Top

Current Atherosclerosis Reports

Published in:

01-03-2021 | Dyslipidemia | Statin Drugs (R. Ceska, Section Editor)

Diabetes, Lipids, and CV Risk

Author: Jan Škrha Jr

Published in: Current Atherosclerosis Reports | Issue 3/2021

Abstract

Purpose of Review

Diabetes is often associated with diabetic dyslipidemia. Both hyperglycemia and disorders of lipid metabolism strongly contribute to development of atherosclerosis, the crucial factor of cardiovascular disease. The aim of the manuscript is to summarize possible treatment to reduce cardiovascular risk.

Recent Findings

Maximal cardiovascular risk reduction is maintained by targeting more pathologic disturbances together. While antihypertensive treatment has not changed much recently, novel PCSK9 inhibitors have significantly improved management of dyslipidemia. Similarly, modern antihyperglycemic agents (SGLT2 inhibitors and GLP-1 receptor agonists) show both significant metabolic effects and cardiovascular benefits.

Summary

Diabetes treatment is no longer glucocentric. Apart from glucose management, there are effective pharmacologic tools for significant reduction of cardiovascular risk.

IDF. IDF Diabetes Atlas. 9th Edition. 2019.

Wang CCL, 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. https://doi.org/10.1161/circulationaha.116.022194.CrossRef

Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J. 2013;34(31):2436–43. https://doi.org/10.1093/eurheartj/eht149.CrossRefPubMedPubMedCentral

Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359(15):1577–89. https://doi.org/10.1056/NEJMoa0806470.CrossRefPubMed

Yan SF, Ramasamy R, Schmidt AM. Receptor for AGE (RAGE) and its ligands-cast into leading roles in diabetes and the inflammatory response. J Mol Med. 2009;87(3):235–47. https://doi.org/10.1007/s00109-009-0439-2.CrossRefPubMed

Wang Z, Jiang Y, Liu N, Ren L, Zhu Y, An Y, et al. Advanced glycation end-product Nepsilon-carboxymethyl-lysine accelerates progression of atherosclerotic calcification in diabetes. Atherosclerosis. 2012;221(2):387–96. https://doi.org/10.1016/j.atherosclerosis.2012.01.019.CrossRefPubMed

Huang CL, Wu IH, Wu YW, Hwang JJ, Wang SS, Chen WJ, et al. Association of lower extremity arterial calcification with amputation and mortality in patients with symptomatic peripheral artery disease. PLoS One. 2014;9(2):e90201. https://doi.org/10.1371/journal.pone.0090201.CrossRefPubMedPubMedCentral

Reusch JE, Draznin BB. Atherosclerosis in diabetes and insulin resistance. Diabetes Obes Metab. 2007;9(4):455–63. https://doi.org/10.1111/j.1463-1326.2006.00620.x.CrossRefPubMed

Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med. 2016;374(14):1321–31. https://doi.org/10.1056/NEJMoa1506930.CrossRefPubMedPubMedCentral

10.

Galmes S, Cifre M, Palou A, Oliver P, Serra F. A Genetic Score of Predisposition to Low-Grade Inflammation Associated with Obesity May Contribute to Discern Population at Risk for Metabolic Syndrome. Nutrients. 2019;11(2). https://doi.org/10.3390/nu11020298.

11.

Osende JI, Badimon JJ, Fuster V, Herson P, Rabito P, Vidhun R, et al. Blood thrombogenicity in type 2 diabetes mellitus patients is associated with glycemic control. J Am Coll Cardiol. 2001;38(5):1307–12. https://doi.org/10.1016/s0735-1097(01)01555-8.CrossRefPubMed

12.

Poznyak A, Grechko AV, Poggio P, Myasoedova VA, Alfieri V, Orekhov AN. The Diabetes Mellitus-Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation. Int J Mol Sci. 2020;21(5). https://doi.org/10.3390/ijms21051835.

13.

Ceriello A. The emerging challenge in diabetes: the "metabolic memory". Vasc Pharmacol. 2012;57(5–6):133–8. https://doi.org/10.1016/j.vph.2012.05.005.CrossRef

14.

Parhofer KG. Interaction between glucose and lipid metabolism: more than diabetic dyslipidemia. Diabetes Metab J. 2015;39(5):353–62. https://doi.org/10.4093/dmj.2015.39.5.353.CrossRefPubMedPubMedCentral

15.

Tell S, Nadeau KJ, Eckel RH. Lipid management for cardiovascular risk reduction in type 1 diabetes. Current Opinion in Endocrinology Diabetes and Obesity. 2020;27(4):207–14. https://doi.org/10.1097/med.0000000000000551.CrossRef

16.

Verges B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia. 2015;58(5):886–99. https://doi.org/10.1007/s00125-015-3525-8.CrossRefPubMedPubMedCentral

17.

Gaede PH, Jepsen PV, Larsen JN, Jensen GV, Parving HH, Pedersen OB. The Steno-2 study. Intensive multifactorial intervention reduces the occurrence of cardiovascular disease in patients with type 2 diabetes. Ugeskr Laeger. 2003;165(26):2658–61.PubMed

18.

Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2019. https://doi.org/10.1093/eurheartj/ehz486.

19.

• Hsu HY, Lin CJ, Lee YS, Wu TH, Chien KL. Efficacy of more intensive lipid-lowering therapy on cardiovascular diseases: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2020;20(1):12. https://doi.org/10.1186/s12872-020-01567-1A meta-analysis of 103,864 patients in 18 trials comparing more intensive lipid-lowering and control groups.CrossRef

20.

Langlois MR, Sniderman AD. Non-HDL Cholesterol or apoB: Which to Prefer as a Target for the Prevention of Atherosclerotic Cardiovascular Disease? Current Cardiology Reports. 2020;22(8). https://doi.org/10.1007/s11886-020-01323-z.

21.

Cholesterol Treatment Trialists C, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, 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. https://doi.org/10.1016/S0140-6736(08)60104-X.CrossRef

22.

Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–61. https://doi.org/10.1016/s0140-6736(16)31357-5.CrossRefPubMed

23.

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97. https://doi.org/10.1056/NEJMoa1410489.CrossRefPubMed

24.

Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097–107. https://doi.org/10.1056/NEJMoa1801174.CrossRefPubMed

25.

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22. https://doi.org/10.1056/NEJMoa1615664.CrossRefPubMed

26.

• Goldberg RB, Stone NJ, Grundy SM. The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA* guidelines on the Management of Blood Cholesterol in diabetes. Diab Care. 2020;43(8):1673–8. https://doi.org/10.2337/dci19-0036Clinical practice guidelines recommendations on management of LDL cholesterol in people with diabetes.CrossRef

27.

Investigators A-H, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67. https://doi.org/10.1056/NEJMoa1107579.CrossRef

28.

Group HTC, Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12. https://doi.org/10.1056/NEJMoa1300955.CrossRef

29.

Lazarte J, Hegele RA. Dyslipidemia Management in Adults with Diabetes. Can J Diabetes. 2020;44(1):53–60. https://doi.org/10.1016/j.jcjd.2019.07.003.CrossRefPubMed

30.

Stahel P, Xiao C, Lewis GF. Control of intestinal lipoprotein secretion by dietary carbohydrates. Curr Opin Lipidol. 2018;29(1):24–9. https://doi.org/10.1097/MOL.0000000000000474.CrossRefPubMed

31.

Patti AM, Rizvi AA, Giglio RV, Stoian AP, Ligi D, Mannello F. Impact of Glucose-Lowering Medications on Cardiovascular and Metabolic Risk in Type 2 Diabetes. Journal of Clinical Medicine. 2020;9(4). https://doi.org/10.3390/jcm9040912.

32.

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. https://doi.org/10.1056/NEJMoa1504720.CrossRef

33.

Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(21):2099. https://doi.org/10.1056/NEJMc1712572.CrossRefPubMed

34.

Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. NEJM. 2019;380(4):347–57. https://doi.org/10.1056/NEJMoa1812389.CrossRefPubMed

35.

Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. https://doi.org/10.1056/NEJMoa1603827.CrossRefPubMedPubMedCentral

36.

Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834–44. https://doi.org/10.1056/NEJMoa1607141.CrossRefPubMed

37.

Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121–30. https://doi.org/10.1016/s0140-6736(19)31149-3.CrossRefPubMed

38.

•• Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Furtado RHM, et al. Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus Systematic Review and Meta-Analysis of Cardiovascular Outcomes Trials. Circulation. 2019;139(17):2022–31. https://doi.org/10.1161/circulationaha.118.038868Systematic review and meta-analysis of cardiovascular outcomes trials with modern antihyperglycemic agents.CrossRefPubMed

39.

Kohsaka S, Lam CSP, Kim DJ, Cavender MA, Norhammar A, Jorgensen ME, et al. Risk of cardiovascular events and death associated with initiation of SGLT2 inhibitors compared with DPP-4 inhibitors: an analysis from the CVD-REAL 2 multinational cohort study. Lancet Diabetes & Endocrinology. 2020;8(7):606–15.CrossRef

40.

Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (PROspective pioglitAzone clinical trial in macroVascular events): a randomised controlled trial. Lancet. 2005;366(9493):1279–89. https://doi.org/10.1016/S0140-6736(05)67528-9.CrossRefPubMed

41.

Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2015;313(6):603–15. https://doi.org/10.1001/jama.2014.18574.CrossRefPubMed

42.

Patel KV, Vaduganathan M. Targeting multiple domains of residual cardiovascular disease risk in patients with diabetes. Curr Opin Cardiol. 2020;35(5):517–23. https://doi.org/10.1097/hco.0000000000000762.CrossRefPubMed

43.

Sjostrom L, Peltonen M, Jacobson P, Sjostrom CD, Karason K, Wedel H, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307(1):56–65. https://doi.org/10.1001/jama.2011.1914.CrossRefPubMed

44.

Stitziel NO, Kanter JE, Bornfeldt KE. Emerging targets for cardiovascular disease prevention in diabetes. Trends Mol Med. 2020;26(8):744–57. https://doi.org/10.1016/j.molmed.2020.03.011.CrossRefPubMed

Title: Diabetes, Lipids, and CV Risk
Author: Jan Škrha Jr
Publication date: 01-03-2021
Publisher: Springer US
Keywords: Dyslipidemia
PCSK9 Inhibitor
Arterial Occlusive Disease
Hyperglycemia
Incretin Mimetics
Incretin Mimetics
Published in: Current Atherosclerosis Reports / Issue 3/2021
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-021-00905-8

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com