Long term use of ACE inhibitors not only lowers BP, but reduces diabetes risk also

Angiotensin-converting enzyme (ACE) inhibitors are high blood pressure drugs that dilate blood vessels to increase blood flow and lower high blood pressure. ACE inhibitors are particularly useful when hypertension is associated with diabetes and also have a protective role for kidneys.

A new study has revealed that long term usage of high blood pressure drugs angiotensin-converting enzyme (ACE) inhibitors to lower blood pressure, is associated with a 24% reduced risk of developing type 2 diabetes (T2D) when compared with placebo. The findings of the research have been presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 September).

Professor Marie Pigeyre of the Genetic and Molecular Epidemiology Laboratory, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada and colleagues have found the protective effect of ACE inhibitors on T2D risk in their study which may be incorporated in future guidelines according to the researchers. .

Although previous research has suggested that ACE inhibitors may prevent T2D, the causal relationship between ACE inhibition and prevention from T2D remains questionable. In this new study, the authors used a 'Mendelian Randomisation' approach. Specifically, they assessed a person's risk of developing T2D based on natural genetic variations that influence the concentration of the ACE enzyme in the blood, and used this to infer the causal effects that ACE inhibitors would have on T2D risk.

First, the authors assessed the association between T2D prevalence and ACE serum concentration in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (N=8,197). Next, they investigated whether 17 genetic variants linked to lower ACE concentrations in the ORIGIN study (N=4,147) were also linked to lower prevalence of T2D in the DIAbetes Genetics Replication And Meta-analysis consortium (n=26,676 cases; 132,532 controls).

The researchers then constructed an ACE concentration-lowering genetic risk score (GRS) and tested it for association with T2D prevalence in the UK Biobank cohort (N=341,872). Finally, they compared the genetically determined effect of lower ACE concentrations on T2D risk to the pharmacological inhibition of ACE versus placebo, with a meta-analysis of randomised clinical trials (including 31,200 patients).

The MR analysis showed that a lower genetically determined ACE serum concentration predicted a lower risk of type 2 diabetes, and a meta-analysis of six RCTs estimated that ACE inhibitors reduced type 2 diabetes risk by 24% compared with placebo.

The authors say: "These results support the protective effect of long-term ACE inhibition on type 2 diabetes risk. Although future research is needed to more accurately clarify the metabolic actions of ACE inhibitors, current evidence supports that targeting ACE may protect a person from developing type 2 diabetes. Furthermore, considering a patient's risk of developing type 2 diabetes may be recommended when prescribing blood-pressure-lowering drugs -- if at high risk of type 2 diabetes, an ACE inhibitor could be considered."

They add: "Current guidelines do not take account of the protective effect of ACE inhibitors on T2D risk and this is something that could be considered."