Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.
Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan.
Int J Mol Sci. 2018 Oct 3;19(10):3021. doi: 10.3390/ijms19103021.
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), < 0.0001) and T2DM (OR: 2.75 (2.72⁻2.78), < 0.0001). The association between T1DM and KOA among the obese (OR: 0.99 (0.54⁻1.67), = 0.0477) was insignificant compared to the non-obese (OR: 1.40 (1.33⁻1.48), < 0.0001). Interestingly, a higher association between T2DM and KOA among non-obese persons (OR: 2.75, (2.72⁻2.79), < 0.0001) compared to the obese (OR: 1.71 (1.55⁻1.89), < 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.
近年来，糖尿病（DM）患者中膝骨关节炎（KOA）的患病率有所增加——这些疾病可能具有肥胖和老龄化等共同的危险因素。因此，我们进行了干到湿实验室研究，以评估台湾所有年龄和性别的 1 型糖尿病（T1DM）和 2 型糖尿病（T2DM）与 KOA 的相关性。使用表型全基因组关联研究门户分析关联强度（比值比：OR）。纳入了 37353 例 T1DM 和 1218254 例 T2DM 人群。我们观察到 KOA 与 T1DM（OR：1.40（1.33-1.47），<0.0001）和 T2DM（OR：2.75（2.72-2.78），<0.0001）之间存在显著关联。与非肥胖者相比，肥胖者（OR：0.99（0.54-1.67），=0.0477）中 T1DM 与 KOA 之间的关联不显著（OR：1.40（1.33-1.48），<0.0001）。有趣的是，与肥胖者相比（OR：1.71（1.55-1.89），<0.0001），非肥胖者（OR：2.75，（2.72-2.79），<0.0001）中 T2DM 与 KOA 之间的关联更高。此外，糖尿病小鼠膝关节的组织病理学和 Western blot 研究显示，羧甲基赖氨酸（晚期糖基化终产物）、基质金属蛋白酶-1 增加，软骨特异性蛋白包括 II 型胶原（Col II）、SOX9 和聚集蛋白（AGN）减少，表明关节软骨和蛋白聚糖恶化。结果表明，DM 与 KOA 密切相关，肥胖可能不是一个混杂因素。
