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Type 2 diabetes, glycaemic traits and cardiovascular disease: a Mendelian Randomization study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.ORCID iD: 0000-0003-2247-8454
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0003-2256-6972
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.ORCID iD: 0000-0003-2071-5866
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Type 2 diabetes (T2D) and its hallmarks insulin resistance, impaired insulin secretion, and hyperglycaemia affect over 400 million persons worldwide and are associated with raised cardiovascular risk, but their causal role has been difficult to dissect due to overlap between risk factors. We used Mendelian randomization analysis, which utilises genetic polymorphisms associated with a risk factor, to assess causal effects of T2D, insulin resistance, insulin secretion, and fasting glucose on mortality, ischaemic stroke, and coronary artery disease (CAD) risk in 120,091 adults in the UK Biobank and in the CARDIoGRAMplusC4D consortium (63,746 cases of CAD and 130,681 controls). We found evidence for a causal effect of T2D on raised CAD risk (odds ratio (OR) per doubling in the odds of T2D, 1.07, 95% confidence interval (CI) 1.05 – 1.09, P = 1.2 x 10-9) and for a causal effect of impaired insulin secretion on the risk of CAD (OR per SD-unit decrease, 1.14, 95% CI 1.06 – 1.22, P = 0.002). The genetic score for insulin resistance was associated with increased coronary artery disease risk; however, sensitivity analysis indicated that the instrument might not be appropriate to use for robust causal inference testing. Our results support previous reports of a causal role of T2D and impaired insulin secretion in coronary artery disease and point to a complex relationship between variants affecting insulin resistance and cardiovascular outcomes.

Keyword [en]
diabetes, insulin resistance, mendelian randomization, uk biobank, heart disease, cardiovascular disease
National Category
Basic Medicine Clinical Medicine
Identifiers
URN: urn:nbn:se:uu:diva-316888OAI: oai:DiVA.org:uu-316888DiVA: diva2:1079252
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2017-03-14Bibliographically approved
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The full text will be freely available from 2017-05-22 03:13
Available from 2017-05-22 03:13

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