Leptin Synthesis Is Resistant to Acute Effects of Insulin in Insulin-Dependent Diabetes Mellitus Patients1

Insulin stimulates ob gene expression and increases serum leptin concentrations in mice and in noninsulin-dependent diabetes mellitus patients. Obese women have higher ob gene messenger ribonucleic acid levels than obese men, suggesting that sex hormones are involved in the regulation of leptin synthesis. We studied the relationship among leptin, insulin, and testosterone in 15 men with insulin-dependent diabetes mellitus (IDDM; age, 29 ± 2 yr; body mass index, 22.7 ± 0.5 kg/m2; body fat, 9.5 ± 1.0%; insulin dose, 44 ± 4 U/day; hemoglobin A1c, 8.1 ± 0.3%; diabetes duration, 12.7 ± 2.0 yr) and 15 healthy control subjects (age, 27 ± 1 yr; body mass index, 22.6 ± 0.4 kg/m2; body fat, 9.6 ± 0.5%) in the fasting state. In addition, the effect of a 4-h euglycemic hyperinsulinemia (∼600 pmol/L) on the plasma leptin concentration was determined. The fasting leptin concentration was negatively correlated to plasma testosterone (r = −0.55; P < 0.05) in IDDM patients. The fasting plasma leptin level rose 25% in healthy subjects (from 1.0 ± 0.2 to 1.3 ± 0.3 ng/mL; P < 0.05). The leptin levels were higher in IDDM subjects (P < 0.01) and remained unchanged (2.7 ± 0.2 vs. 2.7 ± 0.2 ng/mL) during hyperinsulinemia. We reached the following conclusions. 1) In nonobese IDDM patients, leptin synthesis is resistant to the acute effect of insulin. 2) Serum testosterone may contribute to the regulation of leptin synthesis in IDDM patients.