Correlation between Diabetes Mellitus and Knee Osteoarthritis: A Dry-To-Wet Lab Approach

Abstract

Recent years have witnessed an increased prevalence of knee osteoarthritis (KOA) among diabetes mellitus (DM) patients—conditions which might share common risk factors such as obesity and advanced aging. Therefore, we conducted dry-to-wet lab research approaches to assess the correlation of type 1 DM (T1DM) and type 2 DM (T2DM) with KOA among all age and genders of Taiwanese population. The strength of association (odds ratio: OR) was analyzed using a phenome-wide association study portal. Populations of 37,353 T1DM and 1,218,254 T2DM were included. We observed a significant association of KOA with T1DM (OR: 1.40 (1.33–1.47), p< 0.0001) and T2DM (OR: 2.75 (2.72–2.78), p< 0.0001). The association between T1DM and KOA among the obese (OR: 0.99 (0.54–1.67), p = 0.0477) was insignificant compared to the non-obese (OR: 1.40 (1.33–1.48), p < 0.0001). Interestingly, a higher association between T2DM and KOA among non-obese persons (OR: 2.75, (2.72–2.79), p < 0.0001) compared to the obese (OR: 1.71 (1.55–1.89), p < 0.0001) was noted. Further, histopathologic and Western blot studies of diabetic mice knee joints revealed enhanced carboxymethyl lysine (advanced glycation end product), matrix metalloproteinase-1, and reduced cartilage-specific proteins, including type II collagen (Col II), SOX9, and aggrecan (AGN), indicating deteriorated articular cartilage and proteoglycans. Results indicate that DM is strongly associated with KOA, and obesity may not be a confounding factor.

Osteoarthritis and Cartilage Regeneration: Focus on Pathophysiology and Molecular Mechanisms

“…Dubey et al, conducted dry-to-wet lab research approaches to assess the correlation of type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) with knee OA among all age and genders of Taiwanese population discriminating further between obese and non-obese patients [40]. The study population included 37,353 T1DM and 1,218,254 T2DM patients and it was adjusted according to age and gender.…”

Systemic and local diseases associated with the development of diabetic macular edema among Japanese patients with diabetes mellitus

“…Some previous studies reported a significantly higher prevalence of primary osteoarthritis among subjects with DM than among subjects without DM, as well as significant associations with glycemic control and the duration of diabetes. Obesity may be associated with the onset of osteoarthritis [42][43][44]. We are unsure why the present study showed a negative impact of orthoarthritis on DME.…”

Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus

“…Studies have reported a stronger association between TD and knee OA in women; however, no such association was observed in women aged <30 years [11], implicating the role of oestrogen in the pathogenesis of both conditions. Animal studies have shown that ovariectomy increased the risk of T2D [12]; in contrast, a few studies have shown that 17βestradiol (ovarian oestrogen) improves insulin sensitivity and protects insulin production in the diabetic state [13].…”