Patients with lipodystrophy (LD) have been used as a human model for its metabolic features (insulin resistance, hypertriglyceridemia, and diabetes) and in the present study for a polycystic ovarian syndrome (PCOS) phenotype. Leptin deficiency represents a common therapeutic target to improve insulin sensitivity and other metabolic features in women with lipodystrophy. Administration of leptin to patients with LD increases insulin sensitivity and improves its metabolic features.
This prospective, open-label trial investigated whether leptin replacement therapy would increase insulin sensitivity and improve metabolic features of PCOS. Participants were 23 female patients with LD who were enrolled in a leptin replacement trial from 2000 to the present. Most patients exhibited a phenotype similar to PCOS at baseline. Parameters assessed at baseline and after at least 1 year of leptin therapy included free testosterone, SHBG, and IGF-I.
After 1 year of leptin therapy, there was a significant decrease in free testosterone levels from 3.05 (0.6) ng/mL at baseline to 1.7 (0.3) ng/mL (P = 0.02). Levels of SHBG increased from 14.5 (2) to 25 (3.5) nM. No significant changes in the levels of gonadotropins and ovarian size were noted as a result of leptin replacement therapy. There was a significant increase in IGF-I levels after leptin therapy from 150 (14) to 195 (17). Triglycerides and glycosylated hemoglobin decreased significantly in the context of reduced insulin requirements.
These findings show that LD can be used as a model for the common forms of PCOS and that leptin therapy reduces insulin resistance and improves endocrine features of LD.