ACE and Type 2 Diabetes Risk: A Mendelian Randomization Study


Marie Pigeyre 1 2 3, Jennifer Sjaarda 1 2 4, Michael Chong 1 2 4, Sibylle Hess 5, Jackie Bosch 1 6, Salim Yusuf 1 7, Hertzel Gerstein 1 3, Guillaume Paré 8 2 4 7

Main idea: These results support the causal protective effect of ACE inhibitors on type 2 diabetes risk and may guide therapeutic decision making in clinical practice.


Objective: To determine whether ACE inhibitors reduce the risk of type 2 diabetes using a Mendelian randomization (MR) approach.

Research design and methods: A two-sample MR analysis included 17 independent genetic variants associated with ACE serum concentration. The effects of ACE inhibitors on type 2 diabetes risk were estimated from 18 studies of the DIAbetes Genetics Replication And Meta-analysis consortium. A genetic risk score (GRS) underpinning lower ACE concentration was then tested for association with type two diabetes prevalence.

Results: Genetically lower ACE concentrations were associated with a lower risk of type 2 diabetes. This result was replicated in the UK Biobank. After standardization, the ACE GRS was associated. with a larger decrease in diabetes risk per 2.4-mmHg lower mean arterial pressure (MAP) compared with that obtained from an RCT meta-analysis.


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