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The British Journal of Diabetes & Vascular Disease
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Pioglitazone — an oral antidiabetic agent and metabolic syndrome modulator. Can theory translate into practice?

Ian W Campbell

Department, Victoria Hospital, Kirkcaldy, Fife KY2 5AH, Scotland, UK, jackie.wallace{at}faht.scot.nhs.uk

The metabolic syndrome, associated with insulin resistance, is a cluster of cardiovascular risk factors which results in premature morbidity and mortality from atherosclerotic vascular disease. Pioglitazone, a peroxisome-proliferator-activated receptor gamma (PPAR{gamma}) agonist, is an insulin sensitiser with the ability to address key features of the metabolic syndrome: glucose intolerance including type 2 diabetes, hypertension, dyslipidaemia, the pro-coagulant state, endothelial dysfunction, inflammation and atherosclerosis. The greatest potential benefit of pioglitazone is to influence atherogenesis itself through its pleiotrophic effects on vascular risk factors. This has been tested by the PROactive study, results of which are published in September 2005.

Key Words: pioglitazone • insulin resistance • metabolic BET syndrome • pleiotrophic effects • atherogenesis • cardiovascular risk.

References

  • De Courten I., McCarty DJ, Zimmet P. Diagnosis, the scale of the problem and future risks. In: Hitman GA, eds. Type 2 Diabetes, Prediction, Prevention. Chichester: J Wiley, 2005:17-36.
  • Almdal T., Scharling H., Jensen JS, Vestergaard H. The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up. Arch Intern Med 2004;164:1422-6.[Abstract/Free Full Text]
  • Schernthaner G. Cardiovascular mortality and morbidity in type-2 diabetes mellitus. Diabetes Res Clin Pract 1996;31 Suppl:3-13.[CrossRef]
  • Campbell IW, Purcell H. The silent sextet. Br J Diabetes Vasc Dis 2001;1: 3-6.[Free Full Text]
  • Miyazaki Y., Mahankali A., Matsuda M. et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2002;87:2784-91.[Abstract/Free Full Text]
  • Rosenblatt S., Miskin B., Glazer NB, Prince MJ, Robertson KE The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus. Coron Artery Dis 2001;12:413-23.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Campbell IW The Clinical Significance of PPAR Gamma Agonism. Curr Mol Med 2005;5:349-63.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Tan MH, Baksi A., Krahulec B. et al. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care 2005;8:544-50.
  • Xiang AH, Peters R., Kjos S. et al. Continued protection from diabetes during treatment of the TRIPOD Cohort with pioglitazone. Diabetes 2003; 52(suppl 1):A75.
  • Lyon CJ, Law RE, Hsueh WA Minireview: adiposity, inflammation, and atherogenesis. Endocrinology 2003;144:2195-200.[Abstract/Free Full Text]
  • Pittas AG, Joseph NA, Greenberg AS Adipocytokines and insulin resisance. J Clin Endocrinol Metab 2004;89:447-52.[Free Full Text]
  • Melanson KJ, McInnis KJ, Rippe JM, Blackburn G., Wilson PF Obesity and cardiovascular disease risk: research update. Cardiol Rev 2001;9:202-07.[CrossRef][Medline] [Order article via Infotrieve]
  • Campbell IW Long-term glycaemic control with pioglitazone in patients with type 2 diabetes. Int J Clin Pract 2004;58:192-200.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Smith SR, De Jonge L., Volaufova J., Li Y., Xie H., Bray GA Effect of pioglitazone on body composition and energy expenditure: A randomized controlled trial. Metabolism 2005;54:24-32.[Web of Science][Medline] [Order article via Infotrieve]
  • Wajchenberg BL Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 2000;21:697-738.[Abstract/Free Full Text]
  • Matsuzawa Y., Nakamura T., Shimomura I., Kotani K. Visceral fat accumulation and cardiovascular disease. Obes Res 1995;3(suppl 5):645S-647S.[Medline] [Order article via Infotrieve]
  • Bajaj M., Suraamornkul S., Pratipanawatr T. et al. Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes 2003;52:1364-70.[Abstract/Free Full Text]
  • Rasouli N., Raue U., Miles LM et al. Pioglitazone improves insulin sensitivity through a reduction in muscle lipid and a redistribution of lipid into adipose tissue. Am J Physiol Endocrinol Metab 2005;288:930-4.
  • Laakso M. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes 1999;48:937-42.[Abstract]
  • Aronoff S., Rosenblatt S., Braithwaite S., Egan JW, Mathisen AL, Schneider RL 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]
  • Scherbaum WA, Goke B. Metabolic efficacy and safety of once-daily pioglitazone monotherapy in patients with type 2 diabetes: a double-blind, placebo-controlled study. Horm Metab Res 2002;34:589-95.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Schernthaner G., Matthews DR, Charbonnel B., Hanefeld M., Brunetti P. Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial. J Clin Endocrinol Metab 2004;89:6068-76.[Abstract/Free Full Text]
  • Charbonnel B., Matthews DR, Schernthaner G., Hanefeld M., Brunetti P., on behalf of QUARTET study group. A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial. Diabet Med 2005;22:399-405.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Goldberg RB, Kendall DM, Deeg MA et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Circulation 2005;111:1727.
  • Ceriello A., Johns D., Widel M., Eckland DJ, Gilmore KJ, Tan MH Comparison of effect of pioglitazone with metformin or sulfonylurea (monotherapy and combination therapy) on postload glycemia and composite insulin sensitivity index during an oral glucose tolerance test in patients with type 2 diabetes. Diabetes Care 2005;28:266-72.[Abstract/Free Full Text]
  • Einhorn D., Rendell M., Rosenzweig J., Egan JW, Mathisen AL, Schneider RL Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: a randomized, placebo-controlled study. The Pioglitazone 027 Study Group. Clin Ther 2000;22:1395-409.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kipnes MS, Krosnick A., Rendell MS, Egan JW, Mathisen AL, Schneider RL Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study. Am J Med 2001;111:10-17.[Web of Science][Medline] [Order article via Infotrieve]
  • Moules I., Edwards G., Mariz S., Urquhart R., Tan MH Two-year efficacy of the addition of pioglitzone to sulfonylurea therapy in patients with type 2 diabetes. American Diabetes Association 2004.
  • Edwards G., Urquhart R., Moules I., Tan MH, Mariz S. Two-year efficacy of pioglitazone versus gliclazide addition to metformin therapy in T2DM. American Diabetes Association 2004.
  • Konrad T., Lubben G., Franzen C. Pioglitazone lowers blood pressure in hypertensive patients with type 2 diabetes mellitus. American Diabetes Association 2004.
  • Gerber P., Lubben G., Heusler S., Dodo A. Effects of pioglitazone on metabolic control and blood pressure: a randomised study in patients with type 2 diabetes mellitus. Curr Med Res Opin 2003;19:532-9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hirose H., Kawai T., Yamamoto Y. et al. Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes. Metabolism 2002;51:31417.
  • Maruyama M., Terauchi M., Hayashi K., Yamamoto Y., Ishii T., Saruta T. Relation between the effect of pioglitazone treatment of glucose-lipid metabolism, blood pressure and abdominal fat distribution in Type 2 diabetes. Diabetes 2001;50(suppl 2):A125.[CrossRef]
  • Pavo I., Jermendy G., Varkonyi TT et al. Effect of pioglitazone compared with metformin on glycemic control and indicators of insulin sensitivity in recently diagnosed patients with type 2 diabetes. J Clin Endocrinol Metab 2003;88:1637-45.[Abstract/Free Full Text]
  • Goke B. 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;1:329-36.[CrossRef][Medline] [Order article via Infotrieve]
  • Adler AI, Stratton IM, Neil HA et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 2000;421:412-19.
  • Klausen K., Borch-Johnsen K., Feldt-Rasmussen B. et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 2004;110:32-5.[Abstract/Free Full Text]
  • Nakamura T., Matsuda T., Kawagoe Y. et al. Effect of pioglitazone on carotid intima-media thickness and arterial stiffness in type 2 diabetic nephropathy patients. Metabolism 2004;53:1382-6.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hanefeld M., Brunetti P., Schernthaner GH, Matthews DR, Charbonnel BH One-year glycemic control with a sulfonylurea plus pioglitazone versus a sulfonylurea plus metformin in patients with type 2 diabetes. Diabetes Care 2004;27:141-7.[Abstract/Free Full Text]
  • Laakso M., Lehto S., Penttila I., Pyorala K. Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes. Circulation 1993;88:1421-30.[Abstract/Free Full Text]
  • Taskinen MR LDL-cholesterol, HDL-cholesterol or triglycerides - which is the culprit? Diabetes Res Clin Pract 2003;61(suppl 1):S19-S26.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Assmann G., Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Munster study. Am J Cardiol 1992;70:733-7.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Moon YS, Kashyap ML Pharmacologic treatment of type 2 diabetic dyslipidemia. Pharmacotherapy 2004;24:1692-713.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Szapary PO, Rader DJ The triglyceride-high-density lipoprotein axis: an important target of therapy? Am Heart J 2004;148:211-21.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kendall DM The dyslipidemia of diabetes mellitus: giving triglycerides and high-density lipoprotein cholesterol a higher priority? Endocrinol Metab Clin North Am 2005;34:27-48.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cziraky MJ Management of dyslipidemia in patients with metabolic syndrome. J Am Pharm Assoc (Wash DC) 2004;44:478-88.[CrossRef]
  • Willson TM, Cobb JE, Cowan DJ et al. The structure-activity relationship between peroxisome proliferator-activated receptor agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem 1996;39:665-8.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bogacka I., Xie H., Bray GA, Smith SR Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 2005;54:1392-9.[Abstract/Free Full Text]
  • Sakamoto J., Kimura H., Moriyama S. et al. Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem Biophys Res Commun 2000;278:704-11.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA 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]
  • Ishizuka T., Ito O., Tan L. et al. Regulation of cytochrome P-450 4A activity by peroxisome proliferator-activated receptors in the rat kidney. Hypertens Res 2003;26:929-36.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Quin S., Liu T., Kamanna VS, Kashyap ML Pioglitazone stimulates apolipoprotein A-1 production without affecting HDL protein and cholesterol ester removal in HepG2 cells. Circulation 2004;110:III-37-8.
  • Chiquette E., Ramirez G., DeFronzo R. A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors. Arch Intern Med 2004;164:2097-104.[Abstract/Free Full Text]
  • Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004;351:1106-18.[Free Full Text]
  • van Wijk JP, de Koning EJ, Martens EP, Rabelink TJ Thiazolidinediones and blood lipids in type 2 diabetes. Arterioscler Thromb Vasc Biol 2003; 23:1744-9.[Abstract/Free Full Text]
  • Khan M., Xu Y., Edwards G., Urquhart R., Mariz S. Effects of pioglitazone on the components of diabetic dyslipidaemia: results of double-blind, multicentre, randomised studies. Int J Clin Pract 2004;58:907-12.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Nagashima K., Lopez C., Donovan D. et al. Effects of the PPARgamma agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus. J Clin Invest 2005;115:1323-32.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Khan MA, St Peter JV, Xue JL A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with type 2 diabetes who were previously treated with troglitazone. Diabetes Care 2002;25:708-11.[Abstract/Free Full Text]
  • Lawrence JM, Reid J., Taylor GJ, Stirling C., Reckless JPD.Favourable effects of pioglitazone and metformin on LDL subfractions in type 2 diabetes. Atherosclerosis 2003;169:358.
  • Winkler K., Konrad T., Fullert S. et al. Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. Diabetes Care 2003;26:2588-94.[Abstract/Free Full Text]
  • Jokl R., Laimins M., Klein RL, Lyons TJ, Lopes-Virella MF, Colwell JA Platelet plasminogen activator inhibitor 1 in patients with type II diabetes. Diabetes Care 1994;17:818-23.[Abstract]
  • Li D., Chen K., Sinha N. et al. The effects of PPAR-gamma ligand pioglitazone on platelet aggregation and arterial thrombus formation. Cardiovasc Res 2005;65:907-12.[Abstract/Free Full Text]
  • Kato K., Satoh H., Endo Y. et al. Thiazolidinediones down-regulate plasminogen activator inhibitor type 1 expression in human vascular endothelial cells: A possible role for PPARgamma in endothelial function. Biochem Biophys Res Commun 1999;258:431-5.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Yamakawa K., Hosoi M., Fukumoto S. et al. Pioglitazone inhibits plasminogen activator inhibitor-1 expression in human vascular smooth muscle cells. Diabetes 1998;47(suppl 1):A366.
  • Dunn EJ, Grant PJ Type 2 diabetes: an atherothrombotic syndrome. Curr Mol Med 2005;5:323-32.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ziegler D. Type 2 diabetes as an inflammatory cardiovascular disorder. Curr Mol Med 2005;5:309-22.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Tham DM, Wang YX, Rutledge JC Modulation of vascular inflammation by PPARs. Drug News Perspect 2003;16:109-16.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Satoh N., Ogawa Y., Usui T. et al. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 2003;26:2493-9.[Abstract/Free Full Text]
  • Miyazaki Y., Mahankali A., Wajcberg E., Bajaj M., Mandarino LJ, DeFronzo RA Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2004;89: 4312-19.[Abstract/Free Full Text]
  • Goldstein BJ, Scalia R. Adiponectin: A novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 2004;89:2563-8.[Abstract/Free Full Text]
  • Bajaj M., Suraamornkul S., Piper P. et al. Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients. J Clin Endocrinol Metab 2004;89:200-06.[Abstract/Free Full Text]
  • Koshiyama H., Shimono D., Kuwamura N., Minamikawa J., Nakamura Y. Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab 2001;86: 3452-6.[Abstract/Free Full Text]
  • Langenfeld M., Forst T., Hohberg C. et al. Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with type 2 diabetes mellitus. Circulation 2005;111:2525-31.[Abstract/Free Full Text]
  • UK Prospective Diabetes Study (UKPDS) Group. 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]
  • Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854-65.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Charbonnel B., Dormandy J., Erdmann E., Massi-Benedetti M., Skene A. The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients. Diabetes Care 2004;27:1647-53.[Abstract/Free Full Text]
  • Pyorala K., Pedersen TR, Kjekshus J., Faergeman O., Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997; 20:614-20.[Abstract]
  • Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703-13.[Abstract/Free Full Text]
  • Kannel WB, Neaton JD, Wentworth D. et al. Overall and coronary heart disease mortality rates in relation to major risk factors in 325,348 men screened for the MRFIT. Multiple Risk Factor Intervention Trial. Am Heart J 1986;112:825-36.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hansson L., Zanchetti A., Carruthers SG et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998;351:1755-62.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Matthews DR, Charbonnel BH, Hanefeld M., Brunetti P., Schernthaner G. Long-term therapy with addition of pioglitazone to metformin compared with the addition of gliclazide to metformin in patients with type 2 diabetes: a randomized comparative study. Diabetes Metab Res Rev 2005; 21:167-74.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

The British Journal of Diabetes & Vascular Disease, Vol. 5, No. 4, 209-216 (2005)
DOI: 10.1177/14746514050050040601
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Home page
 British Journal of Diabetes & Vascular DiseaseHome page
I. W Campbell
PROactive Study: PROspective pioglitAzone Clinical Trial In macroVascular Events
The British Journal of Diabetes & Vascular Disease, September 1, 2005; 5(5): 272 - 274.
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