Explore the vast range of titles available.

Abstract Context Insulin resistance (IR) and obesity differ among ethnic groups in Singapore, with the Malays more obese yet less IR than Asian-Indians. However, the molecular basis underlying these differences is not clear. Objective As the skeletal muscle (SM) is metabolically relevant to IR, we investigated molecular pathways in SM that are associated with ethnic differences in IR, obesity, and related traits. Design, Setting, and Main Outcome Measures We integrated transcriptomic, genomic, and phenotypic analyses in 156 healthy subjects representing three major ethnicities in the Singapore Adult Metabolism Study. Patients This study contains Chinese (n = 63), Malay (n = 51), and Asian-Indian (n = 42) men, aged 21 to 40 years, without systemic diseases. Results We found remarkable diversity in the SM transcriptome among the three ethnicities, with >8000 differentially expressed genes (40% of all genes expressed in SM). Comparison with blood transcriptome from a separate Singaporean cohort showed that >95% of SM expression differences among ethnicities were unique to SM. We identified a network of 46 genes that were specifically downregulated in Malays, suggesting dysregulation of components of cellular respiration in SM of Malay individuals. We also report 28 differentially expressed gene clusters, four of which were also enriched for genes that were found in genome-wide association studies of metabolic traits and disease and correlated with variation in IR, obesity, and related traits. Conclusion We identified extensive gene-expression changes in SM among the three Singaporean ethnicities and report specific genes and molecular pathways that might underpin and explain the differences in IR among these ethnic groups. Changes in skeletal muscle transcriptomics underlie differences in insulin resistance in the multiethnic Singaporean population.

Human blood glucose levels have likely evolved toward their current point of stability over hundreds of thousands of years. The robust population stability of this trait is called canalization. It has been represented by a hyperbolic function of two variables: insulin sensitivity and insulin response. Environmental changes due to global migration may have pushed some human subpopulations to different points of stability. We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response. We identified studies that measured the insulin sensitivity index (SI) and acute insulin response to glucose (AIRg) in three major ethnic groups: Africans, Caucasians, and East Asians. We identified 74 study cohorts comprising 3,813 individuals (19 African cohorts, 31 Caucasian, and 24 East Asian). We calculated the hyperbolic relationship using the mean values of SI and AIRg in the healthy cohorts with normal glucose tolerance. We found that Caucasian subpopulations were located around the middle point of the hyperbola, while African and East Asian subpopulations are located around unstable extreme points, where a small change in one variable is associated with a large nonlinear change in the other variable. Our findings suggest that the genetic background of Africans and East Asians makes them more and differentially susceptible to diabetes than Caucasians. This ethnic stratification could be implicated in the different natural courses of diabetes onset.

In 95 Asian Indian men, single-nucleotide polymorphisms in the apolipoprotein C3 gene were genotyped to detect variant alleles associated with hypertriglyceridemia. Carriers of the variant alleles had increased plasma apolipoprotein C3 concentrations and reduced triglyceride clearance, as compared with wild-type homozygotes. Nonalcoholic fatty liver disease was found in 38% of the variant-allele carriers but in 0% of the wild-type homozygotes. These results were confirmed in 163 non–Asian Indian men. In Asian Indian men, single-nucleotide polymorphisms in the apolipoprotein C3 gene were genotyped to detect variant alleles associated with hypertriglyceridemia. Nonalcoholic fatty liver disease was found in 38% of the variant-allele carriers but in 0% of the wild-type homozygotes. Several studies have shown a strong relationship among nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes mellitus. 1 – 3 Whether there is a genetic basis for this association remains unknown. Previous studies have suggested that two single-nucleotide polymorphisms (SNPs) in the gene encoding apolipoprotein C3 ( APOC3 ) may be associated with hypertriglyceridemia. 4 – 8 We therefore examined whether these SNPs might confer a predisposition to nonalcoholic fatty liver disease and insulin resistance. We began by studying a cohort of healthy Asian Indian men, a group that has been shown to have a high prevalence of nonalcoholic fatty liver . . .

South Asians are at higher risk than White Caucasians for the development of obesity and obesity-related non-communicable diseases (OR-NCDs), including insulin resistance, the metabolic syndrome, type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Rapid nutrition and lifestyle transitions have contributed to acceleration of OR-NCDs in South Asians. Differences in determinants and associated factors for OR-NCDs between South Asians and White Caucasians include body phenotype (high body fat, high truncal, subcutaneous and intra-abdominal fat, and low muscle mass), biochemical parameters (hyperinsulinemia, hyperglycemia, dyslipidemia, hyperleptinemia, low levels of adiponectin and high levels of C-reactive protein), procoagulant state and endothelial dysfunction. Higher prevalence, earlier onset and increased complications of T2DM and CHD are often seen at lower levels of body mass index (BMI) and waist circumference (WC) in South Asians than White Caucasians. In view of these data, lower cut-offs for obesity and abdominal obesity have been advocated for Asian Indians (BMI; overweight >23 to 24.9 kg m−2 and obesity 25 kg m−2; and WC; men 90 cm and women 80 cm, respectively). Imbalanced nutrition, physical inactivity, perinatal adverse events and genetic differences are also important contributory factors. Other differences between South Asians and White Caucasians include lower disease awareness and health-seeking behavior, delayed diagnosis due to atypical presentation and language barriers, and religious and sociocultural factors. All these factors result in poorer prevention, less aggressive therapy, poorer response to medical and surgical interventions, and higher morbidity and mortality in the former. Finally, differences in response to pharmacological agents may exist between South Asians and White Caucasians, although these have been inadequately studied. In view of these data, prevention and management strategies should be more aggressive for South Asians for more positive health outcomes. Finally, lower cut-offs of obesity and abdominal obesity for South Asians are expected to help physicians in better and more effective prevention of OR-NCDs.

Low serum 25-hydroxyvitamin D (25(OH)D) has been shown to correlate with increased risk of type 2 diabetes. Small, observational studies suggest an action for vitamin D in improving insulin sensitivity and/or insulin secretion. The objective of the present study was to investigate the effect of improved vitamin D status on insulin resistance (IR), utilising randomised, controlled, double-blind intervention administering 100 μg (4000 IU) vitamin D3 (n 42) or placebo (n 39) daily for 6 months to South Asian women, aged 23–68 years, living in Auckland, New Zealand. Subjects were insulin resistant – homeostasis model assessment 1 (HOMA1)>1·93 and had serum 25(OH)D concentration < 50 nmol/l. Exclusion criteria included diabetes medication and vitamin D supplementation >25 μg (1000 IU)/d. The HOMA2 computer model was used to calculate outcomes. Median (25th, 75th percentiles) serum 25(OH)D3 increased significantly from 21 (11, 40) to 75 (55, 84) nmol/l with supplementation. Significant improvements were seen in insulin sensitivity and IR (P = 0·003 and 0·02, respectively), and fasting insulin decreased (P = 0·02) with supplementation compared with placebo. There was no change in C-peptide with supplementation. IR was most improved when endpoint serum 25(OH)D reached ≥ 80 nmol/l. Secondary outcome variables (lipid profile and high sensitivity C-reactive protein) were not affected by supplementation. In conclusion, improving vitamin D status in insulin resistant women resulted in improved IR and sensitivity, but no change in insulin secretion. Optimal vitamin D concentrations for reducing IR were shown to be 80–119 nmol/l, providing further evidence for an increase in the recommended adequate levels. Registered Trial No. ACTRN12607000642482.

We evaluated whether the triglyceride-to-HDL cholesterol (TG/HDL-C) ratio is associated with insulin resistance (IR) in a large multiethnic cohort of obese youths. Obese youths (1,452) had an oral glucose tolerance test and a fasting lipid profile. Insulin sensitivity was estimated using the whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA)-IR and evaluated, in a subgroup of 146 obese youths, by the hyperinsulinemic-euglycemic clamp. The cohort was divided by ethnicity (612 whites, 357 Hispanics, and 483 African Americans) and then stratified into ethnicity-specific tertiles of TG/HDL-C ratio. Differences across tertiles were evaluated, and the association between the TG/HDL-C ratio and insulin sensitivity (WBISI) was defined by a multiple stepwise linear regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was determined to calculate the TG/HDL-C ratio cutoff to identify insulin-resistant subjects by ethnicity. In each ethnic group and across rising tertiles of TG/HDL-C ratio, insulin sensitivity (WBISI) progressively decreased, whereas 2-h glucose and the AUC-glucose progressively increased. The cutoff for TG/HDL-C ratio was 2.27, and the odds of presenting with IR, in youths with TG/HDL-C ratio higher than the cutoff, was 6.023 (95% CI 2.798-12.964; P < 0.001) in white girls and boys, whereas for both Hispanics and African Americans the AUC-ROCs were not significant, thus not allowing the calculation of an optimal cutoff TG/HDL-C value. The TG/HDL-C ratio is associated with IR mainly in white obese boys and girls and thus may be used with other risk factors to identify subjects at increased risk of IR-driven morbidity.

Fast-food consumption has increased greatly in the USA during the past three decades. However, the effect of fast food on risk of obesity and type 2 diabetes has received little attention. We aimed to investigate the association between reported fast-food habits and changes in bodyweight and insulin resistance over a 15-year period in the USA. Participants for the CARDIA study included 3031 young (age 18–30 years in 1985–86) black and white adults who were followed up with repeated dietary assessment. We used multiple linear regression models to investigate the association of frequency of fast-food restaurant visits (fast-food frequency) at baseline and follow-up with 15-year changes in bodyweight and the homoeostasis model (HOMA) for insulin resistance. Fast-food frequency was lowest for white women (about 1·3 times per week) compared with the other ethnic-sex groups (about twice a week). After adjustment for lifestyle factors, baseline fast-food frequency was directly associated with changes in bodyweight in both black (p=0·0050) and white people (p=0·0013). Change in fast-food frequency over 15 years was directly associated with changes in bodyweight in white individuals (p<0·0001), with a weaker association recorded in black people (p=0·1004). Changes were also directly associated with insulin resistance in both ethnic groups (p=0·0015 in black people, p<0·0001 in white people). By comparison with the average 15-year weight gain in participants with infrequent (less than once a week) fast-food restaurant use at baseline and follow-up (n=203), those with frequent (more than twice a week) visits to fast-food restaurants at baseline and follow-up (n=87) gained an extra 4·5 kg of bodyweight (p=0·0054) and had a two-fold greater increase in insulin resistance (p=0·0083). Fast-food consumption has strong positive associations with weight gain and insulin resistance, suggesting that fast food increases the risk of obesity and type 2 diabetes.

Type 2 diabetes in East Asians is characterized primarily by β‐cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1, are secreted in response to meal ingestion, and enhance insulin secretion glucose‐dependently. Incretin‐based drugs, dipeptidyl peptidase‐4 inhibitors (DPP‐4i) and glucagon‐like peptide‐1 receptor agonists, that ameliorate β‐cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta‐analyses of clinical trials on DPP‐4i and glucagon‐like peptide‐1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of β‐cell dysfunction. In addition, we found increased glycated hemoglobin‐lowering effects of DPP‐4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP‐4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP‐4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin‐associated hypoglycemia by DPP‐4i has gained attention with regard to the enhancement of hypoglycemia‐induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin‐based drugs could have potential as a first choice therapy in East Asian type 2 diabetes patients. Wide use of dipeptidyl peptidase‐4 inhibitors (DPP‐4i) as a first choice therapy in Japan. (a) The number of individuals receiving DPP‐4i among those treated with oral antidiabetic drugs (OAD). (b) Profiles of antidiabetic drug use before initiating DPP‐4i.

Background To investigate the relationship between estimated glucose disposal rate (eGDR), a surrogate indicator of insulin resistance, and atherosclerotic cardiovascular diseases (ASCVD) incidence risk. Methods This prospective cohort study utilized data from the 6026 participants from the Multi-Ethnic Study of Atherosclerosis. The eGDR (mg/kg/min) was computed as 21.158 − (0.09 × waist circumference [cm]) − (3.407 × hypertension [yes/no]) − (0.551 × HbA1c [%]). The population was categorized into four subgroups according to the quartiles (Q) of eGDR. Cox proportional hazard models were applied to assess the associations between eGDR and ASCVD incidence, and restricted cubic spine (RCS) was employed to examine the dose–response relationship. Results The mean age of participants was 63.6 ± 10.1 years, comprising 3163 (52.5%) women. Over a median follow-up duration of 14.1 years, 565 (9.4%) developed ASCVD, including 256 (4.2%) myocardial infarctions, 234 (3.9%) strokes, and 358 (5.9%) fatal coronary heart disease. Compared to the lowest quartile, the adjusted hazard ratios (95% confidence intervals) for incident ASCVD for Q2–Q4 were 0.87 (0.68−1.10), 0.63 (0.47−0.84), and 0.43 (0.30−0.64), respectively. Per 1 standard deviation increase in eGDR was associated with a 30% (HR: 0.70, 95% CI 0.60−0.80) risk reduction of ASCVD, with the subgroup analyses indicating that age and hypertension modified the association ( P for interaction < 0.05). RCS analysis indicated a significant and linear relationship between eGDR and ASCVD incidence risk. Conclusion eGDR level was negatively associated with incident ASCVD risk in a linear fashion among the general population. Our findings may contribute to preventive measures by improving ASCVD risk assessment.

Background: Small studies have shown that South Asians (SAs) have more total body, subcutaneous, visceral and hepatic fat and abnormal adipokine levels compared with Whites. However, comprehensive studies of body composition and adipokines in SAs compared with other ethnic groups are lacking. Methods: Using harmonized data, we performed a cross-sectional analysis of two community-based cohorts: Mediators of Atherosclerosis of South Asians Living in America (MASALA, n =906) and Multi-Ethnic Study of Atherosclerosis (MESA which included 2622 Whites, 803 Chinese Americans, 1893 African Americans and 1496 Latinos). General linear models were developed to assess the ethnic differences in ectopic fat (visceral, intermuscular and pericardial fat; and hepatic attenuation), lean muscle mass and adipokines (adiponectin and resistin). Models were adjusted for age, sex, site, alcohol use, smoking, exercise, education, household income and body mass index. Ectopic fat models were additionally adjusted for hypertension, diabetes, high-density lipoprotein and triglycerides. Adipokine models were adjusted for subcutaneous, visceral, intermuscular and pericardial fat; and hepatic attenuation. Results: Compared with all ethnic groups in MESA (Whites, Chinese Americans, African Americans and Latinos), SAs had greater intermuscular fat (pairwise comparisons with each MESA group, P <0.01), lower hepatic attenuation ( P <0.001) and less lean mass ( P <0.001). SAs had greater visceral fat compared with Chinese Americans, African Americans and Latinos ( P <0.05) and greater pericardial fat compared with African Americans ( P <0.001). SAs had lower adiponectin levels compared with other ethnic groups ( P <0.01; except Chinese Americans) and higher resistin levels than all groups ( P <0.001), even after adjusting for differences in body composition. Conclusion: There are significant ethnic differences in ectopic fat, lean mass and adipokines. A less favorable body composition and adipokine profile in SAs may partially explain the increased predisposition to cardiometabolic disease. The mechanisms that underlie these differences warrant further investigation.