Miho Senda

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.

Aliskiren reduces albuminuria and oxidative stress, and elevates glomerular filtration rates in Japanese patients with advanced diabetic nephropathy

Aliskiren reduces albuminuria and oxidative stress, and elevates glomerular filtration rates in Japanese patients with advanced diabetic nephropathy

Identification of the stages of diabetic nephropathy at which angiotensin II receptor blockers most effectively suppress albuminuria.

BACKGROUND It is unclear when angiotensin II receptor blockers (ARBs) produce their strongest antialbuminuric effect (AAE) in patients with diabetic nephropathy. ARBs produce stronger AAEs when urinary excretion of reactive oxygen species (ROS) and/or of angiotensinogen (AGT) is higher before treatment, although the relationship between ROS, AGT, and the urinary albumin-to-creatinine ratio (ACR) is unclear. We sought to define the relationship between ROS and ACR and establish the stage at which ARBs exert maximal AAEs. METHODS Urinary ROS and AGT and the ACR were measured in 277 hypertensive type 2 diabetic patients before ARB treatment, and changes in the ACR were analyzed over 16 weeks. RESULTS Urinary AGT and ROS showed similar changes as the disease progressed, and the increase in ACR often observed in patients with lower ROS and AGT reflects the mild AAE produced by ARBs. ROS and AGT levels and the AAE were all highest in albuminuric patients (ACR = 30-1,000 mg/g creatinine), whereas normoalbuminuric patients (ACR < 30mg/g creatinine) displayed variable ROS values and AAEs. Glycemic control exerted a stronger AAE than ARBs in normoalbuminuric patients, whereas it had a weak AAE in most nephrotic (ACR ≥ 1,000 mg/g creatinine) patients, who had low basal ROS and AGT values. Lowering blood pressure was effective at all stages and appeared to promote an AAE, even in nephrotic patients. CONCLUSIONS ARBs produce a maximal AAE in albuminuric patients, and lowering blood pressure enhances the AAE in patients at all stages, including the nephrotic stage.