Leptin and Body Fat in Type 2 Diabetes and Monodrug Therapy

• Published in: The journal of clinical endocrinology and metabolism 2003-04, Vol.88 (4), p.1543-1553
• Main Authors: Sivitz, William I., Wayson, Sheila M., Bayless, Margaret L., Larson, Linda F., Sinkey, Christine, Bar, Robert S., Haynes, William G.
• Format: Article
• Language: English
• Subjects: Adipose Tissue; Biological and medical sciences; Body Composition; Body Mass Index; Cholesterol, HDL - blood; Cross-Over Studies; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Acids, Nonesterified - blood; Female; Glyburide - therapeutic use; Glycated Hemoglobin A - analysis; Humans; Hypoglycemic Agents - therapeutic use; Insulin - metabolism; Insulin Secretion; Leptin - blood; Male; Medical sciences; Metformin - therapeutic use; Middle Aged
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-021193

To better understand the relations among leptin, insulin, and body fat during the metabolic progression to diabetes and during drug monotherapy, metabolic parameters were examined in subjects classified as 1) type 2 diabetes; 2) impaired fasting glucose or mild diabetes mellitus; 3) nondiabetic, matched for body mass index (BMI); and 4) nonobese, nondiabetic. Diabetic subjects were also studied during no pharmacological treatment, after 3 months of randomization to metformin or glyburide, and after 3 months of cross-over to the opposite drug. Log leptin correlated more with percent body fat (slope, 0.042; confidence interval, 0.036–0.047; r2 = 0.826; P < 0.0001) than with total fat mass, percent truncal or nontruncal fat, or BMI. When normalized to percent fat, leptin did not differ by gender. Leptin normalized to percent fat was 35% less in untreated diabetes than that in BMI-matched controls (P < 0.001). Leptin normalized to percent fat was increased by 25% (P < 0.01) as a result of glyburide therapy compared with pretreatment values, but was unchanged by therapy with metformin. Across a spectrum of subjects with diabetes, impaired fasting glucose/mild diabetes, or BMI-matched nondiabetic controls, normalized leptin significantly correlated with glucose-induced insulin release, but not with insulin sensitivity. Our data suggest that plasma leptin is reduced in untreated type 2 diabetes probably as a consequence of reduced insulin secretion and that circulating leptin concentrations are differentially affected by monodrug therapy.