Download PDF
Exp Clin Endocrinol Diabetes 2005; 113(1): 49-52
DOI: 10.1055/s-2004-830527
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Effect of Pioglitazone on Lipids in Well Controlled Patients with Diabetes Mellitus Type 2 - Results of a Pilot Study

K. G. Parhofer1 , C. Otto1 , H. C. Geiss1 , E. Laubach1 , B. Göke1
  • 1Department of Internal Medicine II, Großhadern, Ludwig-Maximilians University, Munich, Germany
Further Information

Publication History

Received: December 12, 2003 First decision: March 25, 2004

Accepted: June 28, 2004

Publication Date:
21 January 2005 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction: Patients with diabetes mellitus type 2 are characterized by a typical dyslipoproteinemia. Improvement in glucose control usually also ameliorates this dyslipoproteinemia. It is unclear whether different antidiabetic strategies differ in their effects on the lipid profile. Particularly, it is unknown whether glitazones improve lipid values independently of their effects on glucose metabolism.

Methods: Ten patients well controlled on sulfonylureas (HbA1c 6.9 ± 0.5 %) with diabetic dyslipoproteinemia were treated with additional pioglitazone (30 mg/d) for 3 months. Every 4 weeks the sulfonylurea dose was adjusted to keep HbA1c and fasting glucose constant. Before and after 3 months of pioglitazone therapy lipid metabolism was determined in detail (cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, VLDL-triglycerides, lipoprotein(a), LDL-subtype distribution by isopycnic density gradient ultracentrifugation).

Results: Although glucose control remained unchanged (HbA1c 6.9 ± 0.5 % vs. 6.8 ± 0.6 %; fasting glucose concentration 7.7 ± 1.1 vs. 7.3 ± 1.3 mmol/l) we observed a significant reduction in triglyceride concentration (1.9 ± 0.6 vs. 1.4 ± 0.5 mmol/l, - 26 %, p < 0.01), a significant increase in HDL-cholesterol concentration (1.2 ± 0.2 vs. 1.4 ± 0.2 mmol/l, + 14 %, p < 0.05), a significant decrease in LDL/HDL-ratio (3.03 ± 0.77 vs. 2.51 ± 0.61, - 24 %, p < 0.05) and non-significant improvements in total cholesterol, LDL-cholesterol, VLDL-triglycerides, and VLDL-cholesterol concentrations. The LDL-subtype profile improved (significant reduction [- 20 %] in small dense LDL).

Conclusions: This pilot study indicates that at comparable fasting glucose concentration and at comparable HbA1c value pioglitazone is superior to sulfonylureas concerning the improvement of diabetic dyslipoproteinemia. Whether this relates to indirect effects (improvement in insulin sensitivity) or direct effects (stimulation of PPARα) remains to be determined.

Key words

Diabetic dyslipoproteinemia - glitazone - LDL-subtype - small dense LDL - thiazolidinedione

References

  • 1 Beckmann J A, Creager M A, Libby P. Diabetes and atherosclerosis epidemiology, pathophysiology, and management.  JAMA. 2002;  287 2570-2581
    CrossrefPubMedSearch in Google Scholar
  • 2 Camp H S. Thiazolidinediones in diabetes: current status and future outlook.  Curr Opin Investig Drugs. 2003;  4 406-411
    PubMedSearch in Google Scholar
  • 3 Chapman M J, Goldstein S, Lagrange D, Laplaud P M. A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum.  J Lipid Res. 1981;  22 339-358
    PubMedSearch in Google Scholar
  • 4 Goeke B. on behalf of the German Pioglitazone Study Group . Improved glycemic control and lipid profile in a randomized study of pioglitazone compared with acarbose in patients with type 2 diabetes mellitus.  Treat Endocrinol. 2002;  1 329-336
    PubMedSearch in Google Scholar
  • 5 Hanefeld M, Brunetti P, Schernthaner G, Mattews D, Charbonnel B. One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes.  Diab Care. 2004;  27 141-147
    CrossrefPubMedSearch in Google Scholar
  • 6 Keating G M, Ormrod D. Micronised fenofibrate: an updated review of its clinical efficacy in the management of dyslipidaemia.  Drugs. 2002;  62 1909-1944
    PubMedSearch in Google Scholar
  • 7 Lawrence J, Reid J, Taylor G, Stirling C, Reckless J. Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes.  Diab Care. 2004;  27 41-46
    CrossrefPubMedSearch in Google Scholar
  • 8 Satoh N, Ogawa Y, Usui T, Tagami T, Kono S, Uwaugi H, Sugiyama H, Sugawara A, Yamada K, Shimatsu A, Kuzuya H, Nakao K. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect.  Diab Care. 2003;  26 2493-2499
    CrossrefPubMedSearch in Google Scholar
  • 9 Schamberger B M, Geiss H C, Ritter M M, Schwandt P, Parhofer K G. Influence of LDL-apheresis on LDL-subtypes in patients with coronary heart disease and severe hyperlipoproteinemia.  J Lipid Res. 2000;  41 727-733
    PubMedSearch in Google Scholar
  • 10 Shelness G S, Sellers J A. Very-low-density lipoprotein assembly and secretion.  Curr Opin Lipidol. 2001;  2 151-157
    PubMedSearch in Google Scholar
  • 11 Taskinen M R. Diabetic dyslipidaemia: from basic research to clinical practice.  Diabetologia. 2003;  46 733-749
    CrossrefPubMedSearch in Google Scholar
  • 12 Winkler K, Konrad T, Fullert S, Friedrich I, Destani R, Baumstark M W, Krebs K, Wieland H, März W. Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study.  Diab Care. 2003;  26 2588-2594
    CrossrefPubMedSearch in Google Scholar

MD Klaus G. Parhofer

Medical Department II - Großhadern
University of Munich

Marchioninistraße 15

81377 Munich

Germany

Phone: + 498970953010

Fax: + 49 89 70 95 88 79

Email: Klaus.Parhofer@med.uni-muenchen.de