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 ea rly metabolic abnormalities in non-diabetic offspring with one NIDDM p arent 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 diabete s. These were compared with 31 offspring of non-diabetic parents (age 26.9 +/- 5.5 years). After an overnight fast, blood was taken for gluc ose, insulin, C-peptide, insulin receptors, and lipids. All the subjec ts underwent a 75 g oral glucose tolerance test. The positive family h istory 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 - 1 9.9)), p < 0.01, despite similar blood glucose levels. After a glucose challenge (120 min), the increases in both insulin and C-peptide conc entrations were significantly greater in the positive family history g roup (289.2 +/- 214.1 pmol l(-1), 2.23 +/- 1.48 nmol l(-1)), respectiv ely, 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 fo und 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 strong ly support the familial basis of the disease.