Lipids in Type 2 Diabetes

ABSTRACT

Type 2 diabetes increases the risk of cardiovascular disease two- to fourfold compared to the risk in nondiabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors, the cause for an excess risk of cardiovascular disease remains unknown. Lipid and lipoprotein abnormalities in type 2 diabetes include particularly elevated levels of total and very low-density lipoprotein triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate but LDL particles are small and dense. According to prospective population-based studies, total cholesterol is a similar risk factor for coronary heart disease (CHD) in patients with type 2 diabetes as it is in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in patients with type 2 diabetes than in nondiabetic subjects. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol by statins, and the lowering of total triglycerides and the raising of HDL cholesterol by fibrates, are at least as beneficial in diabetic patients as in nondiabetic subjects in the prevention of cardiovascular disease.

KEYWORD

Coronary heart disease - lipids - lipoproteins - type 2 diabetes

REFERENCES

• 1 Pyörälä K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view.  Diabetes Metab Rev . 1987;  3 463-524
• 2 Haffner S M, Lehto S, Rönnemaa T. 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
• 3 Laakso M, Lehto S. Epidemiology of macrovascular disease in diabetes.  Diabetes Rev . 1997;  5 294-315
• 4 Grundy S M, Benjamin I J, Burke G L. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association.  Circulation . 1999;  100 1134-1146
• 5 Miettinen H, Lehto S, Salomaa V. Impact of diabetes on mortality after the first myocardial infarction. The FINMONICA Myocardial Infarction Register Study Group.  Diabetes Care . 1998;  21 69-75
• 6 Taskinen M-R. Insulin resistance and lipoprotein metabolism.  Curr Opin Lipidol . 1995;  6 153-160
• 7 Sarlund H, Pyörälä K, Penttilä I. Early abnormalities in coronary heart disease risk factors in relatives of subjects with noninsulin-dependent diabetes.  Arterioscler Thromb . 1992;  12 657-663
• 8 Laakso M. Insulin resistance and coronary heart disease.  Curr Opin Lipidol . 1996;  7 217-226
• 9 Lempiäinen P, Mykkänen L, Pyörälä K. Insulin resistance syndrome predicts coronary heart disease events in elderly nondiabetic men.  Circulation . 1999;  100 123-128
• 10 Lehto S, Rönnemaa T, Pyörälä K. Cardiovascular risk factors clustering with endogenous hyperinsulinaemia predict death from coronary heart disease in patients with type II diabetes.  Diabetologia . 2000;  43 148-155
• 11 Mykkänen L, Kuusisto J, Haffner S M. Hyperinsulinemia predicts multiple atherogenic changes in lipoproteins in elderly subjects.  Arterioscler Thromb . 1994;  14 518-526
• 12 Austin M A, Mykkänen L, Kuusisto J. Prospective study on small LDLs as a risk factor for noninsulin dependent diabetes mellitus in elderly men and women.  Circulation . 1995;  92 1770-1778
• 13 Rönnemaa T, Laakso M, Kallio V. Serum lipids, lipoproteins, and apolipoproteins and the excessive occurrence of coronary heart disease in noninsulin-dependent diabetic patients.  Am J Epidemiol . 1989;  130 632-645
• 14 Laakso M, Rönnemaa T, Pyörälä K. Atherosclerotic vascular disease and its risk factors in noninsulin-dependent diabetic and nondiabetic subjects in Finland.  Diabetes Care . 1988;  11 449-463
• 15 Harris M I. Hypercholesterolemia in diabetes and glucose intolerance in the U.S. population.  Diabetes Care . 1991;  14 366-374
• 16 Stern M P, Patterson J K, Haffner S M. Lack of awareness and treatment of hyperlipidemia in type II diabetes in a community survey.  JAMA . 1989;  262 360-364
• 17 Laakso M. Epidemiology of diabetic dyslipidemia.  Diabetes Rev . 1995;  3 408-422
• 18 Selby J V, Austin M A, Newman B. LDL subclass phenotypes and the insulin resistance syndrome in women.  Circulation . 1993;  88 381-387
• 19 Barakat H A, Carpenter J W, McLendon V D. Influence of obesity, impaired glucose tolerance, and NIDDM on LDL structure and composition. Possible link between hyperinsulinemia and atherosclerosis.  Diabetes . 1990;  39 1527-1533
• 20 Manzato E, Zambon A, Lapolla A. Lipoprotein abnormalities in well-treated type II diabetic patients.  Diabetes Care . 1993;  16 469-475
• 21 Bucala R, Makita Z, Koschinsky T. Lipid advanced glycosylation: pathway for lipid oxidation in vivo.  Proc Natl Acad Sci USA . 1993;  91 9441-9445
• 22 Abbott W G, Lillioja S, Young A A. Relationships between plasma lipoprotein concentrations and insulin action in an obese hyperinsulinemic population.  Diabetes . 1987;  36 897-904
• 23 Garg A, Helderman J H, Koffler M. Relationship between lipoprotein levels and in vivo insulin action in normal white young white men.  Metabolism . 1988;  37 982-987
• 24 Laakso M, Sarlund H, Mykkänen L. Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degrees of glucose tolerance.  Arteriosclerosis . 1990;  10 223-231
• 25 Howard B V. Insulin resistance and lipid metabolism.  Am J Cardiol . 1999;  84 28J-32J
• 26 Taskinen M R, Beltz W F, Harper I. Effects of NIDDM on very low-density lipoprotein triglyceride and apolipoprotein B metabolism: studies before and after sulfonylurea therapy.  Diabetes . 1986;  35 1268-1277
• 27 Reaven G M, Greenfield M S. Diabetic hypertriglyceridaemia: evidence for three clinical syndromes.  Diabetes . 1981;  30 (suppl 2) 66-75
• 28 Laakso M, Pyörälä K. Adverse effects of obesity on lipid and lipoprotein levels in insulin-dependent and noninsulin-dependent diabetes.  Metabolism . 1988;  39 117-122
• 29 Lewis G F, O'Meara N M, Soltys P A. Fasting hypertriglyceridaemia in noninsulin-dependent diabetes mellitus is an important predictor of postprandial lipid and lipoprotein abnormalities.  J Clin Endocrinol Metab . 1991;  72 934-944
• 30 Stamler J, Vaccaro O, Neaton J D, for the Multiple Risk Factor Intervention Trial Research Group. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.  Diabetes Care . 1993;  16 434-444
• 31 Kannel W B, McGee D L. Diabetes and cardiovascular risk factors: the Framingham Study.  Circulation . 1979;  59 8-13
• 32 Jarrett R J, Shipley M J. Mortality and associated risk factors in diabetics.  Acta Endocrinol . 1985;  110 (suppl 272) 21-26
• 33 Howard B V, Robbins D C, Sievers M L. LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL. The Strong Heart Study.  Arterioscler Thromb Vasc Biol . 2000;  20 830-835
• 34 National Cholesterol Education Program Expert Panel, National Heart, Lung, and Blood Institute. Report of the National Cholesterol Education Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults.  Arch Intern Med . 1988;  148 36-69
• 35 American Diabetes Association. Management of dyslipidemia in adults with diabetes.  Diabetes Care . 1999;  22 (suppl 1) S56-S59
• 36 West K M, Ahuja M M, Bennett P H. The role of circulating glucose and triglyceride concentrations and their interactions with other ``risk factors'' as determinants of arterial disease in nine diabetic population samples from the WHO Multinational Study.  Diabetes Care . 1983;  6 361-369
• 37 Fontbonne A, Eschwege E, Cambien F. Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Results from the 11-year follow-up of the Paris Prospective Study.  Diabetologia . 1989;  32 300-304
• 38 Lehto S, Rönnemaa T, Haffner S M. Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM.  Diabetes . 1997;  48 1354-1359
• 39 Turner R C, Millns H, Neil H A, for the United Kingdom Prospective Diabetes Study Group. Risk factors for coronary artery disease in noninsulin-dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS 23).  BMJ . 1998;  316 823-828
• 40 Downs J R, Clearfield M, Weis S, for the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels.  JAMA . 1998;  279 1615-1622
• 41 Pyörälä K, Pedersen T R, Kjekshus J, for the Scandinavian Simvastatin Survival Study (4S) Group. 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;  20 614-620
• 42 Goldberg R B, Mellies M J, Sacks F M, for the CARE Investigators. 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 2513-2519
• 43 The Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. 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 1349-1357
• 44 Hoogwerf B J, Waness A, Cressman M. Effects of aggressive cholesterol lowering and low-dose anticoagulation on clinical and angiographic outcomes in patients with diabetes. The Post Coronary Artery Bypass Graft Trial.  Diabetes . 1999;  48 1289-1294
• 45 Koskinen P, Mänttäri M, Manninen V. Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study.  Diabetes Care . 1992;  15 820-825
• 46 Rubins H B, Robins S J, Collins D, for the Veterans Affairs High-density Lipoprotein Cholesterol Intervention Trial Study Group, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol.  N Engl J Med . 1999;  341 410-418
• 47 Diabetes Atherosclerosis Intervention Study Investigators. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study.  Lancet . 2001;  357 905-910
• 48 Rosenson R S, Tangney C C. Antiatherothrombotic properties of statins. Implications for cardiovascular event reduction.  JAMA . 1998;  279 1643-1650
• 49 Fruchart J C, Durietz P, Staels B. Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation and atherosclerosis.  Curr Opin Lipidol . 1999;  10 245-257
• 50 Haffner S M. Management of dyslipidemia in adults with diabetes.  Diabetes Care . 1998;  21 160-1678