Hyperlipidemia: Pathogenesis and Management in Diabetes Mellitus

  • Ira J. Goldberg


Aside from acute complications, care for people with diabetes mellitus requires measures to prevent the secondary complications of this disease. Although hyperglycemia is directly linked to microvascular disease of the eye and kidneys, several lines of evidence suggest that the relationship between macrovascular disease and hyperglycemia is not direct. These data include animal studies of the effects of hyperglycemia on the development and/or progression of atherosclerotic lesions in animals, epidemiological correlations of risk factors and vascular disease, and experimental interventions in humans.1,2 In most animals, hyperglycemia alone or in the setting of an atherosclerotic lipoprotein profile created by ingestion of a high fat/high cholesterol diet or by genetic manipulation does not increase atherosclerosis unless the diabetes also worsens the lipid abnormalities. In the rabbit alloxan-induced diabetes will actually prevent atherosclerosis; while the rabbits develop hyperglycemia there is also a shift of the lipoprotein profile towards the presence of large particles that are too big to enter the arterial wal1.3 In human populations, multifactorial analysis correlates lipid abnormalities such as elevated LDL and reduced HDL with coronary heart disease (CHD).4 These lipid parameters are more strongly related to disease development than is fasting glucose or glycosylated hemoglobin. Most important, several intervention trials have clearly demonstrated that reductions in plasma lipoproteins decrease CHD in patients with diabetes.5 In contrast, intervention trials that have shown a reduction in microvascular disease with better glycemic control have, in general, shown less effect on CHD.


Cholesteryl Ester Transfer Protein Coronary Heart Disease Event Hepatic Lipase Hormone Sensitive Lipase Lecithin Cholesterol Acyl Transferase 
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  1. 1.
    Ginsberg HN. Lipoprotein physiology in nondiabetic and diabetic states. Relationship to atherogenesis. Diabetes Care 14: 839–855, 1991.PubMedCrossRefGoogle Scholar
  2. 2.
    Goldberg IJ. Clinical review 124: Diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab 86: 965–71, 2001.PubMedCrossRefGoogle Scholar
  3. 3.
    Nordestgaard BG, Stender S, Kjeldsen K. Reduced atherogenesis in cholesterol-fed diabetic rabbits. Giant lipoproteins do not enter the arterial wall. Arteriosclerosis 8: 421–8, 1998.Google Scholar
  4. 4.
    Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). Br Med J 316: 823–8, 1998.CrossRefGoogle Scholar
  5. 5.
    Steiner G. Lipid intervention trials in diabetes. Diabetes Care 23 Suppl 2: B49–53, 2000.Google Scholar
  6. 6.
    Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. 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 339: 229–34 1998.PubMedCrossRefGoogle Scholar
  7. 7.
    Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA 263: 2893–8, 1990.PubMedCrossRefGoogle Scholar
  8. 8.
    Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 21: 160–78, 1998.PubMedCrossRefGoogle Scholar
  9. 9.
    Eckel RH, Albers JJ, Cheung MC, Wahl PC, Lindgren FT, Bierman EL. High density lipoprotein composition in insulin-dependent diabetes mellitus. Diabetes 30: 132–8 1981.PubMedCrossRefGoogle Scholar
  10. 10.
    Wilson DE, Hata A, Kwong LK, Lingam A, Shuhua J, Ridinger DN, Yeager C, Kaltenborn KC, Iverius PH, Lalouel JM. Mutations in exon 3 of the lipoprotein lipase gene segregating in a family with hypertriglyceridemia, pancreatitis, and non-insulin-dependent diabetes. J Clin Invest 92: 203–11, 1993.PubMedCrossRefGoogle Scholar
  11. 11.
    Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med 37: 249–73, 1992.PubMedGoogle Scholar
  12. 12.
    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 285: 2486–97, 2001.CrossRefGoogle Scholar
  13. 13.
    Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 357:905–10, 2001.Google Scholar
  14. 14.
    Rubins HB, Robins SJ, Collins D, Fye CL, Anderson. W, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 341: 410–8, 1999.PubMedCrossRefGoogle Scholar
  15. 15.
    Guyton JR. Combination drug therapy for combined hyperlipidemia. Curr Cardiol Rep 1: 244–50, 1999.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2004

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  • Ira J. Goldberg

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