Explore the vast range of titles available.

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.

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.

Dietary behaviour modification may change eating habits and reduce the impact of poor nutrition. This study aimed to evaluate the effects of daily consumption of a healthier snack bar on snacking habits and glycated Hb (HbA1c) within a 6-week intervention. In all, twenty-eight participants were randomly allocated to two groups to either consume the bars as the main snack for 6 weeks (n 14) or receipt of the bars was delayed for 6 weeks (n 14) following a stepped-wedge design. All participants had HbA1c concentrations measured at weeks −1, 0, 4, 6, 10 and 12. A short dietary habits questionnaire was self-completed at weeks 0, 6 and 12. Participants consumed the bars they received instead of other snacks, and found that the healthier snack bar was acceptable as part of their daily dietary pattern. Over the 12 weeks, there was a significant reduction in intake of biscuits, cakes and pies (approximately 2 servings/week, P<0·05) in both groups. Fruit juice intake was reduced (approximately 1 serving/week, P=0·029) in the first group. In all, twenty participants (71·4 %) experienced a decrease (n 15) or no change (n 5) in HbA1c (range 0–4 mmol/mol), whereas eight participants experienced an increase in HbA1c (range 0·5–2·5 mmol/mol). There was high compliance with the healthier snack intervention and a trend towards a favourable effect on glucose homoeostasis. Habitual snacking behaviour has the potential to be improved through changes in the food supply, and in the longer term may reduce the impact of poor nutrition on public health.

Childhood obesity is associated with abnormal glucose metabolism and type 2 diabetes mellitus (T2DM). This study evaluated the prevalence of abnormal glucose metabolism in asymptomatic obese children and adolescents, and determined the percentage of T2DM development after 3-6 years of follow-up. During 2007-2013, 177 obese children and adolescents who had normal fasting plasma glucose (FPG<100 mg/dL) were given an oral glucose tolerance test (OGTT). The participants were classified into four groups: normal glucose tolerance (NGT), NGT-hyperinsulinemia (NGT-HI), impaired glucose tolerance (IGT), and diabetes mellitus (DM). Blood chemistries, including FPG, glycated hemoglobin, and lipid profiles, and liver function test were performed every 6-12 months or when the patient developed any symptom or sign indicative of diabetes. Glucose metabolism alterations were detected in 81.4% of the participants: 63.8% with NGT-HI, 15.3% with IGT, and 2.3% with T2DM. The median levels of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with IGT (8.63) were significantly greater than those in the patients with NGT (4.04) (p<0.01). During the follow-up, 22 patients (14.4%) developed T2DM significantly more from the IGT group (nine of 33 cases, 27.3%) than the NGT-HI group (12 of 108 cases, 11.1%) (p=0.022). The predicting parameters for T2DM conversion were weight status, body mass index (BMI), FBG, fasting insulin, alanine transaminase (ALT) levels, and HOMA-IR. Glucose metabolism alteration was commonly found among obese adolescents. Factors associated with T2DM development were greater weight status and the severity of insulin resistance as shown by higher HOMA-IR levels.

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.

Non-Hispanic Black women (BW) have a greater risk of type 2 diabetes (T2D) and insulin resistance (IR) compared to non-Hispanic White women (WW). The mechanisms leading to these differences are not understood, and it is unclear whether synergistic effects of race and obesity impact disease risk. To understand the interaction of race and weight, hepatic and peripheral IR were compared in WW and BW with and without obesity. Hepatic and peripheral IR were measured by a labeled, hyperinsulinemic-euglycemic clamp in BW (n = 32) and WW (n = 32) with and without obesity. Measurements of body composition, cardiorespiratory fitness, and skeletal muscle (SM) respiration were completed. Data were analyzed by mixed model ANOVA. Subjects with obesity had greater hepatic and peripheral IR and lower SM respiration (P < .001). Despite 14% greater insulin (P = .066), BW tended to have lower peripheral glucose disposal (Rd; P = .062), which was driven by women without obesity (P = .002). BW had significantly lower glucose production (P = .005), hepatic IR (P = .024), and maximal coupled and uncoupled respiration (P < .001) than WW. Maximal coupled and uncoupled SM mitochondrial respiration was strongly correlated with peripheral and hepatic IR (P < .01). While BW without obesity had lower Rd than WW, race and obesity did not synergistically impact peripheral IR. Paradoxically, WW with obesity had greater hepatic IR compared to BW. Relationships between SM respiration and IR persisted across a range of body weights. These data provide support for therapies in BW, like exercise, that improve SM mitochondrial respiration to reduce IR and T2D risk.

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.