Metabolic studies in lipoatrophic diabetes: mechanism of hyperglycemia and evidence of resistance to insulin of lipid metabolism.

We determined in 5 control subjects and in one patient with total congenital lipoatrophy (LA) the effect of insulin infusion on glucose flux and some aspects of lipid metabolism. In the post-absorptive state LA had moderate hyperglycemia (9.2 versus 3.80 +/- 0.07 mmol.l-1) and hyperinsulinemia (19 vs 12 +/- 3 mU.l-1) and a massive increase in glucose production (7.51 mg.kg.-1.min-1) and disappearance (7.40 mg.kg-1.min-1) rates (control subjects: 2.29 +/- 0.14 mg.kg-1 min-1). Raising peripheral insulin levels to 28 +/- 3 mU.l-1 suppressed endogenous glucose production in the control subjects whereas in LA significant (2.01 mg.kg-1.min-1) production persisted even when peripheral insulinemia was raised to 58 mU.l-1. Insulin infusion in control subjects increased progressively glucose utilization to a final value of 15.7 +/- 0.7 mg.kg-1.min-1 (corresponding plasma insulin: 482 +/- 44 mU.l-1). Insulin infusion in LA initially lowered glucose level near to normal values and exogenous glucose was infused for an insulin infusion rate of 10 mU.kg-1.min-1; at this insulin infusion rate glucose utilization rate (6.52 mg.kg-1.min-1) was decreased relative to control subjects in spite of higher insulin levels (750 mU.l-1). NEFA, glycerol and ketone bodies (KB) levels were decreased to undetectable levels by insulin infusion in the normal subjects whereas NEFA and glycerol were decreased only in part and KB were not modified in LA. In addition glycerol and KB appearance rates determined in LA were not suppressed by insulin infusion as expected.(ABSTRACT TRUNCATED AT 250 WORDS)