Objective: To determine whether leptin secretion is impaired in diabetes, we compared basal and stimulated plasma leptin levels in diabetic subjects and healthy controls.
Research methods and procedures: Blood samples for assay of leptin and other hormones were obtained at baseline in 54 diabetic patients and 65 controls, and 8 hours, 16 hours, and 40 hours following ingestion of dexamethasone (4 mg) in 6 healthy and 12 controls. C-peptide status was defined as "negative" if < or =0.1 ng/mL or "positive" if > or =0.3 ng/mL, in fasting plasma.
Results: Basal plasma leptin levels were 19.7+/-2.2 ng/mL in nondiabetic subjects, 13.4+/-1.5 ng/ml in C-peptide negative (n = 28) and 26.1+/-3.7 ng/mL in C-peptide positive (n = 26, p = 0.001) diabetic patients. Dexamethasone increased leptin levels of controls (n = 6) to 145+/-17% of baseline values at 8 hours (p = 0.03), 224+/-18% at 16 hours (p = 0.01), and 134+/-18% at 40 hours (p=0.05). The corresponding changes were 108+/-13%, 126+/-23%, and 98+/-16% in C-peptide negative (n=6), and 121+/-10%, 144+/-16% (p=0.03), and 147+/-23% (p=0.11) in C-peptide positive (n = 6) diabetic patients, respectively. The peak stimulated leptin levels were lower in the diabetic patients, compared with controls. Plasma insulin increased (p = 0.02) in controls, but not in the diabetic patients, following dexamethasone.
Discussion: Although diabetic patients have normal plasma leptin levels under basal conditions, their leptin responses to glucocorticoid are impaired, probably because of the concomitant insulin secretory defect. A subnormal leptin secretory response could worsen obesity and insulin resistance in diabetes.