Abstract
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. 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. The 'favourable adiposity' genetic score was cross-sectionally associated with higher weight (effect size per 1 standard deviation higher genetic score: 0.91kg [0.59,1.23]) and BMI (0.30kg/m2 [0.19,0.40]), but higher high-density lipoprotein (0.02mmol/L [0.01,0.02]) and lower triglycerides (-0.04mmol/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]). 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.
Highlights
Changes in weight, glycated haemoglobin (HbA1c), lipids and blood pressure over time display significant variability across individuals with type 2 diabetes, with many and varied determinants including genetic, environmental and lifestyle factors
We show that a ‘favourable adiposity’ genetic score is associated with higher weight but a healthier lipid profile in people with type 2 diabetes, and lower odds of requiring lipid-lowering or anti-hypertensive medication during the course of their disease
We identified 12,787 European type 2 diabetes cases in the UK Biobank using collated general practitioner (GP) records as those not coded as having non-type 2 types of diabetes and either (a) any two of the following criteria were met: (1) quality and outcome framework (QOF) diagnosis codes for diabetes provided by the NHS in GP record data, (2) HbA1c >= 48 mmol/mol (6.5%) and (3) a prescription for glucose-lowering medication, or (b) prescriptions were given for two or more different classes of glucose-lowering medication
Summary
Changes in weight, glycated haemoglobin (HbA1c), lipids and blood pressure over time display significant variability across individuals with type 2 diabetes, with many and varied determinants including genetic, environmental and lifestyle factors. Weight gain in type 2 diabetes is associated with multiple adverse consequences.[1] long-term follow-u p studies have clearly shown a direct relation between the levels of blood pressure, glucose and low-density lipoprotein cholesterol (LDL), and the complications of diabetes.[2,3]. The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated the unequivocal benefit of intensive treatment of dyslipidaemia and hypertension in terms of reducing cardiovascular event rate and mortality rate.[4] If individuals who are more likely to develop diabetes complications can be identified early, both lifestyle advice and pharmacotherapy can be targeted appropriately This could make a very significant difference to outcomes for individuals with type 2 diabetes
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