Urinary Albumin Excretion In Type Research Articles

Novel Assessment of Urinary Albumin Excretion in Type 2 Diabetes Patients by Raman Spectroscopy.

Urinary albumin excretion remains the key biomarker to detect renal complications in type 2 diabetes. As diabetes epidemy increases, particularly in low-income countries, efficient and low-cost methods to measure urinary albumin are needed. In this pilot study, we evaluated the performance of Raman spectroscopy in the assessment of urinary albumin in patients with type 2 diabetes. The spectral Raman analysis of albumin was performed using artificial urine, at five concentrations of albumin and 24 h collection urine samples from ten patients with Type 2 Diabetes. The spectra were obtained after removing the background fluorescence and fitting Gaussian curves to spectral regions containing features of such metabolites. In the samples from patients with type 2 diabetes, we identified the presence of albumin in the peaks of the spectrum located at 663.07, 993.43, 1021.43, 1235.28, 1429.91 and 1633.91 cm−1. In artificial urine, there was an increase in the intensity of the Raman signal at 1450 cm−1, which corresponds to the increment of the concentrations of albumin. The highest concentration of albumin was located at 1630 cm−1. The capability of Raman spectroscopy for detection of small concentrations of urinary albumin suggests the feasibility of this method for the screening of type 2 diabetes renal complications.

Correlation between pulse pressure and urinary albumin excretion in type 2 diabetic patients without microalbuminuria

Correlation between pulse pressure and urinary albumin excretion in type 2 diabetic patients without microalbuminuria

Changes in choroidal thickness and volume are related to urinary albumin excretion in type 2 diabetic patients without retinopathy.

PurposeTo evaluate choroidal thickness and volume in patients with type 2 diabetes and microalbuminuria using spectral-domain optical coherence tomography.MethodsWe recruited 37 diabetic patients without diabetic retinopathy (18 normoalbuminuric and 19 microalbuminuric) and 21 healthy controls. Choroidal thickness and volume were mapped using the automated Early Treatment Diabetic Retinopathy Study grid and a topographic map of thickness was generated manually. Choroid was also measured at 10 locations under the fovea, temporally and nasally.ResultsMean choroidal thickness and volume among patients with diabetes and microalbuminuria was reduced in all locations compared to controls (P<0.05). A sectoral decrease of choroidal thickness and volume was shown between microalbuminuric and normoalbuminuric groups.ConclusionChoroidal changes were present in type 2 diabetic patients before clinical development of retinopathy. Microalbuminuria was associated with a decrease in choroidal thickness and volume in diabetic patients without diabetic retinopathy.

MTORC2 Signaling Regulates Nox4-Induced Podocyte Depletion in Diabetes.

Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Oxidative stress plays a critical role in hyperglycemia-induced glomerular injury. We explored the hypothesis that mammalian target of rapamycin complex 2 (mTORC2) mediates podocyte injury in diabetes. High glucose (HG)-induced podocyte injury reflected by alterations in the slit diaphragm protein podocin and podocyte depletion/apoptosis. This was paralleled by activation of the Rictor/mTORC2/Akt pathway. HG also increased the levels of Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using small interfering RNA (siRNA)-targeting Rictor in vitro decreased HG-induced Nox1 and Nox4, NADPH oxidase activity, restored podocin levels, and reduced podocyte depletion/apoptosis. Inhibition of mTORC2 had no effect on mammalian target of rapamycin complex 1 (mTORC1) activation, described by our group to be increased in diabetes, suggesting that the mTORC2 activation by HG could mediate podocyte injury independently of mTORC1. In isolated glomeruli of OVE26 mice, there was a similar activation of the Rictor/mTORC2/Akt signaling pathway with increase in Nox4 and NADPH oxidase activity. Inhibition of mTORC2 using antisense oligonucleotides targeting Rictor restored podocin levels, reduced podocyte depletion/apoptosis, and attenuated glomerular injury and albuminuria. Our data provide evidence for a novel function of mTORC2 in NADPH oxidase-derived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes. mTORC2 and/or NADPH oxidase inhibition may represent a therapeutic modality for diabetic kidney disease. Antioxid. Redox Signal. 25, 703-719.

GSK-3β inhibitor attenuates urinary albumin excretion in type2 diabetic db/db mice, and delays epithelial-to-mesenchymal transition in mouse kidneys and podocytes.

The mechanism underlying epithelial‑to‑mesenchymal transition (EMT) caused by high glucose (HG) stimulation in diabetic nephropathy (DN) remains to be fully elucidated. The present study investigated the effects of HG on EMT and the activity of glycogen synthase kinase3β (GSK‑3β) in podocytes and the kidneys of db/db mice, and assessed the effects of (2'Z, 3'E)‑6‑bromoindirubin‑3'‑oxime (BIO), an inhibitor of GSK‑3β, on EMT and glomerular injury. The resulting data showed that the activity of GSK‑3β was upregulated by HG and downregulated by BIO in the podocytes and the renal cortex. The expression levels of epithelial markers, including nephrin, podocin and synaptopodin, were decreased by HG and increased by BIO, whereas the reverse were true for mesenchymal markers, including α‑smooth muscle actin (α‑SMA) and fibronectin. The expression levels of β‑catenin and Snail, in contrast to current understanding of the Wnt signaling pathway, were increased by HG and decreased by BIO. In addition, expression of the vitaminD receptor (VDR) was decreased by HG and increased by BIO. In conclusion, the present study revealed that the mechanism by which BIO inhibited HG‑mediated EMT in podocytes and the renal cortex was primarily due to the VDR. Treatment with BIO protected renal function by maintaining the integrity of the filtration membrane and decreasing UAE, but not by regulating blood glucose. Therefore, GSK‑3β may be used as a sensitive biomarker of DN, and its inhibition by BIO may be effective in the treatment of DN.

Serum levels of soluble receptor for advanced glycation end product in type 2 diabetic patients: possible association with urinary albumin excretion

Diabetes is now the major cause of end-stage renal failure worldwide, both in developing and in developed nations. Hyperglycemia is still considered the principal cause of complications of diabetes because of the formation of sugar-derived substances called advanced glycation end products. The formation of advanced glycation end product is markedly accelerated in diabetes because of the increased availability of glucose. The receptor for advanced glycation end products (RAGE) has been shown to be involved in the pathogenesis of diabetic complications. The aim of this work was to assess the possible association between soluble receptor for advanced glycation end products (sRAGE) and urinary albumin excretion in type 2 diabetic patients as an early predictor of microvascular complications such as diabetic nephropathy. The present study was carried on 70 individuals: 10 healthy individuals as control, 20 diabetic patients with normoalbuminuria, 20 diabetic patients with microalbuminuria, and 20 diabetic patients with macroalbuminuria. All participants were subjected to estimation of sRAGE by the sandwich enzyme-linked immunosorbent assay technique together with routine laboratory investigations. The results of this study showed that all diabetic patients had a low level of serum RAGE compared with the control group. Furthermore, a characteristic trend was observed whereas three groups of diabetic patients showed a decrease in RAGE in parallel with the severity of renal involvement. From this point of view, stimulation of sRAGE production should be considered a potential therapeutic target in diabetic patients.

Effects of dipeptidyl peptidase 4 inhbition on urinary albumin excretion in type 2 diabetic patients

Effects of dipeptidyl peptidase 4 inhbition on urinary albumin excretion in type 2 diabetic patients

Mammalian Target of Rapamycin Regulates Nox4-Mediated Podocyte Depletion in Diabetic Renal Injury

Podocyte apoptosis is a critical mechanism for excessive loss of urinary albumin that eventuates in kidney fibrosis. Pharmacological doses of the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduce albuminuria in diabetes. We explored the hypothesis that mTOR mediates podocyte injury in diabetes. High glucose (HG) induces apoptosis of podocytes, inhibits AMP-activated protein kinase (AMPK) activation, inactivates tuberin, and activates mTOR. HG also increases the levels of Nox4 and Nox1 and NADPH oxidase activity. Inhibition of mTOR by low-dose rapamycin decreases HG-induced Nox4 and Nox1, NADPH oxidase activity, and podocyte apoptosis. Inhibition of mTOR had no effect on AMPK or tuberin phosphorylation, indicating that mTOR is downstream of these signaling molecules. In isolated glomeruli of OVE26 mice, there is a similar decrease in the activation of AMPK and tuberin and activation of mTOR with increase in Nox4 and NADPH oxidase activity. Inhibition of mTOR by a small dose of rapamycin reduces podocyte apoptosis and attenuates glomerular injury and albuminuria. Our data provide evidence for a novel function of mTOR in Nox4-derived reactive oxygen species generation and podocyte apoptosis that contributes to urinary albumin excretion in type 1 diabetes. Thus, mTOR and/or NADPH oxidase inhibition may represent a therapeutic modality of diabetic kidney disease.

Association of visceral adiposity with urinary albumin excretion in type 2 diabetics

To decipher the association of visceral adiposity (VA) with 24-hour urinary albumin excretion (24 h-UAE) in type 2 diabetics. We collected the clinical data, VA, subcutaneous adiposity (SA), 24 h-UAE, blood lipids, fasting blood glucose, glycosylated hemoglobin, insulin and tumor necrosis factor (TNF)-α of type 2 diabetic inpatients at our hospital. According to the quartile of VA, the subjects were divided into 4 groups. And their profiles were compared with regards to the level of 24 h-UAE and the incidence of heavy proteinuria. And their relative intensities and the linear relationship of VA and lg (24 h-UAE) were analyzed. lg (24 h-UAE) of groups C and D was larger than that of groups A and B. With the rising level of VA, the prevalence of heavy proteinuria increased. A moderate correlation existed between VA and lg (24 h-UAE) (r = 0.51). lg (24 h-UAE) increased 0.26 units as VA expanded 100 cm(2), i.e. 0.15 units after relative factor adjusting. After gender and triglyceride adjusting, the odds ratio of heavy albuminuria in group C was 2.75 versus that in group A. And the OR was 3.87 in group D. Expansion of VA is a risk factor for an elevated risk of 24 h-UAE. With the expansion of VA, the prevalence of heavy albuminuria increases.

Effects of Multiple Factorial Intervention on Ambulatory BP Profile and Renal Function in Hypertensive Type 2 Diabetic Patients with Overt Nephropathy – A Pilot Study

Accumulating evidence has shown that diabetic patients are increasing in number, and renal and cardiovascular complications are the most common cause of death in diabetic patients. Thus, it would be of considerable value to identify the mechanisms involved in the progression of renal impairment and cardiovascular injury associated with diabetes. Recent evidence also indicated that multifactorial intervention is able to reduce the risk of cardiovascular disease and death among patients with diabetes and microalbuninuria. In this pilot study, we examined the effects of intensified multifactorial intervention, with tight glucose regulation and the use of valsartan and fluvastatin on ambulatory blood pressure (BP) profile, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR), in 20 hypertensive patients (16 male and 4 female) with type 2 diabetes mellitus and overt nephropathy. After 12 months of intensified treatment, office BP, fasting plasma glucose (FPG), and low-density lipoprotein cholesterol (LDLC) were significantly decreased compared to baseline (systolic blood pressure (SBP), 130 ± 2 vs. 150 ± 1 mmHg; diastolic blood pressure (DBP), 76 ± 1 vs. 86 ± 1 mmHg; FPG, 117 ± 5 vs. 153 ± 7 mg/dl; LDLC, 116 ± 8 vs. 162 ± 5 mg/dl, P < 0.0001). Also, compared to the baseline values, the daytime and nighttime ambulatory BP and short-term BP variability were significantly decreased after 12 months. Furthermore, while eGFR was not altered (44.3 ± 5.1 vs. 44.3 ± 6.5 ml/min/1.73 m2, not significant (NS)), UACR showed a significant reduction after 12 months of intensified treatment (1228 ± 355 vs. 2340 ± 381 mg/g-cr, P < 0.05). These results suggest that the intensified multifactorial intervention is able to improve ambulatory BP profile, preserve renal function, and reduce urinary albumin excretion in type 2 diabetic hypertensive patients with overt nephropathy.

Reproducibility of albuminuria in type 2 diabetic subjects. Findings from the Renal Insufficiency And Cardiovascular Events (RIACE) study

Measurement of urinary albumin excretion (UAE) shows important intra-individual variability suggesting the need for multiple assessments. This study aimed at investigating the reproducibility of UAE in type 2 diabetes. UAE was obtained from two to three samples collected in a 3- to 6-month period from 4062 of the 15 773 type 2 diabetic subjects participating in the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study in 2007-08. UAE was assessed as albumin excretion rate (AER) in 24-h urine collections from 833 subjects and albumin:creatinine ratio (A/C) in early-morning urine samples from 3229 patients. Albuminuria was measured by immunonephelometry or immunoturbidimetry. The median coefficient of variation (CV) was 32.5% (interquartile range: 14.3-58.9). Concordance rate between a single UAE and the geometric mean of multiple measurements was 94.6% for normoalbuminuria, 83.5% for microalbuminuria, 91.1% for macroalbuminuria and 90.6% for albuminuria (micro + macro). CV was significantly higher (P < 0.01) for AER measurement than for A/C and with immunoturbidimetry than with immunonephelometry, whereas concordance rates were similar between the two modalities of urine collection and the two assay methods. Receiver-operating characteristic (ROC) plots demonstrated a good performance of single UAE in predicting the geometric mean of multiple measures at the cut-off level of both microalbuminuria (ROC(AUC) 0.926; 95% confidence interval: 0.915-0.937) and macroalbuminuria (ROC(AUC) 0.950; 95% confidence interval: 0.927-0.973). Data from this large cohort indicate that, in type 2 diabetic subjects, a single UAE value, thought to be encumbered with high intra-individual variability, is an accurate predictor of nephropathy stage for clinical and epidemiological purposes.

The relationship between Cognitive Function and Urinary Albumin Excretion in Type 2 Diabetic Patients

The relationship between Cognitive Function and Urinary Albumin Excretion in Type 2 Diabetic Patients

Circulating ApoE Level is Independently Associated with Urinary Albumin Excretion in Type 2 Diabetic Patients

Evidence from many studies suggests that dyslipidemia has a pathogenetic role in the development and progression of diabetic nephropathy. The objective of this study was to evaluate the relationships between serum lipid parameters and urinary albumin excretion in type 2 diabetic patients from Shanghai, China. A total of 1094 type 2 diabetic patients were recruited. The urinary albumin to creatinine ratio (ACR), serum total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), apolipoprotein A I (ApoA I), apolipoprotein B (ApoB), apolipoprotein E (ApoE) and lipoprotein (a) [Lp(a)] were measured and low density lipoprotein cholesterol (LDL-C) was calculated according to the Friedewald formula. An ACR of ≥30 µg/mg was defined as albuminuria, and <30 µg/mg as normoalbuminuria. The levels of ApoE and triglyceride were significantly higher in albuminuric group compared with normoalbuminuric group (p<0.001 and p=0.003, respectively). Differences of ACR among the groups based on the tertile of ApoE and the tertile of triglyceride were significant (both p<0.001). In a multiple linear regression model, ApoE was independently associated with ACR (β=0.003, 95%CI 0.002-0.005, p<0.001). Serum ApoE level was independently associated with urinary albumin excretion in type 2 diabetic patients from Shanghai, China.

AMP-activated Protein Kinase (AMPK) Negatively Regulates Nox4-dependent Activation of p53 and Epithelial Cell Apoptosis in Diabetes

Diabetes and high glucose (HG) increase the generation of NADPH oxidase-derived reactive oxygen species and induce apoptosis of glomerular epithelial cells (podocytes). Loss of podocytes contributes to albuminuria, a major risk factor for progression of kidney disease. Here, we show that HG inactivates AMP-activated protein kinase (AMPK), up-regulates Nox4, enhances NADPH oxidase activity, and induces podocyte apoptosis. Activation of AMPK blocked HG-induced expression of Nox4, NADPH oxidase activity, and apoptosis. We also identified the tumor suppressor protein p53 as a mediator of podocyte apoptosis in cells exposed to HG. Inactivation of AMPK by HG up-regulated the expression and phosphorylation of p53, and p53 acted downstream of Nox4. To investigate the mechanism of podocyte apoptosis in vivo, we used OVE26 mice, a model of type 1 diabetes. Glomeruli isolated from these mice showed decreased phosphorylation of AMPK and enhanced expression of Nox4 and p53. Pharmacologic activation of AMPK by 5-aminoimidazole-4-carboxamide-1-riboside in OVE26 mice attenuated Nox4 and p53 expression. Administration of 5-aminoimidazole-4-carboxamide-1-riboside also prevented renal hypertrophy, glomerular basement thickening, foot process effacement, and podocyte loss, resulting in marked reduction in albuminuria. Our results uncover a novel function of AMPK that integrates metabolic input to Nox4 and provide new insight for activation of p53 to induce podocyte apoptosis. The data indicate the potential therapeutic utility of AMPK activators to block Nox4 and reactive oxygen species generation and to reduce urinary albumin excretion in type 1 diabetes.

Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice

Addition of aliskiren, a direct renin inhibitor, to losartan provides additive reduction of urinary albumin excretion in type 2 diabetic patients. However, the detailed effect of aliskiren on type 2 diabetic nephropathy is still unknown. This study was undertaken to examine the efficacy of aliskiren and the combination of aliskiren with valsartan on type 2 diabetic nephropathy. db/db mice were treated with aliskiren (3 mg/kg per day), valsartan (5 or 10 mg/kg per day), combined aliskiren (3 mg/kg per day) and valsartan (5 mg/kg per day), and hydralazine (80 mg/kg per day), for 6 weeks, and the protective effects against diabetic nephropathy were compared among each group. Aliskiren significantly attenuated albuminuria and glomerular mesangial matrix expansion in db/db mice, which was associated with the improvement of the increased glomerular transforming growth factor-beta and type IV collagen expressions, the increased macrophage infiltration, and the decreased glomerular nephrin expression of db/db mice. These protective effects of aliskiren in db/db mice were attributed to the attenuation of p22(phox)-related nicotinamide adenine dinucleotide phosphate oxidase-induced superoxide. Addition of aliskiren to valsartan treatment provided more beneficial effects on all the above-mentioned parameters than valsartan monotherapy. Aliskiren protected against type 2 diabetic nephropathy, through pleiotropic effects, and significantly enhanced the protective effects of valsartan against diabetic nephropathy in db/db mice.

Association between plasma osteoprotegerin concentrations and urinary albumin excretion in Type 2 diabetes

Osteoprotegerin (OPG) is a recently identified inhibitor of bone resorption. Recent studies indicate that OPG is also associated with endothelial dysfunction in Type 2 diabetes. The aim was to investigate the relationship between plasma OPG levels and urinary albumin excretion (UAE) in Type 2 diabetic patients. This study included 154 newly diagnosed Type 2 diabetic patients and 46 healthy subjects. Plasma OPG and 24-h UAE were measured. High-resolution ultrasound was used to measure flow-mediated (endothelium-dependent arterial) dilation (FMD). Compared with the normoalbuminuric subgroup, OPG levels in the microalbuminuric subgroup were significantly higher, and OPG levels in macroalbuminuria subgroup were significantly higher than those in the normoalbuminuria and albuminuria subgroups. Multiple regression analysis showed that only FMD (r = -0.26), C-reactive protein (r = 0.23), fasting blood glucose (r = 0.25), 2-h blood glucose (r = 0.21), HbA(1c) (r = 0.28), UAE (r = 0.27) and retinopathy (r = 0.27) were significant factors associated with OPG. Pearson's correlation analyses showed a positive correlation between OPG and logUAE (r = 0.440) and negative correlations between OPG and FMD (r = -0.284), and between FMD and logUAE (r = -0.602). Plasma OPG levels are significantly associated with UAE in Type 2 diabetic patients.

High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study

High-dose supplements of thiamine prevent the development of microalbuminuria in experimental diabetes. The aim of this pilot study was to assess whether oral supplements of thiamine could reverse microalbuminuria in patients with type 2 diabetes. Type 2 diabetic patients (21 male, 19 female) with microalbuminuria were recruited at the Diabetes Clinic, Sheikh Zayed Hospital, Lahore, Pakistan, and randomised to placebo and treatment arms. Randomisation was by central office in sequentially numbered opaque, sealed envelopes. Participants, caregivers and those assessing the outcomes were blinded to group assignment. Patients were given 3 x 100 mg capsules of thiamine or placebo per day for 3 months with a 2 month follow-up washout period. The primary endpoint was change in urinary albumin excretion (UAE). Other markers of renal and vascular dysfunction and plasma concentrations of thiamine were determined. UAE was decreased in patients receiving thiamine therapy for 3 months with respect to baseline (median -17.7 mg/24 h; p < 0.001, n = 20). There was no significant decrease in UAE in patients receiving placebo after 3 months of therapy (n = 20). UAE was significantly lower in patients who had received thiamine therapy compared with those who had received placebo (30.1 vs 35.5 mg/24 h, p < 0.01) but not at baseline. UAE continued to decrease in the 2 month washout period in both groups, but not significantly. There was no effect of thiamine treatment on glycaemic control, dyslipidaemia or BP. There were no adverse effects of therapy. In this pilot study, high-dose thiamine therapy produced a regression of UAE in type 2 diabetic patients with microalbuminuria. Thiamine supplements at high dose may provide improved therapy for early-stage diabetic nephropathy. CTRI (India) CTRI/2008/091/000112. Pakistan Higher Education Commission.

Additional effect in reduction of albuminuria due to the combination therapy of angiotensin-converting-enzyme inhibitor and angiotensin II type 1 receptor blocker in type 2 diabetic patients with the angiotensinogen 235T allele

We evaluated the combination therapy of angiotensin-converting-enzyme inhibitor (ACE-I) and angiotensin II type 1 receptor blocker (ARB) offered an additional effect in reduction of albuminuria in type 2 diabetic patients with angiotensinogen (AGT) M235T polymorphism. The study subjects were type 2 diabetic patients with nephropathy who were attending Hirosaki University Hospital. Fifteen patients with 235T allele (TT genotype 9, MT genotype 6) were evaluated who had diabetic nephropathy in stage 2 or 3 and already treated with ACE-I. Each patient administrated ARB (20-40 mg of termisartan) in addition to ACE-I for 16 weeks as the combination therapy. The addition of termisartan induced a significant reduction in systolic blood pressure (BP) of 14.0 mmHg and diastolic BP of 5.4mmHg. The urinary albumin-creatinine ratio (ACR) was also reduced to 48.9%. There was no significant correlation between the reduction rate of ACR and the antihypertensive response of systolic blood pressure (BP) (rs = 0.1277) and of diastolic BP (rs =0.1420) by the addition of termisartan. These results indicated that the combination of ACE-I and ARB had an additional effect on urinary albumin excretion in type 2 diabetic patients with AGT 235T allele. Hirosaki Med. J. 59: 59-64, 2008 ~~****~~*~~~I*J~ ~ft~I*J~*~~ 53UijjIJ~~*)'c:t~# i$ '¥ptI9~8Ji 23 B~ft

N-terminal pro-brain natriuretic peptide (NT-proBNP) in Type 2 diabetes with left ventricular dysfunction

Plasma N-terminal proBNP (NT-proBNP) is released in response to pressure overload, intravascular volume expansion and myocardial ischemia from cardiac ventricles. We studied the relationship between NT-proBNP levels and left ventricular dysfunction and urinary albumin excretion in Type 2 diabetes. The study group consisted of 130 diabetic patients referred for echocardiography. They were divided into four groups according to echocardiographic finding and into three groups according to urinary albumin excretion. NT-proBNP levels were measured by electrochemiluminescence. There were significant differences in NT-proBNP levels among four groups ( P = 0.012), with a highly significant difference between normal and other groups with left ventricular dysfunction. NT-proBNP levels in diastolic dysfunction were significantly higher than normal group (1491.1 pg/mL versus 232.3 pg/mL, P = 0.01), even though there was no difference in ejection fraction (EF) (61.2 ± 7.9% versus 60 ± 8.4%, P = 0.773). NT-proBNP levels showed positive correlation with age (Rs = 0.37, P < 0.001), creatinine (Rs = 0.38, P = 0.001), LVIDS (Rs = 0.56, P = 0.001) and LVIDD (Rs = 0.34, P = 0.04) and negative correlation with EF (Rs = −0.66, P = 0.001). NT-proBNP levels significantly differed among three groups according to urinary albumin excretion ( P = 0.031). These results suggest that NT-proBNP could be used to identify any impairment of left ventricular function in diabetes.

Albuminuria: A Target for Treatment of Type 2 Diabetic Nephropathy

Both renal and cardiovascular morbidity and mortality is increased markedly in patients with type 2 diabetes. Besides the classic risk factors and markers such as glucose, blood pressure, blood lipid profile, and lifestyle (smoking, overweight), novel risk markers are identified, among them urine albumin excretion. Levels of urinary albumin excretion greater than normal are observed frequently in patients with type 2 diabetes. Moderately increased levels of albuminuria, so-called microalbuminuria, are predictive both for progressive renal function loss to diabetic nephropathy, and for cardiovascular morbidity and mortality: the higher the albuminuria level, the more chance of renal and cardiovascular complications. More advanced levels of albuminuria (overt albuminuria) are observed in patients in the diabetic nephropathy state. In this condition, renal and cardiovascular risk are extremely high, and again one may observe that the level of albumin excretion is predictive of renal and cardiovascular outcome. Several drug strategies decrease the level of urinary albumin excretion in type 2 diabetic patients. Data on using drugs that intervene in the renin-angiotensin-aldosterone-system (RAAS) are the most extensive and conclusive. RAAS intervention is a very effective strategy to decrease the amount of albumin in the urine, independent from the blood pressure decreasing characteristics of the treatment. RAAS intervention is associated with long-term renal and cardiovascular protection. Importantly, the degree of short-term albuminuria decrease is associated with the degree of renal and cardiovascular protection: the more albuminuria reduction, the more protection. The protective predictive power of the albuminuria effect of RAAS intervention is not related to (or dissociated from) the blood pressure decreasing effect of these drugs. The protective effect of RAAS intervention is present at normoalbuminuric, microalbuminuric, and overt albuminuria levels. This makes albuminuria a target for therapy in type 2 diabetes. New drug strategies that decrease or prevent albuminuria without affecting other risk factors currently are being tested, and not only will add to underscoring the need to treat albuminuria as a separate target, but also will assist in reducing the enormous residual risk burden of individual diabetic patients.