting glucose levels3,4. The evidence of T2D association for PEPD5 and HNF4A6,7 has been detected in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings derived from East Asians provide new perspectives on the etiology of T2D.
OBJECTIVEThe number of people with metabolic syndrome is increasing worldwide, and changes in socioenvironmental factors contribute to this increase. Therefore, investigation of changes in metabolic syndrome and its components in South Korea, where rapid socioenvironmental changes have occurred in recent years, would be foundational in setting up an effective strategy for reducing this increasing trend.RESEARCH DESIGN AND METHODSWe compared the prevalence and pattern of metabolic syndrome among participants in the Korean National Health and Nutrition Examination Surveys for 1998, 2001, 2005, and 2007. In each survey, stratified, multistage, probability–sampling designs and weighting adjustments were conducted to represent the entire Korean population. The revised National Cholesterol Education Program criteria were used as the definition of metabolic syndrome. All biochemical parameters were measured in a central laboratory.RESULTSA total of 6,907 (mean ± SE age 45.0 ± 0.2 years), 4,536 (45.5 ± 0.2), 5,373 (47.1 ± 0.2), and 2,890 (49.9 ± 0.3) Koreans over 20 years of age have participated in the studies in 1998, 2001, 2005, and 2007, respectively. The age-adjusted prevalence of metabolic syndrome increased significantly from 24.9% in 1998, 29.2% in 2001, and 30.4% in 2005 to 31.3% in 2007. Among the five components, the level of low HDL cholesterol increased the most, by 13.8% over the 10 years. Abdominal obesity and hypertriglyceridemia followed, with 8.7 and 4.9% increases, respectively.CONCLUSIONSBecause dyslipidemia and abdominal obesity were major factors in increasing the prevalence of metabolic syndrome in Koreans for the past 10 years, lifestyle interventions should be conducted at the national level to reduce the burden and consequences of metabolic syndrome.
Aims/hypothesis The aim of this work was to compare the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors between Asian and non-Asian patients with type 2 diabetes. Methods We searched MEDLINE, EMBASE, LILACS, CENTRAL, ClinicalTrials.gov and conference proceedings. Studies were eligible if they were randomised controlled trials with a treatment duration of at least 12 weeks, compared a DPP-4 inhibitor with a placebo as either monotherapy or oral combination therapy, had information on ethnicity and HbA 1c values and were published or described in English. A systematic review and meta-analysis with a meta-regression analysis was conducted. Results Among 809 potentially relevant studies, 55 trials were included. A meta-analysis revealed that DPP-4 inhibitors lowered HbA 1c to a greater extent in studies with ≥50% Asian participants (weighted mean difference [WMD] −0.92%; 95% CI −1.03, −0.82) than in studies with <50% Asian participants (WMD −0.65%; 95% CI −0.69, −0.60). The between-group difference was −0.26% (95% CI −0.36, −0.17, p<0.001). The baseline BMI significantly correlated with the HbA 1c -lowering efficacy of DPP-4 inhibitors. The RR of achieving the goal of HbA 1c <7.0% (53.0 mmol/mol) was higher in studies with ≥50% Asian participants (3.4 [95% CI 2.6, 4.7] vs 1.9 [95% CI 1.8, 2.0]). The fasting plasma glucose-lowering efficacy was higher with monotherapy in the Asiandominant studies, but the postprandial glucose-lowering efficacy and changes in body weight were comparable between the two groups. Conclusions/interpretation DPP-4 inhibitors exhibit a better glucose-lowering efficacy in Asians than in other ethnic groups; this requires further investigation to understand the underlying mechanism, particularly in relation to BMI.
OBJECTIVE -The dysregulation of adipokines is closely associated with the pathogenesis of insulin resistance and type 2 diabetes. Retinol-binding protein-4 (RBP4), a new adipokine, was recently reported to provide a link between obesity and insulin resistance. Here, we examined the relation between plasma RBP4 concentrations and various metabolic parameters in humans.RESEARCH DESIGN AND METHODS -An enzyme-linked immunosorbent assay was developed to measure human RBP4 plasma concentrations, which were then compared with various parameters related to insulin resistance in subjects with normal glucose tolerance (NGT; n ϭ 57), impaired glucose tolerance (IGT; n ϭ 48), and type 2 diabetes (n ϭ 49).RESULTS -Plasma RBP4 concentrations were higher in the IGT and type 2 diabetic groups than in the NGT group (median 18.9 [range 11.2-45.8], 20.9 [9.9 -48.5], and 18.1 g/ml [9.3-30.5], respectively). However, no difference was found between plasma RBP4 concentrations in the IGT and type 2 diabetic groups. Plasma RBP4 concentrations were found to be associated with sex, waist circumference, fasting plasma glucose, and insulin resistance. Of these, sex and fasting plasma glucose levels were found to be independent determinants of plasma RBP4 concentration.CONCLUSIONS -Plasma RBP4 concentrations were found to be elevated in subjects with IGT or type 2 diabetes and to be related to various clinical parameters known to be associated with insulin resistance. Diabetes Care 29:2457-2461, 2006A n increased adipose tissue mass is strongly associated with the pathogenesis of insulin resistance and type 2 diabetes (1). Adipose tissue may be viewed as an endocrine organ that secretes many types of adipokines (such as leptin, tumor necrosis factor ␣, interleukin 6, and adiponectin) that modulate the action of insulin in other tissues (2-5). Moreover, retinol-binding protein-4 (RBP4), a new fat-derived adipokine that specifically binds to retinol (6), has recently been reported to provide a link between obesity and insulin resistance (7). RBP4 was discovered while trying to identify the substance responsible for regulating insulin sensitivity in mice either lacking or overexpressing GLUT4 in adipose tissues (8,9). It is regulated reciproc a l l y i n a d i p o s e t i s s u e o f m i c e overexpressing or lacking GLUT4. Circulating RBP4 levels were reported to be raised in several different mouse models of obesity and insulin resistance (7). In mice lacking GLUT4, rosiglitazone (a peroxisome proliferator-activated receptor ␥ agonist) was found to lower circulating levels of RBP4 and to reduce insulin resistance. Increasing the circulating levels of RBP4 leads to glucose intolerance, whereas knock out of the RBP4 gene increases insulin sensitivity. In addition, treatment of mice with fenretinide (which facilitates the excretion of RBP4 into urine) decreased the insulin resistance induced by a high-fat diet (7).A mechanism whereby RBP4 modulates insulin sensitivity in muscle and liver has been suggested. In skeletal muscle, RBP4 reduces insu...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.