Metabolic abnormalities in offspring of NIDDM patients with a family history of diabetes mellitus.

NIDDM appears to be an inherited condition. Our aim was to identify early metabolic abnormalities in non-diabetic offspring with one NIDDM parent and with a strongly positive (n = 58, age 27.8 +/- 7.0 years) or a negative family history (n = 38, age 27.4 +/- 6.7 years) of diabetes. These were compared with 31 offspring of non-diabetic parents (age 26.9 +/- 5.5 years). After an overnight fast, blood was taken for glucose, insulin, C-peptide, insulin receptors, and lipids. All the subjects underwent a 75 g oral glucose tolerance test. The positive family history group had significantly higher fasting levels of triglycerides (1.09 +/- 0.24 vs control subjects: CS: 0.93 +/- 0.16 mmol l-1, p < 0.001), insulin (102.8 +/- 46.4 vs CS: 77.5 +/- 32.4 pmol l-1, p < 0.01) and C-peptide (0.69 +/- 0.22 vs CS: 0.61 +/- 0.19 nmol l-1, p < 0.05) and lower numbers of insulin receptors per red cell (9.1 x 10(3) (4.5-18.1, 95% confidence intervals) vs CS: (11.2 x 10(3) (6.3-19.9)), p < 0.01, despite similar blood glucose levels. After a glucose challenge (120 min), the increases in both insulin and C-peptide concentrations were significantly greater in the positive family history group (289.2 +/- 214.1 pmol l-1, 2.23 +/- 1.48 nmol l-1), respectively, than in CS (192.4 +/- 170.3 pmol l-1, p < 0.05) (1.54 +/- 0.99 nmol l-1 p < 0.01), respectively. No significant differences were found in fasting and post-challenge glucose levels. The negative family history group had significantly lower numbers of insulin receptors 9.4 x 10(3) (4.1-15.2) compared with CS (p < 0.05). Insulin sensitivity was significantly reduced in the positive family history group (41.6%) compared with control subjects (51.9%), p < 0.01. The results strongly support the familial basis of the disease.