Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
The British Journal of Diabetes & Vascular Disease
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Winkler, K.
Right arrow Articles by März, W.
Right arrow Search for Related Content
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Pioglitazone reduces atherogenic dense low density lipoprotein (LDL) particles in patients with type 2 diabetes mellitus

Karl Winkler

Department of Clinical Chemistry, University of Freiburg, Germany, kwinkler{at}ukl.uni-freiburg.de

Isolde Friedrich

Department of Clinical Chemistry, University of Freiburg, Germany

Manfred W Baumstark

Department of Sports Medicine, University of Freiburg, Germany

Heinrich Wieland

Department of Clinical Chemistry, University of Freiburg, Germany

Winfried März

Department of Clinical Chemistry, University of Freiburg, Germany

Aim The new oral antidiabetic agent pioglitazone improves insulin sensitivity and glycaemic control, lowers triglycerides and increases high density lipoprotein (HDL) cholesterol in type 2 diabetes. The effect of pioglitazone on low density lipoprotein (LDL) subfractions is investigated, herein.

Methods The effect of pioglitazone monotherapy (45 mg o.d. for six months) on LDL subfractions was observed in 30 patients with poorly controlled type 2 diabetes (HbA1C ≥ 7.5% and < 11.5% and triglycerides ≥ 150 mg/dL). The distribution of LDL subfractions was determined by equilibrium density gradient ultracentrifugation before and during treatment.

Results HbA1C (9.5% before and 7.4% on treatment, p<0.001), triglycerides (-135 mg/dL [-32.2%], p=0.002) and apo B in LDL-6 (the most dense LDL subfraction) decreased significantly. The mean diameter of LDL particles increased (19.5 nm before and 19.8 nm on treatment, p=0.005), while the mean LDL density decreased significantly (from 1.0394 kg/L to 1.0381 kg/L on treatment; p=0.033). HDL increased from 36.3 mg/dL to 44.2 mg/dL (+ 21.6%, p<0.001). Total cholesterol and LDL-cholesterol did not change significantly.

Conclusions The results confirm that pioglitazone improves glycaemic control in patients with type 2 diabetes. In addition, pioglitazone reduced the proportion of atherogenic dense LDL. The effects of pioglitazone on lipoprotein metabolism may translate into a reduced risk for atherosclerotic complications in type 2 diabetes.

Key Words: pioglitazone • LDL-subfractions • atherogenic lipoprotein phenotype • triglycerides • high density lipoproteins.

References

  • Fuchtenbusch M., Standl E., Schatz H. Clinical efficacy of new thiazolidinediones and glinides in the treatment of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2000;108:151-63.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Miyazaki Y., Mahankali A., Matsuda M. et al. Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone. Diabetes Care 2001;24:710-19.[Abstract/Free Full Text]
  • Yamasaki Y., Kawamori R., Wasada T. et al. Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD-4833 Glucose Clamp Study Group, Japan. Tohoku J Exp Med 1997;183:173-83.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Aronoff S., Rosenblatt S., Braithwaite S. et al. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group. Diabetes Care 2000;23:1605-11.[Abstract/Free Full Text]
  • Eckland D., Danhof M. Clinical pharmacokinetics of pioglitazone. Exp Clin Endocrinol Diabetes 2000;108:S234-S42.[CrossRef][Web of Science]
  • Stamler J., Vaccaro O., Neaton JD, Wentworth D. Diabetes, Other Risk Factors, and 12-Yr Cardiovascular Mortality for Men Screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434-44.[Abstract]
  • Turner R., Cull C., Holman R. United Kingdom Prospective Diabetes Study 17: A 9-Year Update of a Randomized, Controlled Trial on the Effect of Improved Metabolic Control on Complications in Non-Insulin-dependent Diabetes Mellitus. Ann Intern Med 1996;124:136-45.[Abstract/Free Full Text]
  • Haffner SM, Lehto S., Ronnemaa T. et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction [see comments]. N Engl J Med 1998; 339:229-34.[Abstract/Free Full Text]
  • Haffner SM Management of dyslipidemia in adults with diabetes. Diabetes Care 1998;21:160-78.[Abstract]
  • Reaven GM, Chen Y-DI, Jeppesen J. et al. Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles. J Clin Invest 1993;92:141-6.[Web of Science][Medline] [Order article via Infotrieve]
  • Austin MA, Edwards KL Small, dense low density lipoprotein, and insulin resistance syndrome and noninsulin-dependent diabetes. Curr Opin Lipidol 1996;7:167-71.[Web of Science][Medline] [Order article via Infotrieve]
  • Austin MA, Breslow JL, Hennekens CH et al. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 1988;260:1917-21.[Abstract/Free Full Text]
  • Austin MA, King M.-C, Vranizian KM, Krauss RM The atherogenic lipoprotein phenotype: A proposed genetic marker for coronary heart disease risk. Circulation 1990;82:495-506.[Abstract/Free Full Text]
  • Campos H., Genest JJJ, Blijlevens E. et al. Low density lipoprotein particle size and coronary artery disease. Arterioscler Thromb Vasc Biol 1992;12: 187-95.[Abstract/Free Full Text]
  • Coresh J., Kwiterovich PO, Jr, Smith HH, Bachorik PS Association of plasma triglyceride concentration and LDL particle diameter, density, and chemical composition with premature coronary artery disease in men and women. J Lipid Res 1993;34:1687-97.[Abstract]
  • Griffin BA, Freeman DJ, Tait GW et al. Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk. Atherosclerosis 1994;106:241-53.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Gardner CD, Fortmann SP, Krauss RM Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA 1996;276:875-81.[Abstract/Free Full Text]
  • Stampfer MJ, Krauss RM, Ma J. et al. A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 1996;276:882-8.[Abstract/Free Full Text]
  • Lamarche B., Tchernof A., Moorjani S. et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Circulation 1997;95:69-75.[Abstract/Free Full Text]
  • Gray RS, Robbins DC, Wang W. et al. Relation of LDL size to the insulin resistance syndrome and coronary heart disease in American Indians. The Strong Heart Study. Arterioscler Thromb Vasc Biol 1997;17:2713-20.
  • Nigon F., Lesnik P., Rouis M., Chapman MJ Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor. J Lipid Res 1991;32:1741-53.[Abstract]
  • Anber V., Griffin BA, McConnell M., Packard CJ, Shepherd J. Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans. Atherosclerosis 1996;124:261-71.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Krauss RM The tangled web of coronary risk factors. Am J Med 1991; 90:36S-41S.[Medline] [Order article via Infotrieve]
  • Austin MA, Brunzell JD, Fitch WL, Krauss RM Inheritance of low density lipoprotein subclass patterns in familial combined hyperlipidemia. Arteriosclerosis 1990;10:520-30.[Abstract/Free Full Text]
  • McNamara JR, Jenner JL, Li Z., Wilson PW, Schaefer EJ Change in LDL particle size is associated with change in plasma triglyceride concentration. Arterioscler Thromb 1992;12:1284-90.[Abstract/Free Full Text]
  • Vakkilainen J., Makimattila S., Seppala-Lindroos A. et al. Endothelial dysfunction in men with small LDL particles. Circulation 2000;102:716-21.[Abstract/Free Full Text]
  • King AB A comparison in a clinical setting of the efficacy and side effects of three thiazolidinediones. Diabetes Care 2000;23:557.[Web of Science][Medline] [Order article via Infotrieve]
  • Tack C., Demacker P., Smits P., Stalenhoef A. Troglitazone decreases the proportion of small, dense LDL and increases the resistance of LDL to oxidation in obese subjects. Diabetes Care 1998;21:796-9.[Abstract]
  • Winkler K., Wetzka B., Hoffmann MM et al. Low density lipoprotein (LDL) subfractions during pregnancy: Accumulation of buoyant LDL with advancing gestation. J Clin Endocrinol Metab 2000;85:4543-50.[Abstract/Free Full Text]
  • Baumstark MW, Kreutz W., Berg A. et al. Structure of human low-density lipoprotein subfractions, determined by X-ray small-angle scattering. Biochim Biophys Acta 1990;1037:48-57.[CrossRef][Medline] [Order article via Infotrieve]
  • Watkins P., Whitcomb R. Hepatic dysfunction associated with troglitazone. N Engl J Med 1998;338:916-17.[Free Full Text]
  • Takeda Pharmaceuticals America IELaC. ACTOS Confronting the Challenges and Concerns of Type 2 Diabetes. A Product Monograph. 1999.
  • Belcher G., Matthews D. Safety and tolerability of pioglitazone. Exp Clin Endocrinol Diabetes 2000;108:S267-S73.[CrossRef][Web of Science]
  • Hirshberg B., Muszkat M., Marom T., Shalit M. Natural course of insulin edema. J Endocrinol Invest 2000;23:187-8.[Web of Science][Medline] [Order article via Infotrieve]
  • Group Updsu. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-53.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Vu-Dac N., Schoonjans K., Kosykh V. et al. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest 1995;96:741-50.[Web of Science][Medline] [Order article via Infotrieve]
  • Lehmann J., Moore L., Smith-Oliver T. et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 1995;270:12953-6.[Abstract/Free Full Text]
  • Murakami K., Tobe K., Ide T. et al. A novel insulin sensitizer acts as a coligand for peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. Diabetes 1998;47:1841-7.[Abstract]
  • Vu-Dac N., Schoonjans K., Laine B. et al. Negative regulation of the human apolipoprotein A-I promotor by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. J Biol Chem 1994;269:31012-18.[Abstract/Free Full Text]
  • Reaven G. Pathophysiology of insulin resistance in human disease. Physiol Rev 1995;75:473-86.[Abstract/Free Full Text]
  • Feingold K., Grunfeld C., Pang M. et al. LDL subclass phenotype and triglyceride metabolism in non-insulin dependent diabetes. Arterioscler Thromb Vasc Biol 1992;12:1496-502.[Abstract/Free Full Text]
  • Chen Y., Swami S., Skowronski R. et al. Effect of variations in dietary fat and carbohydrate intake on postprandial lipemia in patients with noninsulin dependent diabetes mellitus. J Clin Endocrinol Metab 1993;76:347-51.[Abstract]
  • Weiland D., Mondon C., Reaven G. Evidence for multiple causality in the development of diabetic hypertriglyceridaemia. Diabetologia 1980;18: 335-40.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Reaven G., Mondon C. Effect of in vivo plasma insulin levels on the relationship between perfusate free fatty acid concentration and triglyceride secretion by perfused rat livers. Horm Metab Res 1984;16:230-2.[Web of Science][Medline] [Order article via Infotrieve]
  • Reaven G. Insulin resistance - how important is it to treat? Exp Clin Endocrinol Diabetes 2000;108:S274-S80.[CrossRef][Web of Science]
  • Kletzien R., Clarke S., Ulrich R. Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol Pharmacol 1992;41:393-8.[Abstract]
  • Steinberg D., Parthasarathy S., Carew T. et al. Beyond cholesterol: modification of low density lipoprotein that increases its atherogenicity. N Engl J Med 1989;320:915-24.[Web of Science][Medline] [Order article via Infotrieve]
  • American Diabetes Association Position Statement. Standards of medical care for patients with diabetes mellitus. Diabetes Care 1999;22:S32-S41.[Web of Science]
  • Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.[Free Full Text]

The British Journal of Diabetes & Vascular Disease, Vol. 2, No. 2, 143-148 (2002)
DOI: 10.1177/14746514020020021301
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Diabetes CareHome page
M. A. Deeg, J. B. Buse, R. B. Goldberg, D. M. Kendall, A. J. Zagar, S. J. Jacober, M. A. Khan, A. T. Perez, M. H. Tan, and on behalf of the GLAI Study Investigators
Pioglitazone and Rosiglitazone Have Different Effects on Serum Lipoprotein Particle Concentrations and Sizes in Patients With Type 2 Diabetes and Dyslipidemia
Diabetes Care, October 1, 2007; 30(10): 2458 - 2464.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes and Vascular Disease ResearchHome page
A. Perez, M. Khan, T. Johnson, and M. Karunaratne
Pioglitazone plus a sulphonylurea or metformin is associated with increased lipoprotein particle size in patients with type 2 diabetes
Diabetes and Vascular Disease Research, May 1, 2004; 1(1): 44 - 50.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Winkler, K.
Right arrow Articles by März, W.
Right arrow Search for Related Content
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?