Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2019

Open Access 01-12-2019 | Diabetes | Review

Serum triglycerides as a risk factor for cardiovascular diseases in type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies

Authors: Xiaofeng Ye, Wen Kong, Mohammad Ishraq Zafar, Lu-Lu Chen

Published in: Cardiovascular Diabetology | Issue 1/2019

Login to get access

Abstract

Objective

The importance of triglycerides (TG) level as a risk factor for cardiovascular diseases (CVD) has been extensively investigated in the general population; however, their relationship in patients with type 2 diabetes mellitus (T2DM) is uncertain. We aimed to assess the association of TG with CVD in T2DM individuals.

Research design and methods

We searched bibliographic databases for studies published until June 2018, reporting on the relationship between TG and CVD in T2DM people. A random-effects model with inverse variance weighting was used to compute pooled estimates of the most fully adjusted risk ratios (RR) and corresponding 95% confidence intervals (CI) according to TG categories, unit TG, and logarithm (log) of TG for CVD.

Results

A total of 31 studies were included, involving 132,044 T2DM patients with 10,733 incident cardiovascular events. The pooled RR (95% CI) of CVD for an increase in baseline TG, log TG by 1-mmol/l and categorized in the highest vs. the lowest TG in T2DM were 1.06 (1.02, 1.09), 1.30 (1.18, 1.42) and 1.30 (1.16, 1.46), corresponding to a CVD risk increase of 6%, 30% and 30%, respectively. The pooled RR (95% CI) of CVD for per 1-mmol/L TG increment in eight studies and TG categories in three studies were 1.03 (0.98, 1.08) and 1.39 (0.92, 2.1) in T2DM patients adjusted for other lipids parameter, respectively.

Conclusions

In T2DM patients, an elevated triglyceride level cannot serve as an independent marker for an increased risk of cardiovascular events, but still, the higher serum TG levels tend to be associated with increased risks of CVD.
Appendix
Available only for authorised users
Literature
1.
WHO. World Health Statistics 2017: monitoring health for the SDGs. Geneva: WHO; 2017.
2.
De Backer G, Ambrosioni E, Borch-Johnsen K, Brotons C, Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham I, Mancia G, et al. European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Eur J Cardiovasc Prev Rehabil. 2003;10(4):S1–10.PubMedCrossRef
3.
Emerging Risk Factors C, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375(9733):2215–22.CrossRef
4.
5.
Laakso M. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes. 1999;48(5):937–42.PubMedCrossRef
6.
Pyorala K, Laakso M, Uusitupa M. Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev. 1987;3(2):463–524.PubMedCrossRef
7.
Lu W, Resnick HE, Jablonski KA, Jones KL, Jain AK, Howard WJ, Robbins DC, Howard BV. Non-HDL cholesterol as a predictor of cardiovascular disease in type 2 diabetes: the strong heart study. Diabetes Care. 2003;26(1):16–23.PubMedCrossRef
8.
Cavero-Redondo I, Peleteiro B, Alvarez-Bueno C, Rodriguez-Artalejo F, Martinez-Vizcaino V. Glycated haemoglobin A1c as a risk factor of cardiovascular outcomes and all-cause mortality in diabetic and non-diabetic populations: a systematic review and meta-analysis. BMJ Open. 2017;7(7):e015949.PubMedPubMedCentralCrossRef
9.
Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S, Boekholdt SM, Khaw KT, Gudnason V. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115(4):450–8.PubMedCrossRef
10.
Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol. 1998;81(4A):7B–12B.PubMedCrossRef
11.
Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626–35.PubMedCrossRef
12.
Sone H, Nakagami T, Nishimura R, Tajima N, Group MS. Comparison of lipid parameters to predict cardiovascular events in Japanese mild-to-moderate hypercholesterolemic patients with and without type 2 diabetes: subanalysis of the MEGA study. Diabetes Res Clin Pract. 2016;113:14–22.PubMedCrossRef
13.
Eliasson B, Gudbjornsdottir S, Zethelius B, Eeg-Olofsson K, Cederholm J, National Diabetes R. LDL-cholesterol versus non-HDL-to-HDL-cholesterol ratio and risk for coronary heart disease in type 2 diabetes. Eur J Prev Cardiol. 2014;21(11):1420–8.PubMedCrossRef
14.
Drexel H, Aczel S, Marte T, Vonbank A, Saely CH. Factors predicting cardiovascular events in statin-treated diabetic and non-diabetic patients with coronary atherosclerosis. Atherosclerosis. 2010;208(2):484–9.PubMedCrossRef
15.
Abu-Lebdeh HS, Hodge DO, Nguyen TT. Predictors of macrovascular disease in patients with type 2 diabetes mellitus. Mayo Clin Proc. 2001;76(7):707–12.PubMedCrossRef
16.
Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72(3):330–43.PubMedCrossRef
17.
Nichols GA, Philip S, Reynolds K, Granowitz CB, Fazio S. Increased residual cardiovascular risk in patients with diabetes and high versus normal triglycerides despite statin-controlled LDL cholesterol. Diabetes Obes Metab. 2019;21(2):366–71.PubMedCrossRef
18.
Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367(4):309–18.PubMedCrossRef
19.
Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, et al. Effects of n − 3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379(16):1540–50.PubMedCrossRef
20.
Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77917 individuals. JAMA Cardiol. 2018;3(3):225–34.PubMedCrossRef
21.
Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22.PubMedCrossRef
22.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12.PubMedCrossRef
23.
Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.PubMedCrossRef
24.
Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA. 1998;279(18):1477–82.PubMedCrossRef
25.
Shi JQ, Copas JB. Meta-analysis for trend estimation. Stat Med. 2004;23(1):3–19 (discussion 159-162).PubMedCrossRef
26.
27.
28.
Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.PubMedCrossRef
29.
30.
Yang SH, Du Y, Li XL, Zhang Y, Li S, Xu RX, Zhu CG, Guo YL, Wu NQ, Qing P, et al. Triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular events in diabetics with coronary artery disease. Am J Med Sci. 2017;354(2):117–24.PubMedCrossRef
31.
Morrison A, Hokanson JE. The independent relationship between triglycerides and coronary heart disease. Vascular health and risk management. 2009;5(1):89–95.PubMedPubMedCentral
32.
Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk. 1996;3(2):213–9.PubMedCrossRef
33.
Klempfner R, Erez A, Sagit BZ, Goldenberg I, Fisman E, Kopel E, Shlomo N, Israel A, Tenenbaum A. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the bezafibrate infarction prevention study and registry. Circ Cardiovasc Qual Outcomes. 2016;9(2):100–8.PubMedCrossRef
34.
Ren Y, Ren Q, Lu J, Guo X, Huo X, Ji L, Yang X. Low triglyceride as a marker for increased risk of cardiovascular diseases in patients with long-term type 2 diabetes: a cross-sectional survey in China. Diabetes/Metab Res Rev. 2018;34(2):e2960.CrossRef
35.
Goldberg IJ. 2017 George Lyman Duff Memorial Lecture: fat in the blood, fat in the artery, fat in the heart: triglyceride in physiology and disease. Arterioscler Thromb Vasc Biol. 2018;38(4):700–6.PubMedPubMedCentralCrossRef
36.
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.PubMedCrossRef
37.
38.
Liu J, Zeng FF, Liu ZM, Zhang CX, Ling WH, Chen YM. Effects of blood triglycerides on cardiovascular and all-cause mortality: a systematic review and meta-analysis of 61 prospective studies. Lipids Health Dis. 2013;12:159.PubMedPubMedCentralCrossRef
39.
Degoulet P, Legrain M, Reach I, Aime F, Devries C, Rojas P, Jacobs C. Mortality risk factors in patients treated by chronic hemodialysis. Report of the Diaphane collaborative study. Nephron. 1982;31(2):103–10.PubMedCrossRef
40.
Lowrie EG, Lew NL. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis. 1990;15(5):458–82.PubMedCrossRef
41.
Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, Goldberg AC, Howard WJ, Jacobson MS, Kris-Etherton PM, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292–333.PubMedCrossRef
42.
Tani S, Yagi T, Atsumi W, Kawauchi K, Matsuo R, Hirayama A. Relation between low-density lipoprotein cholesterol/apolipoprotein B ratio and triglyceride-rich lipoproteins in patients with coronary artery disease and type 2 diabetes mellitus: a cross-sectional study. Cardiovasc Diabetol. 2017;16(1):123.PubMedPubMedCentralCrossRef
43.
Han T, Cheng Y, Tian S, Wang L, Liang X, Duan W, Na L, Sun C. Changes in triglycerides and high-density lipoprotein cholesterol may precede peripheral insulin resistance, with 2-h insulin partially mediating this unidirectional relationship: a prospective cohort study. Cardiovasc Diabetol. 2016;15(1):154.PubMedPubMedCentralCrossRef
44.
Lee SB, Ahn CW, Lee BK, Kang S, Nam JS, You JH, Kim MJ, Kim MK, Park JS. Association between triglyceride glucose index and arterial stiffness in Korean adults. Cardiovasc Diabetol. 2018;17(1):41.PubMedPubMedCentralCrossRef
45.
Robertson RP, Harmon J, Tran PO, Poitout V. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004;53(Suppl 1):S119–24.PubMedCrossRef
46.
Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes. 1995;44(8):863–70.PubMedCrossRef
47.
Zhang M, Wang B, Liu Y, Sun X, Luo X, Wang C, Li L, Zhang L, Ren Y, Zhao Y, et al. Cumulative increased risk of incident type 2 diabetes mellitus with increasing triglyceride glucose index in normal-weight people: The Rural Chinese Cohort Study. Cardiovasc Diabetol. 2017;16(1):30.PubMedPubMedCentralCrossRef
48.
Grundy SM. Hypertriglyceridemia, insulin resistance, and the metabolic syndrome. Am J Cardiol. 1999;83(9b):25f–9f.PubMedCrossRef
49.
Schinner S, Scherbaum WA, Bornstein SR, Barthel A. Molecular mechanisms of insulin resistance. Diabet Med. 2005;22(6):674–82.PubMedCrossRef
50.
Kim JK, Fillmore JJ, Sunshine MJ, Albrecht B, Higashimori T, Kim DW, Liu ZX, Soos TJ, Cline GW, O’Brien WR, et al. PKC-theta knockout mice are protected from fat-induced insulin resistance. J Clin Investig. 2004;114(6):823–7.PubMedCrossRefPubMedCentral
51.
Trovati M, Anfossi G, Cavalot F, Massucco P, Mularoni E, Emanuelli G. Insulin directly reduces platelet sensitivity to aggregating agents. Studies in vitro and in vivo. Diabetes. 1988;37(6):780–6.PubMedCrossRef
52.
Kahn AM, Allen JC, Seidel CL, Zhang S. Insulin inhibits migration of vascular smooth muscle cells with inducible nitric oxide synthase. Hypertension. 2000;35(1 Pt 2):303–6.PubMedCrossRef
53.
Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773–95.PubMedPubMedCentralCrossRef
54.
Hedblad B, Nilsson P, Engstrom G, Berglund G, Janzon L. Insulin resistance in non-diabetic subjects is associated with increased incidence of myocardial infarction and death. Diabet Med. 2002;19(6):470–5.PubMedCrossRef
55.
Meigs JB, Larson MG, D’Agostino RB, Levy D, Clouse ME, Nathan DM, Wilson PW, O’Donnell CJ. Coronary artery calcification in type 2 diabetes and insulin resistance: The Framingham Offspring Study. Diabetes Care. 2002;25(8):1313–9.PubMedCrossRef
56.
Yamazoe M, Hisamatsu T, Miura K, Kadowaki S, Zaid M, Kadota A, Torii S, Miyazawa I, Fujiyoshi A, Arima H, et al. Relationship of insulin resistance to prevalence and progression of coronary artery calcification beyond metabolic syndrome components: shiga epidemiological study of subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 2016;36(8):1703–8.PubMedCrossRef
57.
Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: a meta-analysis. J Ethnopharmacol. 2016;194:260–8.PubMedCrossRef
58.
Boren J, Matikainen N, Adiels M, Taskinen MR. Postprandial hypertriglyceridemia as a coronary risk factor. Clin Chim Acta. 2014;431:131–42.PubMedCrossRef
59.
St-Pierre AC, Cantin B, Dagenais GR, Mauriege P, Bernard PM, Despres JP, Lamarche B. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol. 2005;25(3):553–9.PubMedCrossRef
60.
Kim MK, Ahn CW, Kang S, Nam JS, Kim KR, Park JS. Relationship between the triglyceride glucose index and coronary artery calcification in Korean adults. Cardiovasc Diabetol. 2017;16(1):108.PubMedPubMedCentralCrossRef
61.
Zheng T, Ge B, Liu H, Chen B, Qin L, Xiao L, Song J. Triglyceride-mediated influence of serum angiopoietin-like protein 8 on subclinical atherosclerosis in type 2 diabetic patients: results from the GDMD study in China. Cardiovasc Diabetol. 2018;17(1):84.PubMedPubMedCentralCrossRef
62.
Pierce FT Jr. The relationship of serum lipoproteins to atherosclerosis in the cholesterol-fed alloxanized rabbit. Circulation. 1952;5(3):401–7.PubMedCrossRef
63.
Brecher P, Chobanian AV, Small DM, Van Sickle W, Tercyak A, Lazzari A, Baler J. Relationship of an abnormal plasma lipoprotein to protection from atherosclerosis in the cholesterol-fed diabetic rabbit. J Clin Investig. 1983;72(5):1553–62.PubMedCrossRefPubMedCentral
64.
Nordestgaard BG, Stender S, Kjeldsen K. Reduced atherogenesis in cholesterol-fed diabetic rabbits. Giant lipoproteins do not enter the arterial wall. Arteriosclerosis. 1988;8(4):421–8.PubMedCrossRef
65.
Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495–504.PubMedCrossRef
66.
Toth PP, Granowitz C, Hull M, Liassou D, Anderson A, Philip S. High triglycerides are associated with increased cardiovascular events, medical costs, and resource use: a real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk. J Am Heart Assoc. 2018;7(15):e008740.PubMedPubMedCentralCrossRef
67.
Tada H, Kawashiri MA, Nomura A, Yoshimura K, Itoh H, Komuro I, Yamagishi M. Serum triglycerides predict first cardiovascular events in diabetic patients with hypercholesterolemia and retinopathy. Eur J Prev Cardiol. 2018;25(17):1852–60.PubMedCrossRef
68.
Fox CS, Golden SH, Anderson C, Bray GA, Burke LE, de Boer IH, Deedwania P, Eckel RH, Ershow AG, Fradkin J, et al. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care. 2015;38(9):1777–803.PubMedPubMedCentralCrossRef
69.
70.
Tenenbaum A, Fisman EZ. Omega-3 polyunsaturated fatty acids supplementation in patients with diabetes and cardiovascular disease risk: does dose really matter? Cardiovasc Diabetol. 2018;17(1):119.PubMedPubMedCentralCrossRef
71.
Fruchart JC. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator for management of atherogenic dyslipidaemia. Cardiovasc Diabetol. 2017;16(1):124.PubMedPubMedCentralCrossRef
72.
Fan W, Philip S, Granowitz C, Toth PP, Wong ND. Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey. J Clin Lipidol. 2019;13(1):100–8.PubMedCrossRef
73.
Emerging Risk Factors C, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.CrossRef
Metadata
Title
Serum triglycerides as a risk factor for cardiovascular diseases in type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies
Authors
Xiaofeng Ye
Wen Kong
Mohammad Ishraq Zafar
Lu-Lu Chen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2019
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-019-0851-z

Other articles of this Issue 1/2019

Cardiovascular Diabetology 1/2019 Go to the issue

Original investigation

Impaired branched chain amino acid oxidation contributes to cardiac insulin resistance in heart failure

Correction

Correction to: GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data

Original investigation

Targeting the glucagon receptor improves cardiac function and enhances insulin sensitivity following a myocardial infarction

Original investigation

GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy

Original investigation

Coronary microvascular dysfunction is associated with poor glycemic control amongst female diabetics with chest pain and non-obstructive coronary artery disease

Hypothesis

Disease–treatment interactions in the management of patients with obesity and diabetes who have atrial fibrillation: the potential mediating influence of epicardial adipose tissue

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

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

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