Summary Objective Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects β-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. Design In a crossover design, two diets (‘Standard,’ STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. Patients Thirty women with PCOS. Measurements β-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. Results Paired t-test indicated that the lower-CHO diet induced significant decreases in basal β-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic (‘first-phase’) β-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol- to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P < 0·05). Conclusions In women with PCOS, modest reduction in dietary CHO in the context of a weight-maintaining diet has numerous beneficial effects on the metabolic profile that may lead to a decrease in circulating testosterone.

Relative to Caucasians (C), African-American (AA) children and adults have lower indices of insulin sensitivity (S(i)) and a higher acute insulin response to glucose (AIR(g)). Among AA children, AIR(g) is greater than that which would be predicted based on lower S(i). The objectives of the present study were 1) to determine whether insulin secretory parameters differ in AA vs. C children and adolescents using C-peptide modeling, 2) to determine whether hepatic insulin extraction differs with ethnicity/race using the C-peptide to insulin molar ratio, and 3) to determine whether the relatively greater AIR(g) among African-Americans is due to greater insulin secretion or lesser clearance. Subjects (n = 76) were AA and C children (mean age, approximately 11 yr). A 3-h tolbutamide-modified iv glucose tolerance test and minimal modeling were used to determine S(i) and AIR(g). First phase C-peptide/insulin secretion and basal, first, and second phase beta-cell sensitivity to glucose were determined using C-peptide modeling with standard kinetic parameters developed in adults. The incremental C-peptide to insulin molar ratio over the 3-h test period, an index of hepatic insulin extraction, was calculated with the trapezoidal method. S(i) was lower and AIR(g) was higher in AA vs. C children. First phase C-peptide/insulin secretion and first phase beta-cell sensitivity to glucose were approximately 2-fold greater in AA vs. C children (P < 0.001); there were no between-group differences in basal or second phase beta-cell sensitivity to glucose. Hepatic insulin extraction was lower in AA vs. C (3.77 +/- 1.78% vs. 5.99 +/- 2.18%; P < 0.001). Multiple linear regression modeling indicated that first phase C-peptide/insulin secretion and hepatic insulin extraction contributed independently to AIR(g); however, it was only first phase C-peptide/insulin secretion that explained the significant independent contribution of ethnicity/race to AIR(g) after adjusting for S(i). The results of this study suggest that greater AIR(g) among AA is due to both greater insulin secretion and lesser hepatic insulin extraction, and that AIR(g) above that predicted based on lower S(i) is due to greater insulin secretion. The insulin secretion data await verification that the kinetic parameters used apply to children and AA.

Maternal gestational glucose concentration was significantly associated with offspring insulin sensitivity and β-cell response independent of adiposity. These results suggest that maternal glucose may program the fetus both at the pancreas and at the level of insulin target tissues such as skeletal muscle and liver.

BACKGROUND Offspring of women with gestational diabetes (OGD) have greater risk for obesity and impaired metabolic health. Whether impaired metabolic health occurs in the absence of obesity is not clear. The purpose of this study was to investigate the independent and interactive effects of intrauterine exposure to gestational diabetes and of children's current weight status on their metabolic health. METHODS Children aged 5–10 years (N=51) with and without intrauterine exposure to gestational diabetes (OGD vs CTRL) were grouped into normal weight (BMI<85th %) and overweight (BMI>85th %) according to Centers for Disease Control growth curves. Lipid profile was obtained by fasting blood draw, insulin sensitivity (SI) and secretion by liquid meal tolerance test, and body composition by dual-energy X-ray absorptiometry. RESULTS Despite similar average BMI percentiles among normal weight OGD vs CTRL, and overweight OGD vs CTRL, OGD had greater total %fat and trunk fat adjusted for leg fat compared to CTRL (P<0.05). Overweight children had lower SI (P<0.05) and greater basal, static, and total insulin secretion independent of SI (P<0.05). OGD was independently associated with greater static insulin secretion (P<0.05) and the interaction between OGD and overweight was associated with greater basal insulin secretion independent of SI (P<0.01). OGD and overweight were each associated with lower HDL-C (P<0.05). CONCLUSION Intrauterine exposure to gestational diabetes was associated with greater central adiposity and insulin secretion, and lower HDL-C, irrespective of current weight status. Future research should examine respective contributions of the intrauterine environment and of underlying genotype on children's metabolic health.

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 indices of insulin sensitivity and β-cell function would differ with ethnicity and age. Subjects were 168 healthy, normoglycemic AA and EA girls and women aged 7–12 yr, 18–32 yr, and 40–70 yr. An intravenous glucose tolerance test was used to assess indices of insulin secretion and action: Insulin sensitivity (SI), acute C-peptide secretion (X0); basal, first-phase, second-phase, and total β-cell responsivity to glucose (PhiB, Phi1, Phi2, and PhiTOT, respectively); and the disposition index (DI = SI × PhiTOT). %fat was assessed with dual-energy X-ray absorptiometry. Adiposity was significantly associated with insulin sensitivity among EA (−0.57 P<0.001) but not AA (−0.20, P=0.09). Adiposity appeared stimulatory to β-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 PhiTOT (r = −0.68, P<0.01). These results suggest that the impact of adiposity on insulin secretion and action differs with age and ethnicity.