Troglitazone Reduces Plasma Leptin Concentration but Increases Hunger in NIDDM Patients

Abstract

OBJECTIVE Troglitazone, which improves peripheral insulin resistance of experimental diabetic animals and diabetic patients, affects ob gene expression in the adipose tissue of rodents. The present study was undertaken to examine a hypothesis that clinical administration of troglitazone may reduce circulating leptin levels and affect eating behavior in NIDDM patients. RESEARCH DESIGN AND METHODS Troglitazone was administered at a dosage of 200 mg twice daily for 12 weeks in 20 poorly controlled NIDDM patients. Chronological changes in glycemic control, serum lipids, immunoreactive leptin (IRL) levels, and BMI were measured. Body fat weight was also assessed by bioelectric impedance. RESULTS Troglitazone significantly decreased fasting plasma glucose, serum immunoreactive insulin, and HbA1c levels. Serum levels of IRL and triglyceride were significantly reduced by troglitazone administered for 4, 8, and 12 weeks. Troglitazone administration significantly increased the BMI in NIDDM patients, and two-thirds of the patients complained of increased hunger after the start of troglitazone administration. CONCLUSIONS Troglitazone significantly reduces circulating leptin levels at clinical doses. It may affect the eating behavior of poorly controlled NIDDM patients through the improvement of glycemic control and/or the reduction of circulating leptin.