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Patients With Type 2 Diabetes Do Not Benefit From Leptin

Insulin sensitivity is not improved by low- or high-dose leptin in patients with type 2 diabetes

TUESDAY, May 17 (HealthDay News) -- Recombinant methionyl human (r-Met hu) leptin does not have clinically important effects on insulin sensitivity independent of weight loss in obese people with newly diagnosed type 2 diabetes, according to a study published in the May issue of Diabetes.

Bettina Mittendorfer, Ph.D., from the Washington University School of Medicine in St. Louis, and colleagues evaluated the effect of low- and high-dose leptin treatment on insulin sensitivity in 18 obese (average body mass index, 35.4 kg/m²) individuals with newly diagnosed type 2 diabetes. Participants were randomized to receive placebo (saline) or low-dose (30 mg/day) or high-dose (80 mg/day) r-Met hu leptin for 14 days. A hyperinsulinemic-euglycemic clamp procedure was used together with stable isotopically labeled tracer infusions to measure glucose, glycerol, and fatty acid kinetics in order to assess multiorgan insulin sensitivity before and after treatment.

The investigators found that basal plasma leptin concentrations increased three-fold and 150-fold with low- and high-dose leptin, respectively. Compared to placebo, leptin therapy did not affect insulin-mediated suppression of glucose, glycerol, or palmitate rates of appearance into plasma. Leptin treatment did not increase insulin-mediated stimulation of glucose disposal compared to placebo (average 14.3 µmol/kg body weight/minute before versus 17.5 after treatment for placebo, 18.4 versus 20.7 for low-dose leptin, and 16.7 versus 19.1 for high-dose leptin).

"We found that short-term treatment with either low-dose or high-dose r-Met hu leptin did not improve liver, skeletal muscle, or adipose tissue insulin sensitivity in weight-stable, obese subjects with type 2 diabetes," the authors write.

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