Impact of differences in glucose tolerance on the prevalence of a negative insulinogenic index.

OBJECTIVE: To determine the prevalence of a negative insulinogenic index (change in plasma insulin/change in plasma glucose from 0 to 30 min) from an oral glucose tolerance test according to glucose tolerance category. MATERIALS AND METHODS: Data from the San Antonio Heart Study (n=2494), Japanese American Community Diabetes Study (JACDS; n=594) and Genetics of NIDDM Study (n=1519) were examined. Glucose tolerance was defined by ADA criteria. RESULTS: In the combined cohort, the prevalence of a negative insulinogenic index was significantly higher in diabetes 20/616 (3.2%) compared to normal glucose tolerance 43/2667 (1.6%) (p<0.05). Longitudinally, in the JACDS cohort, the prevalence did not change from baseline (3/594; 0.5%) to 5 (4/505; 0.7%) and 10 years (8/426; 1.9%) (p=0.9) and no subject had a repeat negative insulinogenic index. CONCLUSIONS: A negative insulinogenic index occurs at a low prevalence across glucose tolerance categories although more often in diabetes, but without recurrence over time.

Gestational diabetes or lesser degrees of glucose intolerance and risk of preeclampsia.

OBJECTIVE: We evaluated the association of 1-h oral glucose challenge test (OGCT) and 3-h oral glucose tolerance test (OGTT) results with preeclampsia. METHODS: A retrospective cohort study was performed among 26,105 women. RESULTS: Preeclampsia was associated with the upper OGCT quartiles [114-132 mg/dL: odds ratio (OR) = 1.25, 95% confidence interval (CI) 1.09-1.44; >132 mg/dL: OR = 1.40, 95% CI 1.21-1.61] compared with <98 mg/dL adjusting for age, primigravidity, and gestational diabetes, and also to one abnormal OGTT value (adjusted OR 1.38, 95% CI 1.09-1.75) or gestational diabetes (adjusted OR 1.45, 95% CI 1.15-1.83). CONCLUSION: Higher glucose levels are associated with preeclampsia suggesting a pathophysiological role for glucose metabolism.

Insulin resistance is the best predictor of the metabolic syndrome in subjects with a first-degree relative with type 2 diabetes.

Although obesity is associated with insulin resistance and the metabolic syndrome (MetS), some obese individuals are metabolically healthy. Conversely, some lean individuals are insulin resistant (IR) and at increased cardiometabolic risk. To determine the relative importance of insulin sensitivity, BMI and waist circumference (WC) in predicting MetS, we studied these two extreme groups in a high-risk population. One thousand seven hundred and sixty six subjects with a first-degree relative with type 2 diabetes were stratified by BMI and homeostasis model assessment of insulin resistance (HOMA(IR)) into groups. IR groups had higher triglycerides, fasting glucose, and more diabetes than their BMI-group insulin sensitive (IS) counterparts. Within both IS and IR groups, obesity was associated with higher HOMA(IR) and diastolic blood pressure (BP), but no difference in other metabolic variables. MetS (Adult Treatment Panel III (ATPIII)) prevalence was higher in IR groups (P < 0.001) and more subjects met each MetS criterion (P < 0.001). Within each BMI category, HOMA(IR) independently predicted MetS (P < 0.001) whereas WC did not. Within IS and IR groups, age and WC, but not BMI, were independent determinants of MetS (P < 0.001). WC was a less meaningful predictor of MetS at higher values of HOMA(IR). HOMA(IR) was a better predictor of MetS than WC or BMI (receiver operating characteristic (ROC) area under the curve 0.76 vs. 0.65 vs. 0.59, P < 0.001). In conclusion, insulin sensitivity rather than obesity is the major predictor of MetS and is better than WC at identifying obese individuals with a healthier metabolic profile. Further, as many lean individuals with a first-degree relative with type 2 diabetes are IR and metabolically unhealthy, they may all benefit from metabolic testing.

Ethnic differences in serum lipoproteins and their determinants in South African women.

The objective of the study was to characterize ethnic differences in lipid levels and low-density lipoprotein (LDL) particle size and subclasses in black and white South African women and to explore the associations with insulin sensitivity (S(I)), body composition, and lifestyle factors. Fasting serum lipids and LDL size and subclasses, body composition (dual-energy x-ray absorptiometry), and S(I) (frequently sampled intravenous glucose tolerance test) were measured in normal-weight (body mass index <25 kg/m(2)) black (n = 15) and white (n = 15), and obese (body mass index >30 kg/m(2)) black (n = 13) and white (n = 13) women. Normal-weight and obese black women had lower triglycerides (0.59 +/- 0.09 and 0.77 +/- 0.10 vs 0.89 +/- 0.09 and 0.93 +/- 0.10 mmol/L, P < .05) and high-density lipoprotein cholesterol (1.2 +/- 0.1 and 1.1 +/- 0.1 vs 1.7 +/- 0.1 and 1.6 +/- 0.3 mmol/L, P < .01) than white women. The LDL particle size was not different, but obese black women had more LDL subclass IV (17.3% +/- 1.0% vs 12.5% +/- 1.0%, P < .01). In white women, triglycerides and LDL particle size correlated with S(I) (P < .01), whereas cholesterol levels correlated with body fat (P < .05). Low socioeconomic status, low dietary protein intake, and injectable contraceptive use were the major determinants of unfavorable lipid profiles in black women. Black women had lower triglyceride and high-density lipoprotein cholesterol levels and more small dense LDL particles than white women. The major determinants of serum lipids in black women were socioeconomic status and lifestyle factors, whereas in white women, S(I) and body composition most closely correlated with serum lipids.

Differential effects of abdominal adipose tissue distribution on insulin sensitivity in black and white South African women.

Black South African women are more insulin resistant than BMI-matched white women. The objective of the study was to characterize the determinants of insulin sensitivity in black and white South African women matched for BMI. A total of 57 normal-weight (BMI 18-25 kg/m(2)) and obese (BMI > 30 kg/m(2)) black and white premenopausal South African women underwent the following measurements: body composition (dual-energy X-ray absorptiometry), body fat distribution (computerized tomography (CT)), insulin sensitivity (S(I), frequently sampled intravenous glucose tolerance test), dietary intake (food frequency questionnaire), physical activity (Global Physical Activity Questionnaire), and socioeconomic status (SES, demographic questionnaire). Black women were less insulin sensitive (4.4 +/- 0.8 vs. 9.5 +/- 0.8 and 3.0 +/- 0.8 vs. 6.0 +/- 0.8 x 10(-5)/min/(pmol/l), for normal-weight and obese women, respectively, P < 0.001), but had less visceral adipose tissue (VAT) (P = 0.051), more abdominal superficial subcutaneous adipose tissue (SAT) (P = 0.003), lower SES (P < 0.001), and higher dietary fat intake (P = 0.001) than white women matched for BMI. S(I) correlated with deep and superficial SAT in both black (R = -0.594, P = 0.002 and R = 0.495, P = 0.012) and white women (R = -0.554, P = 0.005 and R = -0.546, P = 0.004), but with VAT in white women only (R = -0.534, P = 0.005). In conclusion, body fat distribution is differentially associated with insulin sensitivity in black and white women. Therefore, the different abdominal fat depots may have varying metabolic consequences in women of different ethnic origins.

Association between the 4 bp proinsulin gene insertion polymorphism (IVS-69) and body composition in black South African women.

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS-69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS-69 genotype were measured in 115 normal-weight (BMI<25 kg/m2) and 138 obese (BMI>or=30 kg/m2) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI>or=35 kg/m2) compared with the normal-weight group (P=0.029). Obese subjects with the insertion allele had greater fat mass (42.3+/-0.9 vs. 38.9+/-0.9 kg, P=0.034) and fat-free soft tissue mass (47.4+/-0.6 vs. 45.1+/-0.6 kg, P=0.014), and more abdominal subcutaneous adipose tissue (SAT, 595+/-17 vs. 531+/-17 cm2, P=0.025) but not visceral fat (P=0.739), than obese homozygotes for the wild-type allele. Only SAT was greater in normal-weight subjects with the insertion allele (P=0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild-type allele in the normal-weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat-free soft tissue mass and fat mass, particularly SAT, in obese black South African women.

Insulin response in relation to insulin sensitivity: an appropriate beta-cell response in black South African women.

OBJECTIVE: The purpose of this study was to characterize differences in the acute insulin response to glucose (AIR(g)) relative to insulin sensitivity (S(I)) in black and white premenopausal normoglycemic South African women matched for body fatness. RESEARCH DESIGN AND METHODS: Cross-sectional analysis including 57 black and white South African women matched for BMI, S(I), AIR(g), and the disposition index (AIR(g) x S(I)) were performed using a frequently sampled intravenous glucose tolerance test with minimal model analysis, and similar measures were analyzed using an oral glucose tolerance test (OGTT). Body composition was assessed by dual-energy X-ray absorptiometry and computed tomography. RESULTS: S(I) was significantly lower (4.4 +/- 0.8 vs. 9.4 +/- 0.8 and 2.9 +/- 0.8 vs. 6.0 +/- 0. 8 x 10(-5) min(-1)/[pmol/l], P < 0.001) and AIR(g) was significantly higher (1,028 +/- 255 vs. 352 +/- 246 and 1,968 +/- 229 vs. 469 +/- 246 pmol/l, P < 0.001), despite similar body fatness (30.9 +/- 1.4 vs. 29.7 +/- 1.3 and 46.8 +/- 1.2 vs. 44.4 +/- 1.3%) in the normal-weight and obese black women compared with their white counterparts, respectively. Disposition index, a marker of beta-cell function, was not different between ethnic groups (3,811 +/- 538 vs. 2,966 +/- 518 and 3,646 +/- 485 vs. 2,353 +/- 518 x 10(-5) min, P = 0.10). Similar results were obtained for the OGTT-derived measures. CONCLUSIONS: Black South African women are more insulin resistant than their white counterparts but compensate by increasing their insulin response to maintain normal glucose levels, suggesting an appropriate beta-cell response for the level of insulin sensitivity.

Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels.

OBJECTIVE: We sought to determine whether an oral disposition index (DI(O)) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DI(O) by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and beta-cell function. RESEARCH DESIGN AND METHODS: A total of 613 Japanese-American subjects (322 men and 291 women) underwent a 75-g oral glucose tolerance test (OGTT) at baseline, 5 years, and 10 years. Insulin sensitivity was estimated as 1/fasting insulin or homeostasis model assessment of insulin sensitivity (HOMA-S). Insulin response was estimated as the change in insulin divided by change in glucose from 0 to 30 min (DeltaI(0-30)/DeltaG(0-30)). RESULTS: DeltaI(0-30)/DeltaG(0-30) demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S with a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the log(e)-transformed estimates included -1 for DeltaI(0-30)/DeltaG(0-30) versus 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin sensitivity measure, the confidence limits for the slope included -1 only for subjects with normal glucose tolerance (NGT) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of DeltaI(0-30)/DeltaG(0-30) and 1/fasting insulin was calculated (DI(O)) and decreased from NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DI(O) predicted cumulative diabetes at 10 years (P < 0.001) independent of age, sex, BMI, family history of diabetes, and baseline fasting and 2-h glucose concentrations. CONCLUSIONS: The DI(O) provides a measure of beta-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.