| 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 |
| Journal: | Diabetic Medicine |
| Published: | 11 Feb 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33501652/ |
| DOI: | https://doi.org/10.1111/dme.14531 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.14531 |
Publication 13779
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Abstract
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.</p>
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.</p>
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]).</p>
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.</p>
14 Keywords
- Adiposity
- Adult
- Aged
- Blood Pressure
- Body Mass Index
- Diabetes Mellitus, Type 2
- Female
- Follow-Up Studies
- Genetic Predisposition to Disease
- Humans
- Male
- Metabolome
- Middle Aged
- Obesity
17 Authors
- Adrian H. Heald
- Susan Martin
- Helene Fachim
- Harry D. Green
- Katherine G. Young
- Nagaraj Malipatil
- Kirk Siddals
- Gabriela Cortes
- Jessica Tyrrell
- Andrew R Wood
- Robin N. Beaumont
- Timothy M. Frayling
- Rachelle Donn
- Ram Prakash Narayanan
- William Ollier
- Martin Gibson
- Hanieh Yaghootkar
Enabling scientific discoveries that improve human health