Glucose Tolerance In Offspring Research Articles

Insulin Sensitivity, Glucose Effectiveness, and Body Fat Distribution Pattern in Nondiabetic Offspring of Patients With NIDDM

To determine the relationship of insulin sensitivity (SI), glucose effectiveness (glucose-dependent glucose transport [SG]), and body fat distribution patterns in glucose-tolerant offspring of patients with non-insulin-dependent diabetes mellitus (NIDDM). Ten glucose-tolerant offspring of patients with NIDDM and 10 age-, sex-, and weight-matched healthy control subjects without family history of diabetes were studied with the minimal model method of Bergman et al. Body fat composition and distribution pattern were assessed by the bioelectrical impedance analyzer and waist-hip circumference ratios (WHR), respectively, in each subject. Mean fasting serum glucose (4.39 +/- 0.17 vs. 3.94 +/- 0.17 mM) and postglucose peak (18.50 +/- 1.50 vs. 13.20 +/- 1.06 mM) levels were significantly greater (P less than 0.05) in the offspring than in the control subjects. Mean fasting serum insulin levels were slightly greater but not significantly different in the offspring versus control subjects (64 +/- 14 vs. 29 +/- 7 pM). After intravenous stimulation with glucose and tolbutamide, the mean serum insulin rose to significantly greater (P less than 0.05) levels at t = 5 and 25 min in the offspring compared with the control subjects. Mean SI was significantly reduced by 45% in the offspring compared with the control subjects (4.77 +/- 0.67 vs. 8.37 +/- 1.24 x 10(-4) min-1.mU-1.L-1). However, SG was not different in the offspring versus control subjects (1.92 +/- 0.12 vs. 2.10 +/- 0.17 x 10(-2) min-1). SI correlated significantly and inversely with the percentage of body fat mass (r = -0.580, P less than 0.05) but not with the WHR (r = -0.019) in the offspring. We found a negative association between SI and basal serum insulin (r = -0.798, P less than 0.01) but not with the poststimulation incremental insulin responses in the offspring. Family history of diabetes independently accounted for at least 27% of variance in the SI in our subjects. Our study confirmed that insulin insensitivity but not a reduced glucose effectiveness exists in young glucose-tolerant offspring of patients with NIDDM. The reduced S1 appears to be causally related to the total body fat content and may be a familial and/or genetic trait in the offspring.

Insulin sensitivity of forearm tissues in prediabetic man.

In genetic prediabetic subjects (the glucose tolerant offspring of two diabetic parents or the identical twin of a known diabetic) serum insulin concentrations after glucose administration are subnormal. Maintenance of glucose tolerance in this setting is apparently paradoxical, suggesting increased tissue insulin sensitivity. Accordingly, forearm tissue insulin sensitivity in nine genetic prediabetic males was compared with that of seven males without familial diabetes. Diabetes was excluded in all subjects by preliminary oral glucose tolerance testing. On the preliminary 3 h oral glucose tolerance test (OGTT) the sum of increments in blood glucose above fasting was greater in prediabetic than in control subjects. Conversely, the sum of increments in serum insulin was subnormal for the first 2 h. The insulin index (the sum of increments in insulin divided by the sum of increments in glucose) was significantly lower in prediabetics throughout the test. High physiologic levels of insulin were produced in the forearm by intrabrachial arterial insulin infusion (100 muU/kg per min for 26 min). Balances of glucose and amino acids across forearm muscle became more positive, as did balances of glucose and free fatty acids across adipose tissue plus skin. There were no differences in response between prediabetic and normal subjects.Hence, the insulin sensitivity of peripheral tissues is normal in genetic prediabetes. Increased tissue insulin sensitivity is not essential to explain coexisting euglycemia and insulinopenia in prediabetes because blood glucose values on the OGTT are, in fact, elevated although still within the range considered normal.

Triamcinolone-augmented glucose tolerance in offspring of diabetic couples

Two groups of Indian “connubial off-spring” (children of diabetic couples) were investigated with standard oral and triamcinolone-augmented glucose tolerance tests (GTT); 110 in Durban and 20 in Cape Town together with smaller control groups. In Cape Town there was no appreciable difference between offspring and controls, but in Durban 14 of 76 offspring with normal standard GTT yielded diabetic augmented GTTs. Offspring with “border-line” standard GTT were usually “diabetic” on the augmented GTT, while in those with diabetic standard GTTs the blood glucose levels were generally unaltered by triamcinolone. Further analysis indicated that triamcinolone augmentation produced “diabetic” tests only in subjects with rather high (though still not diabetic) standard GTTs. A high triamsinolone test appeared no more discriminatory than a high-normal or borderline standard GTT. Triamcinolone tests were abnormal particularly among the older offspring whose standard GTTs were normal (though none was over 49).