title: Recombinant human leptin treatment does not improve insulin action in obese subjects with type 2 diabetes.
abstract: OBJECTIVE
  Leptin therapy improves insulin sensitivity in people with leptin deficiency, but it is not known whether it improves insulin action in people who are not leptin deficient. The purpose of the current study was to determine whether leptin treatment has weight loss-independent effects on insulin action in obese subjects with type 2 diabetes.
  
  
  METHODS
  We conducted a randomized, placebo-controlled trial in obese subjects (BMI: 35.4 ± 0.6 kg/m(2); mean ± SE) with newly diagnosed type 2 diabetes. Subjects were randomized to treatment with placebo (saline), low-dose (30 mg/day), or high-dose (80 mg/day) recombinant methionyl human (r-Met hu) leptin for 14 days. Multiorgan insulin sensitivity before and after treatment was evaluated by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusions to measure glucose, glycerol, and fatty acid kinetics.
  
  
  RESULTS
  Low-dose and high-dose leptin treatment resulted in a threefold (P < 0.01) and 150-fold (P < 0.001) increase in basal plasma leptin concentrations, respectively. However, neither low-dose nor high-dose therapy had an effect on insulin-mediated suppression of glucose, glycerol, or palmitate rates of appearance into plasma compared with placebo. In addition, leptin treatment did not increase insulin-mediated stimulation of glucose disposal compared with placebo (14.3 ± 3.1, 18.4 ± 3.6, 16.7 ± 2.4 vs. 17.5 ± 2.5, 20.7 ± 3.0, 19.1 ± 3.3 μmol/kg body wt/min before vs. after treatment in the placebo, low-dose, and high-dose leptin groups, respectively).
  
  
  CONCLUSIONS
  r-Met hu leptin does not have weight loss-independent, clinically important effects on insulin sensitivity in obese people with type 2 diabetes.
authors.affiliation: Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Mittendorfer
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Horowitz
authors.forename: Alex M
authors.initials: AM
authors.lastname: DePaoli
authors.forename: Mark A
authors.initials: MA
authors.lastname: McCamish
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Patterson
authors.forename: Samuel
authors.initials: S
authors.lastname: Klein
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D020738:Leptin / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D019308:Palmitic Acid / Q000097:blood; D010919:Placebos
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D010919:Placebos; D019308:Palmitic Acid; D005990:Glycerol