Genetic Studies Suggest That Diabetes Risk Is Inherent in the Action of Statins.

[Argirios Argiriou]

October 2, 2014

Bruce Soloway, MD reviewing Swerdlow DI et al. Lancet 2014 Sep 24. Frayling TM. Lancet 2014 Sep 24.

Inhibition of HMG-CoA reductase seems to be tightly linked to excess risk for diabetes.

Statin drugs, which lower LDL cholesterol concentrations by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), significantly raise risk for new-onset type 2 diabetes mellitus. But is this diabetogenic effect inherent in inhibition of HMGCR?

Using the technique of “Mendelian randomization,” researchers identified two single-nucleotide polymorphisms (SNPs) within or near the gene that encodes HMGCR; each SNP has one allele that is associated strongly with low serum LDL cholesterol levels and can be regarded as a proxy for HMGCR inhibition. Data from 43 observational genetic studies (>220,000 patients) showed that, for both SNPs, the alleles associated with low LDL cholesterol levels also were associated with excess incidence and prevalence of type 2 diabetes, as well as with higher body weight, body-mass index, and plasma glucose and insulin levels.

In an updated meta-analysis of 20 statin trials, the researchers again found that statin treatment was associated significantly with new-onset type 2 diabetes (odds ratio, 1.12). In a new meta-analysis of 12 statin trials with data on body weight, statin recipients gained 0.33 kg more than recipients of placebo or standard care.
Comment

These data strongly suggest that the diabetogenic effect of statins is inherent in inhibition of HMGCR and that this effect is mediated by body weight or other modifiable metabolic factors. However, for patients whose baseline cardiovascular risk is sufficiently high, risk reductions that are achieved with statins will greatly outweigh risks associated with excess incidence of type 2 diabetes.

Citation(s):

    Swerdlow DI et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: Evidence from genetic analysis and randomised trials. Lancet 2014 Sep 24; [e-pub ahead of print]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)

    Frayling TM.Statins and type 2 diabetes: Genetic studies on target. Lancet 2014 Sep 24; [e-pub ahead of print]. (Δεν είναι ορατοί οι σύνδεσμοι (links). Εγγραφή ή Είσοδος)

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