Skip to main content
SpringerLink
Log in

Effects of fluvastatin slow-release (xl 80 mg) versus simvastatin (20 mg) on the lipid triad in patients with type 2 diabetes

  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

The lipid triad is the association of small, dense (sd) low-density lipoprotein (LDL), low high-density lipoprotein (HDL), and hypertriglyceridemia, all of which play a role in coronary artery disease in patients with type 2 diabetes. Although statins have demonstrated clear positive effects on cardiovascular morbidity/mortality in patients with diabetes and on single components of the lipid triad, it remains controversial whether they affect all components of the triad in these patients. Therefore, we performed a single-center, parallel-group, prospective, randomized, open-label, blinded-endpoint (PROBE)-type comparison of fluvastatin extended-release (XL) 80 mg (n=48) and simvastatin 20 mg (n=46), each given once daily for 2 months to patients with type 2 diabetes with the lipid triad, who were enrolled after a 1-month lifestyle modification and dietary intervention program. After fluvastatin therapy, LDL (-51%; P > .01), apolipoprotein B (ApoB;-33%; P > .01, intermediate-density LDL (idLDL) (-14.3%; P > .05), sdLDL (-45%; P > .01), and triglycerides (-38%; P > .01) were significantly decreased, and HDL (+14.3%; P > .05) and apolipoprotein A-I (ApoA-I; +7%; P > .05) were increased; large buoyant (lb) LDL did not change (P=NS). Simvastatin therapy decreased LDL (-55.1 %; P > .01), ApoB (-46%; P > .01), lbLDL (-33.3%; P > .05), idLDL (-22.7%; P > .05), sdLDL (-33.3%; P > .05), and triglycerides (-47.9%; P > .01); HDL was not changed (P=NS) after simvastatin, but ApoA-I was increased (+11.3%; P > .01). HDL increases (P > .01) and sdLDL decreases (P > .01) were significantly greater after fluvastatin compared with simvastatin therapy; LDL, triglycerides, ApoB, and idLDL changes were similar after both therapies (P=NS), and lbLDL decreases were greater with simvastatin therapy (P > .05). With both treatments, classic mean LDL and ApoB target levels were achieved in most patients. We conclude that the lipid triad can be controlled with fluvastatin XL 80 mg in patients with type 2 diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Stamler J, Vaccaro O, Neaton JD, Wentworth D. 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.

    Article  PubMed  CAS  Google Scholar 

  2. Turner R, Cull C, Holman R. United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus.Ann Intern Med. 1996;124:136–145.

    PubMed  CAS  Google Scholar 

  3. Lehto S, Ronnemaa T, Haffner SM, Pyorala K, Kallio V, Laakso M. Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM.Diabetes. 1997;46: 1354–1359.

    Article  PubMed  CAS  Google Scholar 

  4. 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. 1998;339:229–234.

    Article  PubMed  CAS  Google Scholar 

  5. Miettinen H, Lehto S, Salomaa V, et al, for the FINMONICA Myocardial Infarction Register Study Group. Impact of diabetes on mortality after the first myocardial infarction.Diabetes Care. 1998;21:69–75.

    Article  PubMed  CAS  Google Scholar 

  6. Vaccaro O, Stamler J, Neaton JD. Sixteen-year coronary mortality in black and white men with diabetes screened for the Multiple Risk Factor Intervention Trial (MRFIT).Int J Epidemiol. 1998; 27:636–641.

    Article  PubMed  CAS  Google Scholar 

  7. Laakso M. Cardiovascular disease in type 2 diabetes: challenge for treatment and prevention.J Intern Med. 2001;249:225–235.

    Article  PubMed  CAS  Google Scholar 

  8. Serrano Rios M. Epidemiology of cardiovascular disease in type 2 diabetes.Int J Clin Pract. 2001; (suppl):4–7.

  9. Sowers JR. Update on the cardiometabolic syndrome.Clin Cornerstone. 2001;4:17–23.

    Article  PubMed  CAS  Google Scholar 

  10. Taskinen MR. Diabetic dyslipidemia.Atheroscler Suppl. 2002;3:47–51.

    Article  PubMed  CAS  Google Scholar 

  11. Taskinen MR. Diabetic dyslipidaemia: from basic research to clinical practice.Diabetologia. 2003; 46:733–749.

    Article  PubMed  Google Scholar 

  12. Vaccaro O, Eberly LE, Neaton JD, Yang L, Riccardi G, Stamler J. Impact of diabetes and previous myocardial infarction on long-term survival: 25-year mortality follow-up of primary screenees of the Multiple Risk Factor Intervention Trial.Arch Intern Med. 2004;164:1438–1443.

    Article  PubMed  Google Scholar 

  13. Temelkova-Kurktschiev T, Hanefeld M. The lipid triad in type 2 diabetes—prevalence and relevance of hypertriglyceridaemia/low high-density lipoprotein syndrome in type 2 diabetes.Exp Clin Endocrinol Diabetes. 2004;112:75–79.

    Article  PubMed  CAS  Google Scholar 

  14. Drexel H, Aczel S, Marte T, et al. Is atherosclerosis in diabetes and impaired fasting glucose driven by elevated LDL cholesterol or by decreased HDL cholesterol?Diabetes Care. 2005;28: 101–107.

    Article  PubMed  CAS  Google Scholar 

  15. Allayee H, Dominguez KM, Aouizerat BE, et al. Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia.J Lipid Res. 2000;41: 245–252.

    PubMed  CAS  Google Scholar 

  16. Austin MA. Triglyceride, small, dense low-density lipoprotein, and the atherogenic lipoprotein phenotype.Curr Atheroscler Rep. 2000;2:200–207.

    Article  PubMed  CAS  Google Scholar 

  17. Betteridge DJ. Diabetic dyslipidaemia.Diabetes Obes Metab. 2000;2(suppl 1):S31-S36.

    Article  PubMed  CAS  Google Scholar 

  18. Boquist S, Hamsten A, Karpe F, Ruotolo G. Insulin and non-esterified fatty acid relations to alimentary lipaemia and plasma concentrations of postprandial triglyceride-rich lipoproteins in healthy middle-aged men.Diabetologia. 2000;43:185–193.

    Article  PubMed  CAS  Google Scholar 

  19. Gervaise N, Garrigue MA, Lasfargues G, Lecomte P. Triglycerides, apo C3 and Lp B: C3 and cardiovascular risk in type II diabetes.Diabetologia. 2000;43:703–708.

    Article  PubMed  CAS  Google Scholar 

  20. Ginsberg HN, Huang LS. The insulin resistance syndrome: impact on lipoprotein metabolism and atherothrombosis.J Cardiovasc Risk. 2000;7:325–331.

    PubMed  CAS  Google Scholar 

  21. Rader DJ, Jaye M. Endothelial lipase: a new member of the triglyceride lipase gene family.Curr Opin Lipidol. 2000;11:141–147.

    Article  PubMed  CAS  Google Scholar 

  22. Adeli K, Taghibiglou C, Van Iderstine SC, Lewis GF. Mechanisms of hepatic very low-density lipoprotein overproduction in insulin resistance.Trends Cardiovasc Med. 2001;11:170–176.

    Article  PubMed  CAS  Google Scholar 

  23. Demant T. Diabetic dyslipoproteinemia: physiopathological bases and treatment prospects.Fortschr Med Orig. 2001;119:37–40.

    PubMed  CAS  Google Scholar 

  24. Frenais R, Nazih H, Ouguerram K, et al. In vivo evidence for the role of lipoprotein lipase activity in the regulation of apolipoprotein AI metabolism: a kinetic study in control subjects and patients with type II diabetes mellitus.J Clin Endocrinol Metab. 2001;86:1962–1967.

    Article  PubMed  CAS  Google Scholar 

  25. Erkelens DW. Insulin resistance syndrome and type 2 diabetes mellitus.Am J Cardiol. 2001; 88:38J-42J.

    Article  PubMed  CAS  Google Scholar 

  26. Guerin M, Le Goff W, Lassel TS, Van Tol A, Steiner G, Chapman MJ. Atherogenic role of elevated CE transfer from HDL to VLDL(1) and dense LDL in type 2 diabetes: impact of the degree of triglyceridemia.Arterioscler Thromb Vasc Biol. 2001;21:282–288.

    PubMed  CAS  Google Scholar 

  27. Huuskonen J, Olkkonen VM, Jauhiainen M, Ehnholm C. The impact of phospholipid transfer protein (PLTP) on HDL metabolism.Atherosclerosis. 2001;155:269–281.

    Article  PubMed  CAS  Google Scholar 

  28. Malloy MJ, Kane JP. A risk factor for atherosclerosis: triglyceride-rich lipoproteins.Adv Intern Med. 2001;47:111–136.

    PubMed  CAS  Google Scholar 

  29. Riemens SC, van Tol A, Scheek LM, Dullaart RP. Plasma cholesteryl ester transfer and hepatic lipase activity are related to high-density lipoprotein cholesterol in association with insulin resistance in type 2 diabetic and non-diabetic subjects.Scand J Clin Lab Invest. 2001;61:1–9.

    Article  PubMed  CAS  Google Scholar 

  30. Rubies-Prat J, Ordonez-Llanos J, Martin S, et al. Low-density lipoprotein particle size, triglyceriderich lipoproteins, and glucose tolerance in non-diabetic men with essential hypertension.Clin Exp Hypertens. 2001;23:489–500.

    Article  PubMed  CAS  Google Scholar 

  31. Taskinen MR. Pathogenesis of dyslipidemia in type 2 diabetes.Exp Clin Endocrinol Diabetes. 2001;109(suppl 2):S180-S188.

    Article  PubMed  CAS  Google Scholar 

  32. Zimmermann R, Panzenbock U, Wintersperger A, et al. Lipoprotein lipase mediates the uptake of glycated LDL in fibroblasts, endothelial cells, and macrophages.Diabetes. 2001;50:1643–1653.

    Article  PubMed  CAS  Google Scholar 

  33. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management.JAMA. 2002;287:2570–2581.

    Article  PubMed  CAS  Google Scholar 

  34. Berneis KK, Krauss RM. Metabolic origins and clinical significance of LDL heterogeneity.J Lipid Res. 2002;43:1363–1379.

    Article  PubMed  CAS  Google Scholar 

  35. Florkowski CM. Management of co-existing diabetes mellitus and dyslipidemia: defining the role of thiazolidinediones.Am J Cardiovasc Drugs. 2002;2:15–21.

    Article  PubMed  CAS  Google Scholar 

  36. Frayn KN. Adipose tissue as a buffer for daily lipid flux.Diabetologia. 2002;45:1201–1210.

    Article  PubMed  CAS  Google Scholar 

  37. Murdoch SJ, Carr MC, Kennedy H, Brunzell JD, Albers JJ. Selective and independent associations of phospholipid transfer protein and hepatic lipase with the LDL subfraction distribution.J Lipid Res. 2002;43:1256–1263.

    PubMed  CAS  Google Scholar 

  38. Ohmura H, Mokuno H, Sawano M, et al. Lipid compositional differences of small, dense low-density lipoprotein particle influence its oxidative susceptibility: possible implication of increased risk of coronary artery disease in subjects with phenotype B.Metabolism. 2002;51: 1081–1087.

    Article  PubMed  CAS  Google Scholar 

  39. Reusch JE. Current concepts in insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome.Am J Cardiol. 2002;90:19G-26G.

    Article  PubMed  CAS  Google Scholar 

  40. Rodrigo E, Gonzalez-Lamuno D, Ruiz JC, et al. Apolipoprotein C-III and E polymorphisms and cardiovascular syndrome, hyperlipidemia, and insulin resistance in renal transplantation.Am J Transplant. 2002;2:343–348.

    Article  PubMed  Google Scholar 

  41. Ruotolo G, Howard BV. Dyslipidemia of the metabolic syndrome.Curr Cardiol Rep. 2002;4: 494–500.

    Article  PubMed  Google Scholar 

  42. Sniderman AD, Lamarche B, Tilley J, Seccombe D, Frohlich J. Hypertriglyceridemic hyperapo B in type 2 diabetes.Diabetes Care. 2002;25:579–582.

    Article  PubMed  Google Scholar 

  43. Talmud PJ, Hawe E, Robertson K, Miller GJ, Miller NE, Humphries SE. Genetic and environmental determinants of plasma high density lipoprotein cholesterol and apolipoprotein AI concentrations in healthy middle-aged men.Ann Hum Genet. 2002;66:111–124.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  45. Ayyobi AF, McGladdery SH, McNeely MJ, Austin MA, Motulsky AG, Brunzell JD. Small, dense LDL and elevated apolipoprotein B are the common characteristics for the three major lipid phenotypes of familial combined hyperlipidemia.Arterioscler Thromb Vasc Biol. 2003;23: 1289–1294.

    Article  PubMed  CAS  Google Scholar 

  46. Ayyobi AF, Brunzell JD. Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia.Am J Cardiol. 2003;92:27J-33J.

    Article  PubMed  CAS  Google Scholar 

  47. Brundert M, Heeren J, Greten H, Rinninger F. Hepatic lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent from SR-BI.J Lipid Res. 2003;44:1020–1032.

    Article  PubMed  CAS  Google Scholar 

  48. Brunzell JD, Ayyobi AF. Dyslipidemia in the metabolic syndrome and type 2 diabetes mellitus.Am J Med. 2003;115(suppl 8A):24S-28S.

    Article  PubMed  CAS  Google Scholar 

  49. Caslake MJ, Packard CJ. Lipoprotein-associated phospholipase A2 (platelet-activating factor acetylhydrolase) and cardiovascular disease.Curr Opin Lipidol. 2003;14:347–352.

    Article  PubMed  CAS  Google Scholar 

  50. Chadarevian R, Foubert L, Beucler I, et al. Lipoprotein lipase activity and common gene variants in severely hypertriglyceridemic patients with and without diabetes.Horm Res. 2003;60:61–67.

    Article  PubMed  CAS  Google Scholar 

  51. Deeb SS, Zambon A, Carr MC, Ayyobi AF, Brunzell JD. Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet.J Lipid Res. 2003;44:1279–1286.

    Article  PubMed  CAS  Google Scholar 

  52. Duong M, Psaltis M, Rader DJ, Marchadier D, Barter PJ, Rye KA. Evidence that hepatic lipase and endothelial lipase have different substrate specificities for high-density lipoprotein phospholipids.Biochemistry. 2003;42:13778–13785.

    Article  PubMed  CAS  Google Scholar 

  53. Erbas T. Metabolic syndrome.Acta Diabetol. 2003;40(suppl 2):S401-S404.

    Article  PubMed  Google Scholar 

  54. Eschwege E. The dysmetabolic syndrome, insulin resistance and increased cardiovascular (CV) morbidity and mortality in type 2 diabetes: aetiological factors in the development of CV complications.Diabetes Metab. 2003;29:6S19–6S27.

    Article  PubMed  CAS  Google Scholar 

  55. Krentz AJ. Lipoprotein abnormalities and their consequences for patients with type 2 diabetes.Diabetes Obes Metab. 2003;5(suppl 1):S19-S27.

    Article  PubMed  CAS  Google Scholar 

  56. LaMonte MJ, Ainsworth BE, DuBose KD, et al. The hypertriglyceridemic waist phenotype among women.Atherosclerosis. 2003;171:123–130.

    Article  PubMed  CAS  Google Scholar 

  57. Le NA. Small, dense low-density lipoprotein: risk or myth?Curr Atheroscler Rep. 2003;5:22–28.

    Article  PubMed  Google Scholar 

  58. Lee W, Min WK, Chun S, et al. Low-density lipoprotein subclass and its correlating factors in diabetics.Clin Biochem. 2003;36:657–661.

    Article  PubMed  CAS  Google Scholar 

  59. Lee SJ, Moye LA, Campos H, Williams GH, Sacks FM. Hypertriglyceridemia but not diabetes status is associated with VLDL containing apolipoprotein CIII in patients with coronary heart disease.Atherosclerosis. 2003;167:293–302.

    Article  PubMed  CAS  Google Scholar 

  60. Maruyama C, Imamura K, Teramoto T. Assessment of LDL particle size by triglyceride/ HDL-cholesterol ratio in non-diabetic, healthy subjects without prominent hyperlipidemia.J Atheroscler Thromb. 2003;10:186–191.

    PubMed  CAS  Google Scholar 

  61. Packard CJ. Triacylglycerol-rich lipoproteins and the generation of small, dense low-density lipoprotein.Biochem Soc Trans. 2003;31:1066–1069.

    PubMed  CAS  Google Scholar 

  62. Rader DJ. Regulation of reverse cholesterol transport and clinical implications.Am J Cardiol. 2003;92:42J-49J.

    Article  PubMed  CAS  Google Scholar 

  63. Rashid S, Watanabe T, Sakaue T, Lewis GF. Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity.Clin Biochem. 2003;36:421–429.

    Article  PubMed  CAS  Google Scholar 

  64. Schlitt A, Bickel C, Thumma P, et al. High plasma phospholipid transfer protein levels as a risk factor for coronary artery disease.Arterioscler Thromb Vasc Biol. 2003;23:1857–1862.

    Article  PubMed  CAS  Google Scholar 

  65. Skoglund-Andersson C, Ehrenborg E, Fisher RM, Olivecrona G, Hamsten A, Karpe F. Influence of common variants in the CETP, LPL, HL and APO E genes on LDL heterogeneity in healthy, middle-aged men.Atherosclerosis. 2003;167:311–317.

    Article  PubMed  CAS  Google Scholar 

  66. Soro A, Jauhiainen M, Ehnholm C, Taskinen MR. Determinants of low HDL levels in familial combined hyperlipidemia.J Lipid Res. 2003;44:1536–1544.

    Article  PubMed  CAS  Google Scholar 

  67. Takahashi T, Hirano T, Okada K, Adachi M. Apolipoprotein CIII deficiency prevents the development of hypertriglyceridemia in streptozotocin-induced diabetic mice.Metabolism. 2003;52: 1354–1359.

    Article  PubMed  CAS  Google Scholar 

  68. Tan KC, Shiu SW, Wong Y. Plasma phospholipid transfer protein activity and small, dense LDL in type 2 diabetes mellitus.Eur J Clin Invest. 2003;33:301–306.

    Article  PubMed  CAS  Google Scholar 

  69. Taskinen MR. LDL-cholesterol, HDL-cholesterol or triglycerides—which is the culprit?Diabetes Res Clin Pract. 2003;61(suppl 1):S19-S26.

    Article  PubMed  CAS  Google Scholar 

  70. Watson KE, Horowitz BN, Matson G. Lipid abnormalities in insulin resistant states.Rev Cardiovasc Med. 2003;4:228–236.

    PubMed  Google Scholar 

  71. Williams PT, Superko HR, Haskell WL, et al. Smallest LDL particles are most strongly related to coronary disease progression in men.Arterioscler Thromb Vasc Biol. 2003;23:314–321.

    Article  PubMed  CAS  Google Scholar 

  72. Zambon A, Deeb SS, Pauletto P, Crepaldi G, Brunzell JD. Hepatic lipase: a marker for cardiovascular disease risk and response to therapy.Curr Opin Lipidol. 2003;14:179–189.

    Article  PubMed  CAS  Google Scholar 

  73. Zambon A, Bertocco S, Vitturi N, Polentarutti V, Vianello D, Crepaldi G. Relevance of hepatic lipase to the metabolism of triacylglycerol-rich lipoproteins.Biochem Soc Trans. 2003;31:1070–1074.

    PubMed  CAS  Google Scholar 

  74. Badellino KO, Rader DJ. The role of endothelial lipase in high-density lipoprotein metabolism.Curr Opin Cardiol. 2004;19:392–395.

    Article  PubMed  Google Scholar 

  75. Broedl UC, Maugeais C, Millar JS, et al. Endothelial lipase promotes the catabolism of ApoB-containing lipoproteins.Circ Res. 2004;94:1554–1561.

    Article  PubMed  CAS  Google Scholar 

  76. Carr MC, Brunzell JD. Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk.J Clin Endocrinol Metab. 2004;89:2601–2607.

    Article  PubMed  CAS  Google Scholar 

  77. Caslake MJ, Packard CJ. Phenotypes, genotypes and response to statin therapy.Curr Opin Lipidol. 2004;15:387–392.

    Article  PubMed  CAS  Google Scholar 

  78. Cziraky MJ. Management of dyslipidemia in patients with metabolic syndrome.J Am Pharm Assoc. 2004;44:478–488.

    Article  Google Scholar 

  79. Hirano T, Ito Y, Koba S, et al. Clinical significance of small dense low-density lipoprotein cholesterol levels determined by the simple precipitation method.Arterioscler Thromb Vasc Biol. 2004;24:558–563.

    Article  PubMed  CAS  Google Scholar 

  80. Hirano T, Ito Y, Koba S, et al. Clinical significance of small dense low-density lipoprotein cholesterol levels determined by the simple precipitation method.Arterioscler Thromb Vasc Biol. 2004; 24:558–563.

    Article  PubMed  CAS  Google Scholar 

  81. Ishida T, Choi SY, Kundu RK, et al. Endothelial lipase modulates susceptibility to atherosclerosis in apolipoprotein-E-deficient mice.J Biol Chem. 2004;279:45085–45092.

    Article  PubMed  CAS  Google Scholar 

  82. Jansen H. Hepatic lipase: friend or foe and under what circumstances?Curr Atheroscler Rep. 2004; 6:343–347.

    Article  PubMed  Google Scholar 

  83. Jaye M, Krawiec J. Endothelial lipase and HDL metabolism.Curr Opin Lipidol. 2004;15:183–189.

    Article  PubMed  CAS  Google Scholar 

  84. Krauss RM. Lipids and lipoproteins in patients with type 2 diabetes.Diabetes Care. 2004;27:1496–1504.

    Article  PubMed  CAS  Google Scholar 

  85. Marcil M, O’Connell B, Krimbou L, Genest J Jr. High-density lipoproteins: multifunctional vanguards of the cardiovascular system.Expert Rev Cardiovasc Ther. 2004;2:417–430.

    Article  PubMed  CAS  Google Scholar 

  86. Pi-Sunyer FX. The epidemiology of central fat distribution in relation to disease.Nutr Rev. 2004; 62:S120-S126.

    Article  PubMed  Google Scholar 

  87. Rohrer L, Hersberger M, von Eckardstein A. High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease.Curr Opin Lipidol. 2004;15:269–278.

    Article  PubMed  CAS  Google Scholar 

  88. Williams CM, Maitin V, Jackson KG. Triacylglycerol-rich lipoprotein-gene interactions in endothelial cells.Biochem Soc Trans. 2004;32:994–998.

    Article  PubMed  CAS  Google Scholar 

  89. Jahangiri A, Rader DJ, Marchadier D, Curtiss LK, Bonnet DJ, Rye KA. Evidence that endothelial lipase remodels high density lipoproteins without mediating the dissociation of apolipoprotein A-I.J Lipid Res. 2005;46:896–903.

    Article  PubMed  CAS  Google Scholar 

  90. St-Pierre AC, Cantin B, Dagenais GR, et al. Low-density lipoprotein subfractions and the longterm risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study.Arterioscler Thromb Vasc Biol. 2005;25:553–559.

    Article  PubMed  CAS  Google Scholar 

  91. Jokubaitis LA. Updated clinical safety experience with fluvastatin.Am J Cardiol. 1994;73:18D-24D.

    Article  PubMed  CAS  Google Scholar 

  92. Tomlinson B, Mak TW, Tsui JY, et al. Effects of fluvastatin on lipid profile and apolipoproteins in Chinese patients with hypercholesterolemia.Am J Cardiol. 1995;76:136A-139A.

    Article  PubMed  CAS  Google Scholar 

  93. Foldes K, Maklary E, Vargha P, et al. Effect of diet and fluvastatin treatment on the serum lipid profile of kidney transplant, diabetic recipients: a 1-year follow up.Transpl Int. 1998;11(suppl 1): S65-S68.

    Article  PubMed  Google Scholar 

  94. Olsson AG, Pauciullo P, Soska V, et al. Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia: a randomized trial.Clin Ther. 2001;23:45–61.

    Article  PubMed  CAS  Google Scholar 

  95. Sonmez A, Baykal Y, Kilic M, et al. Fluvastatin improves insulin resistance in nondiabetic dyslipidemic patients.Endocrine. 2003;22:151–154.

    Article  PubMed  CAS  Google Scholar 

  96. Guan JZ, Murakami H, Yamato K, et al. Effects of fluvastatin in type 2 diabetic patients with hyperlipidemia: reduction in cholesterol oxidation products and VCAM-1.J Atheroscler Thromb. 2004;11:56–61.

    PubMed  CAS  Google Scholar 

  97. Bevilacqua M, Bettica P, Milani M, et al. Effect of fluvastatin on lipids and fibrinolysis in coronary artery disease.Am J Cardiol. 1997;79:84–87.

    Article  PubMed  CAS  Google Scholar 

  98. Bevilacqua M, Guazzini B, Righini V, Barrella M, Toscano R, Chebat E. Metabolic effects of fluvastatin extended release 80 mg and atorvastatin 20 mg in patients with type 2 diabetes mellitus and low serum high-density lipoprotein cholesterol levels: a 4-month, prospective, open-label, randomized, blinded end-point (PROBE) trial.Curr Ther Res. 2004;65:330–344.

    Article  CAS  Google Scholar 

  99. Yuan JN, Tsai MY, Hegland J, Hunninghake DB. Effects of fluvastatin (XU 62–320), an HMG-CoA reductase inhibitor, on the distribution and composition of low density lipoprotein subspecies in humans.Atherosclerosis. 1991;87:147–157.

    Article  PubMed  CAS  Google Scholar 

  100. Marz W, Scharnagl H, Abletshauser C, et al. Fluvastatin lowers atherogenic dense low-density lipoproteins in postmenopausal women with the atherogenic lipoprotein phenotype.Circulation. 2001;103:1942–1948.

    PubMed  CAS  Google Scholar 

  101. Winkler K, Abletshauser C, Hoffmann MM, et al. Effect of fluvastatin slow-release on low density lipoprotein (LDL) subfractions in patients with type 2 diabetes mellitus: baseline LDL profile determines specific mode of action.J Clin Endocrinol Metab. 2002;87:5485–5490.

    Article  PubMed  CAS  Google Scholar 

  102. Winkler K, Abletshauser C, Friedrich I, Hoffmann MM, Wieland H, Marz W. Fluvastatin slowrelease lowers platelet-activating factor acetyl hydrolase activity: a placebo-controlled trial in patients with type 2 diabetes.J Clin Endocrinol Metab. 2004;89:1153–1159.

    Article  PubMed  CAS  Google Scholar 

  103. Shimabukuro M, Higa N, Asahi T, Oshiro Y, Takasu N. Fluvastatin improves endothelial dysfunction in overweight postmenopausal women through small dense low-density lipoprotein reduction.Metabolism. 2004;53:733–739.

    Article  PubMed  CAS  Google Scholar 

  104. Daubresse JC, Machowski R, Pulinx E. Efficacy of simvastatin for lowering cholesterol in noninsulin dependent diabetic patients with hypercholesterolemia.Acta Clin Belg. 1994;49:68–75.

    PubMed  CAS  Google Scholar 

  105. Farrer M, Winocour PH, Evans K, et al. Simvastatin in non-insulin-dependent diabetes mellitus: effect on serum lipids, lipoproteins and haemostatic measures.Diabetes Res Clin Pract. 1994; 23:111–119.

    Article  PubMed  CAS  Google Scholar 

  106. Jeck T, Riesen WF, Keller U. Comparison of bezafibrate and simvastatin in the treatment of dyslipidaemia in patients with NIDDM.Diabet Med. 1997;14:564–570.

    Article  PubMed  CAS  Google Scholar 

  107. Illingworth DR, Crouse JR III, Hunninghake DB, et al. A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial.Curr Med Res Opin. 2001;17:43–50.

    Article  PubMed  CAS  Google Scholar 

  108. Hunninghake DB, Ballantyne CM, Maccubbin DL, Shah AK, Gumbiner B, Mitchel YB. Comparative effects of simvastatin and atorvastatin in hypercholesterolemic patients with characteristics of metabolic syndrome.Clin Ther. 2003;25:1670–1686.

    Article  PubMed  CAS  Google Scholar 

  109. Feldman T, Koren M, Insull W Jr, et al. Treatment of high-risk patients with ezetimibe plus simvastatin co-administration versus simvastatin alone to attain National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals.Am J Cardiol. 2004; 93:1481–1486.

    Article  PubMed  CAS  Google Scholar 

  110. Isaacsohn J, Hunninghake D, Schrott H, et al. Effects of simvastatin, an HMG-CoA reductase inhibitor, in patients with hypertriglyceridemia.Clin Cardiol. 2003;26:18–24.

    Article  PubMed  Google Scholar 

  111. Lewin AJ, Kipnes MS, Meneghini LF, et al. Effects of simvastatin on the lipid profile and attainment of low-density lipoprotein cholesterol goals when added to thiazolidinedione therapy in patients with type 2 diabetes mellitus: a multicenter, randomized, double-blind, placebo-controlled trial.Clin Ther. 2004;26:379–389.

    Article  PubMed  CAS  Google Scholar 

  112. Ballantyne CM, Blazing MA, Hunninghake DB, et al. Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS).Am Heart J. 2003;146:862–869.

    Article  PubMed  CAS  Google Scholar 

  113. Miller M, Dobs A, Yuan Z, Battisti WP, Borisute H, Palmisano J. Effectiveness of simvastatin therapy in raising HDL-C in patients with type 2 diabetes and low HDL-C.Curr Med Res Opin. 2004;20:1087–1094.

    Article  PubMed  CAS  Google Scholar 

  114. Steyn K, Weich HF, Bonnici F, et al. Simvastatin in non-insulin-dependent diabetic patients with hypercholesterolaemia.S Afr Med J. 1992;82:402–406.

    PubMed  CAS  Google Scholar 

  115. Hommel E, Andersen P, Gall MA, et al. Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy.Diabetologia. 1992;35:447–451.

    Article  PubMed  CAS  Google Scholar 

  116. Sartor G, Katzman P, Eizyk E, et al. Simvastatin treatment of hypercholesterolemia in patients with insulin dependent diabetes mellitus.Int J Clin Pharmacol Ther. 1995;33:3–6.

    PubMed  CAS  Google Scholar 

  117. Tikkanen MJ, Laakso M, Ilmonen M, et al. Treatment of hypercholesterolemia and combined hyperlipidemia with simvastatin and gemfibrozil in patients with NIDDM. A multicenter comparison study.Diabetes Care. 1998;21:477–481.

    Article  PubMed  CAS  Google Scholar 

  118. Tomas M, Senti M, Garcia-Faria F, et al. Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients.Arterioscler Thromb Vasc Biol. 2000;20:2113–2119.

    PubMed  CAS  Google Scholar 

  119. Insull W, Kafonek S, Goldner D, Zieve F (ASSET Investigators). Comparison of efficacy and safety of atorvastatin (10 mg) with simvastatin (10 mg) at six weeks.Am J Cardiol. 2001;87:554–559.

    Article  PubMed  CAS  Google Scholar 

  120. Geiss HC, Schwandt P, Parhofer KG. Influence of simvastatin on LDL-subtypes in patients with heterozygous familial hypercholesterolemia and in patients with diabetes mellitus and mixed hyperlipoproteinemia.Exp Clin Endocrinol Diabetes. 2002;110:182–187.

    Article  PubMed  CAS  Google Scholar 

  121. Geiss HC, Parhofer KG, Schwandt P. Atorvastatin compared with simvastatin in patients with severe LDL hypercholesterolaemia treated by regular LDL apheresis.J Intern Med. 1999;245:47–55.

    Article  PubMed  CAS  Google Scholar 

  122. van Tits LJ, Smilde TJ, van Wissen S, de Graaf J, Kastelein JJ, Stalenhoef AF. Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia.J Investig Med. 2004;52:177–184.

    Article  PubMed  Google Scholar 

  123. Hansson L, Hedner T, Dahlof B. Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective randomized open blinded end-point.Blood Press. 1992;1:113–119.

    Article  PubMed  CAS  Google Scholar 

  124. Lindholm LH, Hansson L, Dahlof B, et al. The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report.Blood Press. 1996;5:300–304.

    Article  PubMed  CAS  Google Scholar 

  125. Hansson L, Hedner T, Lindholm L, et al. The Captopril Prevention Project (CAPPP) in hypertensionbaseline data and current status.Blood Press. 1997;6:365–367.

    Article  PubMed  CAS  Google Scholar 

  126. Nauck M, Marz W, Haas B, Wieland H. Homogeneous assay for direct determination of highdensity lipoprotein cholesterol evaluated.Clin Chem. 1996;42:424–429.

    PubMed  CAS  Google Scholar 

  127. Tamasawa N, Matsui J, Ogawa Y, et al. Effect of doxazosin on the size of LDL particle in the type 2 diabetic patients with hypertension.J Diabetes Complications. 2000;14:135–139.

    Article  PubMed  CAS  Google Scholar 

  128. Hoefner DM, Hodel SD, O’Brien JF, et al. Development of a rapid, quantitative method for LDL subfractionation with use of the Quantimetrix Lipoprint LDL system.Clin Chem. 2001;47:266–274.

    PubMed  CAS  Google Scholar 

  129. Matsui J, Tamasawa N, Tanabe J, et al. LDL particle size and lipid composition are risk factors for microalbuminuria in normotensive and normocholesterolemic patients with type 2 diabetes.Diabetes Res Clin Pract. 2004;66:229–236.

    Article  PubMed  CAS  Google Scholar 

  130. Knopp RH, Frolich JJ. Efficacy and safety of fluvastatin in patients with non-insulin-dependent diabetes mellitus and hyperlipidemia: preliminary report.Am J Cardiol. 1994;73:39D-41D.

    Article  PubMed  CAS  Google Scholar 

  131. Mauger JF, Couture P, Paradis ME, Lamarche B. Comparison of the impact of atorvastatin and simvastatin on apoA-I kinetics in men.Atherosclerosis. 2005;178:157–163.

    Article  PubMed  CAS  Google Scholar 

  132. Broyles FE, Walden CE, Hunninghake DB, Hill-Williams D, Knopp RH. Effect of fluvastatin on intermediate density lipoprotein (remnants) and other lipoprotein levels in hypercholesterolemia.Am J Cardiol. 1995;76:129A-135A.

    Article  PubMed  CAS  Google Scholar 

  133. Cheung MC, Sibley SD, Palmer JP, Oram JF, Brunzell JD. Lipoprotein lipase and hepatic lipase: their relationship with HDL subspecies Lp(A-I) and Lp(A-I, A-II).J Lipid Res. 2003;44:1552–1558.

    Article  PubMed  CAS  Google Scholar 

  134. Zambon A, Deeb SS, Brown BG, Hokanson JE, Brunzell JD. Common hepatic lipase gene promoter variant determines clinical response to intensive lipid-lowering treatment.Circulation. 2001;103:792–798.

    PubMed  CAS  Google Scholar 

  135. Zambon A, Deeb SS, Hokanson JE, Brown BG, Brunzell JD. Common variants in the promoter of the hepatic lipase gene are associated with lower levels of hepatic lipase activity, buoyant LDL, and higher HDL2 cholesterol.Arterioscler Thromb Vasc Biol. 1998;18:1723–1729.

    PubMed  CAS  Google Scholar 

  136. Zambon A, Hokanson JE, Brown BG, Brunzell JD. Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density.Circulation. 1999;99:1959–1964.

    PubMed  CAS  Google Scholar 

  137. Borggreve SE, De Vries R, Dullaart RP. Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins.Eur J Clin Invest. 2003; 33:1051–1069.

    Article  PubMed  CAS  Google Scholar 

  138. de Vries R, Borggreve SE, Dullaart RP. Role of lipases, lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in abnormal high density lipoprotein metabolism in insulin resistance and type 2 diabetes mellitus.Clin Lab. 2003;49:601–613.

    PubMed  Google Scholar 

  139. Hansel B, Kontush A, Twickler MT. High-density lipoprotein as a key component in the prevention of premature atherosclerotic disease in the insulin resistance syndrome.Semin Vasc Med. 2004;4: 215–223.

    Article  PubMed  Google Scholar 

  140. Deslypere JP. Clinical implications of the biopharmaceutical properties of fluvastatin.Am J Cardiol. 1994;73:12D-17D.

    Article  PubMed  CAS  Google Scholar 

  141. Barilla D, Prasad P, Hubert M, Gumbhir-Shah K. Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL.Biopharm Drug Dispos. 2004;25:51–59.

    Article  PubMed  CAS  Google Scholar 

  142. Corsini A. The use of statins in optimising reduction of cardiovascular risk: focus on fluvastatin.Int J Clin Pract. 2004;58:494–503.

    Article  PubMed  CAS  Google Scholar 

  143. Schoonjans K, Peinado-Onsurbe J, Fruchart JC, Tailleux A, Fievet C, Auwerx J. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors reduce serum triglyceride levels through modulation of apolipoprotein C-III and lipoprotein lipase.FEBS Lett. 1999;452:160–164.

    Article  PubMed  CAS  Google Scholar 

  144. Bard JM, Dallongeville J, Hagen E, et al. Comparison of the effect of fluvastatin, an hydroxymethyl glutaryl coenzyme A reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by apolipoprotein composition.Metabolism. 1995;44:1447–1454.

    Article  PubMed  CAS  Google Scholar 

  145. Verd JC, Peris C, Alegret M, et al. Different effect of simvastatin and atorvastatin on key enzymes involved in VLDL synthesis and catabolism in high fat/cholesterol fed rabbits.Br J Pharmacol. 1999;127:1479–1485.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrinology and Diabetes Unit and LORENZ Research Center Department of Medicine, Luigi Sacco Hospital (Vialba)-University of Milan, Milan, Italy

    Maurizio Bevilacqua MD, Velella Righini MD, Massimo Barrella MD, Tarcisio Vago MD & Enrica Chebat MD

  2. Geriatric Unit Department of Internal Medicine and Geriatrics, University of Palermo, Palermo, Italy

    Ligia J. Dominguez MD

Authors
  1. Maurizio Bevilacqua MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Velella Righini MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Massimo Barrella MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tarcisio Vago MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Enrica Chebat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ligia J. Dominguez MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bevilacqua, M., Righini, V., Barrella, M. et al. Effects of fluvastatin slow-release (xl 80 mg) versus simvastatin (20 mg) on the lipid triad in patients with type 2 diabetes. Adv Therapy 22, 527–542 (2005). https://doi.org/10.1007/BF02849947

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02849947

Keywords

Search

Navigation