Coronary arterial calcification is associated with albuminuria in type 2 diabetic patient

AIM: Although microalbuminuria has been suggested as an independent risk factor for ischemic heart disease, the relationship between diabetic nephropathy and macroangiopathy remains unclear. Previously, we reported that coronary artery calcification detected by electron beam computed tomography (EBCT) could indicate the degree of coronary atherosclerosis in type 2 diabetic patients. In this study, we examine the association between coronary arterial calcification and microalbuminuria and aortic calcification and microalbuminuria. METHODS: Two hundred and fifty-six patients, including 177 type 2 diabetic patients (106 patients with normoalbuminuria, 71 with microalbuminuria) and 79 non-diabetic patients were evaluated by assessing the urinary albumin excretion rate and using EBCT to determine a coronary calcification score (CCS) and an aortic calcification score (ACS). RESULTS: No differences were observed regarding age, smoking index or BMI. Diabetic patients exhibited a greater CCS than non-diabetic subjects (non-diabetes 33 +/- 75 vs. diabetes 203 +/- 467, p < 0.05). Diabetic patients with microalbuminuria exhibited the most advanced CCS (253 +/- 491, p < 0.05). In contrast, no difference was observed in ACS among three groups. Multiple regression analysis showed that CCS is significantly associated with urinary albumin excretion rate as well as age, duration of diabetes and serum creatinine (R(2) = 0.31), while ACS is strongly associated with age, smoking, serum creatinine, systolic blood pressure and low-density lipoprotein cholesterol level (R(2) = 0.29). CONCLUSION: Increased urinary albumin excretion is associated with coronary arterial calcification in diabetic patients.     

尿脂联素与糖尿病肾病严重程度的相关性研究

目的 探讨尿脂联素与糖尿病肾病严重程度的相关性.方法 150例糖尿病患者根据尿微量白蛋白/肌酐(ACR)分为正常白蛋白尿组(ACR＜ 30 mg/g),微量白蛋白尿组(ACR30～300 mg/g),大量白蛋白尿组(ACR＞ 300 mg/g),每组均为50例.同时选取健康体检者30名作为对照组.应用全自动生化分析仪测定空腹血糖、HbA1c、肌酐、白蛋白、甘油三酯、总胆固醇、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDH-C)等生化指标.采用酶联免疫吸附法测定血、尿脂联素水平.结果 血、尿脂联素及HbA1c水平在对照组、正常白蛋白尿组、微量白蛋白尿组及大量白蛋白尿组中依次升高,差异均有统计学意义(F=62.46,65.26,5.37,P均＜0.05);血肌酐水平随尿白蛋白水平升高依次升高,微量白蛋白尿组及大量白蛋白尿组与对照组之间比较,差异有统计学意义(F=8.25,P＜0.05),微量白蛋白尿组及大量白蛋白尿组与正常白蛋白尿组之间比较无明显统计学意义(P＞0.05);估算的肾小球滤过率(eGFR)随尿白蛋白水平升高依次降低(F=54.67,P＜0.01).Pearson相关分析显示尿脂联素与血肌酐、ACR、血脂联素、HbA1c呈正相关(r=0.66,0.61,0.62,0.35,P均＜0.05),与eGFR呈负相关(r=-0.71,P＜0.01).多元逐步回归分析发现尿脂联素与血肌酐、HbA1c、ACR、eGFR及血脂联素相关(P均＜0.05).结论 尿脂联素与糖尿病肾病的严重程度呈正相关.     

Urinary excretion of advanced glycation endproducts in patients with type 2 diabetes and various stages of proteinuria

OBJECTIVE: The objective of the study was to detect AGE-immunoreactive proteins in urine, and to evaluate AGE excretion at various stages of diabetic nephropathy in type 2 diabetes assessed by the level of proteinuria. METHODS: AGEs were measured in 24-h urine collection of patients with normoalbuminuria (N) (n=22), microalbuminuria (Mi) (n=31), macroalbuminuria (Ma) (n=28), and overt proteinuria with elevated serum creatinine level (PC) (n=25). A competitive ELISA with polyclonal anti-AGE antibodies was used to monitor AGE excretion. RESULTS: Multiple comparison of urine AGE content among various stages of proteinuria showed significant differences (summary p<0.000). Fifty percent of samples from the group of normoalbuminuric, and only 15% of samples from the group of microalbuminuria patients were AGE negative. However, there was no significant difference in AGE excretion between the patients with persistent proteinuria and elevated serum creatinine, and those with macroalbuminuria (PC vs Ma, p=0.265). None of the samples from these two groups of patients with highest AGE content in 24-h urine was negative for AGE-immunoreactivity. In addition, the ratio between 24-h urinary AGEs and urinary albumin excretion was calculated to determine whether total 24-h urinary AGE content is an index of the toxic form of albumin released in the course of diabetic nephropathy. The ratio values were log-transformed and bivariate comparison showed significant differences between the N vs Mi (p=0.006) and Mi vs Ma (p=0.000) groups. However, there was no significant difference (p=0.407) between values in the Ma and PC groups of patients. Multiple stepwise regression analysis indicated a relationship of urinary AGE-immunoreactivity with creatinine clearance values (r=0.52, p<0.001). CONCLUSION: The study demonstrated the presence of AGE-immunoreactivity in the urine of diabetic patients with various stages of proteinuria. Study results pointed to creatinine clearance as the main predictor of AGE excretion. Therefore, the measurement of urinary AGE appears to offer limited extra information in patients with impaired renal function.     

Kidney injury molecule-1 (Kim-1): an early biomarker for nephropathy in type II diabetic patients

Renal damage is a serious major microvascular diabetic complication implicated in the death of diabetic patients, which would necessitate the need for new biomarkers to detect early stage of diabetic nephropathy (DN). Kidney injury molecule-1 (Kim-1), a type I transmembrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. So, the present study was conducted to estimate and evaluate Kim-1 as a biomarker for DN. This cross-sectional study was carried out on 60 male and female type II diabetic patients (whose serum creatinine level was less than 2 mg/dL). Diabetic patients were classified as microalbuminuric with nephropathy (urinary albumin was 30–300 mg/dL) and normoalbuminuric without nephropathy (urinary albumin was <30 mg/dL). Twenty matched apparently healthy subjects were included as control group. Patients and controls were assessed for fasting blood glucose, glycosylated hemoglobin (HbA1c), serum creatinine, blood urea nitrogen (BUN), microalbuminuria, and urinary Kim-1. Urinary Kim-1 levels were elevated significantly tenfold in type II diabetic microalbuminuric patients as compared to the control group and normoalbuminuric diabetic patient. Urinary Kim-1 levels were positively correlated with microalbuminuria, serum creatinine, BUN, duration of diabetes, and BMI. Higher urinary Kim-1 level in T2D particularly in those with nephropathy and its correlation with urinary microalbumin, serum creatinine, blood urea, and BUN may reflect the role of Kim-1 as a biomarker for diagnosis and prognosis of diabetic nephropathy among T2D patients taking into account other risk factors.

     

Effect of zinc supplementation on microalbuminuria in patients with type 2 diabetes: a double blind, randomized, placebo-controlled, cross-over trial

OBJECTIVES: Oxidative stress can contribute to microvascular complications in diabetes. A decisive event associated with this condition may be the decrease in the synthesis of zinc-containing antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. This consideration led us to investigate the effect of zinc supplementation versus placebo on microalbuminuria in diabetic patients in a randomized double blind clinical trial. METHODS: Fifty diabetic patients with microalbuminuria were enrolled. Fasting plasma glucose, HbA1c, lipid profiles, plasma zinc levels and random urine for albumin and creatinine were measured. Patients randomly received 30 mg elemental zinc (group 1) or placebo (group 2) for 3 months. After a 4 week wash-out period, the groups were crossed over (i.e. the zinc group were given placebo, and the placebo group were given zinc) and the protocol was repeated. RESULTS: From an initial number of 50 selected patients (25 in each of two groups), 39 patients (21 in group 1 and 18 in group 2) completed the study. In group 1, after zinc supplementation, urinary albumin excretion decreased significantly from 86.5 ± 57 to 75 ± 71 mg/g (p = 0.01). After placebo, patients in group 1 showed no significant reduction in microalbuminuria (85 ± 72 mg/g to 83 ± 63 mg/g creatinine). In group 2, no change in albumin excretion was observed after placebo treatment (90.5 ± 63 mg/g to 90 ± 60 mg/g creatinine). After zinc supplementation, a significant reduction was observed in albumin excretion, from 90 ± 60 mg/g to 85 ± 57 mg/g creatinine (p = 0.003). CONCLUSIONS: Zinc supplementation reduced albumin excretion in microalbuminuric type 2 diabetic patients. This outcome may be due to the antioxidant effect of zinc.     

2型糖尿病微量白蛋白尿与氧化应激的关系

目的探讨2型糖尿病患者微量白蛋白尿与氧化应激状态的关系。方法将72例2型糖尿病患者分为无微量白蛋白尿的糖尿病组（DM组）和伴有微量白蛋白尿的糖尿病肾病组（DN组）,选择30例无糖尿病患者作正常对照组（NGT组）,测定三组的血清丙二醛（MDA）水平、生化指标及年龄、身高、体质量指数。结果DN组MDA水平明显高于NGT组及DM组,MDA水平与尿微量白蛋白排泄率（UAER）有显著相关性。结论与无微量白蛋白尿的糖尿病患者相比,糖尿病肾病患者存在着严重的氧化应激状态,这可能与UAER的严重程度相关。     

Association study of G1704T and G82S polymorphisms of RAGE gene for microalbuminuria in Japanese type 2 diabetic patients

To clarify whether polymorphisms G1704T and G82S of the RAGE gene were related to microalbuminuria, we performed a case-control study in Japanese type 2 diabetic patients. Polymorphisms G1704T and G82S of the RAGE gene were examined with genomic DNA obtained from 116 type 2 diabetic patients with microalbuminuria (urinary albumin/creatinine ratio between 30 and 300 mg/g of creatinine) (microalbuminuria group), and 232 patients with normoalbuminuria (urinary albumin/creatinine ratio <30 mg/g of creatinine) (normoalbuminuria group). The genotype distribution and T allele frequency of G1704T (9.9%) and S allele frequency of G82S (14.2%) in the microalbuminuria group did not significantly differ from those (T allele frequency, 8.4%; S allele frequency, 12.3%) in the normoalbuminuria group. There were no differences among the genotypes of G1704T and G82S of the RAGE gene regarding age, duration of diabetes, body mass index, glycosylated hemoglobin (HbA1c), blood pressure, and serum lipid levels. These data suggest that G1704T and G82S polymorphisms of the RAGE gene are not related to microalbuminuria in Japanese type 2 diabetic patients.     

Relationship of non-alcoholic hepatic steatosis to cortisol secretion in diet-controlled Type 2 diabetic patients.

AIMS: To examine the association of non-alcoholic hepatic steatosis (HS) with the activity of the hypothalamo-pituitary-adrenal (HPA) axis in Type 2 diabetic individuals. METHODS: The activity of the HPA axis, as measured by 24-h urinary free cortisol (UFC) excretion and serum cortisol levels after 1.0 mg dexamethasone, was measured in 40 diet-controlled, predominantly overweight, Type 2 diabetic patients with non-alcoholic HS and in 40 diabetic patients without HS who were comparable for age, sex and body mass index (BMI). RESULTS: Subjects with non-alcoholic HS had significantly higher 24-h UFC excretion (191 +/- 4 vs. 102 +/- 3 nmol/24 h; P < 0.001) and post-dexamethasone cortisol concentrations (29.1 +/- 2 vs. 14.4 +/- 1 nmol/l; P < 0.001) than those without HS. Patients with HS had significantly higher values for HOMA insulin resistance score, plasma triglycerides and liver enzymes. Age, sex, BMI, waist-hip ratio (WHR), diabetes duration, HbA1c, LDL-cholesterol and blood pressure values were not different between the groups. The differences in urinary and serum cortisol concentrations between the groups remained significant after adjustment for age, sex, BMI, WHR, HOMA insulin resistance score, plasma triglycerides, HbA1c and liver enzymes. In multiple logistic regression analyses, 24-h UFC or serum cortisol concentrations (P < 0.05 and P = 0.02, respectively), along with age and HOMA insulin resistance, predicted the presence of HS, independently of potential confounders. CONCLUSIONS: These results demonstrate that non-alcoholic HS is closely associated with a subtle, chronic overactivity of the HPA axis in diet-controlled Type 2 diabetic individuals.     

Elevation of urinary betaig-h3, transforming growth factor-beta-induced protein in patients with type 2 diabetes and nephropathy

Transforming growth factor-beta (TGF-beta) is a pro-sclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. betaig-h3 is an extracellular matrix protein which is induced in many cells by TGF-beta. This study examined urinary betaig-h3 excretion in diabetic patients with elevated urinary albumin excretion and the clinical application of urinary betaig-h3 as a marker of diabetic nephropathy. Urinary and serum betaig-h3 levels were determined by enzyme-linked immunosorbent assay in 163 type 2 diabetic patients and 101 healthy control subjects of comparable age and weight. The ratio of urinary betaig-h3 and TGF-beta to creatinine was analyzed in patients with different degree of nephropathy. The betaig-h3 to creatinine ratio in urine was elevated in all groups of type 2 diabetics with normoalbuminuria (101.6 +/- 9.27), microalbuminuria (120.2 +/- 14.48), and overt proteinuria (146.3 +/- 16.34), when compared with control subjects (64.8 +/- 7.14) (P < 0.01). There was a positive correlation between urinary betaig-h3 and TGF-beta excretion rate and a positive correlation between urinary betaig-h3 and albumin excretion rate (AER). These data show that urinary levels of betaig-h3 are elevated in type 2 diabetic patients with nephropathy and may be used as a marker of diabetic nephropathy.     

Serum and urinary nitric oxide in Type 2 diabetes with or without microalbuminuria: relation to glomerular hyperfiltration

BACKGROUND: Glomerular hyperfiltration is considered as one of the pathophysiological mechanisms for the development of diabetic nephropathy. Oxidative stress is enhanced in patients with diabetes mellitus. Reportedly, nitric oxide (NO) might be involved in the pathogenesis of hyperfiltration. We investigated the relationship between hyperfiltration and NO system, and malondialdehyde (MDA) levels in Type 2 diabetics with/without microalbuminuria. METHODS: In 39 microalbuminuric, 29 normoalbuminuric Type 2 diabetic patients and 32 healthy controls, serum creatinine, nitrite, nitrate, urinary microalbumin, nitrite, nitrate, plasma MDA and estimated glomerular filtration rate (EGFR) values, calculated according to the Cockcroft and Gault formula, were recorded. RESULTS: Serum and urine NO levels were higher in both microalbuminurics and normoalbuminurics than controls. There were no significant differences in EGFR between groups. However, hyperfiltration was determined in 31% of normoalbuminurics and 20% of microalbuminurics. Serum and urine NO levels were higher in patients with hyperfiltration. Plasma MDA levels were significantly elevated in both microalbuminurics and normoalbuminurics when compared with controls. Serum glucose and microalbuminuria were positively correlated in microalbuminuric diabetics. Serum NO levels were also positively correlated with EGFR in both normoalbuminurics and microalbuminurics. HbA1c levels were positively correlated with both urinary albumin excretion and plasma MDA levels in normoalbuminuric diabetics. CONCLUSIONS: Hyperglycemia is associated with an increased NO biosynthesis and lipid peroxidation. Increased oxidative stress may contribute to the high NO levels in Type 2 diabetes. Furthermore, the high NO levels may lead to hyperfiltration and hyperperfusion, which in turn leads to an increase in urinary albumin excretion and thus causes progression of nephropathy in early Type 2 diabetes.     

Plasma lipids and urinary albumin excretion rate in Type 1 diabetes mellitus: the EURODIAB IDDM Complications Study.

AIMS: To examine the relationship between increased urinary albumin excretion rate and fasting plasma lipids among male and female respondents to the EURODIAB IDDM Complications Study, and attempt to explain inconsistencies in previous reports. METHODS: A cross-sectional study of 3250 randomly selected Type 1 diabetic patients from 31 diabetes clinics in 16 European countries was carried out between 1989 and 1990. Plasma lipids and urinary albumin were measured centrally. The present analysis was confined to the subgroup of 2205 patients attending after a 10-12 h overnight fast. Mean age was 33 years (SD 10) and mean duration of Type 1 diabetes mellitus was 15 years (SD 9). RESULTS: The prevalence of microalbuminuria (24-h urinary albumin excretion rate 20-200 microg/min) was 21.7% (95% confidence interval 19.9-23.5) and macroalbuminuria (24-h urinary albumin excretion rate > 200 microg/min) 7.8% (6.6-9.0). In comparison to patients with normal urinary albumin excretion rate (< 20 microg/min), and after controlling for age, sex, glycaemic control, duration of diabetes and current smoking, macroalbuminuria was associated with significantly (P<0.01) increased fasting plasma triglycerides, cholesterol, LDL-cholesterol, cholesterol:HDL-cholesterol ratio and, in women, reduced HDL-cholesterol. In men and women with microalbuminuria, the only significant association was with increased plasma triglycerides. CONCLUSIONS: These data confirm that there is an association between fasting plasma lipids and increasing urinary albumin excretion rate in European Type 1 diabetic patients. In microalbuminuric patients, however, the association was weaker than previously reported and partly explained by confounding factors.     

Increased resting metabolic rate in patients with type 2 diabetes mellitus accompanied by advanced diabetic nephropathy

Thirty-three patients with type 2 diabetes mellitus (16 men, 17 women) were divided into 3 groups based on urinary excretion of albumin (U-Alb)--group A: U-Alb < 30 mg/d; group B: 30 mg/d < or = U-Alb < or = 300 mg/d; and group C: 300 mg/d < U-Alb. Serum creatinine levels were lower than 2.0 mg/dL in all the subjects. There was no difference in age, sex, therapy, body weight, body mass index (BMI), lean body mass (LBM), or hemoglobin A(1c) (HbA(1c)) levels among the 3 groups. Resting metabolic rate (RMR) (kJ/h/m(2)) and adjusted RMR for lean body mass (kJ/h/m(2)) were significantly increased in group C compared with groups A and B. Hb concentrations, serum albumin levels, and creatinine clearance were much lower in group C than in groups A and B (P < .001). There were no difference in serum urea nitrogen, total cholesterol, cholinesterase and free thyroxine, or plasma insulin-like growth factor I (IGF-I) levels among the 3 groups. Linear regression analysis revealed an inverse correlation between RMR and serum albumin levels, correlation between RMR and U-Alb, and inverse correlation between RMR and Hb concentrations, respectively, in these patients. In conclusion, RMR in diabetic patients correlated directly with U-Alb and inversely with serum albumin and Hb concentration. These findings suggest that RMR is related with urinary albumin loss and anemia in patients with type 2 diabetes mellitus accompanied by diabetic nephropathy.     

影响2型糖尿病患者尿铜蓝蛋白及白蛋白的因素

目的　评价影响 2型糖尿病患者尿铜蓝蛋白 (Cp)及尿白蛋白 (Alb)的因素。 方法　记录及测定 1 0 4 6例 2型糖尿病患者的年龄、性别、糖尿病病程、血压、腰围、臀围、腰臀比、身高、体重、体重指数、空腹血糖、HbA1c、空腹胰岛素、尿素氮、肌酐 (Cr)、尿酸、血脂、血Alb,并留取晨尿测定Cp、Alb及Cr,对尿Alb/Cr、尿Cp/Cr与以上因素行多元线性回归分析。部分患者分入控制血糖组、控制血压组或对照组 ,6个月后复查上述指标 ,比较尿Alb/Cr及尿Cp/Cr的变化。结果　尿Alb/Cr与血白蛋白、血Cr、尿酸、收缩压、体重、体重指数等因素相关 (P <0 .0 5)。尿Cp/Cr与血Alb、收缩压、空腹血糖、HbA1c等因素相关 (P <0 .0 5)。控制血糖和控制血压可降低尿Alb/Cr及尿Cp/Cr。 结论　尿Alb/Cr及尿Cp/Cr均受到糖代谢、脂质代谢、血压及肥胖等因素的影响     

Low serum dehydroepiandrosterone sulfate concentration is a predictor for deterioration of urinary albumin excretion in male patients with type 2 diabetes

We recently found that serum dehydroepiandrosterone sulfate (DHEA-S) concentration correlated inversely with the degree of urinary albumin excretion in a cross-sectional study. We therefore performed an observational study to investigate the relationship between serum DHEA-S concentrations and changes in urinary albumin excretion in male patients with type 2 diabetes to answer the question as to whether DHEA is a causal rather than simply coincidental intermediate linking urinary albumin excretion to cardiovascular disease (CVD). The relationship between serum DHEA-S concentration and changes in urinary albumin excretion was investigated in 207 consecutive male patients with type 2 diabetes. Baseline serum DHEA-S concentration and urinary albumin excretion were measured in 2003. After 12 months, urinary albumin excretion was measured and any changes in urinary albumin excretion were calculated. Patients were divided into tertiles according to DHEA-S concentration. Greater changes in urinary albumin excretion were seen in patients with low DHEA-S concentration (29.6+/-7.6mg/g creatinine) than in patients with high DHEA-S concentration (5.1+/-3.6mg/g creatinine, P=0.0091). An inverse correlation was observed between serum DHEA-S concentration and changes in urinary albumin excretion (r=-0.193, P=0.0052). Multiple regression analysis demonstrated that HbA1c (beta=0.241, P=0.0009), and serum DHEA-S concentration (beta=-0.195, P=0.0054) were independent determinants of changes in urinary albumin excretion. In conclusion, serum DHEA-S concentration was inversely correlated with changes in urinary albumin excretion, which may indicate causality in the increased CVD mortality in male patients with type 2 diabetes and low DHEA-S concentration.     

A screening test for microalbuminuria in type 1 (insulin-dependent) diabetes

In this study we evaluated the acceptability of using the first morning urine albumin concentration (FMAC) and the first morning urine albumin/creatinine (FMA/C) ratio as an indirect estimation of timed albumin excretion in order to screen for microalbuminuria in a large diabetic population. Urinary albumin excretion rate (AER) was determined in samples from 4-h urine collection in 99 type 1 diabetic patients aged 30 +/- 10 years with a mean duration of diabetes of 15 +/- 8 years. The results of timed albumin excretion were successively compared with single-void first morning samples. On the basis of AER, 46 patients were normoalbuminuric (AER less than 20 micrograms/min), 28 microalbuminuric (AER 20-200 micrograms/min), and 25 proteinuric (AER greater than 200 micrograms/min). The relationship of 4-h AER to FMAC and FMA/C ratio was highly significant (r = 0.96 and r = 0.98 respectively). High sensitivity and specificity were found when cut-offs of 20 micrograms/ml and 2.5 mg/mmol were selected for albumin concentration and albumin/creatinine ratio respectively to discriminate between normal and elevated albuminuria. It is concluded that the measurements of albumin concentration and albumin/creatinine ratio in first morning urine samples are highly representative of 4-h timed albumin excretion. Because of their sensitivity, specificity and simplicity to perform, the tests proposed might be used in routine diabetic care and as a screening test for microalbuminuria in type 1 (insulin-dependent) diabetic patients. The not negligible day-to-day variability in albumin excretion confirms the need of several measurements to establish the presence of abnormal levels of albuminuria above all in patients with borderline values and/or clinically unstable metabolic control.     

Adiponectin gene polymorphism (G276T) is not associated with incipient diabetic nephropathy in Japanese type 2 diabetic patients

A single-nucleotide polymorphism (SNP) G276T in the adiponectin gene has been associated with lower plasma adiponectin levels and insulin resistance, which are related to the prevalence of type 2 diabetes or diabetic complications of macroangiopathy. We performed a case-control study to examine whether the SNP276 of the adiponectin gene was also related to early diabetic nephropathy. SNP276 was examined with genomic DNA obtained from 108 type 2 diabetic patients with microalbuminuria (urinary albumin creatinine ratio [ACR] between 30 mg/g x Cr and 300 mg/g x Cr; case subjects), and 208 patients with normoalbuminuria (ACR < 30 mg/g x Cr; control subjects). The genotype distribution and G allele frequency of SNP276 in the case subjects (0.71) did not significantly differ from the control subjects (0.69). There were no differences among the genotypes of the adiponectin gene regarding age, duration of diabetes, body mass index (BMI), hemoglobin A(1c) (HbA(1c)), serum lipids, serum creatinine, and plasma adiponectin levels. These data suggest that SNP276 of the adiponectin gene is not an independent risk factor for incipient diabetic nephropathy in Japanese type 2 diabetic patients.     

Long-term effect of epalrestat, an aldose reductase inhibitor, on the development of incipient diabetic nephropathy in Type 2 diabetic patients

The aim of the present study was to elucidate the long-term effect of epalrestat, an aldose reductase inhibitor (ARI), on renal function in patients with type 2 diabetes mellitus showing microalbuminuria. Patients were allocated to two groups (cases and controls) matched for age, BMI, and the extent of urinary albumin excretion (UAE). Thirty-five type 2 diabetic patients presenting microalbuminuria were included in this study: cases were treated with epalrestat (150 mg/day) for 5 years. No significant changes were found in blood pressure, HbA1c, and total cholesterol in either group during the observation period. In the control group, UAE increased significantly (P<.01) from 82+/-12 mg/g Cr at the baseline to 301+/-111 mg/g Cr at the end of the study, while UAE remained unchanged, 81+/-15 mg/g Cr at the baseline and 87+/-19 mg/g Cr at the end of the study, in the epalrestat-treated group. Reciprocal creatinine measured by an enzyme assay decreased significantly (P<.01) in both groups; however, the reduction rate in the epalrestat-treated group was significantly (P<.05) smaller than that in the control group. These results suggest the potential usefulness of ARIs in preventing the progression of incipient diabetic nephropathy in patients with type 2 diabetes mellitus.     

Elevated albumin excretion and retinal changes in children with type 1 diabetes are related to long-term poor blood glucose control

All diabetic children (n = 113) under 19 years old and with more than 2 years of diabetes attending the Steno Memorial Hospital in 1987 were studied. Normal urinary albumin excretion (less than 30 mg 24 h-1) was found in 96 patients (85%), 15 had microalbuminuria (30-300 mg 24 h-1) (13%), and 2 patients were proteinuric (greater than 300 mg 24 h-1) (2%). Retinal morphology was evaluated by colour fundus photography. Background retinopathy was more frequent in the group with elevated albumin excretion (71%) than in a matched normoalbuminuric group (20%, 2p less than 0.001). Long-term blood glucose control was assessed from all previous HbA1c measurements in the hospital records, an average of nine per patient. The mean observation period was 48 (3-76) months. Children with elevated albumin excretion had a higher mean HbA1c than children with normal urinary albumin excretion (10.3 +/- 1.9 vs 9.2 +/- 1.3% (+/- SD), 2p less than 0.05). Children with retinopathy had an HbA1c of 9.9 +/- 1.7 vs 9.0 +/- 1.2% in patients without retinopathy (2p less than 0.01).     

Does dietary protein intake correlate with markers suggestive of early diabetic nephropathy in children and adolescents with Type 1 diabetes mellitus?

AIMS: To examine the relationship between dietary protein intake and possible early markers of diabetic nephropathy (creatinine clearance (CrCI), kidney volume and albumin excretion rate (AER)). METHODS: One hundred and forty-five subjects with diabetes for 5-10 years, divided into three pubertal groups, participated. Kidney volume was measured by ultrasound, and serum creatinine and HbA1c were assayed. Two or three 24-h urine collections were obtained for albumin, creatinine and urea excretion rates. Dietary protein intake was estimated from urinary urea nitrogen excretion rate. Glomerular filtration rate was estimated by creatinine clearance. RESULTS: Mean protein intake was 1.22 +/- 0.48 g x kg(-1) x day(-1) Protein intake was significantly higher in males than females (P < 0.0001) and highest in prepubertal compared to mid-pubertal and post-pubertal subjects (P < 0.001). In multiple regression analysis, protein intake was positively associated with CrCl (P < 0.0001), and male sex (P < 0.0001) and negatively associated with body surface area (P = 0.0013) and age (P = 0.01). Kidney volume and AER were not related to dietary protein intake. CONCLUSIONS: This cross-sectional study failed to show a significant relationship between dietary protein intake and markers of early nephropathy, other than CrCl. However, a longitudinal, prospective study is required to definitively assess the role of protein intake in the evolution of diabetic nephropathy.     

Variability of albumin excretion in diabetes

The variability of urinary albumin excretion was determined in 3 consecutive overnight urine collections from 152 adult type I diabetic patients (study A) and in two 1-h urine collections from 57 adult type I and type II diabetic patients, obtained at a 10-wk interval (= median, range = 2-30 wk) (study B). In both studies the coefficient of variation (CV) of urinary albumin excretion recorded as urinary albumin concentration (mg/l) was highest (study A: CV 51.1%; study B: CV 61.8%), whereas the CV of the urinary albumin/urinary creatinine ratio (mg/mmol) was lowest (study A: CV 41.9%; study B: CV 50.8%). In study A the CV of urinary albumin excretion rate (microgram/min) (CV 43.5%) did not differ from that of urinary albumin/urinary creatinine ratio. In study B, however, the CV of urinary albumin excretion rate (CV 57.2%) was higher than that of the urinary albumin/urinary creatinine ratio and of fractional albumin clearance (CV 51.0%). The variability of urinary albumin excretion was not related to its magnitude and could not be attributed to variations in plasma glucose, glycosylated haemoglobin or renal tubular glucose reabsorption. This high variability stresses the need to obtain several urine samples before the amount of albumin excreted can be reliably estimated. It is recommended that one does not use urinary albumin concentration but urinary albumin/urinary creatinine ratio or fractional albumin clearance in the assessment of urinary albumin excretion in diabetes management.