Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Apr 22:13:840579.
doi: 10.3389/fendo.2022.840579. eCollection 2022.

Causal Association of Type 2 Diabetes Mellitus and Glycemic Traits With Cardiovascular Diseases and Lipid Traits: A Mendelian Randomization Study

Mingkai Huang  1   2 , Loum-Davadi Laina-Nicaise  1   2 , Lingfeng Zha  1   2 , Tingting Tang  1   2 , Xiang Cheng  1   2
Affiliations

Causal Association of Type 2 Diabetes Mellitus and Glycemic Traits With Cardiovascular Diseases and Lipid Traits: A Mendelian Randomization Study

Mingkai Huang et al. Front Endocrinol (Lausanne). .

Abstract

Objective: We aimed to evaluate the causal effect of type 2 diabetes mellitus (T2DM) and glycemic traits on the risk of a wide range of cardiovascular diseases (CVDs) and lipid traits using Mendelian randomization (MR).

Methods: Genetic variants associated with T2DM, fasting glucose, fasting insulin, and hemoglobin A1c were selected as instrumental variables to perform both univariable and multivariable MR analyses.

Results: In univariable MR, genetically predicted T2DM was associated with higher odds of peripheral artery disease (pooled odds ratio (OR) =1.207, 95% CI: 1.162-1.254), myocardial infarction (OR =1.132, 95% CI: 1.104-1.160), ischemic heart disease (OR =1.129, 95% CI: 1.105-1.154), heart failure (OR =1.050, 95% CI: 1.029-1.072), stroke (OR =1.087, 95% CI: 1.068-1.107), ischemic stroke (OR =1.080, 95% CI: 1.059-1.102), essential hypertension (OR =1.013, 95% CI: 1.010-1.015), coronary atherosclerosis (OR =1.005, 95% CI: 1.004-1.007), and major coronary heart disease event (OR =1.003, 95% CI: 1.002-1.004). Additionally, T2DM was causally related to lower levels of high-density lipoprotein cholesterol (OR =0.965, 95% CI: 0.958-0.973) and apolipoprotein A (OR =0.982, 95% CI: 0.977-0.987) but a higher level of triglycerides (OR =1.060, 95% CI: 1.036-1.084). Moreover, causal effect of glycemic traits on CVDs and lipid traits were also observed. Finally, most results of univariable MR were supported by multivariable MR.

Conclusion: We provided evidence for the causal effects of T2DM and glycemic traits on the risk of CVDs and dyslipidemia. Further investigations to elucidate the underlying mechanisms are warranted.

Keywords: Mendelian randomization; cardiovascular disease; diabetes; glycemic traits; lipid.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mendelian randomization model.
Figure 2
Figure 2
Overview of the main results of Univariable MR.
Figure 3
Figure 3
The association between type 2 diabetes mellitus and outcomes.
Figure 4
Figure 4
The association between fasting glucose (mmol/mol) and outcomes.
Figure 5
Figure 5
The association between fasting insulin (mmol/mol) and outcomes.
Figure 6
Figure 6
The association between HbA1c (mmol/mol) and outcomes.
See this image and copyright information in PMC

References

    1. Woodward M, Zhang X, Barzi F, Pan W, Ueshima H, Rodgers A, et al. The Effects of Diabetes on the Risks of Major Cardiovascular Diseases and Death in the Asia-Pacific Region. Diabetes Care (2003) 26(2):360–6. doi: 10.2337/diacare.26.2.360 - DOI - PubMed
    1. Ning F, Tuomilehto J, Pyörälä K, Onat A, Söderberg S, Qiao Q. Cardiovascular Disease Mortality in Europeans in Relation to Fasting and 2-H Plasma Glucose Levels Within a Normoglycemic Range. Diabetes Care (2010) 33(10):2211–6. doi: 10.2337/dc09-2328 - DOI - PMC - PubMed
    1. Libman IM, Barinas-Mitchell E, Bartucci A, Chaves-Gnecco D, Robertson R, Arslanian S. Fasting and 2-Hour Plasma Glucose and Insulin: Relationship With Risk Factors for Cardiovascular Disease in Overweight Nondiabetic Children. Diabetes Care (2010) 33(12):2674–6. doi: 10.2337/dc10-0085 - DOI - PMC - PubMed
    1. Gore MO, McGuire DK. A Test in Context: Hemoglobin A(1c) and Cardiovascular Disease. J Am Coll Cardiol (2016) 68(22):2479–86. doi: 10.1016/j.jacc.2016.08.070 - DOI - PubMed
    1. Kim HK, Kim CH, Kim EH, Bae SJ, Choe J, Park JY, et al. Impaired Fasting Glucose and Risk of Cardiovascular Disease in Korean Men and Women: The Korean Heart Study. Diabetes Care (2013) 36(2):328–35. doi: 10.2337/dc12-0587 - DOI - PMC - PubMed

MeSH terms