{"id":35023,"date":"2022-11-29T13:00:59","date_gmt":"2022-11-29T13:00:59","guid":{"rendered":"https:\/\/touchendocrinology.com\/?p=35023"},"modified":"2023-02-14T15:38:17","modified_gmt":"2023-02-14T15:38:17","slug":"assessing-the-incidence-of-new-onset-diabetes-mellitus-with-statin-use-a-systematic-review-of-the-systematic-reviews-and-meta-analyses","status":"publish","type":"post","link":"https:\/\/touchendocrinology.com\/diabetes\/journal-articles\/assessing-the-incidence-of-new-onset-diabetes-mellitus-with-statin-use-a-systematic-review-of-the-systematic-reviews-and-meta-analyses\/","title":{"rendered":"Assessing the Incidence of New-onset Diabetes Mellitus with Statin Use: A Systematic Review of the Systematic Reviews and Meta-analyses"},"content":{"rendered":"

Recently, concern has been raised that statin therapy may be associated with new-onset diabetes mellitus (NODM), especially given the wide usage of statins in the treatment of dyslipidaemia and cardiovascular diseases (CVD). Statins have been found to affect not only the functioning of the beta cells of the pancreas, but their use also leads to insulin resistance.1<\/span>\u00a0Beta cell function may be affected by statins through various pathways, including:<\/p>\n

\u2022<\/span>\u00a0blockade of insulin release mediated by glucose transporter 2 (GLUT2)<\/p>\n

\u2022<\/span>\u00a0decreased insulin secretion due to energy depletion caused by a decreased production of ubiquinone<\/p>\n

\u2022<\/span>\u00a0decreased glucose transporter 4 (GLUT4) in adipocytes<\/p>\n

\u2022<\/span>\u00a0inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which leads to increased uptake of plasma low-density lipoprotein cholesterol (LDL-C) that enters and inhibits glucose-mediated insulin release in cells.1,2<\/span><\/p>\n

On the other hand, resistance to insulin in cells has been recently attributed to the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which in turn activates interleukin 1\u03b2<\/span>-causing insulin resistance.1,3<\/span><\/p>\n

The exploration of the diabetogenic effect of statin therapy is on-going worldwide, and the results of such investigations may have a major impact on the management of dyslipidaemias and CVD with statins. An\u00a0observational study analysed the data collected by IMS Health between February 2006 to January 2010 and registered an increase of more than 2.3 times in the fraction of the Indian population receiving statins daily, which rose from 3.35% to 7.78% during this period.4<\/span><\/p>\n

A landmark study by Culver et al. included 153,840 women without diabetes mellitus (DM) and found that statin use at baseline is associated with an increased risk of NODM (hazard ratio (HR) 1.71, 95% confidence interval [CI] 1.61\u20131.83).5<\/span>\u00a0This association was observed even after adjusting for covariates and was found to be a class effect of the statins. This study was important, as it raised many questions on the long-term use of statins and the risk of statin-caused DM. Considering that statins are widely used for the treatment of dyslipidaemia and CVD, the number of patients using statins is set to increase following the concomitant rise in the CVD states.6<\/span>\u00a0In this context, the association of statin therapy with NODM in patients previously free from DM becomes important.7\u20139<\/span>\u00a0A few other studies have shown that the diabetogenic effect of statin is dose dependent, with the risk of NODM increasing at higher doses.10,11<\/span>\u00a0In addition to the dose, the diabetogenic effect of statins can also be determined by the duration of statin use. A population-based control study has shown that the risk of NODM is higher in new statin users.9<\/span>\u00a0Moreover, a study by Dormuth et al. concluded that there is a significant risk of NODM in the first 2 years of therapy, with higher potency statins and maximum risk seen in the first 4 months of therapy.12<\/span><\/p>\n

<\/a>From the preliminary reports mentioned above, it can be concluded that statin use is linked with NODM; however, different studies obtained varying results. As systematic reviews and meta-analyses are considered the best way to generate evidence on any topic, we performed a systematic review of the systematic reviews and meta-analyses published on statin use and NODM incidence. In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and meta-analyses. Compared with the conventional research studies, the information generated by gathering the data from systematic reviews and meta-analyses can help to understand better the relationship between statin use and the risk of NODM.<\/p>\n

Methods<\/h1>\n

We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol, which we registered on Prospero (Prospero registration number CRD42021260658). The study was prepared and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for systematic reviews and meta-analyses.13<\/span><\/p>\n

Search strategy and selection criteria<\/h2>\n

Two authors (HS and PS) independently performed a comprehensive literature search for relevant systematic reviews and meta-analyses of studies reporting the data on statin use and incidence of NODM using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL). We included systematic reviews and meta-analyses published in English from study inception to November 2019. We used keywords such as \u2018statins\u2019, \u2018HMG-CoA reductase inhibitor\u2019, \u2018new-onset diabetes mellitus\u2019, \u2018dyslipidemia\u2019 and \u2018cardiovascular disease\u2019. These keywords were combined using the filters AND\/OR wherever applicable. We also searched the bibliography of the selected articles to retrieve other potential studies.<\/p>\n

Study selection<\/h2>\n

The same two authors (HS and PS) independently assessed the title, abstracts, keywords and full text of the potential studies for inclusion in the search results. Systematic reviews and meta-analyses addressing our research question were included in this systematic review. We did not include articles such as case reports, randomized or non-randomized clinical trials, observational studies, review articles, hypotheses and conference abstracts\/presentations. Following are the parts of our research question, and the keywords and literature search were planned accordingly:<\/p>\n