Hyperglycemia-related advanced glycation end-products is associated with the altered phosphatidylcholine metabolism in osteoarthritis patients with diabetes.

Weidong Zhang,Andrew Furey,Guangju Zhai,Edward W Randell,Guang Sun,Ming Liu,Sergei Likhodii

doi:10.1371/journal.pone.0184105

Abstract

To test whether type 2 diabetic patients have an elevated level of advanced glycation end-products (AGEs) and responsible for altered phosphatidylcholine metabolism, which we recently found to be associated with osteoarthritis (OA) and diabetes mellitus (DM), synovial fluid (SF) and plasma samples were collected from OA patients with and without DM. Hyperglycemia-related AGEs including methylglyoxal (MG), free methylglyoxal-derived hydroimidazolone (MG-H1), and protein bound N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL) levels were measured in both SF and plasma samples using liquid chromatography coupled tandem mass spectrometry methodology. The correlation between these AGEs and phosphatidylcholine acyl-alkyl C34:3 (PC ae C34:3) and C36:3 (PC ae C36:3) were examined. Eighty four patients with knee OA, including 46 with DM and 38 without DM, were included in the study. There was no significant difference in plasma levels of MG, MG-H1, CML, and CEL between OA patients with and without DM. However, the levels of MG and MG-H1, but not CML and CEL in SF were significantly higher in OA patients with DM than in those without (all p ≤0.04). This association strengthened after adjustment for age, body mass index (BMI), sex and hexose level (p<0.02). Moreover, the levels of MG-H1 in SF was negatively and significantly correlated with PC ae C34:3 (ρ = -0.34; p = 0.02) and PC ae C36:3 (ρ = -0.39; P = 0.03) after the adjustment of age, BMI, sex and hexose level. Our data indicated that the production of non-protein bound AGEs was increased within the OA-affected joint of DM patients. This is associated with changes in phosphatidylcholine metabolism and might be responsible for the observed epidemiological association between OA and DM.

Highlights

Osteoarthritis (OA) is the most common joint disease worldwide, affecting 10% of men and 18% of women over 60 years of age [1]
We demonstrated that increased glycation, evidenced by higher levels of MG and MG-H1 in synovial fluid (SF), was associated with altered phosphatidylcholine metabolism, certain plasmalogens within the joint
SF levels of both MG and MG-H1 were higher in OA with diabetes mellitus (DM) than that in OA without DM, presenting evidence in support of a putative mechanism explaining the relationship between OA and DM in epidemiological studies

Summary

Introduction

Osteoarthritis (OA) is the most common joint disease worldwide, affecting 10% of men and 18% of women over 60 years of age [1]. Accumulating evidence suggests that OA is associated with metabolic syndrome (MetS) related conditions, especially type 2 diabetes mellitus (DM) [2,3,4,5,6]. There is substantial evidence to suggest that intracellular glucose toxicity in DM may be mediated through increased production of highly reactive α-ketoaldehydes [8,9,10]. The nonenzymatic reaction of α-ketoaldehydes with protein produces advanced glycation end-products (AGEs). The accumulation of AGEs may play a causal role in the development of complications of DM including OA. AGEs have been implicated in OA [11,12]

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Conclusion