Background Accumulating evidence suggests an independent association between osteoarthritis (OA) and type 2 diabetes mellitus (DM). Our recent work [Zhang, et al. Metabolomics, 2015] found phosphatidylcholine acyl-alkyl C34:3 (PC ae C34:3) and phosphatidylcholine acyl-alkyl C36:3 (PC ae C36:3) were associated with both OA and DM. Both synovial and plasma concentrations of these two metabolites were reduced in knee OA and DM patients, and OA patients with DM had lowest concentration of these two metabolites, suggesting the altered unsaturated phosphatidylcholine metabolism may be responsible for the association between OA and DM.
Objectives We hypothesized hyperglycemia-related production of advanced glycation end-products (AGEs) was involved in the altered phosphatidylcholine metabolism in OA patients and tested this hypothesis in the current study.
Methods Synovial fluid and plasma samples were collected from OA patients with and without DM. Hyperglycemia-related AGEs including methylglyoxal (MG) and methylglyoxal-derived hydroimidazolone (MG-H1) levels were measured in both synovial fluid and plasma samples using UPLC/MS method. The correlation between MG, MG-H1, and PC ae C34:3 and PC ae C36:3 were examined.
Results 84 knee OA patients, including 46 with DM and 38 without DM, were included in the study. We did not find a significant difference in plasma MG-H1 concentration between OA with and without DM. However, we found that log transformed synovial concentrations of MG-H1 in the groups of OA with diabetes were 2.56±0.27 ng/ml which was significantly higher than that in the group of OA without diabetes (2.39 ±0.25 ng/ml, P=0.012). Similarly, synovial concentration of MG was 2.05±0.11 ng/ml in the group of OA with diabetes which was significantly higher than 1.99±0.11 ng/ml in the group of OA without diabetes (P=0.046). The significance remained after adjusting the age, BMI and sex. The correlation between MG-H1 and PC ae C34:3, MG-H1 and PC ae C36:3, MG and PC aeC34:3, and MG and PC ae C36:3 were -0.15, -0.32, -0.23 and -0.06, respectively.
Conclusions We demonstrated that both MG-H1 and MG concentrations in synovial fluid were elevated in OA patients with DM and associated with the levels of PC ae C34:3 and PC ae C36:3, suggesting that hyperglycemia-related AGEs may be responsible for the altered phosphotidylcholine metabolism in OA.
Weidong Zhang, Guang Sun, Sergei Likhodii, Erfan Aref-Eshghi, Patricia E. Harper, Edward Randell, Roger Green, Glynn Martin, Andrew Furey, Proton Rahman, Guangju Zhai. Metabolomic analysis of human synovial fluid and plasma reveals that phosphatidylcholine metabolism is associated with both osteoarthritis and diabetes mellitus. Metabolomics (2016) 12:24. DOI 10.1007/s11306–015–0937-x
Acknowledgement We thank all the study participants who made this study possible, and all the staff who helped us in the collection of samples. The study was funded by Canadian Institutes of Health Research (CIHR), Newfoundland & Labrador RDC, and Memorial University.
Disclosure of Interest None declared