Impaired leptin response to glucocorticoid as a chronic complication of diabetes

Leptin has anorectic, anti-obesity, and insulin-sensitizing properties. We recently reported subnormal responses to the leptin secretagogue dexamethas one in diabetes (DM). To determine whether this defect precedes or follows the occurrence of diabetes, we have studied 37 adults. Il with type 2 DM di agnosed within 6 months prior to study, 16 with chronic (greater than or eq ual to 20 years) DM, and 10 healthy controls. After baseline measurements, subjects ingested dexamethasone (4 mg), followed by blood sampling 16 and 4 0 h later. Nadir plasma cortisol levels (< 2.5 mg/dl) occurred 16 h after d examethasone ingestion in all study groups; this period of maximal biologic al action of dexamethasone was associated with peak plasma leptin levels. T he peak dexamethasone-stimulated plasma leptin responses (% baseline, ISEM) were 188+/-18.7% among healthy controls, 180+/-13.8% among new DM patients , and 127 +/- 10.5% (P < 0.01) in chronic DM patients. Following dexamethas one ingestion, plasma glucose remained stable in the control and new DM gro ups but increased by 240% in the chronic DM patients; in contrast, plasma i nsulin increased significantly in controls and new DM patients bur not in p atients with chronic DM. These results indicate that plasma leptin response s to secretagogue are preserved in newly diagnosed diabetes patients but ma rkedly attenuated in patients with long-standing diabetes, who also were un able to augment insulin secretion during glucocorticoid treatment. Thus, de fective glucocorticoid augmentation of plasma leptin, probably related to P -cell failure, may be a novel chronic complication of diabetes. Theoretical ly, such a defect could contribute to the obesity and insulin resistance as sociated with diabetes. (C) 2000 Elsevier Science Inc. All rights reserved.