Pharmacological PPARγ Stimulation in Contrast to Beta Cell Stimulation Results in an Improvement in Adiponectin and Proinsulin Intact Levels and Reduces Intima Media Thickness in Patients with Type 2 Diabetes

T. Forst; C. Hohberg; S. D. Fuellert; G. Lübben; T. Konrad; M. Löbig; M. M. Weber; C. Sachara; V. Gottschall; A. Pfützner

doi:10.1055/s-2005-870322

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2005; 37(8): 521-527
DOI: 10.1055/s-2005-870322

Original Clinical

Pharmacological PPARγ Stimulation in Contrast to Beta Cell Stimulation Results in an Improvement in Adiponectin and Proinsulin Intact Levels and Reduces Intima Media Thickness in Patients with Type 2 Diabetes

T. Forst^1, ² , C. Hohberg¹ , S. D. Fuellert³ , G. Lübben⁴ , T. Konrad³ , M. Löbig¹ , M. M. Weber² , C. Sachara⁵ , V. Gottschall⁴ , A. Pfützner¹

¹ Institute for Clinical Research and Development, Mainz, Germany
² Johannes Gutenberg University, Dept. Endocrinology and Metabolism, Mainz, Germany
³ Institute for Metabolic Research, Frankfurt, Germany
⁴ TAKEDA Pharma, Aachen, Germany
⁵ ClinResearch, Cologne, Germany

Abstract

The role of intact proinsulin and adiponectin in endothelial dysfunction and insulin resistance has been receiving increasing attention. This study investigates the effect of PPARγ stimulation or beta-cell stimulation on metabolic and vascular parameters in patients with type 2 diabetes. In our study, 173 type 2 diabetic patients were recruited and randomly assigned to pioglitazone 45 mg or glimepiride 1 - 6 mg treatment. Intima media thickness of the carotid artery, glycemic control, insulin resistance, adiponectin and intact proinsulin levels were assessed at baseline and after six months of treatment. Despite similar improvements in metabolic control (HbA_1c after 24 weeks: - 0.8 ± 0.9 % [pioglitazone] vs. - 0.6 ± 0.8 % [glimepiride]; mean ± SD; p < 0.0001, respectively), improvements in intima media thickness (- 0.033 ± 0.052 mm; p < 0.0001), proinsulin intact (- 5.92 ± 10.04 pmol/l; p < 0.0001), adiponectin (10.9 ± 6.3 μg/ml; p < 0.0001) and HOMA score (- 2.21 ± 3.40; p < 0.0001) were observed by pioglitazone but not glimepiride treatment. Reduction in intima media thickness was correlated with improved insulin sensitivity (r = 0.29; p = 0.0003), and proinsulin intact levels (r = 0.22; p = 0.006), while an inverse correlation was found with adiponectin levels (r = - 0.37; p < 0.0001). Measurement of adiponectin and intact proinsulin enables characterization of the metabolic situation and an estimation of atherosclerotic risk in patients with type 2 diabetes.

Key words

Insulin resistance · Diabetes mellitus type 2 · Adiponectin · Intact proinsulin · Intima media thickness

Full Text

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