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Title: | Genetically defined favourable adiposity is not associated with a clinically meaningful difference in clinical course in people with type 2 diabetes but does associate with a favourable metabolic profile |
Authors: | Heald, AH Martin, S Fachim, H Green, HD Young, KG Malipatil, N Siddals, K Cortes, G Tyrrell, J Wood, AR Beaumont, RN Frayling, TM Donn, R Narayanan, RP Ollier, W Gibson, M Yaghootkar, H |
Keywords: | BMI;ectopic fat;favourable adiposity genetic score;HbA1c;metabolic profile;myocardial infarction;stroke;type 2 diabetes |
Issue Date: | 27-Jan-2021 |
Publisher: | John Wiley & Sons Ltd on behalf of Diabetes UK |
Citation: | Heald, A.H. et al. (2021) 'Genetically defined favourable adiposity is not associated with a clinically meaningful difference in clinical course in people with type 2 diabetes but does associate with a favourable metabolic profile', Diabetic Medicine, 38 (9), e14531, pp. 1 - 11. doi: 10.1111/dme.14531 |
Abstract: | Copyright © 2021 The Authors. Aims Change in weight, HbA1c, lipids, blood pressure and cardiometabolic events over time is variable in individuals with type 2 diabetes. We hypothesised that people with a genetic predisposition to a more favourable adiposity distribution could have a less severe clinical course/progression. Methods We involved people with type 2 diabetes from two UK-based cohorts: 11,914 individuals with GP follow-up data from the UK Biobank and 723 from Salford. We generated a ‘favourable adiposity’ genetic score and conducted cross-sectional and longitudinal studies to test its association with weight, BMI, lipids, blood pressure, medication use and risk of myocardial infarction and stroke using 15 follow-up time points with 1-year intervals. Results The ‘favourable adiposity’ genetic score was cross-sectionally associated with higher weight (effect size per 1 standard deviation higher genetic score: 0.91 kg [0.59,1.23]) and BMI (0.30 kg/m2 [0.19,0.40]), but higher high-density lipoprotein (0.02 mmol/L [0.01,0.02]) and lower triglycerides (−0.04 mmol/L [−0.07, −0.02]) in the UK Biobank at baseline, and this pattern of association was consistent across follow-up. There was a trend for participants with higher ‘favourable adiposity’ genetic score to have lower risk of myocardial infarction and/or stroke (odds ratio 0.79 [0.62, 1.00]) compared to those with lower score. A one standard deviation higher score was associated with lower odds of using lipid-lowering (0.91 [0.86, 0.97]) and anti-hypertensive medication (0.95 [0.91, 0.99]). Conclusions In individuals with type 2 diabetes, having more ‘favourable adiposity’ alleles is associated with a marginally better lipid profile long-term and having lower odds of requiring lipid-lowering or anti-hypertensive medication in spite of relatively higher adiposity. |
Description: | Data availability statement: We used patient-level data which was fully anonymised prior to analysis. Any requests for access to the Salford data should be made to Dr Adrian Heald. |
URI: | https://bura.brunel.ac.uk/handle/2438/25387 |
DOI: | https://doi.org/10.1111/dme.14531 |
ISSN: | 0742-3071 |
Other Identifiers: | e14531 ORCiD ID: Hanieh Yaghootkar - https://orcid.org/0000-0001-9672-9477. |
Appears in Collections: | Dept of Life Sciences Research Papers |
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