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Free fatty acid-induced insulin resistance in the obese is not prevented by rosiglitazone treatment.

Dhindsa S, Tripathy D, Sanalkumar N, Ravishankar S, Ghanim H, Aljada A, Dandona P

Diabetes-Endocrinology Center of Western New York, Distinguished Chief of Endocrinology, State University of New York at Buffalo, 3 Gates Circle, Buffalo, New York 14209, USA.

OBJECTIVE: Elevation of free fatty acids (FFAs) by the infusion of triglyceride-heparin emulsion infusion (TG-Hep) causes insulin resistance (IR). We examined the effect of insulin sensitizer (rosiglitazone) on FFA-induced IR. DESIGN: Nine obese subjects underwent a 6-h infusion of TG-Hep before and after 6 wk of rosiglitazone (8 mg/d) treatment. Hyperinsulinemic euglycemic clamps were performed during 0-2 and 4-6 h of TG-Hep. RESULTS: After rosiglitazone for 6 wk, fasting FFA concentration fell, but not significantly (489 +/- 63 at 0 wk; 397 +/- 58 micromol/liter at 6 wk; P = 0.16), whereas C-reactive protein (4.26 +/- 0.95 at 0 wk; 2.03 +/- 0.45 microg/ml at 6 wk) and serum amyloid A (17.36 +/- 4.63 at 0 wk; 8.77 +/- 1.63 microg/ml at 6 wk) decreased significantly. At 0 wk, TG-Hep infusion caused a decrease in glucose infusion rate (GIR) from 4.49 +/- 0.95 mg/kg.min to 3.02 +/- 0.59 mg/kg.min (P = 0.018). Rosiglitazone treatment resulted in an increase in baseline GIR to 6.29 +/- 0.81 mg/kg.min (P = 0.03 vs. 0 wk), which decreased to 4.52 +/- 0.53 mg/kg.min (P = 0.001) after 6 h of TG-Hep infusion. The decrease in GIR induced by TG-Hep infusion was similar before and after rosiglitazone therapy [1.47 +/- 0.50 vs. 1.77 0.3 mg/kg.min (28.9 +/- 6.5 vs. 26.4 +/- 3.7%); P = 0.51]. The rise in FFAs and triglycerides after TG-Hep infusion was significantly lower at 6 wk (P = 0.006 for FFAs; P = 0.024 for triglycerides). CONCLUSIONS: We conclude that rosiglitazone: 1) causes a significant increase in GIR; 2) induces a decrease in inflammatory mediators, C-reactive protein, and serum amyloid A; 3) decreases the rise in FFAs and triglycerides after TG-Hep infusion; and 4) does not prevent FFA-induced IR.

Published 8 September 2005 in J Clin Endocrinol Metab, 90(9): 5058-63.
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