Abstract
INTRODUCTION: Type 2 diabetes (T2D) is multifactorial involving lifestyle, environmental and genetic risk factors. This study aims to investigate the impact of genetic interactions with alcohol and diet quality on glycated haemoglobin A1c (HbA1c) independent of obesity, in a British population. METHODS: Cross-sectional study of 14 089 white British participants from Airwave Health Monitoring Study and a subsample of 3733 participants with dietary data. A T2D genetic risk score (GRS) was constructed, and its interactions with diet on HbA1c were assessed. RESULTS: GRS was associated with a higher HbA1c% (β = 0.03, P < 0.0001) and a higher risk of prediabetes (OR = 1.09, P < 0.0001) and T2D (OR = 1.14, P = 0.006). The genetic effect on HbA1c% was significantly higher in obese participants (β = 1.88, P (interaction) = 0.03). A high intake of wholegrain attenuated the effect on HbA1c% in high-risk individuals P (interaction) = 0.04. CONCLUSION: The genetic effect on HbA1c was almost doubled in obese individuals, compared with those with a healthy weight, and independent of weight, there was a modest offset on HbA1c in high-genetic-risk individuals consuming a diet high in wholegrain. This supports the importance of a healthy diet high in wholegrains and along with maintaining a healthy weight in controlling HbA1c among high-genetic-risk groups.