SAGE Journals Online
Advertisement
Sign In to gain access to subscriptions and/or personal tools.

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Advertisement

Sign In to gain access to subscriptions and/or personal tools.
Therapeutic Advances in Cardiovascular Disease
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
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 Similar articles in PubMed
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 Schindler, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schindler, C.
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?

Reviews

Review: The metabolic syndrome as an endocrine disease: is there an effective pharmacotherapeutic strategy optimally targeting the pathogenesis?

Christoph Schindler, MD

Institute of Clinical Pharmacology, Medical Faculty, Technical University of Dresden, Fiedlerstrasse 27, 01307 Dresden, Germany christoph.schindler@ tu-dresden.de

The metabolic syndrome (MetS) represents a combination of cardiovascular risk determinants such as obesity, insulin resistance and lipid abnormalities such as hypertriglyceridemia, increased free fatty acids, low high-density-cholesterol and hypertension. As a multiple component condition it imparts a doubling of relative risk for atherosclerotic cardiovascular disease (ASCVD). It is currently controversial which component of the syndrome carries what weight. There is even a considerable debate whether the risk for ASCVD is greater in patients diagnosed with MetS than that by the individual risk factors. At present, no unifying pathogenetic mechanism can explain the metabolic syndrome and there is no unique treatment for it. This review summarizes and critically reviews the currently available clinical and scientific evidence for the concept that the MetS is causally an endocrine disease and discusses pharmacotherapeutic strategies targeting the pathogenesis rather than single symptoms of the cluster.

Key Words: Metabolic syndrome • obesity • hypertension • insulin resistance • pharmacotherapy.

References

  • Adamczak, M. et al. (2003) Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens 16: 72—75.[CrossRef][Medline] [Order article via Infotrieve]
  • Agarwal, R. et al. (2006) Anti-inflammatory effects of short-term pioglitazone therapy in men with advanced diabetic nephropathy. Am J Physiol Renal Physiol 290: F600—605.[Abstract/Free Full Text]
  • Alberti, K.G. et al. (2006) Metabolic syndrome — a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 23: 469—480.[CrossRef][Medline] [Order article via Infotrieve]
  • Alberti, K.G. et al. (2005) The metabolic syndrome—a new worldwide definition. Lancet 366: 1059—1062.[CrossRef][Medline] [Order article via Infotrieve]
  • Alberti, K.G. and Zimmet, P.Z. (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15: 539—553.[CrossRef][Medline] [Order article via Infotrieve]
  • Aljada, A. et al. (2001) Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action? J Clin Endocrinol Metab 86: 3250—3256.[Abstract/Free Full Text]
  • Allikmets, K. et al. (1996) Association between plasma renin activity and metabolic cardiovascular risk factors in essential hypertension. J Intern Med 239: 49—55.[CrossRef][Medline] [Order article via Infotrieve]
  • Alwan, A. and King, H. (1999) Definition, diagnosis and Classification of Diabetes Mellitus and its Complications. Part I: Diagnosis and Classification of Diabetes Mellitus. Report of a WHO consultation.
  • Arita, Y. et al. (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257: 79—83.[CrossRef][Medline] [Order article via Infotrieve]
  • Aronne, L.J. (2007) Therapeutic options for modifying cardiometabolic risk factors. Am J Med 120: S26—34.[Medline] [Order article via Infotrieve]
  • Aubert, H. et al. (2003) Weak and non-independent association between plasma TAFI antigen levels and the insulin resistance syndrome. J Thromb Haemost 1: 791—797.[CrossRef][Medline] [Order article via Infotrieve]
  • Balakumar, P. et al. (2007) PPAR dual agonists: Are they opening Pandora's Box? Pharmacol Res.
  • Balkau, B. et al. (2002) Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. Diabetes Metab 28: 364—376.[Medline] [Order article via Infotrieve]
  • Balkau, B. and Charles, M.A. (1999) Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 16: 442—443.[CrossRef][Medline] [Order article via Infotrieve]
  • Banerji, M.A. et al. (1997) Relationship of visceral adipose tissue and glucose disposal is independent of sex in black NIDDM subjects. Am J Physiol 273: E425—432.[Medline] [Order article via Infotrieve]
  • Banos, G. et al. (1997) Vascular reactivity and effect of serum in a rat model of hypertriglyceridemia and hypertension. Am J Hypertens 10: 379—388.[Medline] [Order article via Infotrieve]
  • Barish, G.D. et al. (2006) PPAR delta: a dagger in the heart of the metabolic syndrome. J Clin Invest 116: 590—597.[CrossRef][Medline] [Order article via Infotrieve]
  • Barnett, A.H. et al. (2004) Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 351: 1952—1961.[Abstract/Free Full Text]
  • Baron, A.D. (1996) Insulin and the vasculature—old actors, new roles. J Invest Med 44: 406—412.[Medline] [Order article via Infotrieve]
  • Baroni, M.G. et al. (2001) The G972R variant of the insulin receptor substrate-1 (IRS-1) gene, body fat distribution and insulin-resistance. Diabetologia 44: 367—372.[CrossRef][Medline] [Order article via Infotrieve]
  • Benlian, P. et al. (1996) Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene. N Engl J Med 335: 848—854.[Abstract/Free Full Text]
  • Bergman, R.N. et al. (2007) Abdominal obesity: role in the pathophysiology of metabolic disease and cardiovascular risk. Am J Med 120: S3—8; discussion S29—32.[CrossRef]
  • Bestermann, W. et al. (2005) Addressing the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome in the southeastern United States, part II: treatment recommendations for management of the global cardiovascular risk of hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome. Am J Med Sci 329: 292—305.[CrossRef][Medline] [Order article via Infotrieve]
  • Bigaard, J. et al. (2005) Waist circumference and body composition in relation to all-cause mortality in middle-aged men and women. Int J Obes (Lond) 29: 778—784.[CrossRef][Medline] [Order article via Infotrieve]
  • Blaschke, F. et al. (2006) Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler Thromb Vasc Biol 26: 28—40.[Abstract/Free Full Text]
  • Boden, G. and Shulman, G.I. (2002) Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur J Clin Invest 32 (Suppl 3): 14—23.[CrossRef][Medline] [Order article via Infotrieve]
  • Brousseau, M.E. et al. (2004) Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med 350: 1505—1515.[Abstract/Free Full Text]
  • Brunner, H.R. et al. (1972) Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med 286: 441—449.[Medline] [Order article via Infotrieve]
  • Bruno, G. et al. (2004) Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study. Diabetes Care 27: 2689—2694.[Abstract/Free Full Text]
  • Cardillo, C. et al. (2002a) Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation 106: 1783—1787.[Abstract/Free Full Text]
  • Cardillo, C. et al. (2002b) Improved endothelium-dependent vasodilation after blockade of endothelin receptors in patients with essential hypertension. Circulation 105: 452—456.[Abstract/Free Full Text]
  • Chobanian, A.V. et al. (2003) The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. J Am Med Assoc 289: 2560—2572.[Abstract/Free Full Text]
  • Clark, J.M. (2006) The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 40: S5—10.[Medline] [Order article via Infotrieve]
  • Colditz, G.A. et al. (1995) Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 122: 481—486.[Abstract/Free Full Text]
  • Criqui, M.H. et al. (1993) Plasma triglyceride level and mortality from coronary heart disease. N Engl J Med 328: 1220—1225.[Abstract/Free Full Text]
  • Dallongeville, J. et al. (2003) The Gly16—>Arg16 and Gln27—> Glu27 polymorphisms of beta2-adrenergic receptor are associated with metabolic syndrome in men. J Clin Endocrinol Metab 88: 4862—4866.[Abstract/Free Full Text]
  • Davidson, M.H. et al. (1999) Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. J Am Med Assoc 281: 235—242.[Abstract/Free Full Text]
  • de Dios, S.T. et al. (2003) Inhibitory activity of clinical thiazolidinedione peroxisome proliferator activating receptor-gamma ligands toward internal mammary artery, radial artery, and saphenous vein smooth muscle cell proliferation. Circulation 107: 2548—2550.[Abstract/Free Full Text]
  • Deedwania, P.C. and Fonseca, V.A. (2005) Diabetes, prediabetes, and cardiovascular risk: shifting the paradigm. Am J Med 118: 939—947.[CrossRef][Medline] [Order article via Infotrieve]
  • DeFronzo, R.A. and Ferrannini, E. (1991) Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: 173—194.[Abstract]
  • Despres, J.P. et al. (2005) Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 353: 2121—2134.[Abstract/Free Full Text]
  • Despres, J.P. et al. (1996) Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 334: 952—957.[Abstract/Free Full Text]
  • Diamanti-Kandarakis, E. et al. (2001) Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy. J Clin Endocrinol Metab 86: 4666—4673.[Abstract/Free Full Text]
  • Egan, B.M. et al. (1994) Renin and aldosterone are higher and the hyperinsulinemic effect of salt restriction greater in subjects with risk factors clustering. Am J Hypertens 7: 886—893.[Medline] [Order article via Infotrieve]
  • Ehrmann, D.A. et al. (2006) Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 91: 48—53.[Abstract/Free Full Text]
  • Einhorn, D. et al. (2003) American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 9: 237—252.[Medline] [Order article via Infotrieve]
  • Epstein, M. and Sowers, J.R. (1992) Diabetes mellitus and hypertension. Hypertension 19: 403—418.[Abstract/Free Full Text]
  • Evans, R.M. et al. (2004) PPARs and the complex journey to obesity. Nat Med 10: 355—361.[CrossRef][Medline] [Order article via Infotrieve]
  • Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) (2001) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). J Am Med Assoc 285: 2486—2497.[Free Full Text]
  • Farooqi, I.S. et al. (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110: 1093—1103.[CrossRef][Medline] [Order article via Infotrieve]
  • Ferrannini, E. et al. (1987) Insulin resistance in essential hypertension. N Engl J Med 317: 350—357.[Abstract]
  • Ferrannini, E. (2007) Metabolic syndrome: a solution in search of a problem. J Clin Endocrinol Metab 92: 396—398.[Free Full Text]
  • Festa, A. et al. (2000) Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102: 42—47.[Abstract/Free Full Text]
  • Folli, F. et al. (1997) Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. J Clin Invest 100: 2158—2169.[Medline] [Order article via Infotrieve]
  • Fonseca, V.A. (2005) The metabolic syndrome, hyperlipidemia, and insulin resistance. Clin Cornerstone 7: 61—72.[CrossRef][Medline] [Order article via Infotrieve]
  • Ford, E.S. et al. (2004) Increasing prevalence of the metabolic syndrome among U.S. Adults. Diabetes Care 27: 2444—2449.[Abstract/Free Full Text]
  • Forman, B.M. et al. (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA 94: 4312—4317.[Abstract/Free Full Text]
  • Franks, P.W. and Olsson, T. (2007) Metabolic syndrome and early death: getting to the heart of the problem. Hypertension 49: 10—12.[Free Full Text]
  • Freeman, D.J. et al. (2001) Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 103: 357—362.[Abstract/Free Full Text]
  • Frittitta, L. et al. (2001) The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance. J Clin Endocrinol Metab 86: 5888—5891.[Abstract/Free Full Text]
  • Fumeron, F. et al. (2004) Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study. Diabetes 53: 1150—1157.[Abstract/Free Full Text]
  • Gentili, M. et al. (2001) Distinct expression of endothelin receptor subtypes A and B in luteinized human granulosa cells. Horm Metab Res 33: 573—576.[CrossRef][Medline] [Order article via Infotrieve]
  • Gill, H. et al. (2005) The key role of insulin resistance in the cardiometabolic syndrome. Am J Med Sci 330: 290—294.[CrossRef][Medline] [Order article via Infotrieve]
  • Ginsberg, H.N. (2003) Treatment for patients with the metabolic syndrome. Am J Cardiol 91: 29E—39E.[CrossRef][Medline] [Order article via Infotrieve]
  • Goodfriend, T.L. et al. (1995) Relationships among plasma aldosterone, high-density lipoprotein cholesterol, and insulin in humans. Hypertension 25: 30—36.[Abstract/Free Full Text]
  • Govindarajan, G. et al. (2005) The cardiometabolic syndrome as a cardiovascular risk factor. Am J Med Sci 330: 311—318.[CrossRef][Medline] [Order article via Infotrieve]
  • Grundy, S.M. et al. (2004) Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109: 433—438.[Free Full Text]
  • Grundy, S.M. et al. (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112: 2735—2752.[Free Full Text]
  • Haffner, S.M. et al. (2002) Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 106: 679—684.[Abstract/Free Full Text]
  • Hanefeld, M. et al. (2007) [History and definition(s) of metabolic syndrome.]. Internist (Berl) 48: 117—125.[CrossRef][Medline] [Order article via Infotrieve]
  • Hegele, R.A. (2003) Monogenic forms of insulin resistance: apertures that expose the common metabolic syndrome. Trends Endocrinol Metab 14: 371—377.[CrossRef][Medline] [Order article via Infotrieve]
  • Hokanson, J.E. and Austin, M.A. (1996) Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 3: 213—219.[Medline] [Order article via Infotrieve]
  • Houston, M.C. et al. (2005) Addressing the global cardiovascular risk of hypertension, dyslipidemia, and insulin resistance in the southeastern United States. Am J Med Sci 329: 276—291.[CrossRef][Medline] [Order article via Infotrieve]
  • Hubert, H.B. et al. (1983) Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 67: 968—977.[Abstract/Free Full Text]
  • Hunt, K.J. et al. (2004) National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 110: 1251—1257.[Abstract/Free Full Text]
  • Isomaa, B. et al. (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24: 683—689.[Abstract/Free Full Text]
  • Jacob, S. et al. (1996) Effects of trandolapril and verapamil on glucose transport in insulin-resistant rat skeletal muscle. Metabolism 45: 535—541.[CrossRef][Medline] [Order article via Infotrieve]
  • James, W.P. et al. (2000) Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 356: 2119—2125.[CrossRef][Medline] [Order article via Infotrieve]
  • Jeppesen, J. et al. (2000) High triglycerides and low HDL cholesterol and blood pressure and risk of ischemic heart disease. Hypertension 36: 226—232.[Abstract/Free Full Text]
  • Jiang, C. et al. (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391: 82—86.[CrossRef][Medline] [Order article via Infotrieve]
  • Kahn, R. et al. (2005) The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 28: 2289—2304.[Abstract/Free Full Text]
  • Kasper, S.O. et al. (2006) Rats with low brain angiotensinogen do not exhibit insulin resistance during early aging. Endocrine 30: 167—174.[CrossRef][Medline] [Order article via Infotrieve]
  • Keating, G.M. and Croom, K.F. (2007) Fenofibrate: a review of its use in primary dyslipidaemia, the metabolic syndrome and type 2 diabetes mellitus. Drugs 67: 121—153.[CrossRef][Medline] [Order article via Infotrieve]
  • Keech, A. et al. (2005) Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366: 1849—1861.[CrossRef][Medline] [Order article via Infotrieve]
  • Kendall, D.M. et al. (2006) Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: A double-blind, randomized, pioglitazone-comparative study. Diabetes Care 29: 1016—1023.[Abstract/Free Full Text]
  • Kim, S. et al. (2001) Angiotensin II-responsive element is the insulin-responsive element in the adipocyte fatty acid synthase gene: role of adipocyte determination and differentiation factor 1/sterol-regulatory-element-binding protein 1c. Biochem J 357: 899—904.[CrossRef][Medline] [Order article via Infotrieve]
  • Kissebah, A.H. and Krakower, G.R. (1994) Regional adiposity and morbidity. Physiol Rev 74: 761—811.[Free Full Text]
  • Klover, P.J. et al. (2003) Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 52: 2784—2789.[Abstract/Free Full Text]
  • Laclaustra, M. et al. (2007) 17 Metabolic syndrome pathophysiology: the role of adipose tissue. Nutr Metab Cardiovasc Dis 125—139.
  • Lau, D.C. et al. (2005) Adipokines: molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol 288: H2031—41.[Abstract/Free Full Text]
  • Law, R.E. et al. (2000) Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation 101: 1311—1318.[Abstract/Free Full Text]
  • Le Roith, D. and Zick, Y. (2001) Recent advances in our understanding of insulin action and insulin resistance. Diabetes Care 24: 588—597.[Abstract/Free Full Text]
  • Lee, C.H. et al. (2003) Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science 302: 453—457.[Abstract/Free Full Text]
  • Lee, I.M. et al. (1993) Body weight and mortality. A 27-year follow-up of middle-aged men. J Am Med Assoc 270: 2823—2828.[Abstract/Free Full Text]
  • Lelliott, C. and Vidal-Puig, A.J. (2004) Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation. Int J Obes Relat Metab Disord 28 Suppl 4: S22—28.[CrossRef]
  • Lembo, G. et al. (1994) Insulin blunts sympathetic vasoconstriction through the alpha 2-adrenergic pathway in humans. Hypertension 24: 429—438.[Abstract/Free Full Text]
  • Lexchin, J. (2001) Lifestyle drugs: issues for debate. Cmaj 164: 1449—1451.[Free Full Text]
  • Li, A.C. et al. (2000) Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin Invest 106: 523—531.[Medline] [Order article via Infotrieve]
  • Libby, P. and Plutzky, J. (2007) Inflammation in diabetes mellitus: role of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma agonists. Am J Cardiol 99: 27B—40B.[Medline] [Order article via Infotrieve]
  • Lind, L. et al. (1992) Metabolic cardiovascular risk factors and the renin-aldosterone system in essential hypertension. J Hum Hypertens 6: 27—29.[Medline] [Order article via Infotrieve]
  • Lind, L. et al. (1998) Insulin resistance in essential hypertension is related to plasma renin activity. J Hum Hypertens 12: 379—382.[CrossRef][Medline] [Order article via Infotrieve]
  • Lorenzo, C. et al. (2005) The prevalence of the metabolic syndrome did not increase in Mexico City between 1990—1992 and 1997—1999 despite more central obesity. Diabetes Care 28: 2480—2485.[Abstract/Free Full Text]
  • Luscher, T.F. and Barton, M. (2000) Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation 102: 2434—2440.[Abstract/Free Full Text]
  • Lutchman, G. et al. (2007)The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology.
  • Mancia, G. et al. (2007) Metabolic syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study: daily life blood pressure, cardiac damage, and prognosis. Hypertension 49: 40—47.[Abstract/Free Full Text]
  • Marx, N. et al. (2004) Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells. Circ Res 94: 1168—1178.[Abstract/Free Full Text]
  • Marx, N. et al. (2003) Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 23: 283—288.[Abstract/Free Full Text]
  • Marx, N. et al. (2003) Effect of rosiglitazone treatment on soluble CD40L in patients with type 2 diabetes and coronary artery disease. Circulation 107: 1954—1957.[Abstract/Free Full Text]
  • Marx, N. et al. (1998) Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 83: 1097—1103.[Abstract/Free Full Text]
  • Marx, N. et al. (1998) Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro. Am J Pathol 153: 17—23.[Abstract/Free Full Text]
  • McFarlane, S.I. et al. (2001) Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab 86: 713—718.[Free Full Text]
  • McFarlane, S.I. et al. (2003) Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascular disease. Am J Cardiol 91: 30H—37H.[Medline] [Order article via Infotrieve]
  • McFarlane, S.I. et al. (2002) Clinical review 145: Pleiotropic effects of statins: lipid reduction and beyond. J Clin Endocrinol Metab 87: 1451—1458.[Abstract/Free Full Text]
  • McNeill, A.M. et al. (2005) The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care 28: 385—390.[Abstract/Free Full Text]
  • Mehta, J.L. et al. (2003) Pioglitazone inhibits LOX-1 expression in human coronary artery endothelial cells by reducing intracellular superoxide radical generation. Arterioscler Thromb Vasc Biol 23: 2203—2208.[Abstract/Free Full Text]
  • Mohanty, P. et al. (2004) Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab 89: 2728—2735.[Abstract/Free Full Text]
  • Morgan, D.A. et al. (1995) Renal sympathetic nerve activity is increased in obese Zucker rats. Hypertension 25: 834—883.[Abstract/Free Full Text]
  • Morris, R.S. et al. (1995) Prorenin is elevated in polycystic ovary syndrome and may reflect hyperandrogenism. Fertil Steril 64: 1099—1103.[Medline] [Order article via Infotrieve]
  • Motoshima, H. et al. (2004) Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun 315: 264—271.[CrossRef][Medline] [Order article via Infotrieve]
  • Nawano, M. et al. (1999) Imidapril, an angiotensin-converting enzyme inhibitor, improves insulin sensitivity by enhancing signal transduction via insulin receptor substrate proteins and improving vascular resistance in the Zucker fatty rat. Metabolism 48: 1248—1255.[CrossRef][Medline] [Order article via Infotrieve]
  • Opar, A. (2007) Where now for new drugs for atherosclerosis? Nat Rev Drug Discov 6: 334—335.[CrossRef][Medline] [Order article via Infotrieve]
  • Organization WH (1999) Diagnosis, and Classification of Diabetes Mellitus and its Complications. Report of a WHO consultation.
  • Pasceri, V. et al. (2000) Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation 101: 235—238.[Abstract/Free Full Text]
  • Phillips, G.B. et al. (1995) Serum sex hormone levels and renin-sodium profile in men with hypertension. Am J Hypertens 8: 626—629.[CrossRef][Medline] [Order article via Infotrieve]
  • Piatti, P.M. et al. (1996) Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans. Diabetes 45: 316—321.[Abstract]
  • Pi-Sunyer, F.X. et al. (2006) Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. J Am Med Assoc 295: 761—775.[Abstract/Free Full Text]
  • Reaven, G.M. (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37: 1595—1607.[Abstract]
  • Reaven, G.M. (2006) The metabolic syndrome: is this diagnosis necessary? Am J Clin Nutr 83: 1237—1247.[Abstract/Free Full Text]
  • Reckelhoff, J.F. (2007) Polycystic ovary syndrome: androgens and hypertension. Hypertension 49: 1220—1221.[Free Full Text]
  • Resnick, H.E. et al. (2003) Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease in nondiabetic american indians: the Strong Heart Study. Diabetes Care 26: 861—867.[Abstract/Free Full Text]
  • Ricote, M. et al. (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391: 79—82.[CrossRef][Medline] [Order article via Infotrieve]
  • Ronti, T. et al. (2006) The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf) 64: 355—365.[Medline] [Order article via Infotrieve]
  • Rosen, E.D. et al. (2000) Transcriptional regulation of adipogenesis. Genes Dev 14: 1293—1307.[Free Full Text]
  • Ruderman, N. et al. (1998) The metabolically obese, normal-weight individual revisited. Diabetes 47: 699—713.[Abstract]
  • Saltiel, A.R. and Olefsky, J.M. (1996) Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 45: 1661—1669.[Abstract]
  • Sarafidis, P.A. and Bakris, G.L. (2007) Review: Insulin and endothelin: an interplay contributing to hypertension development? J Clin Endocrinol Metab 92: 379—385.[Abstract/Free Full Text]
  • Sartori, C. and Scherrer, U. (1999) Insulin, nitric oxide and the sympathetic nervous system: at the crossroads of metabolic and cardiovascular regulation. J Hypertens 17: 1517—1525.[Medline] [Order article via Infotrieve]
  • Sattar, N. et al. (2003) Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 108: 414—419.[Abstract/Free Full Text]
  • Schaumberg, D.A. et al. (2005) Effect of intensive glycemic control on levels of markers of inflammation in type 1 diabetes mellitus in the diabetes control and complications trial. Circulation 111: 2446—2453.[Abstract/Free Full Text]
  • Scheen, A.J. et al. (2006) Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet 368: 1660—1672.[CrossRef][Medline] [Order article via Infotrieve]
  • Schindler, C. et al. (2007) Role of the vasodilator peptide angiotensin-(1—7) in cardiovascular drug therapy. Vasc Health Risk Manag 3: 125—137.[Medline] [Order article via Infotrieve]
  • Schindler, C. et al. (2007) Comparison of inhibitory effects of irbesartan and atorvastatin treatment on the renin angiotensin system (RAS) in veins: a randomized double-blind crossover trial in healthy subjects. J Clin Pharmacol 47: 112—120.[Abstract/Free Full Text]
  • Schneider, M.P. et al. (2003) Effect of elevated triglyceride levels on endothelium-dependent vasodilation in patients with hypercholesterolemia. Am J Cardiol 91: 482—484.[CrossRef][Medline] [Order article via Infotrieve]
  • Schrauwen, P. and Hesselink, M.K. (2004) Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. Diabetes 53: 1412—1417.[Abstract/Free Full Text]
  • Schupp, M. et al. (2004) Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation 109: 2054—2057.[Abstract/Free Full Text]
  • Sharma, A.M. et al. (2002) Angiotensin blockade prevents type 2 diabetes by formation of fat cells. Hypertension 40: 609—611.[Abstract/Free Full Text]
  • Sharma, A.M. (2004) Is there a rationale for angiotensin blockade in the management of obesity hypertension? Hypertension 44: 12—19.[Abstract/Free Full Text]
  • Shen, D.C. et al. (1988) Resistance to insulin-stimulated-glucose uptake in patients with hypertension. J Clin Endocrinol Metab 66: 580—583.[Abstract/Free Full Text]
  • Sinha, R. et al. (2002) Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 346: 802—810.[Abstract/Free Full Text]
  • Sjostrom, L. et al. (1998) Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet 352: 167—172.[CrossRef][Medline] [Order article via Infotrieve]
  • Sowers, J.R. et al. (1994) Role of insulin resistance and hyperinsulinemia in development of hypertension and atherosclerosis. J Lab Clin Med 123: 647—652.[Medline] [Order article via Infotrieve]
  • Sowers, J.R. (1997a) Insulin and insulin-like growth factor in normal and pathological cardiovascular physiology. Hypertension 29: 691—699.[Free Full Text]
  • Sowers, J.R. (1997b) Effects of calcium antagonists on insulin sensitivity and other metabolic parameters. Am J Cardiol 79: 24—28; discussion 47—48.[Medline] [Order article via Infotrieve]
  • Sowers. J.R. (2001) Update on the cardiometabolic syndrome. Clin Cornerstone 4: 17—23.[CrossRef][Medline] [Order article via Infotrieve]
  • Sowers, J.R. et al. (2001) Diabetes, hypertension, and cardiovascular disease: an update. Hypertension 37: 1053—1059.[Abstract/Free Full Text]
  • Sowers, J.R. (2004a) Insulin resistance and hypertension. Am J Physiol Heart Circ Physiol 286: H1597—1602.[Abstract/Free Full Text]
  • Sowers, J.R. and Frohlich, E.D. (2004b) Insulin and insulin resistance: impact on blood pressure and cardiovascular disease. Med Clin North Am 88: 63—82.[CrossRef][Medline] [Order article via Infotrieve]
  • Steppan, C.M. et al. (2001) The hormone resistin links obesity to diabetes. Nature 409: 307—312.[CrossRef][Medline] [Order article via Infotrieve]
  • Stolar, M. (2007) Metabolic syndrome: controversial but useful. Cleve Clin J Med 74: 199—202, 205—208.
  • Sung, R.Y. et al. (2003) High prevalence of insulin resistance and metabolic syndrome in overweight/ obese preadolescent Hong Kong Chinese children aged 9—12 years. Diabetes Care 26: 250—251.[Free Full Text]
  • Szmitko, P.E. et al. (2007) Adiponectin and cardiovascular disease: state of the art? Am J Physiol Heart Circ Physiol 292: H1655—1663.[Abstract/Free Full Text]
  • Tack, C.J. et al. (1996) Direct vasodilator effects of physiological hyperinsulin-aemia in human skeletal muscle. Eur J Clin Invest 26: 772—778.[CrossRef][Medline] [Order article via Infotrieve]
  • Tanaka, S. et al. (2003) Ethnic differences in abdominal visceral fat accumulation between Japanese, African-Americans, and Caucasians: a meta-analysis. Acta Diabetol 40 Suppl 1: S302—304.[CrossRef][Medline] [Order article via Infotrieve]
  • Tchernof, A. et al. (1996) The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care 19: 629—637.[Abstract]
  • Third Report of the National Cholesterol Education Program (NCEP) (2002) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106: 3143—3421.[Free Full Text]
  • Tooke, J.E. and Hannemann, M.M. (2000) Adverse endothelial function and the insulin resistance syndrome. J Intern Med 247: 425—431.[CrossRef][Medline] [Order article via Infotrieve]
  • Tripathy, D. et al. (2003) Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes 52: 2882—2887.[Abstract/Free Full Text]
  • Uncu, G. et al. (2002) The role of plasma renin activity in distinguishing patients with polycystic ovary syndrome (PCOS) from oligomenorrheic patients without PCOS. Gynecol Endocrinol 16: 447—452.[Medline] [Order article via Infotrieve]
  • Urbina, E.M. et al. (1999) Association of fasting blood sugar level, insulin level, and obesity with left ventricular mass in healthy children and adolescents: The Bogalusa Heart Study. Am Heart J 138: 122—127.[CrossRef][Medline] [Order article via Infotrieve]
  • Van Gaal, L.F. et al. (2005) Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 365: 1389—1397.[CrossRef][Medline] [Order article via Infotrieve]
  • Velloso, L.A. et al. (1996) Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci USA 93: 12490—12495.[Abstract/Free Full Text]
  • Wang, G. et al. (2005) Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces clinical inflammatory responses in type 2 diabetes with coronary artery disease after coronary angioplasty. Metabolism 54: 590—597.[CrossRef][Medline] [Order article via Infotrieve]
  • Wei, J.N. et al. (2003) National surveillance for type 2 diabetes mellitus in Taiwanese children. J Am Med Assoc 290: 1345—1350.[Abstract/Free Full Text]
  • Weiss, R. et al. (2004) Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 350: 2362—2374.[Abstract/Free Full Text]
  • Wilson, P.W. et al. (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97: 1837—1847.[Abstract/Free Full Text]
  • Wilson, P.W. and Grundy, S.M. (2003) The metabolic syndrome: practical guide to origins and treatment: Part I. Circulation 108: 1422—1424.[Free Full Text]
  • Wolpert, H.A. et al. (1993) Insulin modulates circulating endothelin-1 levels in humans. Metabolism 42: 1027—1030.[CrossRef][Medline] [Order article via Infotrieve]
  • Yanovski, S.Z. and Yanovski, J.A. (2002) Obesity. N Engl J Med 346: 591—602.[Free Full Text]
  • Yuan, G. et al. (2007) Hypertriglyceridemia: its etiology, effects and treatment. Cmaj 176: 1113—1120.[Abstract/Free Full Text]
  • Zilversmit, D.B. (1979) Atherogenesis: a postprandial phenomenon. Circulation 60: 473—485.[Abstract/Free Full Text]
  • Zimmet, P. et al. (2001) Global and societal implications of the diabetes epidemic. Nature 414: 782—787.[CrossRef][Medline] [Order article via Infotrieve]
  • Ziouzenkova, O. et al. (2003) Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: evidence for an antiinflammatory role for lipoprotein lipase. Proc Natl Acad Sci USA 100: 2730—2735.[Abstract/Free Full Text]

Therapeutic Advances in Cardiovascular Disease, Vol. 1, No. 1, 7-26 (2007)
DOI: 10.1177/1753944707082662
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
 Postgrad. Med. J.Home page
K D Bruce and C D Byrne
The metabolic syndrome: common origins of a multifactorial disorder
Postgrad. Med. J., November 1, 2009; 85(1009): 614 - 621.
[Abstract] [Full Text] [PDF]

Home page
 Ther Adv Cardiovasc DisHome page
E. Idelevich, W. Kirch, and C. Schindler
Current pharmacotherapeutic concepts for the treatment of obesity in adults
Therapeutic Advances in Cardiovascular Disease, February 1, 2009; 3(1): 75 - 90.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
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 Similar articles in PubMed
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 Schindler, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schindler, C.
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?

Advertisement