Development Of Microalbuminuria In Type Research Articles

The association between EKG abnormalities and the development of microalbuminuria in type 2 diabetes.

Microalbuminuria is associated with both with chronic kidney disease and various cardiovascular abnormalities. Given the common use of electrocardiograms (EKGs) in diagnosing cardiovascular dysfunction, this study is analyzing the relationship between EKG abnormalities and diabetic nephropathy in type 2 diabetes mellitus (DM) patients. The enrollments of this study were from the 10-year follow-up data (2003–2012) of the Diabetes Management through an Integrated Delivery System project. All study subjects underwent at least 1 EKG measurement. The urinary microalbuminuria was recorded annually. The logistic regression model was used to evaluate the association between EKG abnormalities and the occurrence of diabetic nephropathy in type 2 DM patients. The total of 1189 patients with type 2 DM are included in this study and a total of 552 patients had microalbuminuria during a 10-year follow-up. A significantly higher odds ratio of microalbuminuria occurrence (4.85) was found in the patients with premature supraventricular contraction or tachycardia compared to those without EKG abnormalities. The odds ratios of microalbuminuria occurrence were 1.00, 2.43, 2.64, and 2.98, respectively, for patients with insulin resistance in the Q (quartile) 1(as the reference), Q2, Q3, and Q4, respectively. Our findings can serve as a reference for the association between EKG abnormalities and the development of microalbuminuria in type 2 diabetes.

Association Between Insulin Resistance and Development of Microalbuminuria in Type 2 Diabetes

OBJECTIVEAn association between insulin resistance and microalbuminuria in type 2 diabetes has often been found in cross-sectional studies. We aimed to reassess this relationship in a prospective Taiwanese cohort of type 2 diabetic subjects.RESEARCH DESIGN AND METHODSWe enrolled 738 normoalbuminuric type 2 diabetic subjects, aged 56.6 ± 9.0 years, between 2003 and 2005 and followed them through the end of 2009. Average follow-up time was 5.2 ± 0.8 years. We used urine albumin-to-creatinine ratio to define microalbuminuria and the homeostasis model assessment of insulin resistance (HOMA-IR) to assess insulin resistance. The incidence rate ratio and Cox proportional hazards model were used to evaluate the association between HOMA-IR and development of microalbuminuria.RESULTSWe found incidences of microalbuminuria of 64.8, 83.5, 93.3, and 99.0 per 1,000 person-years for the lowest to highest quartiles of HOMA-IR. Compared with those in the lowest quartile of HOMA-IR, the incidence rate ratios for those in the 2nd, 3rd, and highest quartiles were 1.28 (95% CI 0.88–1.87), 1.44 (0.99–2.08), and 1.52 (1.06–2.20), respectively (trend test: P < 0.001). By comparison with those in the lowest quartile, the adjusted hazard ratios were 1.37 (0.93–2.02), 1.66 (1.12–2.47), and 1.76 (1.20–2.59) for those in the 2nd, 3rd, and highest HOMA-IR quartiles, respectively.CONCLUSIONSAccording to the dose-response effects of HOMA-IR shown in this prospective study, we conclude that insulin resistance could significantly predict development of microalbuminuria in type 2 diabetic patients.

An Update on Diabetic Renal Disease

The hope that diabetic nephropathy would lessen with improvements in management appears not to have been realised. Current epidemiological studies report a continued high frequency of this important micro-vascular complication, with a continued excess mortality when increased levels of urinary albumin loss or reduced filtration function occur. While good glycaemic control ameliorates the development of microalbuminuria in type 1 and type 2 diabetes there is increasing evidence that angiotensin-converting enzyme inhibition and angiotensin receptor blockade are ineffective as primary prevention strategies. Blood pressure control remains the mainstay of treating established diabetic renal disease and a multi-factorial intervention approach in those with type 2 diabetes and microalbuminuria appears to be effective in reducing mortality based on data from one study. The Quality Outcomes Framework initiative for general practice in the United Kingdom has resulted in increased screening for diabetic renal disease with an assumed earlier treatment of blood pressure and introduction of blockers of the renin-angiotensin system. Some novel therapies are under investigation but overall the landscape is largely unchanged.

Homocysteine as a Risk Factor for Development of Microalbuminuria in Type 2 Diabetes

BackgroundKidney function is critical in homocysteine clearance, and plasma homocysteine level is frequently increased in patients with renal failure. On the other hand, recent studies in animals have shown that hyperhomocysteinemia induces renal injury. In this study, we determined whether hyperhomocysteinemia can be a risk factor for the development of microalbuminuria in patients with type 2 diabetes.MethodsA nested case-control study. Of 887 patients with type 2 diabetes who did not have microalbuminuria at baseline, 76 developed microalbuminuria during follow-up (mean, 36.0 ± 11.7 months; range, 18 to 76 months). The control group consisted of 152 age- and sex-matched subjects who did not develop microalbuminuria. Baseline plasma homocysteine concentrations were measured in stored samples.ResultsBaseline plasma homocysteine concentrations and mean HbA1C levels during follow-up were significantly higher in patients who developed microalbuminuria than in those who remained normoalbuminuric. Multivariate logistic regression analysis showed that baseline plasma homocysteine level and mean HbA1C were independent predictors of microalbuminuria in type 2 diabetes.ConclusionHyperhomocysteinemia was associated with increased risk of microalbuminuria in patients with type 2 diabetes supporting the concept that hyperhomocysteinemia has an etiologic role in the pathogenesis of diabetic nephropathy.

Renal Hyperfiltration and the Development of Microalbuminuria in Type 1 Diabetes

OBJECTIVEThe purpose of this study was to examine prospectively whether renal hyperfiltration is associated with the development of microalbuminuria in patients with type 1 diabetes, after taking into account known risk factors.RESEARCH DESIGN AND METHODSThe study group comprised 426 participants with normoalbuminuria from the First Joslin Kidney Study, followed for 15 years. Glomerular filtration rate was estimated by serum cystatin C, and hyperfiltration was defined as exceeding the 97.5th percentile of the sex-specific distribution of a similarly aged, nondiabetic population (134 and 149 ml/min per 1.73 m2 for men and women, respectively). The outcome was time to microalbuminuria development (multiple albumin excretion rate >30 μg/min). Hazard ratios (HRs) for microalbuminuria were calculated at 5, 10, and 15 years.RESULTSRenal hyperfiltration was present in 24% of the study group and did not increase the risk of developing microalbuminuria. The unadjusted HR for microalbuminuria comparing those with and without hyperfiltration at baseline was 0.8 (95% CI 0.4–1.7) during the first 5 years, 1.0 (0.6–1.7) during the first 10 years, and 0.8 (0.5–1.4) during 15 years of follow-up. The model adjusted for baseline known risk factors including A1C, age at diagnosis of diabetes, diabetes duration, and cigarette smoking resulted in similar HRs. In addition, incorporating changes in hyperfiltration status during follow-up had minimal impact on the HRs for microalbuminuria.CONCLUSIONSRenal hyperfiltration does not have an impact on the development of microalbuminuria in type 1 diabetes during 5, 10, or 15 years of follow-up.

Higher HDL cholesterol levels are associated with a lower incidence of chronic kidney disease in patients with type 2 diabetes

Background and aims Type 2 diabetes is one of the most important risk factor for the development of chronic kidney disease (CKD). Recently, it has been shown that lower high-density lipoprotein cholesterol (HDL-C) levels predicted the development of microalbuminuria in type 2 diabetic individuals. We have prospectively assessed the effects of plasma HDL-C levels on the incidence of CKD in a large cohort of type 2 diabetic patients. Methods and results We followed 1987 type 2 diabetic outpatients with normal or near-normal kidney function at baseline for 5 years for the occurrence of incident CKD defined as glomerular filtration rate ≤ 60 mL/min/1.73 m 2 (as estimated by the abbreviated Modified Diet and Renal Disease Study equation). Cox proportional hazards models were used to examine the independent relationship between plasma HDL-C levels and incident CKD. During a median follow-up of 5 years, 11.8% ( n = 234) of participants developed incident CKD. In multivariate regression analysis, higher HDL-C levels were associated with a lower risk of incident CKD (multiple-adjusted hazard ratio 0.76; 95% coefficient intervals 0.61–0.96; p = 0.025) independently of age, gender, body mass index, hypertension, smoking history, diabetes duration, hemoglobin A1c, plasma triglycerides, LDL-cholesterol, presence of diabetic retinopathy, baseline albuminuria, and current use of medications (anti-hypertensive, anti-platelet, lipid-lowering and hypoglycemic drugs). Conclusions Higher plasma levels of HDL-C are associated with a lower risk of incident CKD in a large cohort of type 2 diabetic adults independently of numerous confounding factors.

Comparative effects of enarapril versus losartan on the prevention of diabetic nephropathy in type 2 diabetes patients with microalbuminuria

A prospective randomized open-labeled study was performed to compare the renoprotective effects of enarapril and losartan on the development of microalbuminuria in type 2 diabetic patients with hypertension. Diabetic patients who have hypertension and microalbuminuria at base line (n=19) were recruited. Enarapril (n=11) or losartan (n=8) was randomly chosen by envelope methods and was prescribed for one year. At the end of this study, the blood pressure of patients in these two groups decreased significantly. Urine albumin-creatinine ratio (U-ACR) also decreased in these two groups, however, U-ACR of enarapril group was not significantly different from that of losartan group at any time of this study. Body mass index, HbA1c, blood pressure, and serum lipid profiles were not significantly different between the two groups. From these results, we conclude that the effects of enarapril and losartan on the development of microalbuminuria in type 2 diabetic patients along with hypertension seem to be equivalent in terms of clinical renoprotection.

Persistent Renal Hypertrophy and Faster Decline of Glomerular Filtration Rate Precede the Development of Microalbuminuria in Type 1 Diabetes

Soon after the onset of type 1 diabetes, renal hypertrophy and hyperfiltration become manifest, particularly among patients who will subsequently develop diabetic nephropathy. Whether these early renal dysfunctions are involved in the pathogenesis of diabetic nephropathy is currently unclear. We evaluated, during the same day, kidney volume and glomerular filtration rate (GFR) in 146 patients with type 1 diabetes and normal renal function. All the individuals were then monitored for a mean of 9.5 +/- 4.4 years for the development of microalbuminuria. Kidney volume and GFR were reevaluated in a subset of 68 patients 4 years after baseline. During follow-up, microalbuminuria developed in 27 of 146 diabetic patients. At baseline, kidney volume (312.8 +/- 52.6 vs. 281.4 +/- 46.1 vs. 236.8 +/- 41.6 ml/1.73 m(2), P < 0.05) but not GFR was increased in patients predisposed to microalbuminuria. Risk of progression was higher in patients with increased kidney volume (P = 0.0058). Patients predisposed to microalbuminuria showed a stable increase in kidney volume (P = 0.003), along with a faster decline of GFR (P = 0.01). Persistent renal hypertrophy and faster decline of GFR precede the development of microalbuminuria in type 1 diabetes. These findings support the hypothesis that renal hypertrophy precedes hyperfiltration during the development of diabetic nephropathy.

Circadian changes in blood pressure and their relationships to the development of microalbuminuria in type 1 diabetic patients

Diabetic nephropathy in type I diabetic patients, as it is currently understood, progresses in a stepwise fashion from normoalbuminuria to microalbuminuria, then to overt proteinuria and progression to chronic renal failure, and ultimately to end-stage renal disease. The role of early blood pressure changes in relation to diabetic nephropathy is now better understood in light of recent data using ambulatory blood pressure monitoring as a means to monitor blood pressure changes noninvasively throughout the day. Cross-sectional studies with type I diabetic patients with microalbuminuria have shown that the normal nocturnal blood pressure often fails to fall normally during sleep. The question of which comes first, microalbuminuria or a rise in blood pressure in patients with type I diabetes, was recently addressed in a prospective study. An increase in systolic blood pressure during sleep precedes the development of microalbuminuria and may play a causative role in its development.

Association between high von Willebrand factor levels and the Thr789Ala vWF gene polymorphism but not with nephropathy in type I diabetes

A genetic susceptibility for diabetic kidney disease is suspected since diabetic nephropathy occurs in only 30 to 40% of type I diabetic patients. As elevated von Willebrand factor (vWF) plasma concentrations have been reported to precede the development of microalbuminuria in type I diabetes, we addressed a possible implication of vWF as a genetic determinant for diabetic nephropathy. Three known vWF gene polymorphisms were genotyped in a group of 493 type I diabetic subjects, all showing proliferative retinopathy, but with various stages of renal involvement, which ranged from no microalbuminuria, despite a mean duration of diabetes of 31 years, to advanced nephropathy (GENEDIAB Study): Thr789Ala (Rsa I), M-/M+ (Msp I) (intron 19), and Ala1381Thr (Hph I). Plasma vWF and factor VIII (F VIII) levels were also measured in this population. Plasma vWF and F VIII levels were increased in diabetic subjects with nephropathy (P < 0.001) or with coronary heart disease (CHD; P < 0.001), but there was no interaction of both conditions on plasma levels. The Msp I polymorphism (M-/M+) was weakly associated with nephropathy (P = 0. 04), but this association was not more significant when other risk factors were used in a logistic regression analysis. The vWF Thr789Ala polymorphism was associated with CHD (P = 0.002) and with plasma vWF levels. Logistic regression analysis indicated an independent and codominant effect of the Thr789Ala polymorphism on CHD, but not on nephropathy, with a maximal risk for Ala/Ala homozygotes (OR = 4.2, 95% CI, 1.8 to 9.9, P = 0.0008). It is unlikely that polymorphisms in the vWF gene contribute to the risk for nephropathy in type I diabetic patients. However, the Thr789Ala polymorphism might affect the risk for CHD in this population through modulation of plasma vWF levels.

Estimated urinary albumin index: a predictor of microalbuminuria in type 2 diabetes.

This study examined factors contributing to the development of microalbuminuria in diabetic patients. A total of 236 patients with Type 2 diabetes were studied: 143 were normoalbuminuric and 86 were also normotensive. Multiple regression analysis was used to identify factors influencing the urinary albumin index (UAI), an index of proteinuria based on urinary albumin adjusted for urinary creatinine. Significant factors (retinopathy, systolic blood pressure, and glycosylated haemoglobin) were used to generate a formula for estimating the log(e) UAI. Target values for systolic blood pressure and glycosylated haemoglobin to maintain the urinary albumin index at or below 22 were determined for different degrees of retinopathy. Normoalbuminuric patients were followed for 3 years to evaluate their progression to microalbuminuria. Each month, blood pressure, urinary albumin and creatinine, and glycosylated haemoglobin were measured. In normotensive, normoalbuminuric patients, initial urinary albumin index and log(e) UAI were significantly higher in patients who subsequently developed microalbuminuria. Patients with initial log(e) UAI > 3.09 or initial glycosylated haemoglobin > 6.0% also showed greater progression to microalbuminuria. Hyperglycaemia was an independent factor for the development of microalbuminuria in Type 2 diabetes. The urinary albumin index was most significantly affected by retinopathy, systolic blood pressure, and glycosylated haemoglobin. The estimated loge UAI calculated from these factors is a useful predictor of progression to microalbuminuria.