RELATIONSHIP OF OXIDATIVE STRESS TO URINARY ANGIOTENSIN CONVERTING ENZYME 2 IN TYPE 2 DIABETES MELLITUS PATIENTS.

CONTEXT: Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and cleaves angiotensin II to Angiotensin (1-7), annihilating the deleterious effects of angiotensin II which is known to be a strong activator of oxidative stress. OBJECTIVE: We aimed to evaluate the relationship of oxidative stress to urinary ACE2 (uACE2) in type 2 diabetes mellitus (T2DM) patients. DESIGN: We included consecutive normo or microalbuminuric T2DM patients in an observational transversal study. Routine laboratory investigations, plasma malondialdehyde (MDA, fluorimetric thiobarbituric method) as a marker of prooxidant capacity and superoxide dismutase (SOD, cytochrome reduction method) and catalase (CAT) activity (in erythrocyte lysate by the modification of absorbance method) as two measures of serum antioxidant capacity and uACE2 (ELISA method) were assessed. RESULTS: MDA showed a negative correlation with SOD (r=-0.44, p=0.001), CAT (r=-0.37, p=0.006), uACE2 (r=-0.33, p=0.016) and a positive correlation with glycated haemoglobin (HbA1c) (r=0.49, p<0.001) and associated cardiovascular disease (r=0.42, p=0.001). CAT as also positively correlated to uACE2 (r=0.29, p=0.037). SOD was also negatively correlated with glycemia (r=-0.71, p<0.001) and HbA1c (r=-0.53, p<0.001). Patients with lower MDA (when divided according to median value of 3.88 nmol/mL) had higher uACE2 57.15(40.3-71.2) pg/mL compared to 38.5(31.8-45.95) pg/mL in patients with higher MDA (p<0.001). In multivariate logistic regression uACE2 was the only predictor for MDA above or below its median (OR=0.94, 95%CI[0.90-0.98], p=0.002). CONCLUSION: Increased prooxidant serum capacity is associated with lower uACE2 levels in T2DM patients.

Factors influencing the onset of diabetes mellitus after kidney transplantation: a single French center experience.

Posttransplantation diabetes mellitus (PTDM) is a complication arising mostly during the first 6 months after kidney transplantation. Considering the serious outcomes of chronic hyperglycemia in kidney transplant patients, the recognition of factors that contribute to the onset of PTDM is of particular relevance. A retrospective analysis was performed to document the incidence of and the risk factors for diabetes mellitus occurring in the first year after kidney transplantation among 177 adult patients, without previously known diabetes transplanted between January 1998 and December 2000. PTDM, defined as fasting plasma glucose > or = 126 mg/dL confirmed by repeat testing on a different day, occurred in 48 (27.12%) patients of whom 36 showed transient changes during the first year after transplantation. Univariate analysis identified variables to be associated with the onset of PTDM: older recipient age (P = .05), male gender (P = .03), family history of diabetes (P = .04), advanced donor age (P = .008), absence of induction immunosuppression (P = .04), use of tacrolimus (vs cyclosporine; P = .01), one or more than one (steroid-treated) acute rejection episode(s) (P = .000001), cytomegalovirus infection (P = .02), and use of beta-blockers or diuretics (P = .05). By multivariate analysis, five factors were independently associated with the onset of PTDM: two episodes of rejection (odds ratio = 42.69, P = .000025), one episode of rejection (5.01, P = .007), older recipient age (1.06, P = .017), family history of diabetes (7.24, P = .011), and weight at transplantation (1.03, P = .048). Tacrolimus treatment remained of borderline significance (2.77, P = .05). In addition to traditional risk factors predisposing to the development of type 2 diabetes in the general population, episodes of acute rejection significantly influence the incidence of PTDM.

Adiponectin predicts cardiovascular events in diabetes dialysis patients.

OBJECTIVES: Adiponectin is an insulin-sensitizing, anti-inflammatory adipokine with anti-atherogenic actions in the general population. In dialysis patients it is unclear whether adiponectin conserves its protective value or is, on the contrary, associated to worse prognosis. We assessed the predictive value of adiponectin for atherosclerosis related cardiovascular events in type 2 diabetic dialysis patients. DESIGN AND METHODS: Prevalent diabetic dialysis patients from three dialysis units (n=77) were enrolled in a 3years' prospective observational study. Serum adiponectin, clinical and laboratory parameters were determined at baseline; new occurrence of atherosclerosis related events (coronary events, atherosclerosis obliterans, and stroke) was recorded. RESULTS: Baseline adiponectin was 17.25(9.53-31.97) µg/mL and significantly correlated to HDL cholesterol (r=0.29, p=0.01), triglycerides (r=-0.40, p=0.0004), ferritin (r=-0.29, p=0.02), transferrin (r=-0.28, p=0.02), and uric acid (r=-0.24, p=0.04). In multivariate analysis association to triglycerides (p=0.001), HDL cholesterol (p=0.01) and ferritin (p=0.04) remained significant. 36 new fatal and non-fatal new cardiovascular events occurred, 29 patient died. Cox proportional regression analysis showed that adiponectin below or above a ROC-derived cut-off of 27.33µg/mL significantly influenced event-free survival: hazard ratio (HR) 2.48, 95% confidence interval (CI) (1.09-5.66), p=0.031 along with fasting glucose HR 1.01, 95%CI(1.00-1.02), p=0.01 and history of cardiovascular events at inclusion HR 3.16, 95%CI(1.36-7.32), p=0.007. In multivariate analysis baseline adiponectin HR 5.02, 95%CI(0.98-25.06), p=0.05 and glycemia HR 1.01, 95%CI(1.00-1.02), p=0.01 influenced event-free survival. Adiponectin also predicted cardiovascular events in patients without cardiovascular disease at inclusion but was not associated to overall mortality. CONCLUSIONS: In diabetes dialysis patients low adiponectin favors occurrence of atherosclerosis related cardiovascular events.

Low plasma adiponectin levels predict increased urinary albumin/creatinine ratio in type 2 diabetes patients.

BACKGROUND: Experimental studies have shown that adiponectin has antiproteinuric and nephroprotective effects. The purpose of the study was to assess the value of plasma adiponectin as a predictor of proteinuria in type 2 diabetes (T2D) patients. METHODS: In this one-year prospective follow-up study, we included T2D patients with positive visual test for microalbuminuria (Micral) and negative visual test for proteinuria. Exclusion criteria were: glomerular filtration ratio (GFR) < 30 ml/min, acute infection/inflammation, uncontrolled hypertension, and atherosclerotic complications. The main outcome measure was the change in urinary albumin/creatinine ratio (UACR) after 1 year follow-up (Δ UACR). RESULTS: Fifty-six patients (66% males) completed the study. Their initial mean UACR was 81.58 ± 26.42 mg/g and mean GFR was 81.15 ± 3.96 ml/min. At baseline, simple regression disclosed significant correlations between UACR and plasma adiponectin (r = 0.54, P = 0.00002) and GFR (r = -0.28, P = 0.03); in multiple regression analysis, plasma adiponectin remained the only predictor of UACR (P = 0.00007). Baseline plasma adiponectin was significantly correlated to body mass index (r = -0.28, P = 0.04), waist circumference (r = -0.27, P = 0.05), HDL cholesterol (r = 0.35, P = 0.01), and LDL cholesterol (r = 0.27, P = 0.04). Baseline plasma adiponectin significantly correlated in simple (r = -0.38, P = 0.004) and multiple regression (P = 0.04) to Δ UACR. When patients were divided according to Δ UACR in nonprogressors (Δ UACR < 0) and progressors (Δ UACR > 0), logistic regression showed that baseline GFR (OR = 1.04, CI95%: 1.00-1.09, P = 0.04) and plasma adiponectin (OR = 1.16, CI95%: 1.02-1.32, P = 0.02) were the only factors that predicted whether the patient would be a progressor or not. CONCLUSION: In T2D patients, lower plasma adiponectin levels seem to be predictive of increased UACR.