| 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 |
| Publisher Information: |
Wiley |
| Publication Year: |
2021 |
| Collection: |
eSpace - Manchester Metropolitan University's Research Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://e-space.mmu.ac.uk/636310/; http://dx.doi.org/10.1111/dme.14531 |
| Availability: |
https://e-space.mmu.ac.uk/636310/1/Diabetic%20Medicine%20-%202021%20-%20Heald%20-%20Genetically%20defined%20favourable%20adiposity%20is%20not%20associated%20with%20a%20clinically%20meaningful.pdf |
| Rights: |
cc_by_4 ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.218912A5 |
| Database: |
BASE |