Congenital generalized lipodystrophy with insulin-resistant diabetes.

Hyperglycemia, glucose intolerance, hyperinsulinemia and resistance to exogenous insulin were found in a 10-year-old Japanese boy diagnosed as having congenital generalized lipodystrophy. Studies on insulin receptors of circulating mononuclear leucocytes indicated that insulin-resistant diabetes combined with congenital generalized lipodystrophy may be due to disturbance of insulin binding to membrane receptors. No insulin-binding antibody or antibody that impairs insulin-receptor binding was found. Plasma glucagon showed an exaggerated response to L-arginine before treatment. After treatment with a controlled diet and an oral sulfonylurea (500 mg/day) for 4 weeks, there was improvement in the plasma glucagon response to L-arginine. Improvement in the hyperglycemia, hyperinsulinemia and acanthosis nigricans was also observed. On the other hand, on completion of a 7-day high-fat diet, a marked increase in serum free fatty acids, triglycerides and beta-lipoproteins was observed. The total plasma post-heparin lipolytic activity during the high fat diet was within the normal range. However, the level of protamine-inactivated activity was 3 times that of the control.