Basal and stimulated plasma leptin in diabetic subjects

To determine whether leptin secretion is impaired in diabetes, we compared basal and stimulated plasma leptin levels in diabetic subjects and healthy controls.

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.

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.

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.