Type 2 Diabetes Mellitus and Cardiovascular Health: Evidence of Causal Relationships in a European Ancestry Population
Authors' conclusion
Our MR study demonstrates that genetic liability to T2DM plays causal roles in CAD, MI, stroke, and cardiac structure changes including left ventricular hypertrophy and reduced right atrial dimensions.
Study context
- Population
- European-ancestry GWAS summary data; T2DM GWAS from DIAGRAM consortium80,154 T2DM cases · 853,816 controls
- Comparison
- Genetic predisposition to T2DM
- Outcome
- CAD, MI, stroke, HF, AF and cardiac structure/function by MRI
Methodological detailsbidirectional, two-sample, multivariable Mendelian randomization (MR)
- Bidirectional
- Two-sample
- Multivariable MR
Main finding
As reported in the abstract
CAD, MI, stroke
Genetic predisposition to T2DMOdds ratio (95% CI)P value
CAD
1.104(1.078–1.130)
P = 2.59e-16MI
1.129(1.094–1.166)
P = 6.02e-14Stroke
1.086(1.064–1.109)
P = 1.02e-14Further findings
| Outcome | β (95% CI) | P value |
|---|---|---|
| Cardiac MRI traits: LV mass index, indexed RA minimum and maximum areasT2DM · higher LV mass index | 0.473 (0.193–0.752) | P = 0.001 |
| Cardiac MRI traits: LV mass index, indexed RA minimum and maximum areasT2DM · lower indexed RA minimum area | −0.048 (−0.073 to −0.022) | P = 2.1e-5 |
| Cardiac MRI traits: LV mass index, indexed RA minimum and maximum areasT2DM · lower indexed RA maximum area | −0.042 (−0.065 to −0.019) | P = 4.12e-5 |
Coronary artery disease (CAD), myocardial infarction (MI), stroke – validation in FinnGen cohort
- CAD: OR
- 1.117 (1.075-1.158), P = 1.56e-9 (95% CI)
- MI: OR
- 1.132 (1.083-1.184), P = 4.27e-8 (95% CI)
- Stroke: OR
- 1.138 (1.107-1.170), P = 3.52e-20 (95% CI)
CAD, MI, stroke – multivariable MR adjusted for cardiometabolic traits
- CAD: OR
- 1.063 (1.031-1.097), P = 1.11e-4 (95% CI)
- MI: OR
- 1.088 (1.042-1.135), P = 1.12e-4 (95% CI)
- Stroke: OR
- 1.066 (1.032-1.101), P = 1.18e-4 (95% CI)
- Consistent findings
RA size after adjusting for risk factors
- Minimum area: β
- −0.041 (−0.072 to −0.010), P = 0.009 (95% CI)
- Maximum area: β
- −0.039 (−0.069 to −0.008), P = 0.012 (95% CI)
- Remained significant
Mediators of T2DM–LV mass index relationship
- Apolipoprotein A1 and SBP are important mediators
Reverse causation
- No reverse causal associations identified
Original publication
Type 2 Diabetes Mellitus and Cardiovascular Health: Evidence of Causal Relationships in a European Ancestry Population. ESC Heart Fail. Published 12 June 2024. doi:10.
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