Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was the evaluation of a predictive genetic marker for nephropathy and hypertension in patients with type-I-diabetes mellitus (IDDM). The study was performed on 247 pediatric patients with IDDM. The mean age was 15.5 years (range 3.1-29.3), the mean duration of diabetes was 7.6 years (range 0.1-25.7). Age-related blood pressure and nocturnal albumin excretion rate were compared with the insertion/deletion-(I/D) polymorphism of the angiotensin-I converting enzyme gene. The genotype distribution did not differ significantly between IDDM patients (ID 48%, D 28%, I 24%) and the control group (ID 44%, D 37%, I 19%). Neither in the entire group, nor in patients with IDDM for more than 5 years, was a correlation found bet-ween allele distribution and albumin excretion rate. No correlation was found between genotype and blood pressure. When patients with a chronological age above 12 years were analysed separately, the genotype distribution between the groups with normal and elevated blood pressure showed no significant difference. The previously reported association of the I/D-polymorphism with nephropathy could not be confirmed in this study. The development of microalbuminuria, nephropathy and hypertension will be followed in our pediatric patients.
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PMID:Angiotensin I-converting enzyme-gene-polymorphism: relationship to albumin excretion and blood pressure in pediatric patients with type-I-diabetes mellitus. 935 52

We investigated familial clustering of diabetic retinopathy and nephropathy in the families of 372 subjects from the Diabetes Control and Complications Trial (DCCT). These subjects had 467 first-degree relatives with IDDM or NIDDM. Family sizes ranged from two to six. A complete data set was obtained from 241 relatives of 217 DCCT subjects. Among the DCCT subjects, 53% were in the intensive treatment group and 47% were in the conventional group; 44% were from the primary prevention cohort (no retinopathy or microalbuminuria at the DCCT baseline) and 56% were from the secondary intervention cohort (mild-to-moderate nonproliferative retinopathy and <200 mg/24 h albumin excretion rate [AER] at baseline). Retinopathy and nephropathy were assessed with seven-field stereo fundus photography and timed urinary AER measurements. Retinopathy was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. ETDRS scores and AERs were adjusted for the DCCT treatment group and for significant covariates from among sex, age, diabetes duration, HbA1c value, and body weight. Familial associations were assessed by comparing the prevalence of retinopathy and nephropathy in diabetic relatives of the respective positive versus negative DCCT subjects. To determine family clustering of the severity of retinopathy or nephropathy, the intraclass (familial) correlation was computed from the log-adjusted retinopathy and nephropathy scores of DCCT subjects and their relatives for all family members and sib-sib relationships. For parent-offspring, mother-child, and father-child relationships, the pairwise estimate of the correlations was computed. A correlation of 0.2 was considered to be biologically meaningful a priori. Among families of patients in the intensive and conventional groups combined, there was an increased risk of severe retinopathy (an ETDRS score > or =47, clinically significant macular edema, or laser treatment in either eye) among relatives of retinopathy-positive vs. retinopathy-negative DCCT subjects in the secondary intervention cohort (odds ratio [OR], 3.1; 95% CI 1.2-7.8; P < 0.05). There was no increase in the risk of retinopathy of any severity (microaneurysms or worse) in the relatives of retinopathy-positive vs. retinopathy-negative DCCT subjects of the primary prevention cohort. There was an increased risk of nephropathy (AER >40 mg/24 h) in relatives of nephropathy-positive versus nephropathy-negative DCCT subjects of the secondary intervention cohort (OR, 5.4; 95% CI 2.2-13.7; P < 0.001). The risk of severe retinopathy in the relatives of positive versus negative subjects from the conventional treatment group alone (OR, 4.3; 95% CI 1.01-18.6; P < 0.05) was statistically significant and somewhat greater than that among relatives of the subjects in intensive treatment group (OR, 2.4; 95% CI 0.7-8.1), which was not significant. Correlations for the severity of retinopathy were 0.187 (all family members), 0.327 (parent-offspring), 0.249 (father-child), 0.391 (mother-child), and 0.060 (sib-sib), using the combined treatment group families. All these correlations were statistically significant (P < 0.05), except for sib-sib. The results showed similar trends when the families from the conventional and intensive treatment groups were analyzed separately. Correlations for nephropathy in the combined treatment group families were 0.063 (all family members), 0.138 (parent-offspring), 0.170 (father-child), 0.103 (mother-child), and 0.107 (sib-sib). None of these correlations is statistically significant. The lack of significant correlation for the severity of nephropathy may reflect the relatively short duration of diabetes in the offspring of these families and the known high intrasubject variability of AERs. These data provide the first available evidence that the severity of diabetic retinopathy is influenced by familial (possibly genetic) factors and confirmatory evidence that such factors influence the development
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PMID:Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group. 935 33

A cross-sectional study was conducted on the prevalence and epidemiology of micro- and macroalbuminuria in diabetic outpatients in Gondar, Ethiopia. Microalbuminuria was defined as a mean urinary albumin concentration of 30-299mg L-1 in morning urine of three consecutive visits. The frequency of micro- and macroalbuminuria was 32% and 15% in IDDM patients and 37% and 20% in NIDDM patients, respectively. When only patients with a duration of more than 5 years were considered, micro- and macroalbuminuria were prevalent in 33% and 23% of IDDM, and 36% and 31% of NIDDM patients, respectively. In multiple regression analysis, urinary albumin levels (log) were significantly associated with systolic blood pressure and duration in IDDM patients even when proteinuric patients were excluded from the analysis. In NIDDM patients duration and diastolic blood pressure were significant predictors of urinary albumin concentrations. In order to delay chronic complications, screening for microalbuminuria by stick-testing in urine should be introduced into routine laboratory practice in developing countries.
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PMID:Prevalence and epidemiology of micro- and macroalbuminuria in Ethiopian diabetic patients. 936 76

We investigated the contribution of polymorphisms in the angiotensin II type 1 receptor gene (AGTR1) to renal complications in an inception cohort of 152 insulin-dependent diabetic (IDDM) patients examined 15-21 years after diabetes onset. This nested case-control study included 79 normoalbuminuric control subjects and 73 cases with evidence of nephropathy ranging from microalbuminuria to overt proteinuria. Subjects were genotyped for two AGTR1 polymorphisms (T573-->C and A1166-->C), and an adjacent CA repeat microsatellite. Allele C1166 and the 140 bp allele of the microsatellite were more frequent among nephropathy cases than normoalbuminuric control subjects (0.322 vs 0.247, and 0.618 vs 0.521, respectively), but these differences were not statistically significant. Although not significant by themselves, the AGTR1 polymorphisms contributed significantly to the risk of diabetic nephropathy when accompanied by poor glycaemic control. Among patients with frequent severe hyperglycaemia during the first decade of diabetes, the relative risk of nephropathy among allele C1166 carriers was 12.1 (95% CI: 3.7-39.8), whereas it was only 1.4 (95% CI: 0.6-3.5) among allele A1166 homozygotes. The difference between relative risks was highly significant (chi(2) = 8.25, p = 0.004 with 1 df). A similar pattern of higher risk of microalbuminuria, specifically among those carriers of allele C1166 who had poor glycaemic control was also found in an independent study of a cross-sectional sample of 551 IDDM individuals, although the effect was smaller in magnitude. We conclude that DNA sequence differences in the AGTR1 gene may modify the noxious effects of hyperglycaemia on the kidney. Allele C1166 carriers might especially benefit from nephropathy prevention programmes.
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PMID:Synergistic effect of angiotensin II type 1 receptor genotype and poor glycaemic control on risk of nephropathy in IDDM. 938 21

We assessed the relationship between erythrocyte Na+/H+ antiport activity and myocardial anatomical-functional parameters (by Doppler echocardiography) in normotensive IDDM patients, with and without microalbuminuria. We studied 33 normotensive IDDM subjects and 14 matched healthy controls (group 4). Based on urinary albumin excretion rate (UAER), 23 diabetics were normoalbuminuric, 10 microalbuminuric (group 3). Normoalbuminurics were divided up for normal (group 1, n = 13) or high (group 2, n = 10) antiport activity. We evaluated fasting glycaemia and 24-h urine glucose output, HbA1c, plasma lipids, urea, creatinine and electrolyte clearances, UAER, erythrocyte Na+/H+ countertransport, M-Mode and 2D echocardiograms with Doppler analysis. Antiport, which was higher in diabetics than controls, was significantly overactive in groups 2 and 3 vs group 4, independently from UAER. Diabetics showed left ventricular volume, cardiac mass and systolic function within the control range. In left ventricular diastolic filling, while peak E was similar in diabetic and healthy people, the late peak transmitral flow velocity (peak A) was significantly higher in diabetics than controls, and this was also true in groups 2 and 3 vs group 4. Antiport activity was positively related to peak A (p < 0.03). These observations suggest that (a) the Na+/H+ antiport may be overactive in diabetes, apart from microalbuminuria; (b) increased Na+/H+ antiport activity, in normotensive IDDM people, may be associated with preclinical diastolic myocardial dysfunction ("incipient diabetic cardiomyopathy"?).
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PMID:Erythrocyte Na+/H+ exchange and preclinical abnormalities of the left ventricular diastolic function in normotensive type 1 (insulin-dependent) diabetic patients. 940 45

We have recently described heterogeneity in renal structure in non-insulin-dependent diabetic patients (NIDDM) with microalbuminuria (MA; defined as albumin excretion rate from 20 to 200 micrograms/min). Thus, at variance with IDDM patients, "typical" diabetic glomerulopathy by light microscopy is observed only in a third of NIDDM with MA (Category II, CII). Further, despite persistent MA, 30% of NIDDM have normal or near normal renal structure (Category I, CI). Another one-third shows "atypical" patterns of renal injury with absent or mild diabetic glomerular changes, associated with disproportionately severe tubulointerstitial lesions and/or arteriolar hyalinosis and global glomerular sclerosis (Category III, CIII). The aims of this study were to evaluate whether similar patterns of renal lesions could be confirmed in a larger group of NIDDM with MA and to investigate tubular function in order to understand the mechanisms underlying MA in NIDDM patients. Renal biopsies were performed in 53 NIDDM with MA. Categories I, II and III were found in 41%, 26% and 33% of NIDDM with MA, respectively. All 8 patients with proliferative diabetic retinopathy were in CII. We also studied the urinary daily excretion rate of alpha 1-microglobulin (alpha 1 m), a low molecular weight protein, which is a useful indicator of tubular function. alpha 1 m was markedly increased only in CII patients (CI vs. CII vs. CIII: 6.2 +/- 1.2 vs. 13.7 +/- 2.1 vs. 7.3 +/- 0.9 mg/day, ANOVA, P < 0.01). In conclusion, we confirm that there is heterogeneity in renal structure in NIDDM patients with MA. This heterogeneity is not due to renal diseases other than diabetes. Increased alpha 1 m and proliferative retinopathy are useful indicators of the subgroup of MA NIDDM patients with typical diabetic glomerulopathy. It is suggested that diabetic microangiopathy explains the simultaneous occurrence of typical diabetic glomerulopathy, proliferative retinopathy and tubular dysfunction in a subgroup of NIDDM patients with MA.
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PMID:Renal structure and function in non-insulin dependent diabetic patients with microalbuminuria. 940 19

The aim of this study was to determine whether renal functional reserve (RFR) is altered in insulin-dependent diabetic (IDDM) patients according to the stage of diabetic nephropathy. RFR was examined in 33 IDDM patients in similar glycaemic and metabolic control and compared to 12 healthy control subjects, during eight 1 h clearance periods prior to, during and after a 3-h stimulation by amino acid infusion (4.5 mg x kg(-1) x min[-1]). RFR was calculated as the difference between stimulated and baseline glomerular filtration rates (GFR). In 14 early normotensive diabetic patients with normal urinary albumin excretion, mean baseline GFR (133 +/- 3 ml x min(-1) x 1.73 m[-2]) was higher whereas RFR (10 +/- 4 ml x min(-1) x 1.73 m[-2]) was lower (p < 0.05) than in control subjects (113 +/- 4 and 28 +/- 2 ml x min(-1) x 1.73 m(-2), respectively). In 10 normotensive patients who had lived with IDDM for 16 years and who had microalbuminuria, baseline GFR and RFR (109 +/- 7 and 24 +/- 6 ml x min(-1) x 1.73 m(-2), respectively) were similar to those in control subjects. In 9 patients who had suffered IDDM for 23 years and had developed macroalbuminuria and hypertension, baseline GFR (78 +/- 8 ml x min(-1) x 1.73 m[-2]) was lower than in control subjects (p < 0.05) and RFR (8 +/- 4 ml x min(-1) x 1.73 m[-2]) was not significant. In addition, renal vascular resistance decreased significantly during infusion (p < 0.05) in microalbuminuric normotensive patients as well as in control subjects (by 9 +/- 4 and 11 +/- 4 mmHg x l(-1) x min(-1) x 1.73 m(-2), respectively) but not in normoalbuminuric normotensive or macroalbuminuric hypertensive patients. These results indicate that microalbuminuric normotensive patients retain a normal RFR, whereas RFR is reduced or suppressed at two opposite stages of the disease: in normoalbuminuric normotensive patients with a high GFR and in macroalbuminuric hypertensive patients with a decreased GFR. This dissimilar impairment reveals permanent glomerular hyperfiltration in both early IDDM without nephropathy and IDDM with overt diabetic nephropathy, but not in IDDM with incipient nephropathy.
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PMID:Renal functional reserve in IDDM patients. 949 35

Microalbuminuria (MA) is associated with microangiopathy (renal and retinal lesions) in insulin-dependent diabetic (IDDM) patients. In contrast MA does not reflect microvascular damage in a substantial number of non-insulin-dependent diabetic (NIDDM) patients. MA predicts cardiovascular disease in NIDDM patients with increased von Willebrand factor (vWF) plasma levels which are hypothesized to reflect endothelial dysfunction. However, it is not known whether MA is consequent to generalised endothelial dysfunction or to renal injury. Thus, this study evaluated vWF plasma levels in relation to renal and retinal structural abnormalities in NIDDM patients with MA. Kidney biopsies, fundoscopy and measures of vWF plasma levels were performed in 32 NIDDM patients with MA. These patients were allocated to two renal structural categories: A) Without renal structural abnormalities (C I, n = 10): normal or near-normal renal structure, and B) With renal structural abnormalities (n = 22), further divided into: C II (n = 12) with typical diabetic nephropathology, predominantly glomerulopathy, and C III (n = 10) with atypical patterns of renal injury (more advanced tubulo-interstitial and arteriolar than glomerular changes). vWF plasma levels were significantly higher in category B (C II: 195+/-49% and C III: 161+/-46%) than in category A (C I: 119+/-42%), (chi-square, p < 0.05). Diabetic retinopathy was also related to vWF plasma levels (ANOVA, p < 0.05). These data suggest that there are two types of MA in NIDDM: one associated with increased vWF levels, established renal injury and frequently retinopathy, and the other characterized by normal vWF levels, normal renal structure and absent or mild diabetic retinopathy. We propose that vWF plasma levels in NIDDM patients with MA may help to identify patients with important renal structural changes, increased retinopathy risk and, perhaps, generalised endothelial dysfunction. Whether vWF plasma levels predict end-stage renal disease and cardiovascular events deserves longitudinal studies.
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PMID:Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure. 949 59

Nephropathy is a frequent complication of long term diabetes. Diabetic nephropathy is the major determinant of premature morbidity and mortality both in insulin-dependent (IDDM) and in non-insulin dependent-diabetes mellitus (NIDDM). There is good evidence that genetic predisposition plays a major role in development of diabetic nephropathy. This hypothesis is based on the observation that diabetic nephropathy clusters within families, both in IDDM and NIDDM. Components of the renin-angiotensin system (RAS) are plausible candidate genes to examine for a association with microalbuminuria and diabetic nephropathy. In this study we compared the distribution of PstI melting polymorphism at the ACE locus among NIDDM patients with diabetic nephropathy and in patients who, despite long duration of NIDDM, remain without this complication. The 220 NIDDM patients for whom DNA was available were classified into two groups according to their renal status: normoalbuminuric control subjects (n = 80) who are NIDDM patients with an A/C ratio < 2.5 and nephropathy cases (n = 140) who are NIDDM patients with A/C ratio > 2.5. Albumin excretion rate was assayed by radioimmunoassay. HbA1c was assayed using HPLC methods, creatinine--using Jaffe methods and DNA analysis using PCR reaction, and then after the amplification product was digested with PstI enzyme. The study revealed that PstI sequence differences ("+/= and -") in the ACE gene do not contribute to genetic susceptibility to diabetic nephropathy in NIDDM.
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PMID:[Is PstI polymorphism of the angiotensin I converting enzyme gene associated with nephropathy development in non-insulin-dependent diabetes mellitus (preliminary study)]. 949 4

C-peptide is co-secreted with insulin and has generally been considered not to possess biological activity. However, several recent studies during the last five years have demonstrated that administration of C-peptide in physiological amounts to type 1 diabetes (IDDM) patients on a short term basis (1-3h) results in decreased glomerular hyperfiltration, augmented glucose utilization and improved autonomic nerve function. More prolonged administration (1-3 months) of C-peptide to IDDM patients is accompanied by improvements in both renal function (diminished microalbuminuria) and autonomic and sensory nerve function. Both in vitro and in vivo data indicate that C-peptide may have a role in the regulation of insulin secretion. C-peptide's mechanism of action is not known but it may be related to its ability to stimulate Na+, K(+)-ATPase, activity, probably by activating a receptor coupled to a pertussis toxin-sensitive G-protein with subsequent activation of Ca2(+)-dependent intracellular signaling pathways. In conclusion, the combined findings indicate that C-peptide is a biologically active hormone. The possibility that C-peptide therapy in IDDM patients may be beneficial should be considered.
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PMID:Ernst-Friedrich-Pfeiffer Memorial Lecture. New aspects of C-peptide physiology. 950 42


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