Association of coffee consumption with type 2 diabetes and glycemic traits: a Mendelian randomization study.

Background/objectives: Habitual coffee consumption was inversely associated with type 2 diabetes (T2D) and hyperglycemia in observational studies, but the causality of the association remains uncertain. This study tested a causal association of genetically predicted coffee consumption with T2D using the Mendelian randomization (MR) method.

Subjects/methods: We used five single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) associated with habitual coffee consumption in a previous genome-wide association study among Koreans. We analyzed the associations between IVs and T2D, fasting blood glucose (FBG), 2h-postprandial glucose (2h-PG), and glycated haemoglobin (HbA1C) levels. The MR results were further evaluated by standard sensitivity tests for possible pleiotropism.

Results: MR analysis revealed that increased genetically predicted coffee consumption was associated with a reduced prevalence of T2D; ORs per one-unit increment of log-transformed cup per day of coffee consumption ranged from 0.75 (0.62-0.90) for the weighted mode-based method to 0.79 (0.62-0.99) for Wald ratio estimator. We also used the inverse-variance-weighted method, weighted median-based method, MR-Egger method, and MR-PRESSO method. Similarly, genetically predicted coffee consumption was inversely associated with FBG and 2h-PG levels but not with HbA1c. Sensitivity measures gave similar results without evidence of pleiotropy.

Conclusions: A genetic predisposition to habitual coffee consumption was inversely associated with T2D prevalence and lower levels of FBG and 2h-PG profiles. Our study warrants further exploration.