J Korean Diabetes.  2022 Mar;23(1):28-34. 10.4093/jkd.2022.23.1.28.

Lipid Variability and Diabetes Mellitus

• Lee J
• Lee SH

• KMID: 2528408
• DOI: http://doi.org/10.4093/jkd.2022.23.1.28

Abstract

Diabetic dyslipidemia is characterized by hypertriglyceridemia, low HDL (high-density lipoprotein)-cholesterol, elevated LDL (low-density lipoprotein)-cholesterol, and predominance of small dense LDL particles caused by insulin resistance in type 2 diabetes or insulin deficiency in type 1 diabetes. Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease in diabetes, and lowering lipid levels can reduce its morbidity and mortality. Current guidelines for dyslipidemia management recommend that the LDL-C goal be lower than 55~100 mg/dL depending on the underlying risk factors. However, higher visit-to-visit variability in cholesterol levels might be an independent predictor of major adverse cardiovascular events and poor renal outcomes in diabetes. In this review, we focused on clinical implications of lipid variability in diabetes.

Keyword

Cholesterol; LDL; Diabetes complications; Dyslipidemias; Triglycerides

Reference

1.Oh HJ., Yang DM., Kim CH., Jeon JG., Jung NH., Kim CY, et al. Exploring mortality rates for major causes of death in Korea. Open Public Health J. 2019. 12:16–25.

2.American Diabetes Association. 9. Cardiovascular disease and risk management. Diabetes Care. 2017. 40(Suppl 1):S75–87.

3.Hirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb. 2018. 25:771–82.

4.Bekele S., Yohannes T., Mohammed AE. Dyslipidemia and associated factors among diabetic patients attending Du-rame General Hospital in Southern Nations, Nationalities, and People's Region. Diabetes Metab Syndr Obes. 2017. 10:265–71.

5.Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010. 376:1670–81.

6.Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of statin therapy in older people: a meta-anal-ysis of individual participant data from 28 randomised controlled trials. Lancet. 2019. 393:407–15.

7.Reaven GM. Compensatory hyperinsulinemia and the development of an atherogenic lipoprotein profile: the price paid to maintain glucose homeostasis in insulin-resistant individuals. Endocrinol Metab Clin North Am. 2005. 34:49–62.

8.Wu L., Parhofer KG. Diabetic dyslipidemia. Metabolism. 2014. 63:1469–79.

9.Bonilha I., Hajduch E., Luchiari B., Nadruz W., Le Goff W., Sposito AC. The reciprocal relationship between LDL metabolism and type 2 diabetes mellitus. Metabolites. 2021. 11:807.

10.Srivastava RAK. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Mol Cell Biochem. 2018. 440:167–87.

11.Monaldi B., Bologna G., Costa GG., D'Agostino C., Ferrante F., Filice M, et al. Adherence to statin treatment following a myocardial infarction: an Italian population-based sur-vey. Clinicoecon Outcomes Res. 2015. 7:273–80.

12.Heeschen C., Hamm CW., Laufs U., Snapinn S., Böhm M., White HD. Withdrawal of statins increases event rates in patients with acute coronary syndromes. Circulation. 2002. 105:1446–52.

13.Zhang L., Wang W., Man F., Pan Q., Guo L. The effect of statin adherence on patients with type 2 diabetes after percutaneous coronary intervention for acute coronary syndrome. Cardiovasc Drugs Ther 2022. DOI: doi: 10.1007/s10557-021-07260-5. [Epub ahead of print].

14.Sposito AC., Carvalho LS., Cintra RM., Araújo AL., Ono AH., Andrade JM, et al. Rebound inflammatory response during the acute phase of myocardial infarction after sim-vastatin withdrawal. Atherosclerosis. 2009. 207:191–4.

15.Rodriguez F., Maron DJ., Knowles JW., Virani SS., Lin S., Heidenreich PA. Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease. JAMA Cardiol. 2019. 4:206–13.

16.Stephenson MC., Leverton E., Khoo EY., Poucher SM., Johansson L., Lockton JA, et al. Variability in fasting lipid and glycogen contents in hepatic and skeletal muscle tis-sue in subjects with and without type 2 diabetes: a 1H and 13C MRS study. NMR Biomed. 2013. 26:1518–26.

17.Tsalamandris C., Panagiotopoulos S., Allen TJ., Waldrip L., Van Gaal B., Goodall I, et al. Long-term intraindividual variability of serum lipids in patients with type I and type II diabetes. J Diabetes Complications. 1998. 12:208–14.

18.Bardini G., Dicembrini I., Rotella CM., Giannini S. Lipids seasonal variability in type 2 diabetes. Metabolism. 2012. 61:1674–7.

19.Rhee EJ., Han K., Ko SH., Ko KS., Lee WY. Increased risk for diabetes development in subjects with large variation in total cholesterol levels in 2,827,950 Koreans: a nationwide population-based study. PLoS One. 2017. 12:e0176615.

20.Lee SH., Kim HS., Park YM., Kwon HS., Yoon KH., Han K, et al. HDL-cholesterol, its variability, and the risk of diabetes: a nationwide population-based study. J Clin Endocrinol Metab. 2019. 104:5633–41.

21.Kwon YH., Kim SK., Cho JH., Kwon H., Park SE., Oh HG, et al. The association between persistent hypertriglyceridemia and the risk of diabetes development: The Kang-buk Samsung Health Study. Endocrinol Metab (Seoul). 2018. 33:55–61.

22.Kreger BE., Odell PM., D'Agostino RB., Wilson PF. Long-term intraindividual cholesterol variability: natural course and adverse impact on morbidity and mortality–the Framingham Study. Am Heart J. 1994. 127:1607–14.

23.Hsu WH., Lai CW., Chen SC., Chiou HC., Hsiao PJ., Shin SJ, et al. Greater low-density lipoprotein cholesterol variability increases the risk of cardiovascular events in patients with type 2 diabetes mellitus. Endocr Pract. 2019. 25:918–25.

24.Wan EYF., Yu EYT., Chin WY., Barrett JK., Mok AHY., Lau CST, et al. Greater variability in lipid measurements associated with cardiovascular disease and mortality: a 10-year diabetes cohort study. Diabetes Obes Metab. 2020. 22:1777–88.

25.Wang MC., Li CI., Liu CS., Lin CH., Yang SY., Li TC, et al. Effect of blood lipid variability on mortality in patients with type 2 diabetes: a large single-center cohort study. Cardiovasc Diabetol. 2021. 20:228.

26.Sheng CS., Miao Y., Ding L., Cheng Y., Wang D., Yang Y, et al. Prognostic significance of visit-to-visit variability, and maximum and minimum LDL cholesterol in diabetes mellitus. Lipids Health Dis. 2022. 21:19.

27.Gosmanova EO., Mikkelsen MK., Molnar MZ., Lu JL., Yes-sayan LT., Kalantar-Zadeh K, et al. Association of systolic blood pressure variability with mortality, coronary heart disease, stroke, and renal disease. J Am Coll Cardiol. 2016. 68:1375–86.

28.Kim MK., Han K., Kim HS., Park YM., Kwon HS., Yoon KH, et al. Effects of variability in blood pressure, glucose, and cholesterol concentrations, and body mass index on endstage renal disease in the general population of Korea. J Clin Med. 2019. 8:755.

29.Li L., Wang F., Xu M., Lu JL., Zhao ZY., Li M, et al. Association of visit-to-visit variabilities in metabolic factors with chronic kidney disease in Chinese adults living in Shang-hai. Biomed Environ Sci. 2021. 34:761–72.

30.Chang YH., Chang DM., Lin KC., Hsieh CH., Lee YJ. High-density lipoprotein cholesterol and the risk of ne-phropathy in type 2 diabetic patients. Nutr Metab Cardiovasc Dis. 2013. 23:751–7.

31.Ceriello A., De Cosmo S., Rossi MC., Lucisano G., Geno-vese S., Pontremoli R, et al. Variability in HbA_1c, blood pressure, lipid parameters and serum uric acid, and risk of development of chronic kidney disease in type 2 diabetes. Diabetes Obes Metab. 2017. 19:1570–8.

32.Matsuoka-Uchiyama N., Uchida HA., Okamoto S., Onishi Y., Katayama K., Tsuchida-Nishiwaki M, et al. The association of postprandial triglyceride variability with renal dysfunction and microalbuminuria in patients with type 2 diabetic mellitus: a retrospective and observational study. J Diabetes Res. 2022. 2022:3157841.

33.Wan EYF., Yu EYT., Chin WY., Lau CST., Mok AHY., Wang Y, et al. Greater variability in lipid measurements associated with kidney diseases in patients with type 2 diabetes mellitus in a 10-year diabetes cohort study. Sci Rep. 2021. 11:8047.

34.Epstein M., Vaziri ND. Statins in the management of dyslipidemia associated with chronic kidney disease. Nat Rev Nephrol. 2012. 8:214–23.

35.Mann DM., Glazer NL., Winter M., Paasche-Orlow MK., Muntner P., Shimbo D, et al. A pilot study identifying statin nonadherence with visit-to-visit variability of low-den-sity lipoprotein cholesterol. Am J Cardiol. 2013. 111:1437–42.

36.Kim MK., Han K., Park YM., Kwon HS., Kang G., Yoon KH, et al. Associations of variability in blood pressure, glucose and cholesterol concentrations, and body mass index with mortality and cardiovascular outcomes in the general population. Circulation. 2018. 138:2627–37.

37.Smit RAJ., Jukema JW., Postmus I., Ford I., Slagboom PE., Heijmans BT, et al. Visit-to-visit lipid variability: clinical significance, effects of lipid-lowering treatment, and (pharmaco) genetics. J Clin Lipidol. 2018. 12:266–76.e3.

38.Bangalore S., Breazna A., DeMicco DA., Wun CC., Messerli FH. Visit-to-visit low-density lipoprotein cholesterol variability and risk of cardiovascular outcomes: insights from the TNT trial. J Am Coll Cardiol. 2015. 65:1539–48.

39.Keating AJ., Campbell KB., Guyton JR. Intermittent non-daily dosing strategies in patients with previous statin-in-duced myopathy. Ann Pharmacother. 2013. 47:398–404.

40.Qamar A., Giugliano RP., Keech AC., Kuder JF., Murphy SA., Kurtz CE, et al. Interindividual variation in low-density lipoprotein cholesterol level reduction with evolocumab: an analysis of FOURIER trial data. JAMA Cardiol. 2019. 4:59–63.