Plasma Levels Of Methylglyoxal Research Articles

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

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.

Reactive Metabolites and AGE-RAGE-Mediated Inflammation in Patients following Liver Transplantation

Recent investigations have indicated that reactive metabolites and AGE-RAGE-mediated inflammation might play an important role in the pathogenesis of ischemia-reperfusion injury in liver transplantation. In this observational clinical study, 150 patients were enrolled following liver transplantation from deceased donors. The occurrence of short-term complications within 10 days of transplantation was documented. Blood samples were collected prior to transplantation, immediately after transplantation, and at consecutive time points, for a total of seven days after transplantation. Plasma levels of methylglyoxal were determined using HPLC, whereas plasma levels of L-arginine, asymmetric dimethylarginine, advanced glycation endproducts-carboxylmethyllysine, soluble receptor for advanced glycation endproducts, and total antioxidant capacity were measured by ELISA. Patients following liver transplantation were shown to suffer from increased RAGE-associated inflammation with an AGE load mainly dependent upon reactive carbonyl species-derived AGEs. In contrast, carboxylmethyllysine-derived AGEs were of a minor importance. As assessed by the ratio of L-arginine/asymmetric dimethylarginine, the bioavailability of nitric oxide was shown to be reduced in hepatic IRI, especially in those patients suffering from perfusion disorders following liver transplantation. For the early identification of patients at high risk of perfusion disorders, the implementation of asymmetric dimethylarginine measurements in routine diagnostics following liver transplantation from deceased donors should be taken into consideration.

Increased plasma methylglyoxal level, inflammation, and vascular endothelial dysfunction in diabetic nephropathy

Objectives To investigate the association of plasma levels of methylglyoxal (MG) and markers of inflammation/endothelial dysfunction with diabetic nephropathy (DN). Design and methods Plasma levels of MG, cytokines, and adhesion molecules were measured in type 2 diabetic patients (T2DM), T2DM patients with DN, and the controls. Results Plasma MG levels in DN were significantly higher than those in T2DM and the controls (312 ± 135 vs. 212 ± 73 and 312 ± 135 vs. 147 ± 78 nmol/L, respectively, P < 0.001). The plasma levels of MG were positively correlated with the fasting glucose, HbA1c, and urinary albumin/creatinine ratio ( r = 0.754, P < 0.05). Plasma levels of IL-6, TNF-α, and adhesion molecules were markedly increased in DN compared to T2DM patients and the controls. Conclusions Increased plasma levels of MG, cytokines, and adhesion molecules are associated with DN. These markers may be useful in predicting the development of DN.

Methylglyoxal Is a Predictor in Type 2 Diabetic Patients of Intima-Media Thickening and Elevation of Blood Pressure

We test whether plasma level of methylglyoxal (MG) is an independent risk factor predicting the progression of diabetic macroangiopathy or microangiopathy in type 2 diabetic patients. We measured in 50 type 2 diabetic patients plasma levels of MG and 3-deoxyglucosone (DG) using an electrospray ionization-liquid chromatography-mass spectrometry. We assessed the correlations between baseline levels of MG or DG and the percentage changes after 5 years of clinical parameters linked to diabetic macroangiopathy or microangiopathy, that is, intima-media thickness (IMT), systolic blood pressure (SBP), the amount of urinary albumin excretion (ACR), pulse wave velocity (PWV), and estimated glomerular filtration rate (eGFR). Multiple regression analysis was performed using the percentage changes in IMT, SBP, ACR, PWV, and eGFR over the 5-year period as the independent or objective variables and the values of MG, DG, glycohemoglobin A1c, body mass index, triglyceride, and diabetic duration at the baseline as the dependent variables. The values of IMT, PWV, SBP, and ACR all increase, but eGFR reduces with time during the 5-year period. Baseline level of MG correlates significantly with the percentage changes of IMT, SBP, ACR, PWV, and eGFR, whereas that of DG does only with ACR. A multiple regression analysis reveals that MG is an independent risk factor for the percentage changes of IMT, PWV, and SBP but not for those of ACR and eGFR. DG is an independent risk factor for the percentage change of ACR. MG is a predictor in type 2 diabetic patients of intima-media thickening, of increase of PWV, and of elevation of SBP.