Risk Constellations in Patients with the Metabolic Syndrome: Epidemiology, Diagnosis, and Treatment Patterns

  • Steven M. Haffner
    Address correspondence to Steven M. Haffner, MD, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900.
    Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA
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      The prevalence of diabetes mellitus is increasing worldwide. Among other complications, diabetes is associated with the risk of coronary heart disease (CHD) that is thought to be equal to the risk of CHD in subjects without diabetes with previous myocardial infarction. Studies have shown that CHD risk factors start to increase long before the onset of clinical diabetes. Furthermore, the risk factors that are present in prediabetic individuals are also components of the highly prevalent metabolic syndrome. This suggests that treatment of CHD risk factors may effectively reduce the incidence of type 2 diabetes. Lifestyle interventions have proved effective in preventing the onset of type 2 diabetes in subjects with impaired glucose tolerance. A number of post hoc studies have reported consistent reductions in the incidence of type 2 diabetes in hypertensive patients treated with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). As a result of these positive data, ongoing prospective studies are investigating whether antihypertensive agents prevent or delay the onset of diabetes in patients at risk. Telmisartan, a selective oral ARB that is indicated for first-line therapy of essential hypertension, may provide improved tolerability compared with ACE inhibitors. Therefore, the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) program is investigating the effectiveness of telmisartan in the prevention or delay of type 2 diabetes. The program comprises ONTARGET and the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND).


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        • Wild S.
        • Roglic G.
        • Green A.
        • et al.
        Global prevalence of diabetes.
        Diabetes Care. 2004; 27: 1047-1053
        • Haffner S.M.
        • 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.
        N Engl J Med. 1998; 339: 229-234
        • Stratton I.M.
        • Adler A.I.
        • Neil H.A.
        • et al.
        Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35).
        BMJ. 2000; 321: 405-412
        • Adler A.I.
        • Stratton I.M.
        • Neil H.A.
        • et al.
        Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36).
        BMJ. 2000; 321: 412-419
        • Haffner S.M.
        • Stern M.P.
        • Hazuda H.P.
        • et al.
        Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes?.
        JAMA. 1990; 263: 2893-2898
        • Hu F.B.
        • Stampfer M.J.
        • Haffner S.M.
        • et al.
        Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2 diabetes.
        Diabetes Care. 2002; 25: 1129-1134
      1. 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: 2486-2497
        • Alberti K.G.M.M.
        • Zimmet P.Z.
        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. 1998; 15: 539-553
        • Alberti K.
        • George M.M.
        • Zimmet P.
        • et al.
        The metabolic syndrome—a new worldwide definition.
        Lancet. 2005; 366: 1059-1062
        • Ford E.S.
        • Giles W.H.
        • Dietz W.H.
        Prevalence of the metabolic syndrome among US adults.
        JAMA. 2002; 287: 356-359
        • Festa A.
        • D’Agostino Jr, R.
        • Howard G.
        • et al.
        Chronic subclinical inflammation as part of the insulin resistance syndrome.
        Circulation. 2000; 102: 42-47
        • Lakka H.M.
        • Laaksonen D.E.
        • Lakka T.A.
        • et al.
        The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.
        JAMA. 2002; 288: 2709-2716
        • Alexander C.M.
        • Landsman P.B.
        • Teutsch S.M.
        • Haffner S.M.
        NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older.
        Diabetes. 2003; 52: 1210-1214
        • Hunt K.J.
        • Resendez R.G.
        • Williams K.
        • et al.
        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. 2004; 110: 1251-1257
        • Lorenzo C.
        • Okoloise M.
        • Williams K.
        • et al.
        The metabolic syndrome as predictor of type 2 diabetes.
        Diabetes Care. 2003; 26: 3153-3159
        • The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
        Report of the Expert Committee on the diagnosis and classification of diabetes mellitus.
        Diabetes Care. 2003; 26: S5-S10
        • Simpson R.W.
        • Shaw J.E.
        • Zimmet P.Z.
        The prevention of type 2 diabetes—lifestyle change or pharmacotherapy? A challenge for the 21st century.
        Diabetes Res Clin Pract. 2003; 59: 165-180
        • Knowler W.C.
        • Barrett-Connor E.
        • Fowler S.E.
        • et al.
        Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
        N Engl J Med. 2002; 346: 393-403
        • Chiasson J.L.
        • Josse R.G.
        • Gomis R.
        • et al.
        Acarbose for prevention of type 2 diabetes mellitus.
        Lancet. 2002; 359: 2072-2077
        • Buchanan T.A.
        • Xiang A.H.
        • Peters R.K.
        • et al.
        Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women.
        Diabetes. 2002; 51: 2796-2803
        • Pan X.R.
        • Li G.W.
        • Hu Y.H.
        • et al.
        Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance.
        Diabetes Care. 1997; 20: 537-544
        • Tuomilehto J.
        • Lindstrom J.
        • Eriksson J.G.
        • et al.
        Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
        N Engl J Med. 2001; 344: 1343-1350
        • West of Scotland Coronary Prevention Study Group
        Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS).
        Circulation. 1998; 97: 1440-1445
        • Keech A.
        • Colquhoun D.
        • Best J.
        • et al.
        Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose.
        Diabetes Care. 2003; 26: 2713-2721
        • Sever P.S.
        • Dahlöf B.
        • Poulter N.R.
        • et al.
        Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA).
        Lancet. 2003; 361: 1149-1158
        • Collins R.
        • Armitage J.
        • Parish S.
        • et al.
        MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5,963 people with diabetes.
        Lancet. 2003; 361: 2005-2016
        • Yusuf S.
        • Sleight P.
        • Pogue J.
        Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients.
        N Engl J Med. 2000; 342: 145-153
        • The ALLHAT Officers and Coordinators
        Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic.
        JAMA. 2002; 288: 2981-2997
        • Dahlöf B.
        • Devereux R.B.
        • Kjeldsen S.E.
        • et al.
        Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE).
        Lancet. 2002; 359: 995-1003
        • Pfeffer M.A.
        • Swedberg K.
        • Granger C.B.
        • et al.
        Effects of candesartan on mortality and morbidity in patients with chronic heart failure.
        Lancet. 2003; 362: 759-766
        • Julius S.
        • Kjeldsen S.E.
        • Weber M.
        • et al.
        Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine.
        Lancet. 2004; 363: 2022-2031
        • Hansson L.
        • Lindholm L.H.
        • Niskanen L.
        • et al.
        Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension.
        Lancet. 1999; 353: 611-616
        • Reneland R.
        • Alvarez E.
        • Andersson P.E.
        • et al.
        Induction of insulin resistance by beta-blockade but not ACE-inhibition.
        J Hum Hypertens. 2000; 14: 175-180
        • Olsen M.H.
        • Fossum E.
        • Hoieggen A.
        Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension.
        J Hypertens. 2005; 23: 891-898
        • Gerstein H.C.
        • Yusuf S.
        • Holman R.
        • et al.
        Rationale, design and recruitment characteristics of a large, simple international trial of diabetes prevention.
        Diabetologia. 2004; 47: 1519-1527
        • Teo K.
        • Yusuf S.
        • Anderson C.
        • et al.
        Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients.
        Am Heart J. 2004; 148: 52-61
        • Dykewicz M.S.
        Cough and angioedema from angiotensin-converting enzyme inhibitors.
        Curr Opin Allergy Clin Immunol. 2004; 4: 267-270
        • Teo K.K.
        • Yusuf S.
        • Ramos B.
        Importance of an oral glucose tolerance test in identifying high prevalence of dysglycemia in individuals at high cardiovascular risk.
        J Am Coll Cardiol. 2005; 43 (Abstract 1128-1200): A211