Plasma Adiponectin Plays an Important Role in Improving Insulin Resistance With Glimepiride in Elderly Type 2 Diabetic Subjects

Abstract

OBJECTIVE—We investigated the effect of glimepiride, a third-generation sulfonylurea hypoglycemic agent, on insulin resistance in elderly patients with type 2 diabetes, in connection with plasma adiponectin and 8-epi-prostagrandin F2α (8-epi-PGF2α), an oxidative stress marker.

RESEARCH DESIGN AND METHODS—A total of 17 elderly patients with type 2 diabetes received 12 weeks of treatment with glimepiride. Homeostasis assessment model of insulin resistance (HOMA-IR), homeostasis assessment model of β-cell function, HbA_1c, C-peptide in 24-h pooled urine (urine CPR), and plasma concentrations of 8-epi-PGF2α, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor type 1, and adiponectin were measured at various times. The metabolic clearance rate of glucose (MCR-g) was also assessed by a hyperinsulinemic-euglycemic clamp.

RESULTS—After 8 weeks of glimepiride treatment, significant reductions were observed in HbA_1c (from 8.4 ± 1.9 to 6.9 ± 1.0%), HOMA-IR (from 2.54 ± 2.25 to 1.69 ± 0.95%), and plasma TNF-α concentrations (from 4.0 ± 2.0 to 2.6 ± 2.5 pg/ml). MCR-g was significantly increased from 3.92 ± 1.09 to 5.73 ± 1.47 mg · kg⁻¹ · min⁻¹. Plasma adiponectin increased from 6.61 ± 3.06 to 10.2 ± 7.14 μg/ml. In control subjects, who maintained conventional treatment, no significant changes were observed in any of these markers.

CONCLUSIONS—Glimepiride remarkably improved insulin resistance, suggested by a significant reduction in HOMA-IR, an increase in MCR-g, and a reduction in HbA_1c without changing extrapancreatic β-cell function and urine CPR. Increased plasma adiponectin and decreased plasma TNF-α may underlie the improvement of insulin resistance with glimepiride.