Age-related changes in insulin sensitivity and ß-cell function among European-American and African-American women.

Type 2 diabetes (T2D) is more prevalent among African-American (AA) than European-American (EA) women for reasons that are unknown. Ethnic differences in physiological processes related to insulin sensitivity (S(I)) and secretion, and age-related changes in these processes, may play a role. The purpose of this study was to identify ethnicity- and age-related differences in S(I) and ß-cell responsivity among AA and EA females, and to determine whether these differences are independent of body composition and fat distribution. Healthy, normoglycemic females aged 7-12 years (n = 62), 18-32 years (n = 57), and 40-70 years (n = 49) were recruited for entry into this study. Following an overnight fast, S(I), intravenous glucose tolerance (Kg), acute C-peptide secretion (X0), and basal, first-phase, second-phase, and total ß-cell responsivity to glucose (PhiB, Phi1, Phi2, and Phi(TOT), respectively) were measured by an intravenous glucose tolerance test. Total % body fat was assessed by dual-energy X-ray absorptiometry, and intra-abdominal adiposity (IAAT) by computed tomography. Main effects of age group and ethnicity were measured with analysis of covariance, adjusting for % fat, IAAT, and S(I) as indicated. AA had lower S(I), and higher Kg, X0, Phi1, and Phi(TOT) (P < 0.05), which remained after adjustment for % fat and IAAT. Greater X0, Phi1, and Phi(TOT) among AA were independent of S(I). Advancing age was associated with greater Phi2 among both EA and AA. To conclude, inherent ethnic differences in ß-cell function exist independently of adiposity and S(I). Future research should examine whether ethnic differences in ß-cell physiology contribute to disparities in T2D risk.

Adiposity and ß-cell function: relationships differ with ethnicity and age.

The prevalence of type 2 diabetes is higher among African Americans (AA) vs. European Americans (EA), is highest at middle age, and is related to obesity. This study was conducted to test the hypothesis that the association of adiposity (percent body fat (%fat)) with indexes of insulin sensitivity (S(I)) and ß-cell function would differ with ethnicity and age. Subjects were 168 healthy, normoglycemic AA and EA girls and women aged 7-12 years, 18-32 years, and 40-70 years. An intravenous glucose tolerance test (IVGTT) was used to assess indexes of insulin secretion and action: S(I), acute C-peptide secretion (X0); basal, first-phase, second-phase, and total ß-cell responsivity to glucose (PhiB, Phi1, Phi2, and Phi(TOT), respectively); and the disposition index (DI = S(I) × Phi(TOT)). %Fat was assessed with dual energy X-ray absorptiometrys. Adiposity was significantly associated with S(I) among EA (-0.57, P < 0.001) but not AA (-0.20, P = 0.09). Adiposity appeared stimulatory to ß-cell function in the two groups of younger subjects and in EA, but inhibitory in postmenopausal women, particularly AA postmenopausal women. Among AA postmenopausal women, %fat was inversely associated with Phi1 (r = -0.57, P < 0.05) and Phi(TOT) (r = -0.68, P < 0.01). These results suggest that the impact of adiposity on insulin secretion and action differs with age and ethnicity.

Effects of low- and high-glycemic index/glycemic load diets on coronary heart disease risk factors in overweight/obese men.

Chronic insulin resistance contributes to subclinical inflammation, thrombosis/impaired fibrinolysis, and dyslipidemia. The effect of dietary carbohydrate, specifically of glycemic index (GI) and glycemic load (GL), on established and emerging coronary heart disease risk factors has not been elucidated fully. We conducted a randomized crossover feeding study of matched diets differing only in GI and GL in 24 overweight or obese but otherwise healthy men to investigate the effects on insulin sensitivity, inflammation, thrombosis/fibrinolysis, lipoproteins/lipids, and body composition. All meals for the high- and low-GI/GL diets were prepared in a metabolic kitchen. Each participant consumed both diets in random order for 4 weeks each, with a 4-week washout period in between. Each participant underwent a frequently sampled intravenous glucose tolerance test for assessment of insulin sensitivity; blood sampling for the measurement of inflammatory markers, coagulation factors, and lipoproteins/lipids; and dual-energy x-ray absorptiometry for assessment of body composition at the beginning and end of each dietary period. There were no statistically significant differences in glucose metabolism factors, inflammatory markers, or coagulation factors after 4 weeks on the high- and low-GI/GL diets. The high-GI/GL diet resulted in a slightly greater reduction in fat mass and a slightly greater increase in lean mass compared with the low-GI/GL diet. The high-GI/GL diet resulted in significant, but unexpected, reductions in total and low-density lipoprotein cholesterol, whereas high-density lipoprotein cholesterol concentration was significantly reduced on the high-GI/GL diet compared with the low-GI/GL diet. Overall, high- and low-GI/GL diets of 4 weeks' duration had no consistent effects on coronary heart disease risk factors in this group of overweight/obese men.

Obesity attenuates the contribution of African admixture to the insulin secretory profile in peripubertal children: a longitudinal analysis.

The pubertal transition has been identified as a time of risk for development of type 2 diabetes, particularly among vulnerable groups, such as African Americans (AAs). Documented ethnic differences in insulin secretory dynamics may predispose overweight AA adolescents to risk for type 2 diabetes. The objectives of this longitudinal study were to quantify insulin secretion and clearance in a cohort of 90 AA and European American (EA) children over the pubertal transition and to explore the association of genetic factors and adiposity with repeated measures of insulin secretion and clearance during this critical period. Insulin sensitivity was determined by intravenous glucose tolerance test (IVGTT) and minimal modeling; insulin secretion and clearance by C-peptide modeling; genetic ancestry by admixture analysis. Mixed-model longitudinal analysis indicated that African genetic admixture (AfADM) was independently and positively associated with first-phase insulin secretion within the entire group (P < 0.001), and among lean children (P < 0.01). When examined within pubertal stage, this relationship became significant at Tanner stage 3. Total body fat was a significant determinant of first-phase insulin secretion overall and among obese children (P < 0.001). Total body fat, but not AfADM, was associated with insulin clearance (P < 0.001). In conclusion, genetic factors, as reflected in AfADM, may explain greater first-phase insulin secretion among peripubertal AA vs. EA; however, the influence of genetic factors is superseded by adiposity. The pubertal transition may affect the development of the beta-cell response to glucose in a manner that differs with ethnic/genetic background.

Insulin sensitivity in African-American and white women: association with inflammation.

Whether the contribution of inflammation to risk for chronic metabolic disease differs with ethnicity is not known. The objective of this study was to determine: (i) whether ethnic differences exist in markers of inflammation and (ii) whether lower insulin sensitivity among African Americans vs. whites is due to greater inflammatory status. Subjects were African-American (n = 108) and white (n = 105) women, BMI 27-30 kg/m(2). Insulin sensitivity was assessed with intravenous glucose tolerance test and minimal modeling; fat distribution with computed tomography; body composition with dual-energy X-ray absorptiometry; markers of inflammation (tumor necrosis factor (TNF)-alpha, soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2, C-reactive protein (CRP), and interleukin (IL)-6) with enzyme-linked immunosorbent assay (ELISA). Whites had greater intra-abdominal adipose tissue (IAAT), insulin sensitivity, and concentrations of TNF-alpha, sTNFR-1, and sTNFR-2 than African Americans. Greater TNF-alpha in whites vs. African Americans was attributed to greater IAAT in whites. Among whites, but not African Americans, CRP was independently and inversely associated with insulin sensitivity, after adjusting for IAAT (r = -0.29 P < 0.05, and r = -0.13 P = 0.53, respectively). Insulin sensitivity remained lower in African Americans after adjusting for CRP (P < 0.001). In conclusion, greater IAAT among whites may be associated with greater inflammation. Insulin sensitivity was lower among African Americans, independent of obesity, fat distribution, and inflammation.