Changes in body composition in patients with severe lipodystrophy after leptin replacement therapy.

Leptin, an adipocyte hormone, when replaced in patients with lipodystrophy, improves insulin resistance, hyperglycemia, dyslipidemia, and hepatic steatosis. Changes in body composition accompany this metabolic improvement. We studied 14 patients (3 men and 11 women); 12 of who had generalized lipodystrophy (7 congenital, 5 acquired), and 2 patients had partial lipodystrophy. Body composition and related parameters were evaluated at baseline and after 4 and 12 months of leptin therapy. Baseline body mass index (BMI) was 21.7 +/- 0.8 kg/m(2), the percent body fat was 9.5% +/- 1.6%, and the serum leptin level was 1.7 +/- 0.3 ng/mL. On treatment, serum leptin levels increased by 10-fold. All patients reported a decrease in appetite on therapy. After 4 months, both daily caloric intake and resting energy expenditure (REE) decreased. The liver volume decreased (baseline = 3,055 +/- 281 cm(3); 4 months = 2,433 +/- 243 cm(3), P =.006). Dual energy x-ray absorptiometry (DEXA) demonstrated significant decreases in fat mass (5.4 +/- 0.8 kg to 5.0 +/- 0.8 kg; P =.003) and lean body mass (51.2 +/- 3.2 kg to 48.3 +/- 3.4 kg; P =.003) at 4 months on therapy. There was no impact of leptin therapy on bone mineral content, mineral density, and metabolism. Changes in body composition occurred during the first 4 months of leptin therapy, but then stabilized and were sustained thereafter.