title: Leptin and body fat in type 2 diabetes and monodrug therapy.
abstract: 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; r(2) = 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.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Iowa City Veterans Affairs Medical Center and University of Iowa, Iowa City, Iowa 52246, USA. william-sivitz@uiowa.edu
authors.forename: William I
authors.initials: WI
authors.lastname: Sivitz
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Wayson
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Bayless
authors.forename: Linda F
authors.initials: LF
authors.lastname: Larson
authors.forename: Christine
authors.initials: C
authors.lastname: Sinkey
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bar
authors.forename: William G
authors.initials: WG
authors.lastname: Haynes
mesh_terms: D000273:Adipose Tissue; D001823:Body Composition; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D020738:Leptin / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged
chemical_list: D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D008687:Metformin