N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus.

BACKGROUND: Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? METHODS: We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. RESULTS: The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15-38)  vs. 42 (22-66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1-4.4) vs. 1.2 (0.3-4.2) mg/L), IL-6 (2.3 (1.5-3.2) vs. 1.5 (1.5-2.5) pg/mL), leptin (1647 (1176-2480) vs. 1223 (876-2313) pmol/L), and lower adiponectin levels (7.2 (5.3-9.3) vs. 10.0 (7.2-13.5) mg/L) and Matsuda ISI (2.4 (1.7-3.7) vs. 4.2 (2.9-6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. CONCLUSIONS: NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

The impact of regional origin on the incidence of gestational diabetes mellitus in a multiethnic European cohort.

Introduction: Women with migration background present specific challenges related to risk stratification and care of gestational diabetes mellitus (GDM). Therefore, this study aims to investigate the role of ethnic origin on the risk of developing GDM in a multiethnic European cohort. Methods: Pregnant women were included at a median gestational age of 12.9 weeks and assigned to the geographical regions of origin: Caucasian Europe (n = 731), Middle East and North Africa countries (MENA, n = 195), Asia (n = 127) and Sub-Saharan Africa (SSA, n = 48). At the time of recruitment maternal characteristics, glucometabolic parameters and dietary habits were assessed. An oral glucose tolerance test was performed in mid-gestation for GDM diagnosis. Results: Mothers with Caucasian ancestry were older and had higher blood pressure and an adverse lipoprotein profile as compared to non-Caucasian mothers, whereas non-Caucasian women (especially those from MENA countries) had a higher BMI and were more insulin resistant. Moreover, we found distinct dietary habits. Non-Caucasian mothers, especially those from MENA and Asian countries, had increased incidence of GDM as compared to the Caucasian population (OR 1.87, 95%CI 1.40 to 2.52, p < 0.001). Early gestational fasting glucose and insulin sensitivity were consistent risk factors across different ethnic populations, however, pregestational BMI was of particular importance in Asian mothers. Discussion: Prevalence of GDM was higher among women from MENA and Asian countries, who already showed adverse glucometabolic profiles at early gestation. Fasting glucose and early gestational insulin resistance (as well as higher BMI in women from Asia) were identified as important risk factors in Caucasian and non-Caucasian patients.

Breath biomarkers of insulin resistance in pre-diabetic Hispanic adolescents with obesity.

Insulin resistance (IR) affects a quarter of the world's adult population and is a major factor in the pathogenesis of cardio-metabolic disease. In this pilot study, we implemented a non-invasive breathomics approach, combined with random forest machine learning, to investigate metabolic markers from obese pre-diabetic Hispanic adolescents as indicators of abnormal metabolic regulation. Using the ReCIVA breathalyzer device for breath collection, we have identified a signature of 10 breath metabolites (breath-IR model), which correlates with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (R = 0.95, p < 0.001). A strong correlation was also observed between the breath-IR model and the blood glycemic profile (fasting insulin R = 0.91, p < 0.001 and fasting glucose R = 0.80, p < 0.001). Among tentatively identified metabolites, limonene, undecane, and 2,7-dimethyl-undecane, significantly cluster individuals based on HOMA-IR (p = 0.003, p = 0.002, and p < 0.001, respectively). Our breath-IR model differentiates between adolescents with and without IR with an AUC-ROC curve of 0.87, after cross-validation. Identification of a breath signature indicative of IR shows utility of exhaled breath metabolomics for assessing systemic metabolic dysregulation. A simple and non-invasive breath-based test has potential as a diagnostic tool for monitoring IR progression, allowing for earlier detection of IR and implementation of early interventions to prevent onset of type 2 diabetes mellitus.

Association between vitamin D3 levels and insulin resistance: a large sample cross-sectional study.

Previous studies have shown that vitamin D3 may be a potential factor in insulin resistance, but the relationship between vitamin D3 and insulin resistance still remains controversial. At present, more research is needed to explore the relationship between vitamin D3 and insulin resistance. The samples from 2009 to 2018 in NHANES database were analyzed to Investigate the relationship and the potential mechanism. We performed a cross-sectional study of five periods in the NHANES database. Finally, 9298 participants were selected through strict inclusion and exclusion criteria, Multivariate logistic regression analysis and curve fitting were conducted to explore the relationship between vitamin D3 level and insulin resistance. Moreover, subgroup analysis was used to further prove the association. The results revealed that there was a strong association between vitamin D3 and insulin resistance (OR 0.82, 95% CI 0.72-0.93). However, subgroup analyses indicated that this correlation varied between individuals and races. There was a negative correlation between vitamin D3 level and insulin resistance, which provides a new proof for exploring the influencing factors of insulin resistance. More well-designed studies are still needed to further elaborate on these associations.

Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals.

BACKGROUND: Alcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between alcohol use and insulin action in a prospective cohort of Latino individuals with and without HCV. METHODS: One hundred fifty-three nondiabetic Latino individuals (60 HCV+, 93 HCV-) underwent clinical evaluation and metabolic testing; 56 had repeat testing over a median follow-up of 1.5 years. Peripheral IR and hepatic IR were measured via steady-state plasma glucose (SSPG) and endogenous glucose production during a two-step, 240-min insulin suppression test. Insulin secretion (IS) was measured using the graded glucose infusion test. Alcohol use was categorized as none, moderate (≤1 drink/day for women and ≤2 drinks/day for men), and heavy (>moderate). Multivariable models including HCV status assessed associations of alcohol use with baseline SSPG, hepatic IR and IS, and changes in these parameters over time. RESULTS: Overall, the median age was 44 years, 63.4% were male, 66.7% overweight/ obese, and 31.9% had heavy lifetime alcohol use while 60.4% had moderate lifetime alcohol use. SSPG and IS were similar by levels of alcohol use at baseline and alcohol use was not statistically significantly associated with change in these measures over time. However, lifetime daily heavy alcohol use (vs. not heavy, coef 2.4 µU-mg/kg-min-ml, p = 0.04) and HCV status (coef 4.4 µU-mg/kg-min-ml, p = 0.0003) were independently associated with higher baseline hepatic IR, and current heavy alcohol use was associated with greater change in hepatic IR in follow-up (coef 5.8 µU-mg/kg-min-ml, p = 0.03). CONCLUSIONS: In this cohort of Latino individuals, lifetime and current heavy alcohol use influenced hepatic IR and its change over time. Strategies to decrease rates of heavy alcohol use or increase abstinence along with lifestyle modification and anti-HCV therapy to reduce metabolic risk are critical to prevent adverse liver and metabolic outcomes in Latino individuals.

Effect of Gut Microbial Enterotypes on the Association between Habitual Dietary Fiber Intake and Insulin Resistance Markers in Mexican Children and Adults.

Dietary fiber (DF) is a major substrate for the gut microbiota that contributes to metabolic health. Recent studies have shown that diet-metabolic phenotype effect might be related to individual gut microbial profiles or enterotypes. Thus, the aim of this study was to examine whether microbial enterotypes modify the association between DF intake and metabolic traits. This cross-sectional study included 204 children (6-12 years old) and 75 adults (18-60 years old). Habitual DF intake was estimated with a Food Frequency Questionnaire and biochemical, clinical and anthropometric data were obtained. Gut microbiota was assessed through 16S sequencing and participants were stratified by enterotypes. Correlations adjusting for age and sex were performed to test the associations between dietary fiber components intake and metabolic traits. In children and adults from the Prevotella enterotype, a nominal negative correlation of hemicellulose intake with insulin and HOMA-IR levels was observed (p < 0.05), while in individuals of the other enterotypes, these associations were not observed. Interestingly, the latter effect was not related to the fecal short-chain-fatty acids profile. Our results contribute to understanding the enterotype influence on the diet-phenotype interaction, which ultimate could provide evidence for their use as potential biomarkers for future precision nutrition strategies.

Comparison of islet cell function, insulin sensitivity, and incretin axis between Asian-Indians with either impaired fasting glucose or impaired glucose tolerance, and normal healthy controls.

AIMS: The objective of this study was to compare the islet cell function, insulin sensitivity, and incretin axis between Asian-Indian subjects with either impaired fasting glucose (IFG), or impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). MATERIALS AND METHODS: Prediabetes subjects underwent a mixed meal tolerance test(MMTT) after overnight fasting. Samples for glucose, insulin, glucagon, and glucagon-like peptide-1 (GLP-1) were collected at 0, 30, 60, and 120 min. Insulin secretion sensitivity index -2 (ISSI-2) for beta-cell function and Matsuda index for insulin sensitivity were assessed. Alpha cell function was assessed by measuring the area under the curve (AUC) 0-120 glucagon/AUC0-120 glucose. RESULTS: A total of sixty subjects were recruited with 20 in each group. The beta-cell function represented by ISSI-2 was impaired in prediabetes subjects as compared to NGT group (IFG: 2.09 ± 0.44 vs. NGT: 3.04 ± 0.80, P < 0.0001, and IGT: 2.33 ± 0.59 vs. NGT: 3.04 ± 0.80, P = 0.002). Similarly, AUC0-120 glucagon/AUC0-120 glucose was also lower in prediabetes group as compared to healthy controls (IFG: 0.41(0.54) vs. NGT: 1.07(0.39), P = 0.003 and IGT: 0.57(0.38) vs. NGT: 1.07(0.39), P = 0.001). CONCLUSION: Asian-Indian prediabetes subjects have reduced beta-cell function with lesser glucagon secretion during MMTT as compared to normal healthy controls.

Glucose-lowering action through targeting islet dysfunction in type 2 diabetes: Focus on dipeptidyl peptidase-4 inhibition.

Dipeptidyl peptidase-4 (DPP-4) inhibition is a glucose-lowering medication for type 2 diabetes. It works through stimulation of insulin secretion and inhibition of glucagon secretion in a glucose-dependent manner, resulting in lowered fasting and postprandial glycemia with low risk of hypoglycemia. As impaired insulin secretion and augmented glucagon secretion are key factors underlying hyperglycemia in type 2 diabetes, DPP-4 inhibition represents a therapy that targets the underlying mechanisms of the disease. If insufficient in monotherapy, it can preferably be used in combination with metformin, which targets insulin resistance, and also in combination with sodium-glucose cotransporter 2 inhibition, thiazolidinediones and insulin, which target other mechanisms. In individuals of East Asian origin, islet dysfunction is of particular importance for the development of type 2 diabetes. Consequently, it has been shown in several studies that DPP-4 is efficient in these populations. This mini-review highlights the islet mechanisms of DPP-4 inhibition, islet dysfunction as a key factor for hyperglycemia in type 2 diabetes and that, consequently, DPP-4 is of particular value in populations where islet dysfunction is central, such as in individuals of East Asian origin.

Adiponectin is associated with insulin sensitivity in white European men but not black African men.

AIMS: We aimed to assess ethnic differences in inflammatory markers and their relationships with insulin sensitivity and regional adiposity between white European and black African men. METHODS: A total of 53 white European and 53 black African men underwent assessment of inflammatory markers alongside Dixon-magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue and intrahepatic lipid. A hyperinsulinaemic-euglycaemic clamp was used to measure whole-body and adipose tissue insulin sensitivity. To assess ethnic differences in relationships, the statistical significance of an interaction term between adipokines and ethnic group was tested in multivariable regression models. RESULTS: The black African men exhibited significantly lower adiponectin and tumour necrosis factor-α (TNF-α) and greater interleukin-10 (IL-10) compared to white European men (all p < 0.05). There were no statistically significant ethnic differences in leptin, resistin, IL-6, interferon-γ, IL-13, IL-1ß, IL-8 and vascular endothelial growth factor. Several relationships differed significantly by ethnicity such that they were stronger in white European than black African men including IL-6 with visceral adipose tissue; adiponectin with subcutaneous adipose tissue; leptin with intrahepatic lipid; adiponectin, IL-6 and TNF-α with whole-body insulin sensitivity and TNF-α with adipose tissue insulin sensitivity (all pinteraction <0.05). Leptin significantly predicted whole-body insulin sensitivity in white European (R2  = 0.51) and black African (R2  = 0.29) men; however, adiponectin was a statistically significant predictor in only white European men (R2  = 0.22). CONCLUSIONS: While adiponectin is lower in black African men, its insulin sensitising effects may be greater in white men suggesting that the role of adipokines in the development of type 2 diabetes may differ by ethnicity.

Association between insulin resistance and left ventricular hypertrophy in asymptomatic, Black, sub-Saharan African, hypertensive patients: a case-control study.

BACKGROUND: Conflicting information exists regarding the association between insulin resistance (IR) and left ventricular hypertrophy (LVH). We described the associations between obesity, fasting insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), and LVH in Black patients with essential hypertension. METHODS: A case-control study was conducted at the Centre Médical de Kinshasa (CMK), the Democratic Republic of the Congo, between January and December 2019. Cases and controls were hypertensive patients with and without LVH, respectively. The relationships between obesity indices, physical inactivity, glucose metabolism and lipid disorder parameters, and LVH were assessed using linear and logistic regression analyses in simple and univariate exploratory analyses, respectively. When differences were observed between LVH and independent variables, the effects of potential confounders were studied through the use of multiple linear regression and in conditional logistic regression in multivariate analyses. The coefficients of determination (R2), adjusted odds ratios (aORs), and their 95% confidence intervals (95% CIs) were calculated to determine associations between LVH and the independent variables. RESULTS: Eighty-eight LVH cases (52 men) were compared against 132 controls (81 men). Variation in left ventricular mass (LVM) could be predicted by the following variables: age (19%), duration of hypertension (31.3%), body mass index (BMI, 44.4%), waist circumference (WC, 42.5%), glycemia (20%), insulinemia (44.8%), and HOMA-IR (43.7%). Hypertension duration, BMI, insulinemia, and HOMA-IR explained 68.3% of LVM variability in the multiple linear regression analysis. In the logistic regression model, obesity increased the risk of LVH by threefold [aOR 2.8; 95% CI (1.06-7.4); p = 0.038], and IR increased the risk of LVH by eightfold [aOR 8.4; 95 (3.7-15.7); p < 0.001]. CONCLUSION: Obesity and IR appear to be the primary predictors of LVH in Black sub-Saharan African hypertensive patients. The comprehensive management of cardiovascular risk factors should be emphasized, with particular attention paid to obesity and IR. A prospective population-based study of Black sub-Saharan individuals that includes the use of serial imaging remains essential to better understand subclinical LV deterioration over time and to confirm the role played by IR in Black sub-Saharan individuals with hypertension.

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children.

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and ß-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and ß-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and ß-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between ß-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and ß-carotenoids rather than that of ß-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Variation in plasma glucagon levels according to obesity status in Japanese Americans with normal glucose tolerance.

Japanese Americans living in the United States are genetically identical to Japanese people, but have undergone a rapid and intense westernization of their lifestyle. This study investigated variability in glucagon secretion after glucose loading among Japanese Americans with normal glucose tolerance (NGT) according to obesity status. The 75-g oral glucose tolerance test (OGTT) was performed for 138 Japanese Americans (aged 40-75 years) living in Los Angeles. Plasma glucagon levels measured using the sandwich enzyme-linked immunosorbent assay were compared according to body mass index (BMI) categories among 119 individuals with NGT. The individuals were classified into three categories according to their BMI values: <22 kg/m2 (n = 37), 22-24.9 kg/m2 (n = 46), and ≥25 kg/m2 (n = 36). Fasting plasma glucagon levels and glucagon-area under the curve levels during the OGTT were the highest in the BMI ≥25 kg/m2 group. Fasting glucagon levels were correlated with BMI (r = 0.399, p < 0.001), fasting insulin levels (r = 0.275, p = 0.003) and the homeostasis model assessment-insulin resistance (r = 0.262, p = 0.004). In conclusion, our findings suggest that fasting hyperglucagonemia is associated with obesity and insulin resistance even during the NGT stage in the Japanese American population.

Fatty Acid Metabolism and Associations with Insulin Sensitivity Differs Between Black and White South African Women.

PURPOSE: Genetic differences in desaturase genes and consequently fatty acid metabolism have been reported. The aims were to examine ethnic differences in serum fatty acid composition and desaturase indices, and assess the ethnic-specific associations with insulin sensitivity (IS) and liver fat in black and white South African (SA) women. METHODS: In this cross-sectional study including 92 premenopausal black (n = 46) and white (n = 46) SA women, serum fatty acid composition was measured in cholesteryl ester (CE) and nonesterified fatty acid (NEFA) fractions. Desaturase activities were estimated as product-to-precursor ratios: stearoyl-CoA desaturase-1 (SCD1-16, 16:1n-7/16:0); δ-5 desaturase (D5D, 20:4n-6/20:3n-6), and δ-6 desaturase (D6D, 18:3n-6/18:2n-6). Whole-body IS was estimated from an oral glucose tolerance test using the Matsuda index. In a subsample (n = 30), liver fat and hepatic IS were measured by 1H-magnetic resonance spectroscopy and hyperinsulinemic euglycemic clamp, respectively. RESULTS: Despite lower whole-body IS (P = .006), black women had higher CE D5D and lower D6D and SCD1-16 indices than white women (P < .01). CE D6D index was associated with lower IS in white women only (r = -0.31, P = .045), whereas D5D index was associated with higher IS in black women only (r = 0.31, P = .041). In the subsample, D6D and SCD1-16 indices were positively and D5D was negatively associated with liver fat (P < .05). Conversely, CE SCD1-16 was negatively associated with hepatic IS (P < .05), but not independently of liver fat. CONCLUSIONS: Ethnic differences in fatty acid-derived desaturation indices were observed, with insulin-resistant black SA women paradoxically showing a fatty acid pattern typical for higher insulin sensitivity in European populations.

Investigating the changes in the levels of HbA1c, blood fat and insulin sensitivity in elder patients with type II diabetes mellitus due to combined medication of pioglitazone and melbine and single-use of pioglitazone.

This study was founded for the purpose investigate the differences in effects of combined medication of pioglitazone and melbine and single-use of pioglitazone on the levels of hba1c, blood fat and insulin sensitivity of elder patients with type II diabetes mellitus (T2DM), to provide clinical reference and guidance for the treatment of T2DM in elder patients. For this purpose, we selected a total of 120 elder patients with T2DM who visited the clinic or were admitted to this hospital between July 2016 and July 2017 and divided them into the observation group and the control group (n=60 for each group). For the control group, they only took pioglitazone for treatment, while those in the observation additionally took melbine for treatment. Then, we observed the levels of FPG, 2hPG, HbA1c, blood fat, FINS, 2hINS and HOMA-IR. Results showed that after treatment, significant decreases were seen in levels of FPG, 2hPG and HbA1c in patients of two groups compared to the levels before treatment, and the levels in the observation group decreased more evidently than those in the control group (p<0.05); besides, the levels of total glyceride, total cholesterol and LDL-C were all significantly lower than those before treatment, with an elevated HDL-C, and those levels of TG, TC and LDL-C in the observation group were significantly lower than those in the control group; the level of HDL-C was higher than the control group (p<0.05). Similar decreases were identified in the levels of FINS, 2hFINS and HOMA-IR after treatment (p<0.05), and the levels in the observation group were also significantly lower than those in the control group (p<0.05). In the observation group, the incidence rate of adverse reactions was 10% (6/60), while in the control group was 8.33% (5/60), but the difference between the two groups showed no statistical significance (p>0.05). It is concluded that combined medication of pioglitazone and melbine can effectively reduce the levels of plasma glucose, blood fat and the HOMA-IR, with an elevated sensitivity to insulin, but no severe adverse reactions, manifesting a promising safety in long-term administration. It is worthy of being promoted in clinical practice.

Prevalence of Insulin Resistance in the Hungarian General and Roma Populations as Defined by Using Data Generated in a Complex Health (Interview and Examination) Survey.

Data mainly from one-off surveys clearly show that the health of Roma, the largest ethnic minority of Europe, is much worse than that of the general population. However, results from comprehensive exploratory studies are missing. The aim of our study was to create a complex database for comparative and association studies to better understand the background of the very unfavourable health of Roma, especially the high burden of cardiometabolic diseases. A three-pillar (questionnaire-based, physical and laboratory examinations) health survey was carried out on randomly selected samples of the Hungarian general (HG, n = 417) and Roma (HR, n = 415) populations, and a database consisting of more than half a million datapoints was created. Using selected data, the prevalence rates of metabolic syndrome (MetS) and of its components were determined, and to estimate the risk of insulin resistance (IR), surrogate measures (the homeostasis model assessment of insulin resistance index, quantitative insulin sensitivity check index, McAuley and TyG indices and the TG/HDL-C ratio) were calculated. Receiver operating characteristic curve analysis and Youden's method were used to define the optimal cut-off values of each IR index. The prevalence of MetS was very high in both study populations (HG: 39.8%, HR: 44.0%) with no statistically significant difference between the two groups in females or males. The prevalence of MetS showed a very marked increase in the HR 35-49 years age group. Among surrogate measures, the TyG index showed the greatest power for predicting IR/MetS at a cut-off value of 4.69 (77% sensitivity, 84% specificity) and indicated a 42.3% (HG) and 40.5% (HR) prevalence of IR. The prevalence of MetS and IR is almost equally very unfavourable in both groups; thus, the factors underlying the high premature mortality burden of Roma should be further clarified by investigating the full spectrum of risk factors available in the database, with a special focus on the access of Roma people to preventive and curative health services.

Risk factors for insulin resistance in midlife Singaporean women.

OBJECTIVES: To understand the extent to which risk factors for insulin resistance are mediated by body mass index (BMI), visceral adipose tissue (VAT), physical activity and performance, and the inflammatory markers interleukin (IL)-6, tumor necrosis factor (TNF)- α, and high-sensitivity C-reactive protein (hs-CRP). STUDY DESIGN: A wide range of socio-demographic characteristics of Chinese, Malay and Indian women attending routine gynecologic care in Singapore were prospectively collected. Physical performance was objectively measured by hand grip strength and the Short Physical Performance Battery. Percent VAT was determined by dual-energy X-ray absorptiometry. Fasting serum concentrations of glucose, insulin, IL-6, TNF- α, and hs-CRP were measured. MAIN OUTCOME MEASURE: was insulin resistance, expressed as the homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: 1159 women were analyzed, mean age 56.3 (range 45-69) years, comprising women of Chinese (84.0%), Indian (10.2%), and Malay (5.7%) ethnic origins. The adjusted mean differences for obesity (0.66, 95% CI 0.32-1.00), VAT area in the highest vs lowest tertile (1.03, 95% CI 0.73-1.34), low physical performance (0.63, 95% CI 0.05-1.24), and highest vs lowest tertile of TNF- α (0.35, 95% CI 0.13-0.57) were independently associated with HOMA-IR. Women of Malay and Indian ethnicity had higher crude HOMA-IR than Chinese women. However, after adjustment for obesity, VAT, physical performance, and TNF- α, no differences in mean HOMA-IR remained, when comparing Chinese women with those of Malay ethnicity (0.27, 95% CI -0.12 to 0.66) and with those of Indian ethnicity (0.30, 95% CI -0.01 to 0.66). CONCLUSIONS: Insulin resistance was independently associated with obesity, high VAT, low physical performance, and high levels of TNF- α in midlife Singaporean women. These variables entirely explained the significant differences in insulin resistance between women of Chinese, Malay and Indian ethnicity.

Obesity in African-Americans: The role of physiology.

The disproportionate obesity in African American (AA) women has a physiologic basis and can be explained by the interactive effects of insulin secretion, insulin clearance, insulin sensitivity and the glycaemic load of the diet. This review will present data supporting a physiologic basis for obesity propensity in obesity-prone AA women that resides in their unique metabolic/endocrine phenotype: high beta-cell responsiveness, low hepatic insulin extraction and relatively high insulin sensitivity, which together result in a high exposure of tissues and organs to insulin. When combined with a high-glycaemic (HG) diet (that stimulates insulin secretion), this underlying propensity to obesity becomes manifest, as ingested calories are diverted from energy production to storage. Our data indicate that both weight loss and weight loss maintenance are optimized with low-glycaemic (LG) vs HG diet in AA. Whether greater obesity in AA is mechanistically related to their greater prevalence of type 2 diabetes is debatable. This review provides data indicating that obesity is not strongly related to insulin resistance in AA. Rather, insulin resistance in AA is associated with relatively low adipose tissue in the leg, consistent with a genetic predisposition to impaired lipid storage. Greater bioenergetic efficiency has been reported in AA and, via resultant oxidative damage, could plausibly contribute to insulin resistance. In summary, it is proposed here that a subset of AA women are predisposed to obesity due to a specific metabolic/endocrine phenotype. However, greater diabetes risk in AA has an independent aetiology based on impaired lipid storage and mitochondrial efficiency/oxidative stress.

Plasma Ceramides and Triglycerides Are Elevated during Pregnancy in Association with Markers of Insulin Resistance in Hutterite Women.

Changes in maternal insulin sensitivity and circulating lipids typically occur during the metabolic transitions of pregnancy and lactation. Although ceramides can cause insulin resistance in mammals, their potential roles during pregnancy and lactation are unknown. We hypothesized that changes in lipids like ceramide and triglycerides could occur across different reproductive states and relate to insulin resistance. Our objectives were to comprehensively characterize lipids in the plasma of pregnant, lactating, and nonpregnant and nonlactating (NPNL) women, and to evaluate the relationship between ceramides and the triglyceride index, a proxy of insulin resistance. Middle-aged Hutterite women from the South Dakota Rural Bone Health Study were classified by reproductive status as nonpregnant and nonlactating (NPNL; 19 observations), pregnant (14 observations), or lactating (31 observations). Several plasma lipids were elevated in pregnancy such as ceramides, triglycerides, and total- and high-density lipoprotein cholesterol. The triglyceride index was highest during pregnancy and was positively associated with long- and very long-chain ceramides. Lipidomics revealed lipid signatures specific to reproductive state, including triglycerides, phosphatidylcholines, sphingomyelins, and cholesteryl esters, which were also related to the triglyceride index. Our data support the possibility that ceramides contribute to the development of insulin resistance during pregnancy, and reveal distinct lipid signatures associated with pregnancy and lactation.

Pathogenesis of type 2 diabetes risk in black Africans: a South African perspective.

The prevalence of type 2 diabetes (T2D) is higher in black Africans than their European counterparts. This review summarizes the research exploring the pathogenesis of T2D in populations of African ancestry compared to white Europeans and shows that the pathogenesis differs by ethnicity. Black Africans present with a phenotype of low insulin sensitivity and hyperinsulinaemia as a result of increased insulin secretion and reduced hepatic insulin clearance. Whether hyperinsulinaemia precedes insulin resistance or is merely a compensatory mechanism is yet to be determined. Black Africans have lower visceral adipose tissue and ectopic fat deposition and greater peripheral (gluteo-femoral) fat deposition than their European counterparts. This suggests that black Africans are more sensitive to the effects of ectopic fat deposition, or alternatively, that ectopic fat is not an important mediator of T2D in black Africans. Importantly, ethnic disparities in T2D risk factors may be confounded by differences in sociocultural and lifestyle factors. Future longitudinal and dietary intervention studies, in combination with genetic analyses, are needed for a better understanding of the pathophysiology of T2D in black Africans. This will be key for effective prevention and management strategies.

Associations between omega-6 polyunsaturated fatty acids, hyperinsulinemia and incident diabetes by race/ethnicity: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND & AIMS: Omega-6 polyunsaturated fatty acids (PUFAs) have been shown to relate to insulin resistance and type 2 diabetes (T2D), but influence of race/ethnicity has not been investigated. The aim of this study was to determine whether omega-6 PUFAs, and estimated desaturase enzyme activity, are associated with fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and incident T2D, and whether associations differ by race/ethnicity. METHODS: This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 6282). Associations between baseline plasma phospholipid fatty acids (LA, Linoleic Acid; GLA, γ-linoleic acid; DGLA, Dihomo-γ-linolenic acid; AA, arachidonic acid; D5D, delta-5 desaturase; D6D, delta-6 desaturase), fasting glucose, insulin, and HOMA-IR [(fasting insulin - fasting glucose)/22.5] were evaluated using linear regression. Associations between omega-6 PUFAs (N = 5508 after excluding diabetics at baseline) and T2D incidence were assessed using Cox proportional hazards regression. Analyses were replicated/stratified by race/ethnicity (White, Black, Chinese, Hispanic) and tests for interaction were assessed by inclusion of a cross-product term in models. RESULTS: In fully adjusted models, insulin and HOMA-IR were positively associated with LA (insulin: 0.213 per SD, p = 0.01; HOMA-IR: 0.252 per SD, p < 0.001), GLA (insulin: 0.010 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), DGLA (insulin: 0.279 per SD, p < 0.001; HOMA-IR: 0.175 per SD, p < 0.001) and D6D activity (insulin: 0.001 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), and inversely associated with AA (insulin -0.272 per SD, p < 0.001; HOMA-IR: -0.125 per SD, p = 0.03) and D5D activity (insulin: -0.530 per SD, p < 0.001; HOMA-IR: -0.322 per SD, p < 0.001), while weak or no associations were observed with fasting glucose, and associations appeared to differ by race/ethnicity. After accounting for HOMA-IR at baseline, LA was inversely (HR: 0.87, p = 0.003) and DGLA (HR: 1.17, p < 0.001) and AA (HR: 1.15, p = 0.001) were positively associated with T2D in the overall population, but associations were attenuated or no longer present when stratified by race/ethnicity (P-interaction >0.05). CONCLUSIONS: Results confirm previous reports that omega-6 PUFAs are associated with hyperinsulinemia. Findings suggest omega-6 PUFAs are more likely markers of hyperinsulinemia rather than a protective/risk factor for T2D and indicate racial/ethnic differences in associations, but further research is needed to confirm findings.