Insulin resistance was explored in vivo and in vitro in 3 lipoatrophic diabetic girls (12, 15 and 19 years old = L1, L2 and L3). Patients L1 and L2 were explored with fasting hyperglycaemia (9 mmol/l); patient L3 was normoglycaemic. All had abnormal OGTT with marked
hyperinsulinemia. Their basal
glucose productions, measured by [6,6(-2)H]
glucose constant infusion, were 3.3, 2.6 and 3.4 mg kg-1 min-1, respectively; they did not correlate with fasting plasma
glucose.
Glucose production in response to a 2 mg kg-1 min- unlabeled
glucose infusion, was normally suppressed in L2, but was incompletely suppressed (by 1.5 mg kg-1 min-1) in L1 and L3. The dose-response curve during hyperinsulinemic euglycaemic clamp at 1, 2 and 10 mU kg-1 min-1
insulin infusion was shifted to the right in all three patients. However the maximal
glucose disposal rates were close to normal (9 and 9 mg kg-1 min-1) in L1 and L3, while it remained very low (3.6 mg kg-1 min-1
at 10 mU kg-1 min-1
insulin infusion) in L2. The endogenous insulin secretion (plasma
C-peptide) was also incompletely suppressed during
insulin infusion. Thus, the in vivo
insulin resistance of
lipoatrophic diabetes concerns not only
glucose disposal but also hepatic
glucose output and insulin secretion; in addition, the alterations of
glucose metabolism were not the same in all subjects. The in vitro studies showed no pre-receptor defect (anti-
insulin antibodies,
insulin receptor antibodies).
Insulin binding to erythrocytes and cultured fibroblasts was normal.(ABSTRACT TRUNCATED AT 250 WORDS)