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

Abstract

Abstract-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. (Hypertension. 2010;56:471-476.)Key Words: methylglyoxal Ⅲ 3-deoxyglucosone Ⅲ diabetic macroangiopathy Ⅲ hypertension Ⅲ intima-media thickness Ⅲ pulse wave velocity U nder hyperglycemia and/or oxidative stress in diabetes mellitus, a variety of toxic ␣-oxoaldehydes are produced, and these in turn react with protein amino groups, eventually leading to formation of advanced glycation end products (AGEs). 1-3 These ␣-oxoaldehydes also interfere with various cellular functions, independent of their effect on AGE modification of proteins, and influence the intracellular signaling by multiple pathways. [1][2][3] Among toxic ␣-oxoaldehydes, the present studies were focused on methylglyoxal (MG), because the in vitro studies and animal experiments in experimental diabetic models by us and others have suggested that MG is pathologically involved in the progression of both macroangiopathy and microangiopathy: MG plays a major role in vascular damage to endothelial cells and in the development of hypertension, of insulin resistance, and of nephropathy. [1][2][3][4][5][6][7][8][9][10] The primary biosynthetic pathway of MG in diabetic patients remains elusive, but MG is known to be produced from a variety of sources. That is, MG can be produced not only from glucose but also from a variety of substances and is not necessarily produced from hyperglycemia only. 1,2,11 Elevated blood concentrations of MG have been re...

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A Decline in Glomerular Filtration Rate Rather than Renal Arterial Stenotic Lesions, per se, Predicts Cardiovascular-Renal Events in Type 2 Diabetic Patients

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