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The Role of Lipids in the Development of Diabetic Microvascular Complications

Implications for Therapy

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Abstract

Dyslipidemia is a major factor responsible for coronary heart disease and its reduction decreases coronary risk in patients with diabetes mellitus. However, the association of dyslipidemia with microvascular complications and the effect of intervention with lipid-lowering therapy in diabetes have been less investigated. We present the systematic review of association and intervention studies pertaining to dyslipidemia and microvascular disease in diabetes and also review possible mechanisms. Dyslipidemia may cause or exacerbate diabetic retinopathy and nephropathy by alterations in the coagulation-fibrinolytic system, changes in membrane permeability, damage to endothelial cells and increased atherosclerosis. Hyperlipidemia is associated with faster decline in glomerular filtration rate and progression of albuminuria and nephropathy. Recent evidence also suggests a role of lipoprotein(a) in progression of retinopathy and nephropathy in patients with diabetes mellitus. Lipid-lowering therapy, using single agents or a combination of drugs may significantly benefit diabetic retinopathy and diabetic nephropathy. In particular, hydroxymethyl glutaryl coenzyme A reductase inhibitors may be effective in preventing or retarding the progression of microvascular complications because of their powerful lipid-lowering effects and other additional mechanisms. However, most of the data are based on short-term studies, and need to be ascertained in long-term studies. Until more specific guidelines are available, aggressive management of diabetic dyslipidemia, according to currently accepted guidelines, should be continued for the prevention of macrovascular disease which would also benefit microvascular complications.

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Notes

  1. Use of the registered name is for identification purposes only and does not imply endorsement.

References

  1. Pyorala K, Laasko M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev 1987; 3: 463–524

    PubMed  CAS  Google Scholar 

  2. Grundy SM, Benjamin IJ, Burke GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 1999; 100: 1134–46

    PubMed  CAS  Google Scholar 

  3. Pyorala K, Pedersen TR, Kjekshus J, et al. 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 (4): 614–20

    PubMed  CAS  Google Scholar 

  4. 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. The Care Investigators. Circulation 1998; 98: 2513–9

    PubMed  CAS  Google Scholar 

  5. 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: 1349–57

    Google Scholar 

  6. 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. J Am Med Assoc 1998; 279: 1615–22

    CAS  Google Scholar 

  7. Rubins HB, 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. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341 (6): 410–8

    PubMed  CAS  Google Scholar 

  8. Koskinen P, Manttari M, Manninen V, et al. Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. Diabetes Care 1992; 15 (7): 820–5

    PubMed  CAS  Google Scholar 

  9. Hoogeveen RC, Gambhir JK, Gambhir DS, et al. Evaluation of Lp[a] and other independent risk factors for CHD in Asian Indians and their USA counterparts. J Lipid Res 2001; 42 (4): 631–8

    PubMed  CAS  Google Scholar 

  10. Bostom AG, Cupples LA, Jenner JL, et al. Elevated plasma lipoprotein (a) and coronary heart disease in men aged 55 years and younger: a prospective study. JAMA 1996; 276 (7): 544–8

    PubMed  CAS  Google Scholar 

  11. Anand SS, Enas EA, Pogue J, et al. Elevated lipoprotein (a) levels in South Asians in North America. Metabolism 1998; 47 (2): 182–4

    PubMed  CAS  Google Scholar 

  12. Luthra K, Misra A, Srivastava LM. Lipoprotein (a): biology and role in atherosclerotic vascular diseases. Curr Sci 1999; 76: 1553–60

    CAS  Google Scholar 

  13. Heesen BJ, Wolfenbuttel BH, Leurs PB, et al. Lipoprotein (a) levels in relation to diabetic complications in patients with non-insulin dependent diabetes. Eur J Clin Invest 1993; 23: 580–4

    PubMed  CAS  Google Scholar 

  14. James RW, Boemi M, Sirolla C, et al. Lipoprotein (a) and vascular disease in diabetic patients. Diabetologia 1995; 38: 711–4

    PubMed  CAS  Google Scholar 

  15. Freyberger H, Schifferdecker E, Schatz H. Regression of hard exudates in diabetic background retinopathy in therapy with etofibrate antilipemic agent. Med Klin 1994; 89 (11): 594–7, 633

    CAS  Google Scholar 

  16. Ebeling P, Koivisto VA. Occurrence and interrelationships of complications in insulin-dependent diabetes in Finland. Acta Diabetol 1997; 34: 33–8

    PubMed  CAS  Google Scholar 

  17. Dithmar S, Curcio CA, Le NA, et al. Ultrastructural changes in Bruch’s membrane of apolipoprotein E-deficient mice. Invest Ophthalmol Vis Sci 2000; 41: 2035–42

    PubMed  CAS  Google Scholar 

  18. Kawamura M, Heinecke JW, Chait A. Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway. J Clin Invest 1994; 94 (2): 771–8

    PubMed  CAS  Google Scholar 

  19. Asakawa H, Tokunaga K, Kawakami F. Elevation of fibrinogen and thrombinantithrombin III complex levels of type 2 diabetes mellitus patients with retinopathy and nephropathy. J Diabetes Complications 2000; 14 (3): 121–6

    PubMed  CAS  Google Scholar 

  20. Vaccaro O, Pema AF, Mancini FP, et al. Plasma homocysteine and microvascular complications in type 1 diabetes. Nutr Metab Cardiovasc Dis 2000; 10 (6): 297–304

    PubMed  CAS  Google Scholar 

  21. Hopkins PN, Wu LL, Hunt SC, et al. Lipoprotein (a) interactions with lipid and nonlipid risk factors in early familial coronary artery disease. Arterioscler Thromb Vasc Biol 1997; 17 (11): 2783–92

    PubMed  CAS  Google Scholar 

  22. Rhoads GG, Dahlen G, Berg K, et al. Lp (a) lipoprotein as a risk factor for myocardial infarction. JAMA 1986; 256 (18): 2540–4

    PubMed  CAS  Google Scholar 

  23. Enas EA, Dhawan J, Petkar S. Coronary artery disease in Asian Indians: lessons learnt and the role of lipoprotein (a). Indian Heart J 1997; 49 (1): 25–34

    PubMed  CAS  Google Scholar 

  24. Kureishi Y, Luo Z, Shiojima I, et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and, promotes angiogenesis in normocholesterolemic animals. Nat Med 2000; 6 (9): 1004–10

    PubMed  CAS  Google Scholar 

  25. Kissebah AH, Kohner EM, Lewis B, et al. Plasma-lipids and glucose/insulin relationship in non-insulin-requiring diabetics with and without retinopathy. Lancet 1975; I (7916): 1104–8

    Google Scholar 

  26. West KM, Erdreich LJ, Stober JA. A detailed study of risk factors for retinopathy and nephropathy in diabetes. Diabetes 1980; 29 (7): 501–8

    PubMed  CAS  Google Scholar 

  27. Eckel RH, McLean E, Albers JJ, et al. Plasma lipids and microangiopathy in insulin-dependent diabetes mellitus. Diabetes Care 1981; 4 (4): 447–53

    PubMed  CAS  Google Scholar 

  28. Dornan TL, Carter RD, Bron AJ, et al. Low density lipoprotein cholesterol: an association with the severity of diabetic retinopathy. Diabetologia 1982; 22 (3): 167–70

    PubMed  CAS  Google Scholar 

  29. Weber B, Burger W, Hartmann R, et al. Risk factors for the development of retinopathy in children and adolescents with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1986; 29 (1): 23–9

    PubMed  Google Scholar 

  30. Miccoli R, Odello G, Giampietro O, et al. Circulating lipid levels and severity of diabetic retinopathy in type I diabetes mellitus. Ophthalmic Res 1987; 19 (1): 52–6

    PubMed  CAS  Google Scholar 

  31. Agardh CD, Agardh E, Bauer B, et al. Plasma lipids and plasma lipoproteins in diabetics with and without proliferative retinopathy. Acta Med Scand 1988; 223 (2): 165–9

    PubMed  CAS  Google Scholar 

  32. Mouton DP, Gill AJ. Prevalence of diabetic retinopathy and evaluation of risk factors: a review of 1,005 diabetic clinic patients. S Afr Med J 1988; 74 (8): 399–402

    PubMed  CAS  Google Scholar 

  33. Kostraba JN, Klein R, Dorman JS, et al. The epidemiology of diabetes complications study: IV. Correlates of diabetic background and proliferative retinopathy. Am J Epidemiol 1991; 133 (4): 381–91

    PubMed  CAS  Google Scholar 

  34. Klein BE, Moss SE, Klein R, et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XIII. Relationship of serum cholesterol to retinopathy and hard exudate. Ophthalmology 1991; 98: 1261–5

    PubMed  CAS  Google Scholar 

  35. Marshall G, Garg SK, Jackson WE, et al. Factors influencing the onset and progression of diabetic retinopathy in subjects with insulin-dependent diabetes mellitus. Ophthalmology 1993; 100 (8): 1133–9

    PubMed  CAS  Google Scholar 

  36. Sjolie AK, Stephenson J, Aldington S, et al. Retinopathy and vision loss in insulindependent diabetes in Europe. The EURODIAB IDDM Complications Study. Ophthalmology 1997; 104: 252–60

    PubMed  CAS  Google Scholar 

  37. Lloyd CE, Klein R, Maser RE, et al. The progression of retinopathy over 2 years: the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. J Diabetes Complications 1995; 9 (3): 140–8

    PubMed  CAS  Google Scholar 

  38. Kordonouri O, Danne T, Hopfenmuller W, et al. Lipid profiles and blood pressure: are they risk factors for the development of early background retinopathy and incipient nephropathy in children with insulin-dependent diabetes mellitus? Acta Paediatr 1996; 85: 43–8

    PubMed  CAS  Google Scholar 

  39. Chew EY, Klein ML, Ferris III FL, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol 1996; 114: 1079–84

    PubMed  CAS  Google Scholar 

  40. Larsson LI, Alm A, Lithner F, et al. The association of hyperlipidemia with retinopathy in diabetic patients aged 15–50 years in the county of Umea. Acta Ophthalmol Scand 1999; 77: 585–91

    PubMed  CAS  Google Scholar 

  41. Cohen RA, Hennekens CH, Christen WG, et al. Determinants of retinopathy progression in type 1 diabetes mellitus. Am J Med 1999; 107 (1): 45–51

    PubMed  CAS  Google Scholar 

  42. Kremser BG, Falk M, Kieselbach GF. Influence of serum lipid fractions on the course of diabetic macular edema after photocoagulation. Ophthalmologica 1995; 209: 60–3

    PubMed  CAS  Google Scholar 

  43. Winocour PH, Bhatnagar D, Ishola M, et al. Lipoprotein (a) and microvascular diseases in type 1 (insulin-dependent) diabetes. Diabet Med 1991; 8 (10): 922–7

    PubMed  CAS  Google Scholar 

  44. Maser RE, Usher D, Becker DJ, et al. Lipoprotein (a) concentration shows little relationship to IDDM complications in the Pittsburgh Epidemiology of Diabetes Complications Study cohort. Diabetes Care 1993; 16 (5): 755–8

    PubMed  CAS  Google Scholar 

  45. Willems D, Dorchy H, Dufrasne D. Serum lipoprotein (a) in type 1 diabetic children and adolescents: relationships with HbA1c and subclinical complications. Eur J Pediatr 1996; 155 (3): 175–8

    PubMed  CAS  Google Scholar 

  46. Westerhuls LW, Venekamp WJ. Serum lipoprotein-a levels and glyco-metabolic control in insulin and non-insulin dependent diabetes mellitus. Clin Biochem 1996; 29 (3): 255–9

    Google Scholar 

  47. Kim CH, Perk HJ, Park JY, et al. High serum lipoprotein (a) levels in Korean type 2 diabetic patients with proliferative diabetic retinopathy. Diabetes Care 1998; 21 (12): 2149–51

    PubMed  CAS  Google Scholar 

  48. Guerci B, Meyer L, Sommer S, et al. Severity of diabetic retinopathy is linked to lipoprotein (a) in type 1 diabetic patients. Diabetes Metab 1999; 25 (5): 412–8

    PubMed  CAS  Google Scholar 

  49. Verrotti A, Lobefalo L, Chiarelli F, et al. Lipids and lipoproteins in diabetic adolescents and young adults with retinopathy. Eye 1997; 11 (Pt 6): 876–81

    PubMed  Google Scholar 

  50. Ritter MM, Loscar M, Richter WO, et al. Lipoprotein (a) in diabetes mellitus. Clin Chim Acta 1993; 214 (1): 45–54

    PubMed  CAS  Google Scholar 

  51. Morisaki N, Yokote K, Tashiro J, et al. Lipoprotein (a) is a risk factor for diabetic retinopathy in the elderly. J Am Geriatr Soc 1994; 42 (9): 965–7

    PubMed  CAS  Google Scholar 

  52. Murakami J, Kumasaka K, Kawano K, et al. Lp (a) serum concentrations in diabetes mellitus. Rinsho Byori 1994; 42 (12): 1273–8

    PubMed  CAS  Google Scholar 

  53. Onuma T, Kikuchi T, Shimura M, et al. Lipoprotein (a) as an independent risk factor for diabetic retinopathy in male patients in non-insulin-dependent diabetes mellitus. Tohoku J Exp Med 1994; 173 (2): 209–16

    PubMed  CAS  Google Scholar 

  54. Suzuki T, Oba K, Igan Y, et al. Relation of apolipoprotein (a) phenotypes to diabetic retinopathy in elderly type 2 diabetes. J Nippon Med Sch 2002; 69 (1): 31–8

    PubMed  CAS  Google Scholar 

  55. Lip PL, Jones AF, Price N, et al. Do intraocular angiotensin II levels, plasma prothrombotic factors and endothelial dysfunction contribute to proliferative diabetic retinopathy? Acta Ophthalmol Scand 1998; 76 (5): 533–6

    PubMed  CAS  Google Scholar 

  56. Van Eck WF. The ffect of low fat diet on serum lipids in diabetes and its signifcance in diabetic retinopathy. Am J Med 1959; 27: 96

    Google Scholar 

  57. King RC, Dobree JH, Kok D’A, et al. Exudative diabetic retinopathy: spontaneous changes and effect of a corn oil diet. Br J Ophthalmol 1963; 47: 666–72

    PubMed  CAS  Google Scholar 

  58. Cullen JF, Ireland JT, Oliver MF. A controlled trial of Atromid therapy in exudative diabetic retinopathy. Trans Ophthalmol Soc U K 1964; 84: 281–95

    PubMed  CAS  Google Scholar 

  59. Houtsmuller AJ. Treatment of exudative diabetic retinopathy with atromid-S. Ophthalmologica 1968; 156 (1): 2–5

    PubMed  CAS  Google Scholar 

  60. Duncan LJ, Cullen JF, Ireland JT, et al. A three-year trial of atromid therapy in exudative diabetic retinopathy. Diabetes 1968; 17: 458–67

    PubMed  CAS  Google Scholar 

  61. Harrold BP, Marmion VJ, Gough KR. A double-blind controlled trial of Clofibrate in the treatment of diabetic retinopathy. Diabetes 1969; 18 (5): 285–91

    PubMed  CAS  Google Scholar 

  62. Gordon B, Chang S, Kavanagh M, et al. The effects of lipid lowering on diabetic retinopathy. Am J Ophthalmol 1991; 112: 385–91

    PubMed  CAS  Google Scholar 

  63. Fried LF, Forrest KY, Ellis D, et al. Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes. J Diabetes Complications 2001; 15 (3): 113–9

    PubMed  CAS  Google Scholar 

  64. Sen K, Misra A, Kumar A, et al. Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia. Diabetes Res Clin Pract 2002; 56: 1–11

    PubMed  CAS  Google Scholar 

  65. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels: Cholesterol and Recurrent Events Trial Investigators. N Engl J Med 1996; 335 (14): 1001–9

    PubMed  CAS  Google Scholar 

  66. Janknecht P, Schumann M, Hansen LL. Reduction of retinal exudates in diabetic retinopathy after heparin-induced extracorporeal LDL-precipitation (HELP): a case report. Eur J Ophthalmol 1996; 6 (3): 340–2

    PubMed  CAS  Google Scholar 

  67. Widder RA, Brunner R, Walter P, et al. Improvement of visual acuity in patients suffering from diabetic retinopathy after membrane differential filtration: a pilot study. Transfus Sci 1999; 21 (3): 201–6

    PubMed  CAS  Google Scholar 

  68. Hammes HP, Weiss A, Fuhrer D, et al. Acceleration of experimental diabetic retinopathy in the rat by omega-3 fatty acids. Diabetologia 1996; 39: 251–5

    PubMed  CAS  Google Scholar 

  69. Moorhead JF, Chan MK, El Nahas M, et al. Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease. Lancet 1982; II (8311): 1309–11

    Google Scholar 

  70. Kasiske BL, O’Donnell MP, Schmitz PG, et al. Renal injury of diet-induced hypercholesterolemia in rats. Kidney Int 1990; 37 (3): 880–91

    PubMed  CAS  Google Scholar 

  71. Kasiske BL, O’Donnell MP, Cleary MP, et al. Treatment of hyperlipidemia reduces glomerular injury in obese Zucker rats. Kidney Int 1988; 33 (3): 667–72

    PubMed  CAS  Google Scholar 

  72. Harris KP, Purkerson ML, Yates J, et al. Lovastatin ameliorates the development of glomerulosclerosis and uremia in experimental nephrotic syndrome. Am J Kidney Dis 1990; 15 (1): 16–23

    PubMed  CAS  Google Scholar 

  73. Mogensen CE. Natural history of cardiovascular and renal disease in patients with type 2 diabetes: effect of therapeutic interventions and risk modification. Am J Cardiol 1998; 82 (9B): 4R–8R

    PubMed  CAS  Google Scholar 

  74. Jensen T, Borch-Johnsen 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 (3): 144–8

    PubMed  CAS  Google Scholar 

  75. Takemura T, Yoshioka K, Aya N, et al. Apolipoproteins and lipoprotein receptors in glomeruli in human kidney diseases. Kidney Int 1993; 43 (4): 918–27

    PubMed  CAS  Google Scholar 

  76. Rovin BH, Tan LC. LDL stimulates mesangial fibronectin production and chemoattractant expression. Kidney Int 1993; 43 (1): 218–25

    PubMed  CAS  Google Scholar 

  77. Jones SL, Close CF, Mattock MB, et al. Plasma lipid and coagulation factor concentrations in insulin dependent diabetics with microalbuminuria. BMJ 1989; 298 (6672): 487–90

    PubMed  CAS  Google Scholar 

  78. Mulec H, Johnsen SA, Wiklund O, et al. Cholesterol: a renal risk factor in diabetic nephropathy? Am J Kidney Dis 1993; 22 (1): 196–201

    PubMed  CAS  Google Scholar 

  79. Orchard TJ, Dorman JS, Maser RE, et al. Factors associated with avoidance of severe complications after 25 yr of IDDM. Pittsburgh Epidemiology of Diabetes Complications Study I. Diabetes Care 1990; 13 (7): 741–7

    PubMed  CAS  Google Scholar 

  80. 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 (4): 237–43

    PubMed  CAS  Google Scholar 

  81. Olivarius Nde F, Andreasen AH, Keiding N, et al. Epidemiology of renal involvement in newly-diagnosed middle-aged and elderly diabetic patients: cross-sectional data from the population-based study “Diabetes Care in General Practice”, Denmark. Diabetologia 1993; 36 (10): 1007–16

    PubMed  Google Scholar 

  82. Coonrod BA, Ellis D, Becker DJ, et al. Predictors of microalbuminuria in individuals with IDDM. Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care 1993; 16 (10): 1376–83

    PubMed  CAS  Google Scholar 

  83. Reverter JL, Senti M, Rubies-Prat J, et al. Relationship between lipoprotein profile and urinary albumin excretion in type II diabetic patients with stable metabolic control. Diabetes Care 1994; 17 (3): 189–94

    PubMed  CAS  Google Scholar 

  84. Ellis D, Lloyd C, Becker DJ, et al. The changing course of diabetic nephropathy: low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria. Am J Kidney Dis 1996; 27 (6): 809–18

    PubMed  CAS  Google Scholar 

  85. Smulders YM, Rakic M, Stehouwer CD, et al. Determinants of progression of microalbuminuria in patients with NIDDM: a prospective study. Diabetes Care 1997; 20 (6): 999–1005

    PubMed  CAS  Google Scholar 

  86. Colhoun HM, Lee ET, Bennett PH, et al. Risk factors for renal failure: the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia 2001; 44 Suppl. 2: S46–53

    PubMed  CAS  Google Scholar 

  87. Vannini P, Ciavarella A, Flammini M, et al. Lipid abnormalities in insulindependent diabetic patients with albuminuria. Diabetes Care 1984; 7 (2): 151–4

    PubMed  CAS  Google Scholar 

  88. Hovind P, Rossing P, Tarnow L, et al. Progression of diabetic nephropathy. Kidney Int 2001; 59 (2): 702–9

    PubMed  CAS  Google Scholar 

  89. Krolewski AS, Warram JH, Christlieb AR. Hypercholesterolemia: a determinant of renal function loss and deaths in IDDM patients with nephropathy. Kidney Int Suppl 1994; 45: S125–31

    PubMed  CAS  Google Scholar 

  90. Soedamah-Muthu SS, Colhoun HM, Taskinen MR, et al. Differences in HDL-cholesterol: ApoA-I + ApoA-II ratio and ApoE phenotype with albuminuric status in type 1 diabetic patients. Diabetologia 2000; 43 (11): 1353–9

    PubMed  CAS  Google Scholar 

  91. Breyer JA, Bain RP, Evans JK, et al. Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group. Kidney Int 1996; 50 (5): 1651–8

    PubMed  CAS  Google Scholar 

  92. Sarnak MJ, Levey AS. Epidemiology, diagnosis, and management of cardiac disease in chronic renal disease. J Thromb Thrombolysis 2000; 10 (2): 169–80

    PubMed  CAS  Google Scholar 

  93. Sakurai T, Akiyama H, Oka T, et al. Serum lipids status in patients with diabetic uremia on 10 years of maintenance hemodialysis. Kidney Int Suppl 1999; 71: S216–8

    PubMed  CAS  Google Scholar 

  94. Quaschning T, Schomig M, Keller M, et al. Non-insulin-dependent diabetes mellitus and hypertriglyceridemia impair lipoprotein metabolism in chronic hemodialysis patients. J Am Soc Nephrol 1999; 10 (2): 332–41

    PubMed  CAS  Google Scholar 

  95. Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int 2001; 59 (1): 260–9

    PubMed  CAS  Google Scholar 

  96. Hirano T. Lipoprotein abnormalities in diabetic nephropathy. Kidney Int Suppl 1999; 71: S22–4

    PubMed  CAS  Google Scholar 

  97. Yoshino G, Hirano T, Kazumi T. Atherogenic lipoproteins and diabetes mellitus. J Diabetes Complications 2002; 16 (1): 29–34

    PubMed  Google Scholar 

  98. Kronenberg F, Utermann G, Dieplinger H. Lipoprotein (a) in renal disease. Am J Kidney Dis 1996; 27: 1–25

    PubMed  CAS  Google Scholar 

  99. Groop PH, Vibreti GC, Elliot TG, et al. Lipoprotein (a) in type 1 diabetic patients with renal disease. Diabet Med 1994; 11 (10): 961–7

    PubMed  CAS  Google Scholar 

  100. Gall MA, Rossing P, Hommel E, et al. Apolipoprotein (a) in insulin-dependent diabetic patients with and without diabetic nephropathy. Scand J Clin Lab Invest 1992; 52 (6): 513–21

    PubMed  CAS  Google Scholar 

  101. Guerci B, Igau B, Zeigler O, et al. Lack of relationship between Lp (a) particle levels and albumin excretion rate in type 1 diabetic patients. Diab Metab 1994; 20 (6): 526–31

    CAS  Google Scholar 

  102. Tarnow L, Rossing P, Nielsen FS, et al. Increased plasma apolipoprotein (a) levels in IDDM patients with diabetic nephropathy. Diabetes Care 1996; 19 (12): 1382–7

    PubMed  CAS  Google Scholar 

  103. Boemi M, Sirolla C, Fumelli P, et al. Renal disease as a determinant of increased lipoprotein (a) concentrations in diabetic patients. Diabetes Care 1999; 22 (12): 2033–6

    PubMed  CAS  Google Scholar 

  104. Clodi M, Oberbauer R, Bodlaj G, et al. Urinary excretion of apolipoprotein (a) fragments in type 1 diabetes mellitus patients. Metabolism 1999; 48 (3): 369–72

    PubMed  CAS  Google Scholar 

  105. Hadjadj S, Gallois Y, Simard G, et al. Lack of relationship in long-term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein epsilon, lipoprotein lipase and cholesteryl ester transfer protein. Genetique de la Nephropathie Diabetique Study Group. Donnees Epidemiologiques sur le Syndrome d’Insulino-Resistance Study Group. Nephrol Dial Transplant 2000; 15 (12): 1971–6

    PubMed  CAS  Google Scholar 

  106. Hernandez C, Chacon P, Marti R, et al. Relationship of lipoprotein (a) and its phenotypes with the albumin excretion rate in diabetic patients: a multivariate analysis. Nephron 2000; 85 (1): 27–33

    PubMed  CAS  Google Scholar 

  107. Lam KS, Pang RW, Wat MS, et al. Apolipoprotein (a) levels and phenotypes in NIDDM patients with microalbuminuria and albuminuria. Nephrol Dial Transplant 1996; 11 (11): 2229–36

    PubMed  CAS  Google Scholar 

  108. Clodi M, Oberbauer R, Waldhausl W, et al. Urinary excretion of Apo (a) fragments in NIDDM patients. Diabetologia 1997; 40 (12): 1455–60

    PubMed  CAS  Google Scholar 

  109. Abdella NA, Mojiminiyi OA, Akanji AO, et al. Serum lipoprotein (a) concentration as a cardiovascular risk factor in Kuwaiti type 2 diabetic patients. J Diabetes Complications 2001; 15 (5): 270–6

    PubMed  CAS  Google Scholar 

  110. Nakagawa H, Kida Y, Haneda M, et al. Relationship between the stage of diabetic nephropathy and serum lipoprotein (a) concentrations — influence of hypoproteinemia [Japanese]. Nippon Jinzo Gakkai Shi 1996; 38 (11): 513–8

    PubMed  CAS  Google Scholar 

  111. Kim SI, Han DC, Lee HB. Lovastatin inhibits transforming growth factor-betal expression in diabetic rat glomeruli and cultured rat mesangial cells. J Am Soc Nephrol 2000; 11 (1): 80–7

    PubMed  CAS  Google Scholar 

  112. Jandeleit-Dahm K, Cao Z, Cox AJ, et al. Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy. Kidney Int Suppl 1999; 71: S31–6

    PubMed  CAS  Google Scholar 

  113. Hommel E, Andersen P, Gall MA, et al. Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy. Diabetologia 1992; 35 (5): 447–51

    PubMed  CAS  Google Scholar 

  114. Nielsen S, Schmitz O, Moller N, et al. Renal function and insulin sensitivity during simvastatin treatment in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 1993; 36 (10): 1079–86

    PubMed  CAS  Google Scholar 

  115. Lam KS, Cheng IK, Janus ED, et al. Cholesterol-lowering therapy may retard the progression of diabetic nephropathy. Diabetologia 1995; 38 (5): 604–9

    PubMed  CAS  Google Scholar 

  116. 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 (12): 1891–5

    PubMed  CAS  Google Scholar 

  117. Smulders YM, van Eeden AE, Stehouwer CD, et al. Can reduction in hypertriglyceridemia slow progression of microalbuminuria in patients with non-insulindependent diabetes mellitus? Eur J Clin Invest 1997; 27 (12): 997–1002

    PubMed  CAS  Google Scholar 

  118. Nagai T, Tomizawa T, Nakajima K, et al. Effect of bezafibrate or pravastatin on serum lipid levels and albuminuria in NIDDM patients. J Atheroscler Thromb 2000; 7 (2): 91–6

    PubMed  CAS  Google Scholar 

  119. McFarlane SI, Muniyappa R, Francisco R. Pleiotropic effects of statins: lipid reduction and beyond. J Clin Endocrinol Metab 2002; 87 (4): 1451–8

    PubMed  CAS  Google Scholar 

  120. Oda H, Keane WF. Recent advances in statins and the kidney. Kidney Int Suppl 1999; 71: S2–5

    PubMed  CAS  Google Scholar 

  121. Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, et al. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest 1998; 101 (12): 2711–9

    PubMed  CAS  Google Scholar 

  122. Park JK, Muller DN, Mervaala EM, et al. Cerivastatin prevents angiotensin II-induced renal injury independent of blood pressure- and cholesterol-lowering effects. Kidney Int 2000; 58 (4): 1420–30

    PubMed  CAS  Google Scholar 

  123. Massy ZA, Kim Y, Guijarro C, et al. Low-density lipoprotein-induced expression of interleukin-6, a marker of human mesangial cell inflammation: effects of oxidation and modulation by lovastatin. Biochem Biophys Res Commun 2000; 267 (2): 536–40

    PubMed  CAS  Google Scholar 

  124. Goppelt-Struebe M, Hahn A, Iwanciw D, et al. Regulation of connective tissue growth factor (ccn2; ctgf) gene expression in human mesangial cells: modulation by HMG CoA reductase inhibitors (statins). Mol Pathol 2001; 54 (3): 176–9

    PubMed  CAS  Google Scholar 

  125. Vrtovsnik F, Couette S, Prie D, et al. Lovastatin-induced inhibition of renal epithelial tubular cell proliferation involves a p21ras activated, AP-1-dependent pathway. Kidney Int 1997; 52 (4): 1016–27

    PubMed  CAS  Google Scholar 

  126. Vrtovsnik F, Essig M, Iimura O, et al. Effect of lipid-lowering strategies on tubular cell biology. Kidney Int Suppl 1999; 71: S92–6

    PubMed  CAS  Google Scholar 

  127. Nishimura M, Tanaka T, Yasuda T, et al. Effect of pravastatin on type IV collagen secretion and mesangial cell proliferation. Kidney Int Suppl 1999; 71: S97–S100

    PubMed  CAS  Google Scholar 

  128. Forrest KY, Maser RE, Pambianco G, et al. Hypertension as a risk factor for diabetic neuropathy: a prospective study. Diabetes 1997; 46: 665–70

    PubMed  CAS  Google Scholar 

  129. Berenyi MR, Straus B, Miglietta OE. Treatment of diabetic neuropathy with Clofibrate. J Am Geriatr Soc 1971; 19: 763–72

    PubMed  CAS  Google Scholar 

  130. Martinez-Triguero ML, Salvador A, Samper MJ, et al. Lipoprotein (a) and other risk factors in patients with non-insulin-dependent diabetes mellitus. Coron Artery Dis 1994; 5 (9): 755–60

    PubMed  CAS  Google Scholar 

  131. 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 (19): 2486–97

    Google Scholar 

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Misra, A., Kumar, S., Vikram, N.K. et al. The Role of Lipids in the Development of Diabetic Microvascular Complications. Am J Cordiovosc Drugs 3, 325–338 (2003). https://doi.org/10.2165/00129784-200303050-00004

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