Dynamic Leptin Secretion in Obesity and Diabetes

Abstract

The analysis of plasma leptin levels in relation to metabolic pathophysiology has focused predominantly on specimens collected under basal conditions. The findings from such studies indicate that fasting leptin levels are directly correlated with measures of adiposity (such as BMI or body fat) in lean and obese subjects as well as in persons with diabetes. We and others have reported that administration of glucocorticoids results in significant increases (usually a doubling above baseline) in plasma leptin levels. Similar reports have shown that exogenous insulin also stimulates leptin production leading to increases in plasma leptin levels. Thus, glucocorticoids and insulin can be deployed as leptin secretagogues to probe the metabolic physiology and pathophysiology of dynamic leptin secretion. This chapter discusses the results of dynamic leptin secretion in relation to obesity and diabetes. Healthy subjects respond with a doubling of plasma leptin levels following challenge with a single dose (1–4 mg) of dexamethasone, and also show ~50 % increase in leptin levels following infusion of insulin under clamped euglycemic conditions. Evaluation of dynamic leptin secretion across a wide range of adiposity—in lean, obese, and massively obese individuals—indicates that the leptinemic responses to glucocorticoid and insulin are largely preserved in lean and obese persons but attenuated in massively obese individuals. Basal leptin levels lie within the expected range for BMI in people with diabetes. However, dynamic leptin levels in response to glucocorticoid challenge reveal a significant leptin secretory defect. Similarly, patients with diabetes show subnormal leptin secretory response to insulin. We propose the term “diabetic dysleptinemia” to describe the defective dynamic leptin secretion in patients with diabetes.