ABSTRACT

Background and aim:
Diabetic microvascular complications pose significant health challenges for individuals. The influence of modifiable lifestyle factors, such as coffee intake, on these complications has not been conclusively determined, highlighting the need for a causality assessment.

Methods and results:  
Utilizing Mendelian randomization (MR), this study explored the causal links between coffee intake, plasma caffeine levels, and diabetic microvascular complications using data from FinnGen. Single nucleotide polymorphisms associated with coffee intake and plasma caffeine levels were identified through genome-wide association study meta-analyses. The univariable MR analysis indicated a slightly increased risk for diabetic retinopathy (OR 1.006; 95% CI: 1.002–1.010; P = 0.003) and a suggestively elevated risk for nephropathy (OR 1.011; 95% CI: 1.001–1.022; P = 0.036) associated with genetically predicted higher coffee intake, while no significant effect on neuropathy was observed. Multivariable MR analysis, adjusted for smoking, revealed a significant protective effect of coffee intake on diabetic retinopathy (OR 0.895; 95% CI: 0.856–0.936; P = 9.468×10-7) and a suggestive reduction in risk for diabetic nephropathy (OR 0.828; 95% CI: 0.712–0.963; P = 0.014). Higher plasma caffeine levels were also suggestively protective against these complications.

Conclusions:
Our findings suggest that genetically predicted higher coffee intake and plasma caffeine levels are protective for diabetic retinopathy and nephropathy. Further research is necessary to substantiate these findings and to investigate their potential impact on diabetes management strategies.

‍