Abstract
Although the diagnosis of type 2 (noninsulin-dependent) diabetes mellitus is made when blood glucose levels exceed values which increase the risk of micro-vascular complications, macrovascular disease is the major complication of type 2 diabetes mellitus. Both epidemiological and prospective data have demonstrated that treatment of hyperglycaemia is markedly effective in reducing the risk of microvascular disease but is less potent in reducing that of myocardial infarction, stroke and peripheral vascular disease. Treatment of other cardiovascular risk factors, although by definition less prevalent than hyperglycaemia, appears to be more effective in preventing macrovascular disease than treatment of hyperglycaemia. In recent years, data from intervention trials have suggested that greater benefits with respect to the prevention of macrovascular disease can be achieved by effective treatment of hypertension and hypercholesterolaemia, and by the use of small doses of aspirin (acetylsalicylic acid) than by treating hyperglycaemia alone. On the other hand, the UK Prospective Diabetes Study (UKPDS), which examined the impact of intensive glucose and blood pressure (BP) control on micro- and macrovascular complications, is the only intervention trial to include only patients with type 2 diabetes mellitus. The UKPDS data, the epidemic increase in the number of patients with type 2 diabetes mellitus and their high cardiovascular risk have, however, initiated several new trials addressing, in particular, the possible benefits of treatment of the most common form of dyslipidaemia (high serum triglyceride and low high density lipoprotein cholesterol levels) in these patients. Type 2 diabetes mellitus is thus a disease associated with a high vascular risk, where the majority of patients need, and are likely to benefit from, pharmacological treatment of several cardiovascular risk factors provided treatment targets have not been achieved by life-style modification.
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Trovati M, Anfossi G. Insulin, insulin resistance and platelet function: similarities with insulin effects on cultured vascular smooth muscle cells. Diabetologia 1998; 41: 609–22
Yki-Järvinen H. Pathogenesis of non-insulin-dependent diabetes mellitus. Lancet 1994; 343: 91–5
Yki-Järvinen H. Role of insulin resistance in the pathogenesis of NIDDM. Diabetologia 1995; 38: 1378–88
Viskin S, Kitzis I, Lev E, et al. Treatment with beta-adrenergic blocking agents after myocardial infarction: from randomized trials to clinical practice. J Am Coll Cardiol 1995; 25: 1327–32
Zuanetti G, Latini R, Maggioni AP, et al. for the GISSI-3 investigators. Effect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction. Data from the GISSI-3 study. Circulation 1997; 96: 4239–45
Moye LA, Pfeffer MA, Wun CC, et al. Uniformity of captopril benefit in the SAVE study: subgroup analysis. Survival and Ventricular Enlargement Study. Eur Heart J 1994; 15: 2–8
Torp-Pedersen C, Kober L, Carlsen J. Angio-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study. Am Heart J 1996; 132: 235–43
Malmberg K for the DIGAMI study group. Prospective randomized study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ 1997; 314: 1512–5
The Bypass Angioplasty Revascularization Investigation (BARI) investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med 1996; 335: 217–25
Van Belle E, Bauters C, Hubert E, et al. Restenosis rates in diabetic patients: a comparison of coronary stenting and balloon angioplasty in native coronary vessels. Circulation 1997; 96: 1454–60
Barsness GW, Peterson ED, Ohman EM, et al. Relationship between diabetes mellitus and long-term survival after coronary bypass and angioplasty. Circulation 1997; 96: 2551–6
Kleinman NS, Lincoff AM, Kereiakes DJ, et al. Diabetes mellitus, glycoprotein IIb/IIIa blockade, and heparin: evidence for a complex interaction in a multicenter trial. EPILOG investigators. Circulation 1998; 97: 1912–20
Stamler J, Vaccaro O, Neaton JD, et al., for the Multiple Risk Factor Intervention Trial Research Group. Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care 1993; 16: 434–44
The Hypertension in Diabetes Study Group. Hypertension in diabetes study (HDS): I. Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factors for cardiovascular and diabetic complications. J Hypertens 1993; 11: 309–17
The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157: 2413–46
Haffner SM, D’Agostino RJ, Mykkanen L, et al. Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study. Diabetes Care 1999; 22: 562–8
Harris MI, Hadden WC, Knowler WC, et al. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20–74 years. Diabetes 1987; 36: 523–34
Laakso M. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes 1999; 48: 937–42
Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 1995; 18: 258–68
Turner RC, Millns H, Neil HAW, et al., for the United Kingdom Prospective Diabetes Study Group. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23). BMJ 1998; 316: 823–8
Juhan-Vague I, Alessi MC. PAI-1, obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost 1997; 78: 656–60
Sobel BE. Insulin resistance and thrombosis: a cardiologist’s view. Am J Cardiol 1999; 84: 37J–41J
Savage S, Estacio RO, Jeffers B, et al. Urinary albumin excretion as a predictor of diabetic retinopathy, neuropathy, and cardiovascular disease in NIDDM. Diabetes Care 1996; 19: 1243–8
Neil A, Hawkins M, Potok M, et al. A prospective populationbased study of microalbuminuria as a predictor of mortality in NIDDM. Diabetes Care 1993; 16: 996–1003
Gall MA, Borch-Johnsen K, Hougaard P, et al. Albuminuria and poor glycemic control predict mortality in NIDDM. Diabetes 1995; 44: 1303–9
Jager A, Kostense PJ, Nijpels G, et al. Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn Study. Diabetologia 1998; 41: 694–700
Fioretto P, Stehouwer CD, Mauer M, et al. Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure. Diabetologia 1998; 41: 233–6
UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998; 17: 713–20
Curb JD, Pressel SL, Cutler JA, et al. for the Systolic Hypertension in the Elderly Program Cooperative Research Group. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older patients with isolated systolic hypertension. JAMA 1996; 276: 1886–92
Tuomilehto J, Rastenyte D, Birkenhäger WH, et al. for the Systolic Hypertension in Europa Trial Investigators. Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension [abstract]. N Engl J Med 1999; 340: 677–84
Hansson L, Lindholm LH, Niskanen L, et al. Principal results of the Captopril Prevention Project (CAPPP): effect of angiotensin converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension. Lancet 1998; 353: 611–6
Estacio RO, Jeffers BW, Hiatt WR, et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med 1998; 338: 645–52
Tatti P, Pahor M, Byington RP, et al. Outcome results of the fosinopril versus amlodipine cardiovascular events randomized trial (FACET) in patients with hypertension and NIDDM. Diabetes Care 1998; 21: 597–603
Hansson L, Zanchetti A, Carruthers SG, et al., for the HOT study group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomized trial. Lancet 1998; 351: 1755–62
Drury PL. Diabetes and arterial hypertension. Diabetologia 1983; 24: 1–9
Parving HH, Andersen AR, Smidt UM, et al. Diabetic nephropathy and arterial hypertension. Diabetologia 1983; 24: 10–2
The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 145–53
The Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000; 342: 154–60
Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987; 317: 1237–45
Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study [see comments]. JAMA 1998; 279: 1615–22
Goldberg RB, Mellies MJ, Sacks FM, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels. Subgroup analyses in the cholesterol and recurrent events (CARE) trial. Circulation 1998; 98: 2513–9
Pyörälä K, Pedersen TR, Kjekshus J, et al. Cholesterol lowering with simvastatin imrpoves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Survival Study (4S). Diabetes Care 1997; 20: 614–20
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349–57
Rader DJ, Haffner SM. Role of fibrates in the management of hypertriglyceridemia. Am J Cardiol 1999; 83: 30F–5
Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 1998; 21: 160–78
A strategy for arterial risk assessment and management in type 2 (non-insulin-dependent) diabetes mellitus. European Arterial Risk Policy Group on behalf of the International Diabetes Federation European Region. Diabetic Med 1997; 14: 611–21
Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995; 28: 103–17
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: 837–52
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854–65
Final report on the aspirin component of the ongoing Physicians’ Health Study. Steering Committee of the Physicians’ Health Study Research Group [see comments]. N Engl J Med 1989; 321: 129–35
ETDRS Investigators. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. JAMA 1998; 268: 1292–300
Antiplatelet Trialists’ Collaboration. Collaborative overview of randomized trails of antiplatelet therapy I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994; 308: 80–106
Harpaz D, Gottlieb S, Graff E, et al. Effects of aspirin treatment on survival in non-insulin-dependent diabetic patients with coronary artery disease. Israeli Bezafibrate Infarction Prevention Study Group. Am J Med 1998; 105: 494–9
Haffner SM, Lehto S, Rönnemaa 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: 229–34
Yudkin JS, Chaturvedi N. Developing risk stratification charts for diabetic and nondiabetic subjects. Diabet Med 1999; 16: 219–27
Pyörälä K, Wood D. Prevention of coronary heart disease in clinical practice. European recommendations revised and reinforced [editorial; comment]. Eur Heart J 1998; 19: 1413–5
U.K. Prospective Diabetes Study Group. UKPDS 28: a randomized trial of efficacy of early addition of metformin in sulfonylurea-treated type 2 diabetes. Diabetes Care 1998; 21: 87–92
Yki-Järvinen H, Ryysy L, Nikkilä K, et al. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus: a randomized, controlled trial. Ann Intern Med 1999; 130: 389–96
Valle T, Koivisto VA, Reunanen A, et al. Glycemic control in patients with diabetes in Finland. Diabetes Care 1999; 22: 575–9
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Yki-Järvinen, H. Management of Type 2 Diabetes Mellitus and Cardiovascular Risk. Drugs 60, 975–983 (2000). https://doi.org/10.2165/00003495-200060050-00001
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DOI: https://doi.org/10.2165/00003495-200060050-00001