ArticleInflammopharmacology2024
Genetic proxies for therapy of insulin drug targets and risk of osteoarthritis: a drug-target Mendelian randomization analysis.
Article in Inflammopharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Targeting inflammation-metabolism crosstalk: current status and challenges of novel therapeutic strategies for osteoarthritis.Frontiers in medicine · 2025Review
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4 authors.
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Abstract
backgroundThe potential effects of insulin therapy on osteoarthritis (OA) risk are poorly understood. This study aimed to explore the causal relationship between insulin therapy and OA.
methodsMendelian randomization (MR) analysis was performed to examine the association between genetically proxied inhibition of insulin targets and the risk of overall, hip (HOA) and knee OA (KOA). We then performed univariable MR using summary statistics regarding insulin target genes derived from the DrugBank database. Data related to blood glucose reduction levels were used as a proxy for insulin levels. Two phenotypes, type 2 diabetes, and glycosylated hemoglobin levels, were selected as positive controls to confirm the direction and validity of the proxies. The OA datasets were derived from the UK Biobank cohort. Multivariable MR was adjusted for body mass index, sedentary behavior, cigarette smoking, frequency of alcohol intake, age, and genetic sex.
resultsGenetically proxied insulin therapy was associated with an increased risk of overall OA [odds ratio (OR):1.2595; 95% confidence interval (CI):1.0810-1.4675] and HOA (OR:1.4218; 95%CI:1.1240-1.7985), which remained consistent across multiple MR methods. After adjusting for confounders, we found evidence supporting a significant causal link with a higher risk of overall OA and HOA. A further two-step MR analysis revealed no significant mediation effects from the six mediators in the associations.
conclusionThere was a causal association between genetically proxied insulin therapy and a higher risk of OA, especially HOA.
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