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Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes

  • Lipid Abnormalities and Cardiovascular Prevention (G De Backer, Section Editor)
  • Published:
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Abstract

Purpose of Review

Current preventive and treatment guidelines for type 2 diabetes have failed to decrease the incidence of comorbidities, such as dyslipidemia and ultimately heart disease. The goal of this review is to describe the physiological and metabolic lipid alterations that develop in patients with type 2 diabetes mellitus. Questions addressed include the differences in lipid and lipoprotein metabolism that characterize the dyslipidemia of insulin resistance and type 2 diabetes mellitus. We also examine the relevance of the new AHA/ADA treatment guidelines to dyslipidemic individuals.

Recent Findings

In this review, we provide an update on the pathophysiology of diabetic dyslipidemia, including the role of several apolipoproteins such as apoC-III. We also point to new studies and new agents for the treatment of individuals with type 2 diabetes mellitus who need lipid therapies.

Summary

Type 2 diabetes mellitus causes cardiovascular disease via several pathways, including dyslipidemia characterized by increased plasma levels of apoB-lipoproteins and triglycerides, and low plasma concentrations of HDL cholesterol. Treatments to normalize the dyslipidemia and reduce the risk for cardiovascular events include the following: lifestyle and medication, particularly statins, and if necessary, ezetimibe, to significantly lower LDL cholesterol. Other treatments, more focused on triglycerides and HDL cholesterol, are less well supported by randomized clinical trials and should be used on an individual basis. Newer agents, particularly the PCSK9 inhibitors, show a great promise for even greater lowering of LDL cholesterol, but we await the results of ongoing clinical trials.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Geiss LS, Wang J, Cheng YJ, et al. Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980-2012. JAMA. 2014;312(12):1218–26.

    Article  CAS  PubMed  Google Scholar 

  2. National Diabetes Statistics Report: estimates of diabetes and its burden in the United States, 2014. Centers for Disease Control and Prevention 2014.

  3. World Health Organization. Cardiovascular diseases (CVDs). http://www.who.int/mediacentre/factsheets/fs317/en/

  4. Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67.

    Article  PubMed  CAS  Google Scholar 

  5. Gotto Jr AM, Pownall HJ, Havel RJ. Introduction to the plasma lipoproteins. Methods Enzymol. 1986;128:3–41.

    Article  CAS  PubMed  Google Scholar 

  6. Ginsberg HN. Lipoprotein physiology. Endocrinol Metab Clin N Am. 1998;27(3):503–19.

    Article  CAS  Google Scholar 

  7. Lamarche B, Couture P. Dietary fatty acids, dietary patterns, and lipoprotein metabolism. Curr Opin Lipidol. 2016;26(1):42–7.

    Article  CAS  Google Scholar 

  8. Ginsberg HN, Fisher EA. The ever-expanding role of degradation in the regulation of apolipoprotein B metabolism. J Lipid Res. 2009;50(Suppl):S162–6.

    PubMed  PubMed Central  Google Scholar 

  9. Tomkin GH, Owens D. Abnormalities in Apo B-containing lipoproteins in diabetes and atherosclerosis. Diabetes Metab Res Rev. 2001;17:27–43.

    Article  CAS  PubMed  Google Scholar 

  10. Havel RJ. Lipid transport function of lipoproteins in blood plasma. Am J Phys. 1987;253:E1–5.

    CAS  Google Scholar 

  11. de Man FH, Cabezas MC, Van Barlingen HHJJ, Erkelens DW, De Bruin TWA. Triglyceride-rich lipoproteins in non-insulin dependent diabetes mellitus:post-prandial metabolism and relation to premature atherosclerosis. Eur J Clin Investig. 1996;26:89–108.

    Article  Google Scholar 

  12. Goldberg IJ. Clinical review 124, diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab. 2001;86:965–71.

    Article  CAS  PubMed  Google Scholar 

  13. Mahley RW, Ji ZS. Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein. J Lipid Res. 1999;40:1–16.

    CAS  PubMed  Google Scholar 

  14. Phillips C, Bennett A, Anderton K. Intestinal rather than hepatic microsomal triglyceride transfer protein as a cause of postprandial dyslipidemia in diabetes. Metabolism. 2002;51:847–52.

    Article  CAS  PubMed  Google Scholar 

  15. Phillips C, Owens D, Collins P, Tomkin GH. Microsomal triglyceride transfer protein: does insulin resistance play a role in the regulation of chylomicron assembly? Atherosclerosis. 2002;160:355–60.

    Article  CAS  PubMed  Google Scholar 

  16. Haidari M, Leung N, Mahbub F, et al. Fasting and postprandial overproduction of intestinally derived lipoproteins in an animal model of insulin resistance. J Biol Chem. 2002;277(35):31646–55.

    Article  CAS  PubMed  Google Scholar 

  17. Dressel U, Allen TL, Pippal JB, Rohde PR, Lau P, Muscat GEO. The peroxisome proliferator-activated receptor β/δ agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Mol Endocrinol. 2003;17:2477–93.

    Article  CAS  PubMed  Google Scholar 

  18. Xiao C, Dash S, Morgantini C, Adeli K, Lewis GF. Gut peptides are novel regulators of intestinal lipoprotein secretion: experimental and pharmacological manipulation of lipoprotein metabolism. Diabetes. 2015;64(7):2310–8.

    Article  CAS  PubMed  Google Scholar 

  19. Adeli K, Lewis GF. Intestinal lipoprotein overproduction in insulin-resistant states. Curr Opin Lipidol. 2008;19:221–8.

    Article  CAS  PubMed  Google Scholar 

  20. Brunzell JD. Familial lipoprotein lipase deficiency. SourceGeneReviews 2015.

  21. Cohn JS, Patterson BW, Uffelman KD, Davignon J, Steiner G. Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensitivity. Journal of Clinical Endocrinology & Metabolism. 2004;89:3949–55.

    Article  CAS  Google Scholar 

  22. Nagashima K, Lopez C, Donovan D, et al. Effects of the PPAR agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus. JCI. 2005;115:1323–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ginsberg HN, Zhang Y-L, Hernandez-Ono A. A metabolic syndrome: focus on dyslipidemia. Obesity. 2006;14(Suppl):41S–9S.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang Y-L, Hernandez-Ono A, Ko C, Yasunaga K, Huang L-S, Ginsberg HN. Regulation of hepatic apolipoprotein B-lipoprotein assembly and secretion by the availability of fatty acids 1: differential effects of delivering fatty acids via albumin or remnant-like emulsion particles. J Biol Chem. 2004;279:19362–74.

    Article  CAS  PubMed  Google Scholar 

  25. Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest. 1995;95:158–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cooper AD. Hepatic uptake of chylomicron remnants. J Lipid Res. 1997;38(11):2173–92.

    CAS  PubMed  Google Scholar 

  27. Wu X, Sakata N, Dixon JL, Ginsberg HN. Exogenous VLDL stimulates apolipoprotein B from HepG2 cells by both pre- and post-translational mechanisms. J Lipid Res. 1994;35:1200–10.

    CAS  PubMed  Google Scholar 

  28. Grimaldi PA, Teboul L, Inadera H, Gaillard D, Amri E-Z. Trans-differentiation of myoblasts to adipoblasts: triggering effects of fatty acids and thiazolidinediones. Prostaglandins Leukot Essent Fatty Acids. 1997;57:71–5.

    Article  CAS  PubMed  Google Scholar 

  29. Melish J, Le NA, Ginsberg H, Steinberg D, Brown WV. Dissociation of apoprotein B and triglyceride production in very-low-density lipoproteins. Am J Phys. 1980;239(5):E354–62.

    CAS  Google Scholar 

  30. Ma W, Wu JH, Wang Q, et al. Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study. Am J Clin Nutr. 2015;101(1):153–63.

    Article  CAS  PubMed  Google Scholar 

  31. Adiels M, Boren J, Caslake MJ, et al. Overproduction of VDLD1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia. Arterioscler Thromb Vasc Biol. 2005;25:1697–703.

    Article  CAS  PubMed  Google Scholar 

  32. Keeny SJ, Aubert RE, Geiss LS. Prevalence and incidence of insulin-dependent diabetes in America. NIH. National Institute of Health 1995.

  33. Adiels M, Olofsson SO, Taskinen MR, Boren J. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Artheroscler Thromb Vasc Biol. 2008;28:1225–36.

    Article  CAS  Google Scholar 

  34. Sharma V, Forte TM, Ryan RO. Influence of apolipoprotein AV on the metabolic fate of triacylglycerol 1. Curr Opin Lipidol. 2013;24(2):153–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Robciuc MR, Maranghi M, Lahikainen A, et al. Angptl3 deficiency is associated with increased insulin sensitivity, lipoprotein lipase activity, and decreased serum free fatty acids. Arterioscler Thromb Vasc Biol. 2013;33(7):1706–13.

    Article  CAS  PubMed  Google Scholar 

  36. Kurra S, Ballantyne CM. Special patient populations: diabetes and metabolic syndrome. In Clinical lipidology: a companion to braunwald's heart disease. Elsevier Health Sciences 2009;443–462.

  37. Berneis KK, Krauss RM. Metabolic origins and clinical significance of the LDL heterogeneity. J Lipid Res. 2009;43:1363–79.

    Article  CAS  Google Scholar 

  38. Mello AP, da Silva IT, Abdalla DS, Damasceno NR. Electronegative low-density lipoprotein: origin and impact on health and disease. Atherosclerosis. 2011;215:257–65.

    Article  CAS  PubMed  Google Scholar 

  39. Rizzo M, Berneis K. Low-density lipoprotein size and cardiovascular risk assessment. QJM. 2006;99:1–14.

    Article  CAS  PubMed  Google Scholar 

  40. Timmins JM, Lee JY, Boudyguina E, et al. Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-1. J Clin Invest. 2005;115:1333–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chahil TJ, Ginsberg HN. Diabetic dyslipidemia. Endocrinol Metab Clin N Am. 2006;35:491–510.

    Article  CAS  Google Scholar 

  42. Lewis GF, Radar DJ. New insights into the regulation of HDL. Metabolism and reverse cholesterol transport. Circ Res. 2005;96:1221–32.

    Article  CAS  PubMed  Google Scholar 

  43. 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 Investig. 2003;33:1051–69.

    Article  CAS  Google Scholar 

  44. Horowitz BS, Goldberg IJ, Merab J, Vanni T, Ramakrishnan R, Ginsberg HN. Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A-I in subjects with low levels of high density lipoprotein cholesterol. J Clin Invest. 1993;91:1743–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. • Xiao C, Dash S, Morgantini C, Hegele RA, Lewis GF. Pharmacological targeting of the atherogenic dyslipidemia complex: the next frontier in CVD prevention beyond lowering LDL cholesterol. Diabetes. 2016;65(7):1767–78. A thourough desciption on the regulatory effect of GLP-1 and GLP-2 on intestinal lipoprotein secretion and postprandial lipemia

    Article  CAS  PubMed  Google Scholar 

  46. Brinton EA, Eiseberg S, Breslow JL. Human HDL cholesterol levels are determined by apoA-I fractional catabolic rate, which correlates inversely with estimate of HDL particle size. Arterioscler Thromb. 1994;14:707–20.

    Article  CAS  PubMed  Google Scholar 

  47. Liu J, Hernandez-Ono A, Graham MJ, Galton VA, Ginsberg HN. Type 1 deiodinase regulates ApoA-I gene expression and ApoA-I synthesis independent of thyroid hormone signaling. Arterioscler Thromb Vasc Biol. 2016;36(7):1356–66.

    Article  CAS  PubMed  Google Scholar 

  48. Riemens S, van Tol A, Sluiter W, Dullaart R. Elevated plasma cholesteryl ester transfer in NIDDM: relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein. Atherosclerosis. 1998;140:71–9.

    Article  CAS  PubMed  Google Scholar 

  49. Deeb SS, Zambon A, Carr MC. Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet. J Lipid Res. 2003;44:1279–86.

    Article  CAS  PubMed  Google Scholar 

  50. • Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus—mechanisms, management, and clinical considerations. Circulation. 2016;133(24):2459–502. This review points out to the mechanisms, history, controversies, and pharmacological agents for cardiovascular management in the patient with diabetes mellitus

    Article  CAS  PubMed  Google Scholar 

  51. Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013.

  52. Drozda Jr JP, Ferguson Jr TB, Jneid H, et al. 2015 ACC/AHA focused update of secondary prevention lipid performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2016;67(5):558–87.

    Article  PubMed  Google Scholar 

  53. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 53.

  54. Ryden L, Standl E, Bartnik M, for the Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. Eur Heart J. 2007;28:88–136.

    Article  CAS  PubMed  Google Scholar 

  55. Pavlovic J, Greenland P, Deckers JW et al. Comparison of ACC/AHA and ESC guideline recommendations following trial evidence for statin use in primary prevention of cardiovascular disease: results from the population-based Rotterdam Study. JAMA Cardiol 2016.

  56. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2016;346(6):393–403.

    Google Scholar 

  57. American Diabetes Association. Standards of medical care in diabetes—2016. Diabetes Care 2016;39(suppl 1).

  58. Siegel RD, Cupples A, Schaefer EJ, Wilson PWF. Lipoproteins, apolipoproteins, and low-density lipoprotein size among diabetics in the Framingham Offspring Study. Metabolism. 1996;45(10):1267–72.

    Article  CAS  PubMed  Google Scholar 

  59. Howard BV, Cowan LD, Go O, Welty TK, Robbins DC, Lee ET. Adverse effects of diabetes on multiple cardiovascular disease risk factors in women. Diabetes Care. 1998;21:1258–65.

    Article  CAS  PubMed  Google Scholar 

  60. Juutilainen A, Kortelainen S, Lehto S, et al. Gender difference in the impact of type 2 diabetes on coronary heart disease risk. Diabetes Care. 2004;27:2898–904.

    Article  PubMed  Google Scholar 

  61. Haffner SM, Miettinen H, Stern MP. Relatively more atherogenic coronary heart disease risk factors in prediabetic women than in prediabetic men. Diabetologia. 1997;40:711–7.

    Article  CAS  PubMed  Google Scholar 

  62. • PD Rosenblit. Common medications used by patients with type 2 diabetes mellitus: what are their effects on the lipid profile? Cardiovasc Diabetol 2016;15(95). An overview on type 2 diabetes mellitus treatment effects on lipid profile and their overall potential impact on ASCVD risk.

  63. Choe EY, Cho Y, Choi Y, et al. The effect of DPP-4 inhibitors on metabolic parameters in patients with type 2 diabetes. Diabetes Metab J. 2014;38(3):211–9.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Harris KB, McCarty DJ. Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus. Ther Adv Endocrinol Metab. 2015;6(1):3–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2016;18(8):783–94.

    Article  CAS  PubMed  Google Scholar 

  66. Rosenthal N, Meininger G, Ways K, et al. Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus. Ann N Y Acad Sci. 2016;1358:28–43.

    Article  CAS  Google Scholar 

  67. Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S, Study 05 Group. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015;38(3):365–72.

    Article  CAS  PubMed  Google Scholar 

  68. Rosenstock J, Rigby SP, Ford DM, Tao B, Chou HS. The glucose and lipid effects of colesevelam as monotherapy in drug-naïve type 2 diabetes. Horm Metab Res. 2014;46(5):348–53.

    CAS  PubMed  Google Scholar 

  69. Monami M, Vitale V, Ambrosio ML, et al. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: meta-analysis of placebo-controlled trials. Adv Ther. 2012;29(9):736–46.

    Article  CAS  PubMed  Google Scholar 

  70. Doggrell SA. Clinical trials with thiazolidinediones in subjects with type 2 diabetes—is pioglitazone any different from rosiglitazone? Expert Opin Pharmacother. 2008;9(3):405–20.

    Article  CAS  PubMed  Google Scholar 

  71. Chiquette E, Ramirez G, Defronzo R. A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors. Arch Intern Med. 2004;164(19):2097–104.

    Article  CAS  PubMed  Google Scholar 

  72. Yau H, Rivera K, Lomonaco R, Cusi K. The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus. Curr Diab Rep. 2013;13(3):329–41.

    Article  CAS  PubMed  Google Scholar 

  73. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2016 executive summary. Endocr Pract. 2016;22(1):84–113.

    Article  PubMed  Google Scholar 

  74. Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA. 2016;316(3):313–24.

    Article  CAS  PubMed  Google Scholar 

  75. Scheen AJ. SGLT2 inhibitors: benefit/risk balance. Curr Diab Rep. 2016;16(10):92.

    Article  PubMed  CAS  Google Scholar 

  76. Wilding JP, Rajeev SP, DeFronzo RA. Positioning SGLT2 inhibitors/incretin-based therapies in the treatment algorithm. Diabetes Care. 2016;39(supp2:S):154–64.

    Article  Google Scholar 

  77. Kernan WA, Viscoli CM, Furie KL, Winder TR, IRIS Trial Investigators. Pioglitazone after ischemic stroke or transient ischemic attack. NE J Med. 2016;374(14):1321–31.

    Article  CAS  Google Scholar 

  78. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.

    Article  CAS  PubMed  Google Scholar 

  79. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Marso SP, Bain SC, Consoli A, Eliaschewitz FG. SUSTAIN-6 investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. NE J Med 2016.

  81. Mooradian AD. Cardiovascular disease in type 2 diabetes mellitus: current management guidelines. Arch Intern Med. 2003;163(1):33–40.

    Article  PubMed  Google Scholar 

  82. Warraich HJ, Wong ND, Rana JS. Role for combination therapy in diabetic dyslipidemia. Curr Cardiol Rep. 2015;17(5):32.

    Article  PubMed  Google Scholar 

  83. Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117–25.

    Article  CAS  PubMed  Google Scholar 

  84. National Cholesterol Education Program. Third report of the expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–97.

    Article  Google Scholar 

  85. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2007;30(Suppl):S4–S41.

    Article  CAS  Google Scholar 

  86. Ginsberg HN. Efficacy and mechanism of action of statins in the treatment of diabetic dyslipidemia. J Clin Endocrinol Metab. 2006;91:383–92.

    Article  CAS  PubMed  Google Scholar 

  87. Buse JB, Ginsberg HN, Bakris GL, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus. A scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care. 2007;30:162–72.

    Article  CAS  PubMed  Google Scholar 

  88. • Collins R, Armitage J, Parish S, HPSCG. MRC/BHF heart protection study of cholesterol-lowering with simvastatin in 5,963 people with diabetes. Lancet. 2005;361:2005–16. A randomized trial of the effect of simvastatin vs placebo in patients with diabetes that provides direct evidence that cholesterol-lowering therapy is beneficial for these people even if they do not show manifestation of coronary disease or high cholesterol concentrations

    Google Scholar 

  89. • Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97. A comparison of the combination of simvastatin and ezetimibe with simvastatin and placebo on the cardiovascular outcome in patients with acute coronary syndromes

    Article  CAS  PubMed  Google Scholar 

  90. Frick MH, Elo MO, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. NE J Med. 1987;317:1237–45.

    Article  CAS  Google Scholar 

  91. 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.

    Article  CAS  PubMed  Google Scholar 

  92. Bezafibrate Infarction Prevention (BIP) study1. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000;102(1):21–7.

    Article  Google Scholar 

  93. •• Keech A, Simes RJ, Barter P. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–61. A control trial study of individuals with type 2 diabetes mellitus not on statin therapy, randomized to take fenofibrate vs placebo for 5 years to assess the effect of fenofibrate on cardiovascular disease events in these patients

    Article  CAS  PubMed  Google Scholar 

  94. Scott R, O'Brien R, Fulcher G, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care. 2009;32:493–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Anderson RT, Narayan KM, Feeney P, et al. Effect of intensive glycemic lowering on health-related quality of life in type 2 diabetes: ACCORD trial. Diabetes Care. 2011;34(4):807–12.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Accord Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575–85.

    Article  CAS  Google Scholar 

  97. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74.

    Article  PubMed  Google Scholar 

  98. Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12.

    Article  PubMed  CAS  Google Scholar 

  99. Mann CJ, Yen FT, Grant AM, Bihan BE. Mechanisms of plasma cholesteryl ester transport in hypertriglyceridemia. J Clin Invest. 1991;88:2059–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Tall AR, Granot E, Tabas I, et al. Accelerated transfer of cholesteryl esters in dyslipidemic plasma: role of cholesteryl ester transfer protein. J Clin Invest. 1987;79:1217–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Deckelbaum RJ, Granot E, Oschry Y, Rose L, Eisenberg S. Plasma triglyceride determines structure-composition in low and high density lipoproteins. Arteriosclerosis. 1984;4:225–31.

    Article  CAS  PubMed  Google Scholar 

  102. •• Reyes-Soffer G, Millar JS, Ngai C et al. Cholesteryl ester transfer protein inhibition with anacetrapib decreases fractional clearance rates of high-density lipoprotein apolipoprotein A-I and plasma cholesteryl ester transfer protein. Artheroscler Thromb Vasc Biol 2016;115. A study on the effects of CETP inhibition on the kinetics of CETP in humans.

  103. Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109–22.

    Article  CAS  PubMed  Google Scholar 

  104. Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. NE J Med. 2012;367(22):2089–99.

    Article  CAS  Google Scholar 

  105. •• Nicholls SJ, Lincoff AM, Barter PJ, et al. Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: rationale and design of the ACCELERATE trial. Am Heart J. 2015;170(6):1061–9. A contol trial study on 12,092 individual with high-risk vascular disease, randomized to take evacetrapib or placebo in addition to standard medical therapy and to acess its effect on the cardiovascular morbidity and mortality

    Article  CAS  PubMed  Google Scholar 

  106. Rader DJ, Tall AR. The not-so-simple HDL story: is it time to revise the HDL cholesterol hypothesis? Nat Med. 2012;18(9):1344–6.

    Article  CAS  PubMed  Google Scholar 

  107. McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012;59(25):2344–53.

    Article  CAS  PubMed  Google Scholar 

  108. •• Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis. Ann Intern Med. 2015;163(1):40–51. A phase 3 randomized controlled trial to compare treatment of hypercholesterolemia with and without PCSK9 antibodies which has proven PCSK9 inhibitors to be safe and effective for adults with dyslipidemia

    Article  PubMed  Google Scholar 

  109. • Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489–99. A randomized trial involving 2341 patients at high risk for cardiovascular events and at maximum dose of statin randomly assigned to receive alirocumab over a period of 78 weeks

    Article  CAS  PubMed  Google Scholar 

  110. • Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500–9. This study points to the long-term effect of evolocumab plus standard therapy, as compared with standard therapy alone on reducing LDL cholesterol levels and the incidence of cardiovascular events

    Article  CAS  PubMed  Google Scholar 

  111. • Yang X, Lee SR, Choi YS, et al. Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results. J Lipid Res. 2016;57(4):706–13. A study on the effects of volanesorsen (an antisense drug that targets apoC3 mRNA ) vs placebo in patients with hypertriglyceridemia

    Article  CAS  PubMed  Google Scholar 

  112. Gutierrez MJ, Rosenberg NL, Macdougall DE, et al. Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014;34(3):676–83.

    Article  CAS  PubMed  Google Scholar 

  113. Jani RH, Pai V, Jha P, et al. A multicenter, prospective, randomized, double-blind study to evaluate the safety and efficacy of Saroglitazar 2 and 4 mg compared with placebo in type 2 diabetes mellitus patients having hypertriglyceridemia not controlled with atorvastatin therapy (PRESS VI). Diabetes Technol Ther. 2014;16(2):63–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. •• Look AHEAD Research Group. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol 2016. This study points to the association between weight loss and the incidence of cardiovascular disease in people with type 2 diabetes from the LOOK AHEAD study after ~10-year follow-up.

  115. Szalat A, Durst R, Leitersdorf E. Managing dyslipidaemia in type 2 diabetes mellitus. Best Pract Res Clin Endocrinol Metab. 2016;30(3):431–44.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. College of Physicians and Surgeons, Department of Medicine, Division of Preventive Medicine and Nutrition, Columbia University Medical Center, 622 West 168th Street, PH-10-305, New York, NY, 10032, USA

    Maryam Khavandi, Francisco Duarte, Henry N. Ginsberg & Gissette Reyes-Soffer

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  1. Maryam Khavandi
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  2. Francisco Duarte
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  3. Henry N. Ginsberg
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  4. Gissette Reyes-Soffer
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Correspondence to Gissette Reyes-Soffer.

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Conflict of Interest

Maryam Khavandi has no conflicts related to this article.

Gissette Reyes-Soffer consults for Merck, Inc. and Genzyme, Inc. and has given lectures for Sanofi/Regeron and Merck.

Henry Ginsberg consults for or has given lectures for Sanofi-Regeneron, Merck, Amgen, Kowa, Ionis, AstraZeneca, Bristol-Myers Squibb, Resverlogix, Lilly, and Pfizer.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Lipid Abnormalities and Cardiovascular Prevention

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Khavandi, M., Duarte, F., Ginsberg, H.N. et al. Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes. Curr Cardiol Rep 19, 7 (2017). https://doi.org/10.1007/s11886-017-0818-1

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