Severe lipodystrophy is known to be associated with leptin deficiency, insulin resistance, hypertriglyceridemia and hepatic steatosis.  Thus, the authors assessed whether leptin-replacement would ameliorate this condition and its complications.  Nine female patients (ages 15 to 42 years; 8 with diabetes mellitus) with lipodystrophy of various types, with serum leptin levels of less than 4 mg/ml, and with high insulin levels received recombinant methionlyl human leptin subcutaneously twice a day for four months in escalating dosages (0.03 mg to 0 – 0.4 mg/kg/day) to obtain low, intermediate, and high physiologic serum levels of leptin.  During the treatment, the serum leptin levels increased from a mean of 1.3 +/- 0.3 mg per ml to 11.1 +/- 2.5 mg per ml.

The glycosylated hemoglobin values in the diabetic patients decreased, a mean reduction of 1.9%.  After four months of therapy, the average triglyceride levels decreased by 60% and the liver volume diminished in size by an average of 28% in all patients.  Leptin also led to a discontinuation or a large reduction in the anti-diabetes therapy.  The self-reported daily caloric intake also decreased significantly.  No major problems or side effects occurred.  The authors concluded that leptin replacement improved glycemic control and decreased triglyceride levels in patients with lipodystrophy and leptin deficiency. 

Elif AO, et al. N Engl J Med 2002;346:570-578.

Editor’s Comment: These investigators demonstrated that leptin deficiency contributes to insulin resistance and other metabolic abnormalities associated with severe lipodystrophy.  The reduction of glycosylated hemoglobin associated with leptin therapy is important, reflecting improved diabetic control.  This could lead, if the effect persists, to a decrease in the relative risk of retinopathy and/or nephropathy in the diabetic population.  The decreased triglyceride levels may reflect a reduced relative risk of adverse cardiovascular events.  The alterations that characterize lipodystrophy are known to be refractory to other treatments, and, therefore, this paper reports a novel action of this hormone in addition to its known role in the control of energy homeostasis.

For those readers wishing more information regarding leptin, consult the article in the last issue (GGH 2002 Vol 18:2), which is entitled “The Endocrine Function of Adipose Tissue” and the article entitled “Molecular Physiology of Leptin and Its Receptor” (GGH 1998 Vol 14:2).  Several articles from the literature concerning leptin have been abstracted in GGH since 1998.

Fima Lifshitz, MD