STUDY OF GENETIC PREDIABETIC SOUTH INDIAN SUBJECTS - IMPORTANCE OF HYPERINSULINEMIA AND BETA-CELL DYSFUNCTION

OBJECTIVE - To study 1) whether abdominal adiposity was present in adu lt offspring of two NIDDM parents, 2) whether abdominal adiposity was associated with the development of glucose intolerance, and 3) the ass ociation of pancreatic beta-cell function with impaired glucose tolera nce (IGT) and NIDDM in these groups. RESEARCH DESIGN AND METHODS - One hundred offspring whose parents both had NIDDM were studied (60 men, 40 women, mean age 34 +/- 6.9) years, BMI 27.4 +/- 4.1 kg/m(2)). None had a history of glucose intolerance. Nondiabetic control subjects wit h no family history of diabetes were also studied for comparison (21 m en, 19 women, age 36 +/- 10.3 years, BMI 26 +/- 3.7 kg/m(2)). A standa rd oral glucose tolerance test was done for all, and plasma glucose, C -peptide, and insulin responses were measured. Abdominal fat measureme nts at L-4-L-5 were made using a computed axial tomography scan. Subcu taneous fat (SF), visceral fat (VF), and total fat (TF) areas were mea sured and VF/SF ratio was calculated. An index of insulin secretion (D elta I/G) was derived as the ratio of incremental insulin at 30 min di vided by 30-min plasma glucose. RESULTS - IGT was detected in 32 offsp ring and diabetes in 21 offspring. Diabetic men had a higher TF area t han the other groups. SF; VF; and VF/SF ratios were similar in control men and in offspring with normal glucose tolerance (NGT), IGT, or dia betes. Among control subjects, women had significantly lower VF than m en. Female offspring had higher VF than the control subjects, but intr agroup variations were absent. Fasting insulin and all C-peptide respo nses were higher in NGT compared with control subjects (P < 0.02). The 2-h insulin and C-peptide responses were higher in IGT subjects (P < 0.005). In diabetic subjects, the insulin-to-glucose ratio, C-peptide- to-glucose ratio, and Delta I/G were significantly low compared with a ll other groups (P < 0.005). Multiple logistic regression analysis sho wed that the area of insulin response had a positive association and D elta I/G had a negative association with diabetes, while age, sex, BMI , waist-to-hip ratio, abdominal fat areas, fasting and 2-h insulin, ar ea of insulin, and the C-peptide measurements did not show independent associations. Two-hour insulin showed a positive association with IGT , while increasing area of insulin showed a negative association. CONC LUSIONS-Visceral adiposity seemed to precede glucose intolerance only in women, but it had no independent association with IGT or NIDDM. Ins ulin resistance, indicated by higher plasma insulin response, and insu lin secretory defect, indicated by low Delta I/G at 30 min, were assoc iated with diabetes. beta-cell defect was not independently associated with IGT. Increased abdominal visceral adiposity does not appear to b e a prerequisite for development of IGT or diabetes in Asian Indians w ith a strong genetic predisposition for diabetes.