The Impact of Blood Glucose and Antidiabetic Medications on Osteoarthritis: A Mendelian Randomization Study

Abstract

Objective Blood glucose metabolism is a crucial risk factor for the onset of osteoarthritis (OA). Our aim is to assess the causal relationship between blood glucose levels and the incidence of osteoarthritis, as well as the impact of antidiabetic medications on osteoarthritis outcomes, using Mendelian randomization (MR) methods. Methods This is a two-sample Mendelian randomization design. Osteoarthritis was chosen as the outcome, and causal relationships with three exposures—glycated hemoglobin (HbA1c), fasting blood glucose (FG), and postprandial two-hour blood glucose (2hGlu)—were evaluated. Additionally, this study examined the relationship between common antidiabetic medication target genes (GCK, HFE, HK1, HKDC1, TCF7L2, and INS) and osteoarthritis. The inverse variance-weighted method (IVW) is primarily employed for effect estimation. Results HbA1c levels were negatively correlated with hip OA (OR 0.725, 95% CI 0.558–0.944) but not associated with knee OA or OA at any site. FG levels were negatively correlated with hip OA (OR 0.675, 95% CI 0.547–0.834) and OA at any site (OR 0.889, 95% CI 0.801–0.986). Gene predictions revealed a negative correlation between GCK and hip OA (OR 0.359, 95% CI 0.238–0.542), HFE and hip OA(OR 0.332, 95% CI 0.181–0.607), HK1 and knee OA (OR 0.735, 95% CI 0.565–0.955) and OA at any site (OR 0.743, 95% CI 0.636–0.868), HKDC1 and knee OA(OR 0.731, 95% CI 0.555–0.963) and OA at any site (OR 0.771, 95% CI 0.655–0.908), while INS shows a positive correlation with knee OA (OR 17.277, 95% CI 4.408–67.722) and OA at any site (OR 4.168, 95% CI 1.844–9.422). Conclusion MR analysis revealed a correlation between reduced HbA1c levels and an increased risk of hip OA, and FG was associated with an increased risk of hip OA and OA at any site. Gene predictions suggest that activating GCK, HFE, HK1, and HKDC1 genes with antidiabetic medications may reduce the risk of developing osteoarthritis. Consideration of antidiabetic medications for treating osteoarthritis is plausible, but clinical validation is necessary.