Leptin and body fat in type 2 diabetes and monodrug therapy.
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.
Sivitz
William I
WI
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
Wayson
Sheila M
SM
Bayless
Margaret L
ML
Larson
Linda F
LF
Sinkey
Christine
C
Bar
Robert S
RS
Haynes
William G
WG
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
D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D008687:Metformin