Statin use associated with an increased risk of type 2 diabetes: JAMA Study
USA: Statin use is associated with an increased type 2 diabetes risk but not with other pleiotropic effects of statin-induced decrease of the LDL-cholesterol level on other diseases, finds a recent study in JAMA Network Open.
Pleiotropic effects of statins include improvement of endothelial dysfunction, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory responses, and stabilization of atherosclerotic plaques.
Observational studies suggest that statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, may be associated with beneficial effects in many noncardiovascular diseases.
Against the above background, Ge Liu, Vanderbilt University Medical Center, Nashville, Tennessee, and colleagues aimed to construct a weighted HMG-CoA reductase (HMGCR) gene genetic risk score (GRS) using variants in the HMGCR gene affecting low-density lipoprotein cholesterol as an instrumental variable for mendelian randomization analyses. They tested associations with candidate noncardiovascular phenotypes previously associated with statin use in observational studies.
For this purpose, the researchers conducted a cohort study including 53 385 unrelated adults of European ancestry with genome-wide genotypes available from BioVU (a practice-based biobank, used for discovery) and 30 444 unrelated adults with European ancestry available in the Electronic Medical Records and Genomics (eMERGE; a research consortium that conducts genetic research using electronic medical records, used for replication). An HMGCR GRS was calculated.
Main outcome was the association between the HMGCR GRS and the presence or absence of 22 noncardiovascular phenotypes previously associated with statin use in clinical studies.
Of the 53 385 people in BioVU, 56.1% were women; mean age was 59.9 years.
Key findings of the study include:
· The finding between the HMGCR GRS and the noncardiovascular phenotypes of interest in this cohort was significant only for type 2 diabetes.
· An HMGCR GRS equivalent to a 10-mg/dL decrease in the low-density lipoprotein cholesterol level was associated with an increased risk of type 2 diabetes (odds ratio [OR], 1.09).
· The HMGCR GRS was not associated with other phenotypes; the closest were increased risk of Parkinson disease (OR, 1.30) and kidney failure (OR, 1.18).
· Of the 30 444 individuals in eMERGE, 55.0% were women; mean age was 68.7 years.
· The association between the HMGCR GRS and type 2 diabetes was replicated in this cohort (OR, 1.09); however, the HMGCR GRS was not associated with Parkinson disease (OR, 0.93) and kidney failure (OR, 1.18) in the eMERGE cohort.
"A mendelian randomization approach using variants in the HMGCR gene replicated the association between statin use and increased type 2 diabetes risk but provided no strong evidence for pleiotropic effects of statin-induced decrease of the low-density lipoprotein cholesterol level on other diseases," wrote the authors.
Reference:
The study titled, "A Mendelian Randomization Approach Using 3-HMG-Coenzyme-A Reductase Gene Variation to Evaluate the Association of Statin-Induced Low-Density Lipoprotein Cholesterol Lowering With Noncardiovascular Disease Phenotypes," is published in JAMA Network Open.
DOI: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780701
