Drugs

, Volume 59, Issue 5, pp 1101–1111 | Cite as

Diabetic Dyslipidaemia Current Treatment Recommendations

Disease Management

Abstract

Insulin deficiency and hyperglycaemia in type 1 (insulin-dependent) diabetes mellitus produce lipid abnormalities, which can be corrected by appropriate insulin therapy. Diabetic nephropathy, which is the main risk factor for coronary heart disease (CHD) in type 1 diabetes, causes pro-atherosclerotic changes in lipid metabolism. Detection and treatment of elevated cholesterol levels is likely to be of benefit in these patients.

Type 2 (noninsulin-dependent) diabetes mellitus is associated with abnormal lipid metabolism, even when glycaemic control is good and nephropathy absent. Elevated triglyceride levels, reduced high density lipoprotein (HDL) cholesterol and a preponderance of small, dense low density lipoprotein (LDL) particles are the key abnormalities that constitute diabetic dyslipidaemia. The prevalence of hypercholesterolaemia is the same as for the nondiabetic population, but the relative risk of CHD is greatly increased at every level of cholesterol. Based on effectiveness, tolerability and clinical trial results, treatment with HMG-CoA reductase inhibitors to lower LDL cholesterol is recommended as primary therapy. These agents are also moderately effective at reducing triglyceride and increasing HDL cholesterol levels. If hypertriglyceridaemia predominates, treatment with fibric acid derivatives is appropriate, although there is currently only limited clinical trial evidence that the risk of CHD will be reduced.

In type 1 diabetes, but particularly in type 2 diabetes, lipid disorders are likely to contribute significantly to the increased risk of macrovascular complications, especially CHD. Management of the disordered lipid metabolism should be given a high priority in the clinical care of all patients with diabetes.

Keywords

Coronary Heart Disease Event High Density Lipoprotein Cholesterol Level Fibric Acid Derivative Diabetic Dyslipidaemia Baseline Triglyceride Level 

References

  1. 1.
    Krolewski AS, Kosinski EJ, Warram JH, et al. Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus. Am J Cardiol 1987; 59: 750–5PubMedCrossRefGoogle Scholar
  2. 2.
    Jensen T, Borch-Jonsen K, Kofoed-Enevoldsen A, et al. Coronary heart disease in young type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors. Diabetologia 1987; 30: 144–8PubMedCrossRefGoogle Scholar
  3. 3.
    Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J 1986; 111: 383–90PubMedCrossRefGoogle Scholar
  4. 4.
    Garcia MJ, McNamara PM, Gordon T, et al. Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study. Diabetes 1974; 23: 105–11PubMedGoogle Scholar
  5. 5.
    Stamler J, Vaccaro O, Neaton JD, et al. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993; 16: 434–44PubMedCrossRefGoogle Scholar
  6. 6.
    Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med 1991; 151: 1141–7PubMedCrossRefGoogle Scholar
  7. 7.
    The DCCT Research Group. Lipid and lipoprotein levels in patients with IDDM. Diabetes Control and Complications Trial experience. Diabetes Care 1992; 15: 886–94CrossRefGoogle Scholar
  8. 8.
    Brunzell JD, Porte Jr D, Bierman EL. Abnormal lipoprotein-lipase-mediated plasma triglyceride removal in untreated diabetes mellitus associated with hypertriglyceridemia. Metabolism 1979; 28: 901–7PubMedCrossRefGoogle Scholar
  9. 9.
    Tsai EC, Hirsch IB, Brunzell JD, et al. Reduced plasma peroxy radical trapping capacity and increased susceptibility of LDL to oxidation in poorly controlled IDDM. Diabetes 1994; 43: 1010–4PubMedCrossRefGoogle Scholar
  10. 10.
    Watts GF, Nauomova R, Slavin BM, et al. Serum lipids and lipoproteins in insulin dependent diabetics with persistent microalbuminuria. Diabetic Med 1989; 6: 25–30PubMedCrossRefGoogle Scholar
  11. 11.
    Jenkins AJ, Steele JS, Janus ED, et al. Increased plasma lipoprotein (a) in IDDM patients with microalbuminuria. Diabetes 1991; 40: 787–90PubMedCrossRefGoogle Scholar
  12. 12.
    Gordon T, Castelli WP, Hjortland MC, et al. Diabetes, blood lipids and the role of obesity in coronary heart disease risk for women. The Framingham study. Ann Intern Med 1977; 87: 393–7PubMedGoogle Scholar
  13. 13.
    Biesbroeck RC, Albers JJ, Wahl PW, et al. Abnormal concentration of high density lipoproteins in non-insulin-dependent diabetics. Diabetes 1982; 31: 126–31PubMedGoogle Scholar
  14. 14.
    Feingold KR, Grunfield C, Doerrler W, et al. LDL subclass phenotypes and triglyceride metabolism in non-insulin dependent diabetes. Arterioscler Thromb 1992; 12: 1496–502PubMedCrossRefGoogle Scholar
  15. 15.
    Haffner SM, Mykkanen L, Stern MP, et al. Greater effect of diabetes on LDL size in women than in men. Diabetes Care 1994; 17: 1164–71PubMedCrossRefGoogle Scholar
  16. 16.
    Dimitriadis E, Griffin M, Owens D, et al. Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition. Diabetologia 1995; 38: 1300–6PubMedCrossRefGoogle Scholar
  17. 17.
    Haffner SM, Agil A, Mykkanen L, et al. Plasma oxidizability in subjects with normal glucose tolerance, impaired glucose tolerance, and NIDDM. Diabetes Care 1995; 18: 646–53PubMedCrossRefGoogle Scholar
  18. 18.
    Pfeifer MA, Brunzell JD, Best JD, et al. The response of plasma triglyceride, cholesterol, and lipoprotein lipase to treatment in non-insulin-dependent diabetic subjects without familial hypertriglyceridemia. Diabetes 1983; 32: 525–31PubMedCrossRefGoogle Scholar
  19. 19.
    Dunn FL, Raskin P, Bilheimer DW, et al. The effect of diabetic control on very low-density lipoprotein-triglyceride metabolism in patients with type II diabetes mellitus and marked hypertriglyceridemia. Metabolism 1984; 33: 117–23PubMedCrossRefGoogle Scholar
  20. 20.
    Niskanen L, Uusitupa M, Sarlund H, et al. Microalbuminuria predicts the development of serum lipoprotein abnormalities favouring atherogenesis in newly diagnosed type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1990; 33: 237–43PubMedCrossRefGoogle Scholar
  21. 21.
    Jenkins AJ, Steele JS, Janus ED, Santamaria JD, Best JD. Plasma apolipoprotein (a) is increased in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 1992; 35: 1055–9PubMedCrossRefGoogle Scholar
  22. 22.
    Lopes-Virella MF, Wohltmann HJ, Mayfield RK, et al. Effect of metabolic control on lipid, lipoprotein, and apolipoprotein levels in 55 insulin-dependent diabetic patients. A longitudinal study. Diabetes 1983; 32: 20–5PubMedGoogle Scholar
  23. 23.
    Jenkins AJ, Klein RL, Chassereau CN, et al. LDL from patients with well-controlled IDDM is not more susceptible to in vitro oxidation. Diabetes 1996; 45: 762–7PubMedCrossRefGoogle Scholar
  24. 24.
    Jenkins AJ, Best JD. The role of lipoprotein (a) in the vascular complications of mellitus. J Intern Med 1995; 237: 359–65PubMedCrossRefGoogle Scholar
  25. 25.
    Maser RE, Wolfson Jr SK, Ellis D, et al. Cardiovascular disease and arterial calcification in insulin-dependent diabetes mellitus. Interrelations and risk factor profiles. Arterioscler Thromb 1991; 11: 958–65PubMedCrossRefGoogle Scholar
  26. 26.
    Kjaer K, Hangaard J, Petersen NE, et al. Effect of simvastatin in patients with type 1 (insulin-dependent) diabetes mellitus and hypercholesterolemia. Acta Endocrinol 1992; 126: 229–32PubMedGoogle Scholar
  27. 27.
    Haffner SM, Stern MP, Hazuda HP, et al. Cardiovascular risk factors in confirmed pre-diabetic individuals. Does the clock start ticking before the onset of clinical diabetes? JAMA 1990; 263: 2893–8PubMedCrossRefGoogle Scholar
  28. 28.
    Mykkanen L, Kuusisto J, Pyorala K, et al. Cardiovascular disease risk factors as predictors of type 2 (non-insulin-dependent) diabetes mellitus in elderly subjects. Diabetologia 1993; 36: 553–9PubMedCrossRefGoogle Scholar
  29. 29.
    Barrett-Connor E, Grundy SM, Holbrook MJ. Plasma lipids and diabetes mellitus in an adult community. Am J Epidemiol 1981; 115: 657–63Google Scholar
  30. 30.
    Chait A, Brazg RL, Tribble DL, et al. Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. Am J Med 1993; 94: 347–9CrossRefGoogle Scholar
  31. 31.
    Mattock MB, Keen H, Viberti GC, et al. Coronary heart disease and urinary albumin excretion rate in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1988; 31: 82–7PubMedCrossRefGoogle Scholar
  32. 32.
    Harris MI. Hypercholesterolemia in diabetes and glucose intolerance in the US population. Diabetes Care 1991; 14: 366–74PubMedCrossRefGoogle Scholar
  33. 33.
    Ginsberg HN. Very low density lipoprotein metabolism in diabetes mellitus. Diabetes Metab Rev 1987; 3: 571–589PubMedCrossRefGoogle Scholar
  34. 34.
    Howard BV. Pathogenesis of diabetic dyslipidemia. Diabetes Rev 1995; 3: 423–32Google Scholar
  35. 35.
    Harno K, Nikkila EA, Kuusi T. Plasma HDL cholesterol and post heparin plasma hepatic endothelial lipase activity: relationship to obesity and non-insulin dependent diabetes. Diabetologia 1990; 19: 281–9Google Scholar
  36. 36.
    Stewart JM, Kilpatrick ES, Cathcart S, et al. Low-density lipoprotein particle size in type 2 diabetic patients and age matched controls. Ann Clin Biochem 1994; 31: 153–9PubMedGoogle Scholar
  37. 37.
    Lahdenpara S, Syvanne M, Kahri J, et al. Regulation of low-density lipoprotein particle size distribution in NIDDM and coronary disease: importance of serum triglycerides. Diabetologia 1996; 39: 453–61CrossRefGoogle Scholar
  38. 38.
    Haffner SM, Mykkanen L, Robbins D, et al. A preponderance of small dense LDL is associated with specific insulin, proinsulin and the components of the insulin resistance syndrome in non-diabetic subjects. Diabetologia 1995; 38: 1328–36PubMedCrossRefGoogle Scholar
  39. 39.
    Betteridge DJ. LDL heterogeneity: implications for atherogenicity in insulin resistance and NIDDM. Diabetologia 1997; 40: S149–51PubMedCrossRefGoogle Scholar
  40. 40.
    Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin-resistance syndrome (Syndrome X). Diabetes 1992; 41: 715–22PubMedCrossRefGoogle Scholar
  41. 41.
    Malmström R, Packard CJ, Caslake M, et al. Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia 1997; 40: 454–62PubMedCrossRefGoogle Scholar
  42. 42.
    Pollare T, Vessby B, Lithell H. Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. Arterioscler Thromb 1991; 11: 1192–203PubMedCrossRefGoogle Scholar
  43. 43.
    Carey DG, Jenkins AB, Campbell LV, et al. Abdominal fat and insulin resistance in normal and overweight women. Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes 1996; 45: 633–8PubMedCrossRefGoogle Scholar
  44. 44.
    Bjorntorp P. Metabolic implications of body fat distribution. Diabetes Care 1991; 14: 1132–43PubMedCrossRefGoogle Scholar
  45. 45.
    Jarrett RJ, Shipley MJ. The Whitehall Study: comparative mortality rates and indices of risk in diabetics. Acta Endocrinol 1985; 110 Suppl. 272: 21–6Google Scholar
  46. 46.
    Turner RC, Millns H, Neil HAW, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23). BMJ 1998; 316: 823–8PubMedCrossRefGoogle Scholar
  47. 47.
    Fontbonne A, Eschwege E, Cambien F, et al. Hypertriglyceri-daemia 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: 300–4Google Scholar
  48. 48.
    Laakso M, Lehto S, Penttila I, et al. Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes. Circulation 1993; 88(Pt1): 1421–30PubMedCrossRefGoogle Scholar
  49. 49.
    Welborn TA, Knuiman M, McCann V, et al. Clinical macro-vascular disease in Caucasoid diabetic subjects: logistic regression analysis of risk variables. Diabetologia 1984; 27: 568–73PubMedCrossRefGoogle Scholar
  50. 50.
    Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301–7PubMedCrossRefGoogle Scholar
  51. 51.
    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. JAMA 1998; 279: 1615–22PubMedCrossRefGoogle Scholar
  52. 52.
    Pyorala K, Pedersen TR, Tjekshus Jet al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. Diabetes Care 1997; 20: 614–20PubMedCrossRefGoogle Scholar
  53. 53.
    Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996; 335: 1001–9PubMedCrossRefGoogle Scholar
  54. 54.
    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: 1349–57CrossRefGoogle Scholar
  55. 55.
    Koskinen P, Manttari M, Manninen V, et al. Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. Diabetes Care 1992; 15: 820–5PubMedCrossRefGoogle Scholar
  56. 56.
    Bloomfield Rubins H, Robins SJ, Collins D 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: 410–8CrossRefGoogle Scholar
  57. 57.
    Elkeles RS, Diamond JR, Poulter C, et al. Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled study of bezafibrate: the St Mary’s, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) study. Diabetes Care 1998; 21: 641–8PubMedCrossRefGoogle Scholar
  58. 58.
    Schneider SH, Ruderman NB. Exercise and NIDDM [technical review]. Diabetes Care 1990; 13: 785–9Google Scholar
  59. 59.
    American Diabetes Association. Diabetes and exercise [position statement]. Diabetes Care 1997; 20 Suppl. 1: 551Google Scholar
  60. 60.
    Franz MJ, Horton ES, Bantle JP, et al. Nutrition principles for the management of diabetes and related complications. Diabetes Care 1994; 17: 490–518PubMedGoogle Scholar
  61. 61.
    Taskinen M-R, Kuusi T, Helve E, et al. Insulin therapy induces anti-atherogenic changes of serum lipoproteins in non-insulin-dependent diabetes. Arteriosclerosis 1988; 8: 168–77PubMedCrossRefGoogle Scholar
  62. 62.
    Greenfield M, Doberne L, Rosenthal M, et al. Lipid metabolism in non-insulin-dependent diabetes mellitus: effect of glipizide therapy. Arch Intern Med 1982; 142: 1498–500PubMedCrossRefGoogle Scholar
  63. 63.
    DeFronzo RA, Goodman AM. Efficacy of metfonnin in patients with non-insulin dependent diabetes mellitus. N Engl J Med 1995; 333: 541–9PubMedCrossRefGoogle Scholar
  64. 64.
    Hanefeld M, Fischer S, Schulze J, et al. Therapeutic potentials of acarbose as first-line drug in NIDDM insufficiently treated with diet alone. Diabetes Care 1991; 14: 732–7PubMedCrossRefGoogle Scholar
  65. 65.
    Mahmoud NG, Perez JE, Antonucci TK, et al. Cardiac and glycemic benefits of troglitazone treatment in NIDDM. Diabetes 1997; 46: 433–9CrossRefGoogle Scholar
  66. 66.
    Goldberg R, La Belle P, Zupkis R, et al. Comparison of the effects of lovastatin and gemfibrozil on lipids and glucose control in non-insulin-dependent diabetes mellitus. Am J Cardiol 1990; 66: 16B-21BCrossRefGoogle Scholar
  67. 67.
    Garg A, Grundy SM. Management of dyslipidemia in NIDDM. Diabetes Care 1990; 13: 153–69PubMedCrossRefGoogle Scholar
  68. 68.
    Jones P, Kafonek S, Laurora I, et al. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (The CURVES Study). Am J Cardiol 1998; 81: 582–7PubMedCrossRefGoogle Scholar
  69. 69.
    Black DM, Bakker-Arkema R, Heinonen T, et al. Efficacy and safety of atorvastatin in hyperlipidemic patients with concurrent hypertension or non-insulin-dependent diabetes mellitus [abstract]. 17th Scientific Meeting of the International Society of Hypertension: 1998 Jun 6–14; AmsterdamGoogle Scholar
  70. 70.
    Bakker-Arkema RG, Davidson MH, Goldstein RJ, et al. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. JAMA 1996; 275: 128–33PubMedCrossRefGoogle Scholar
  71. 71.
    Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health System Pharm 1995; 52(15): 1639–45Google Scholar
  72. 72.
    American Diabetes Association. Management of dyslipidemia in adults with diabetes [position statement]. Diabetes Care 1998; 21: 179–82Google Scholar
  73. 73.
    Schoonjans K, Staels B, Auerx J. Role of the peroxisome proliferator-activator receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 1996; 37: 907–25PubMedGoogle Scholar
  74. 74.
    Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 1998; 21; 160–78PubMedCrossRefGoogle Scholar
  75. 75.
    Lahdenpera S, Tilly-Kiesi M, Vuorinen-Markkola H, et al. Effects of gemfibrozil on low-density lipoprotein particle size, density distribution, and composition in patients with type 2 diabetes. Diabetes Care 1993; 16: 584–92PubMedCrossRefGoogle Scholar
  76. 76.
    O’Neal DN, O’Brien RC, Timmins KL, et al. Gemfibrozil treatment increases low-density lipoprotein particle size in type 2 diabetes mellitus but does not alter in vitro oxidizability. Diabet Med 1998; 15: 870–7PubMedCrossRefGoogle Scholar
  77. 77.
    De Man FH, Cabezas MC, Van-Barlingen HH, et al. Triglyceride-rich lipoproteins in non-insulin-dependent diabetes mellitus: post-prandial metabolism and relation to premature atherosclerosis. Eur J Clin Invest 1996; 26: 89–108PubMedCrossRefGoogle Scholar
  78. 78.
    Glueck CJ, Oakes N, Speirs J, et al. Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias. Am J Cardiol 1992; 70: 1–9PubMedCrossRefGoogle Scholar
  79. 79.
    Wiklund O, Bergman M, Bondjers G, et al. Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia. Am J Med 1993; 94: 13–20PubMedCrossRefGoogle Scholar
  80. 80.
    Malasanos TH, Stacpoole PW. Biological effects of ω-3 fatty acids in diabetes mellitus. Diabetes Care 1991; 14: 1160–79PubMedCrossRefGoogle Scholar
  81. 81.
    Schectman G, Kaul S, Kissebah A. Effect of fish oil concentrate on lipoprotein composition in NIDDM. Diabetes 1988; 37: 1567–73PubMedCrossRefGoogle Scholar
  82. 82.
    Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA 1990; 264: 723–6PubMedCrossRefGoogle Scholar
  83. 83.
    Carlson LA, Hamsten A, Aspland A. Pronounced lowering of serum levels of Lp(a) in hyperlipidemic subjects with nicotinic acid. J Intern Med 1989; 225: 271–6CrossRefGoogle Scholar
  84. 84.
    Kahn SE, Beard JC, Schwartz MW, et al. Increased B-cell secretory capacity as a mechanism for islet cell adaptation to nicotinic acid-induced insulin resistance. Diabetes 1990; 38: 562–8CrossRefGoogle Scholar
  85. 85.
    Crouse JR. Hypertriglyceridemia: a cotraindication to the use of bile acid binding resins. Am J Med 1987; 83: 243–8PubMedCrossRefGoogle Scholar
  86. 86.
    Garg A, Grundy SM. Cholestyramine therapy for dyslipidemia in non-insulin-dependent diabetes mellitus: a short-term, double-blind, crossover trial. Ann Intern Med 1994; 121: 416–22PubMedGoogle Scholar
  87. 87.
    Darling GM, Johns JA, McCloud PI, et al. Estrogen and progestin compared with simvastatin for hypercholesterolemia in postmenopausal women. N Engl J Med 1997; 337: 595–601PubMedCrossRefGoogle Scholar
  88. 88.
    De Graaf J, Swinkels DW, Demacker PNM, et al. Differences in the low density lipoprotein subfraction profile between oral contraceptive users and controls. J Clin Endocrinol Metab 1993; 76: 197–202PubMedCrossRefGoogle Scholar
  89. 89.
    Brussaard HE, Gevers Leuven JA, Frolich M, et al. Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NTDDM. Diabetologia 1997; 40: 843–9PubMedCrossRefGoogle Scholar
  90. 90.
    Robinson JG, Folsom AR, Nabulsi AA, et al. Can postmenopausal hormone replacement improve plasma lipids in women with diabetes? Diabetes Care 1996; 19: 480–5PubMedCrossRefGoogle Scholar
  91. 91.
    Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605–13PubMedCrossRefGoogle Scholar
  92. 92.
    Hebert PR, Gaziano M, Chan KS, et al. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials. JAMA 1997; 278: 313–21PubMedCrossRefGoogle Scholar
  93. 93.
    Blauw GJ, Lagaay AM, Smelt AHM, et al. Stroke, statins, and cholesterol. Ameta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors. Stroke 1997; 28: 946–50PubMedCrossRefGoogle Scholar
  94. 94.
    O’Neal DN, Lewicki J, Ansari MZ, et al. Lipid levels and peripheral vascular disease in diabetic and non-diabetic subjects. Atherosclerosis 1998; 136: 1–8PubMedCrossRefGoogle Scholar
  95. 95.
    Lam KSL, Cheng IKP, Janus ED, et al. Cholesterol-lowering therapy may retard the progression of diabetic nephropathy. Diabetologia 1995; 38: 604–9PubMedCrossRefGoogle Scholar
  96. 96.
    Tonolo G, Ciccarese M, Brizzi P, et al. Reduction of albumin excretion rate in normotensive microalbuminuric type 2 diabetic patients during long-term simvastatin treatment. Diabetes Care 1997; 20: 1891–5PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  1. 1.Department of Medicine, St Vincent’s HospitalThe University of MelbourneFitzroyAustralia

Personalised recommendations