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 dexamethasone in diabetes (DM). To determine whether this defect precedes or follows the occurrence of diabetes, we have studied 37 adults: 11 with type 2 DM diagnosed within 6 months prior to study, 16 with chronic (> or =20 years) DM, and 10 healthy controls. After baseline measurements, subjects ingested dexamethasone (4 mg), followed by blood sampling 16 and 40 h later. Nadir plasma cortisol levels (<2.5 mg/dl) occurred 16 h after dexamethasone ingestion in all study groups; this period of maximal biological action of dexamethasone was associated with peak plasma leptin levels. The peak dexamethasone-stimulated plasma leptin responses (% baseline, +/-SEM) 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 dexamethasone ingestion, plasma glucose remained stable in the control and new DM groups but increased by 240% in the chronic DM patients; in contrast, plasma insulin increased significantly in controls and new DM patients but not in patients with chronic DM. These results indicate that plasma leptin responses to secretagogue are preserved in newly diagnosed diabetes patients but markedly attenuated in patients with long-standing diabetes, who also were unable to augment insulin secretion during glucocorticoid treatment. Thus, defective glucocorticoid augmentation of plasma leptin, probably related to beta-cell failure, may be a novel chronic complication of diabetes. Theoretically, such a defect could contribute to the obesity and insulin resistance associated with diabetes.
Dagogo-Jack
S
S
Division of Endocrinology, Diabetes and Metabolism, Box 8127, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, USA. sdagogo@medicine.umsmed.edu
Liu
J
J
Askari
H
H
Tykodi
G
G
Umamaheswaran
I
I
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003907:Dexamethasone; D003920:Diabetes Mellitus / Q000097:blood* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008297:Male; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D005938:Glucocorticoids; D007328:Insulin; D020738:Leptin; D003907:Dexamethasone; D006854:Hydrocortisone