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Influence of Rosiglitazone Treatment on ß-Cell Function in Type 2 Diabetes: Evidence of an Increased Ability of Glucose to Entrain High-Frequency Insulin Pulsatility

Medical Department M (Endocrinology and Diabetes) (C.B.J., M.H., N.P., O.S.), Århus University Hospital, 8000 Århus, Denmark; Medical Department (C.B.J., A.P.), Kolding Sygehus, 6000 Kolding, Denmark; Center for Metabolism and Endocrinology (F.L.), Huddinge University Hospital, Karolinska Institute, 17177 Stockholm, Sweden; and Institute of Clinical Pharmacology (O.S.), University of Århus, Århus, Denmark

Address all correspondence and requests for reprints to: Claus B. Juhl, M.D., Medical Department M (Endocrinology and Diabetes), Århus University Hospital, Nørrebrogade 44, 8000 Århus C, Denmark. E-mail: cbj{at}dadlnet.dk.

Thiazolidinediones have well-established insulin-sensitizing effects. Their impact on insulin secretion is less clarified. Consequently, we sought to determine potential effects of a thiazolidinedione (rosiglitazone) on the ß-cell function. Twenty type 2 diabetic individuals were randomized to receive rosiglitazone (rosi) 4 mg twice daily or placebo (pla) for 13 wk. Before treatment and at the end of the treatment period, the patients underwent an iv glucose tolerance test (0.3 g/kg), a hyperglycemic (15 mmol/liter) clamp with arginine (5 g) stimulation, assessment of baseline high-frequency insulin pulsatility, and glucose-entrained insulin pulsatility (6 mg/kg·min every 10 min), and a hyperinsulinemic euglycemic clamp. Fasting plasma glucose was reduced (pla, 8.2 ± 2.1 vs. 8.8 ± 2.6 mmol/liter; rosi, 8.6 ± 7.1 vs. 7.1 ± 1.2 mmol/liter; P < 0.01), and insulin sensitivity was increased by rosiglitazone treatment (M value: pla, 5.3 ± 1.8 vs. 5.4 ± 1.6 mg/kg·min; rosi, 5.9 ± 2.2 vs. 7.4 ± 1.3 mg/kg·min; P = 0.05). First-phase insulin secretion and insulin secretory capacity were unaffected. Glucose-entrained insulin secretion was increased as assessed by spectral power analysis (P = 0.05). In conclusion, rosiglitazone treatment for 3 months in type 2 diabetic patients exerts no action on insulin secretion per se. Improved glucose-entrained high-frequency insulin pulsatility suggests an increased ability of the ß-cell to sense and respond to glucose changes within the physiological range.

This work was supported by Glaxo-SmithKline. F.L. was employed at Glaxo-SmithKline at the time of study conductance.

Abbreviations: ApEn, Approximate entropy; AUC, area(s) under the curve; IVGTT, iv glucose tolerance test; TZD, thiazolidinedione.

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