Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As angiotensin-converting enzyme inhibition is accompanied by a marked decrease in glomerular protein loss, the hypothesis was tested that an increase of the glomerular transcapillary hydraulic pressure difference by exogenous angiotensin II would increase microalbuminuria in patients with insulin (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Acute effects of increasing doses of angiotensin II (1, 3 and 6 ng/kg/min) were studied on mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction (FF), total renal vascular resistance (TRVR), and urinary albumin excretion rate (UAER) in 11 IDDM and 11 NIDDM microalbuminuric patients. Angiotensin II infusion changed MAP from 100 +/- 3 mmHg at baseline to 105 +/- 3, 111 +/- 3, and 116 +/- 3 mmHg (P < 0.001), ERPF from 542 +/- 29 to 478 +/- 24, 429 +/- 23, and 382 +/- 19 ml/min (P < 0.001), FF from 20.2 +/- 0.06 to 23.1 +/- 0.7, 27.1 +/- 1.1, and 29.8 +/- 1.2% (P < 0.001), and TRVR from 9454 +/- 809 to 11,158 +/- 930, 13,310 +/- 1206, and 15,538 +/- 1362 dyne s cm-5 (P < 0.001). GFR and UAER, however, did not change significantly. Therefore, during angiotensin II infusion ERPF decreased, while FF and TRVR increased. As UAER and GFR remained unchanged, the presumed rise in intraglomerular capillary pressure by exogenous angiotensin II did not increase UAER. We suggest that during manipulation of the renin-angiotensin system, as in other renal diseases with proteinuria, factors other than glomerular transcapillary hydraulic pressure determine the degree of urinary albumin loss in microalbuminuric IDDM and NIDDM patients.
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PMID:Urinary albumin excretion rate during angiotensin II infusion in microalbuminuric patients with insulin and non-insulin-dependent diabetes mellitus. 913 45

Alterations in the metabolism of glycosaminoglycans (GAG) may play a role in the pathogenesis of diabetic-associated microangiopathy. Consequently, the relationship between diabetic nephropathy and retinopathy and urinary GAG distribution was assessed in 96 IDDM patients in comparison to 103 healthy controls. GAG concentration in 24h urine samples was determined by precipitation with cetylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (P = 0.0008) in urinary GAG excretion between patients (24.3 +/- 1.5 mg/24 h, mean +/- SEM) and controls (16.2 +/- 0.75 mg/24 h) could be detected. In patients with IDDM of longer duration, GAG excretion was increased (< or = 10 yr: 20.8 +/- 2.1 vs > 10 yr: 27.4 +/- 2.1 mg/24 h; P = 0.03). Furthermore, IDDM patients with class 4 nephropathy and retinopathy exhibited a markedly higher GAG excretion compared to those without nephropathy (33.1 +/- 3.0 vs 22.6 +/- 1.7 mg/24 h, P = 0.005) or retinopathy (29.7 +/- 2.8 vs 21.2 +/- 1.7 mg/24 h, P = 0.009). An increased urinary GAG concentration was detected in IDDM patients with albuminuria (> 300 mg/24 h: 29.9 +/- 3.3 vs < 30 mg/24 h: 23.0 +/- 1.7 mg/24 h; P = 0.048), proteinuria (> 0.5 g/24 h: 30.3 +/- 3.7 vs < 0.05 g/24 h: 22.7 +/- 1.6 mg/24 h) and in patients with augmented serum creatinine in comparison to those with normal values (> 0.12 mg/L: 34.9 +/- 2.3 vs < 0.12 mg/L: 22.4 +/- 1.6 mg/24 h; P = 0.01). The results demonstrate a close relationship renal GAG excretion and the presence of microangiopathy in IDDM patients.
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PMID:Diabetic microangiopathy and urinary glycosaminoglycans. 922 10

Proteinuria and nephropathy have been found to cluster in families of non-insulin-dependent diabetic (NIDDM) Pima Indian, and in Caucasian insulin-dependent diabetic (IDDM) patients. No information is at present available for Caucasian NIDDM patients. The aim of the present study was to determine whether micro-macroalbuminuria (AER+) is associated with albumin excretion rate abnormalities in diabetic and non-diabetic siblings of probands with NIDDM and AER+. We identified 169 Caucasian families with one NIDDM proband (the patient with longest known NIDDM duration) (101 families with only NIDDM siblings, 33 families with both NIDDM and non-NIDDM siblings and 35 families with only non-NIDDM siblings). Of the probands 56 had AER+ [Prob-NIDDM-(AER+)], 78 had AER-[Prob-NIDDM-(AER-)], 74 siblings of Prob-NIDDM-(AER+), and 113 siblings of Prob-NIDDM-(AER-) also had NIDDM. Data on albuminuria and retinopathy from multiple sibling pairs when the size of the sibship was more than two was adjusted according to a weighting factor. The odds ratio for AER+, in siblings of Prob-NIDDM-(AER+) adjusted for age, hypertension, glycated haemoglobin A1c and other confounding variables was 3.94 (95% confidence intervals: 1.93-9.01) as compared to siblings of Prob-NIDDM-(AER-). The 74 siblings of Prob-NIDDM-(AER+) had higher prevalence of proliferative retinopathy than siblings of Prob-NIDDM-(AER-) (14 vs 2%; p < 0.01). We also identified 66 non-diabetic siblings of 41 NIDDM probands with AER+ and 36 non-diabetic siblings of 27 NIDDM probands with AER-. Albumin excretion was two times higher, although still within the normal range, in the non-diabetic siblings of Prob-NIDDM-(AER+) than in siblings of Prob-NIDDM-(AER-) [median = 13.5 (range 0.5-148) vs 6.6 (range 1-17) micrograms/min (p < 0.05)]. In conclusion higher rates of albumin excretion aggregate in Caucasian families with NIDDM. Proliferative retinopathy is more frequently observed in families showing a clustering of AER+ and NIDDM. These findings suggest that familial factors play a role in the pathogenesis of renal and retinal complications in NIDDM.
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PMID:Clustering of albumin excretion rate abnormalities in Caucasian patients with NIDDM. The Italian NIDDM Nephropathy Study Group. 924 3

A rate of albumin excretion rate above 20 micrograms/min is a predicting factor of overt nephropathy in Type I diabetes. It has not yet been established whether this is the case also for Type II diabetes, where microalbuminuria is antecedent to general and cardiovascular mortality but not to end-stage renal disease. The reasons accounting for this discrepancy between Type I and Type II diabetes have not been fully elucidated. In principle two different hypotheses can be postulated to explain these findings. Firstly it can be suggested that overt proteinuria is not detected with similar incidence rates in microalbuminuric patients with the two types of diseases because Type II diabetics are older and more prone to develop cardiovascular events. Therefore these patients would die frequently before developing overt proteinuria not because microalbuminuria is not a predicting factor of End-stage Renal Disease, but rather because the follow-up period is not long enough to monitor the patients till the very moment they develop renal complications. Alternatively it is possible that microalbuminuria reflect a systemic, endothelial and vascular disorder rather than glomerular structural abnormalities in these patients. We have recently described a clustering of clinical features encompassing microalbuminuria, hypertension, peripheral extrahepatic insulin resistance, renal and cardiac hypertrophy and altered cation membrane transport systems, not in the overall Type II diabetic population, but only in a cohort of these patients. Evidences in keeping with a strict association between insulin resistance, hypertension and microalbuminuria in a subgroup of Type II diabetic patients have been recently reported by several authors both in cross-sectional and longitudinal studies. However the hypothesis that microalbuminuria reflects a systemic endothelial and vascular disorder in Type II diabetic patients, does not rule out the possibility that these systemic disturbances are also associated with histologic abnormalities of the kidney. With regard to the characteristics of renal histology in Type II diabetic patients with and without microalbuminuria, preliminary data from our laboratory demonstrate that there is no evidence of any renal disorder other than diabetes in microalbuminuric Type II diabetic patients. More particularly in this subset of patients we observed typical features of diabetic nephropathology (glomerular, tubulo-interstitial and arteriolar changes), while a substantial number of patients with increased albumin excretion rate exhibited either marked tubulo-interstitial lesions or arteriolar hyalinosis or both, in absence of significant glomerular changes. These findings suggest that it is not true that Type II diabetic patients with microalbuminuria show quite often normal renal histology, but rather than hyperglycemia may cause different patterns of renal injury as compared to Type I Diabetes. Furthermore always with regard to renal histology, it has been pointed out that in Type I diabetes glomerulopathy (especially mesangial) is the crucial change, whereas recent studies found considerable structural heterogeneity amongst proteinuric Type II diabetic patients with relatively high incidence of renal diseases other than diabetes. However parallel studies in a small group of micromacroalbuminuric Type II diabetic patients reported the typical glomerular changes, usually shown by Type I diabetic patients with similar patterns of renal damage. The issue of the relationships between microalbuminuria, hypertension and the development of overt nephropathy in Type II diabetes has been also examined in Pima Indians. The clinical scenario found in these patients does closely resemble that of Caucasian Type I diabetic patients.
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PMID:Relationships among microalbuminuria, insulin resistance and renal-cardiac complications in insulin dependent and non insulin dependent diabetes. 928 31

Cigarette smoking was known to promote the progression of diabetic nephropathy in patients with type 1 diabetes, but its influence on the course of diabetic nephropathy in patients with type 2 diabetes had not been previously established. In a prospective follow-up study we therefore compared the progression of nephropathy in type 2 diabetic patients with or without tobacco consumption. Initiation of dialysis treatment or death of the patient were the end points of the study. 36 patients with type 2 diabetes complicated with diabetic nephropathy were included in the study, 16 smoked and 20 did not. The main outcome measures were proteinuria, arterial blood pressure, HbAlc, serum-creatinine and creatinine clearance, which were controlled at least every six months. In the smoking diabetic patients the mean (SD) creatinine-clearance decreased from 82 +/- 10 to 10 +/- 6 ml/min/1.73 m2 over a period of 62 +/- 21 months. The rate of decline of the creatinine-clearance was 1.24 +/- 0.34 ml/min/month. In the non-smoking patients the creatinine-clearance decreased from 79 +/- 8 to 9 +/- 3 ml/min/1.73 m2 within 79 +/- 27 months. The rate of decline in the creatinine-clearance was 0.99 +/- 0.35 ml/min/month (p < 0.025). HbAlc, systolic and diastolic blood pressure as well as serum cholesterol and triglycerides were not significantly different in both patient groups. Therefore, we conclude that cigarette smoking promotes the progression of diabetic nephropathy in patients with type 2 diabetes, just as it is known in type 1 diabetic patients.
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PMID:Influence of cigarette-smoking on the progression of clinical diabetic nephropathy in type 2 diabetic patients. 934 85

Urinary excretion rate and total clearances of albumin, IgG, IgA and alpha 1-microglobulin, together with selectivity index and proteinuria, were determined by computerized nephelometry in 187 IDDM and NIDDM diabetic out-patients and in 39 healthy subjects in order to perform a prompt clinical assessment of diabetic nephropathy. Significant correlations between nephelometric and RIA procedures were demonstrated for the urinary excretion of albumin (p < 0.001) and total IgG (p < 0.001) in diabetic patients and healthy subjects. Nephelometry allowed us to classify diabetic patients in different stages of nephropathy: non nephropathic, normoalbuminuric with hyperfiltration, with incipient (microalbuminuric) and overt nephropathy (macroalbuminuric). Thirty consecutive subjects were analyzed within 1 h from the beginning of the procedure. A normal tubular function was demonstrated in non nephropathic, hyperfiltering and in 34% of microalbuminuric diabetic patients. On the contrary, in 66% of microalbuminuric and in 93% of macroalbuminuric patients alpha 1-microglobulin urinary levels were found above the upper normal limit. Urinary excretion of IgA was significantly increased only in macroalbuminuric diabetic patients (p < 0.001); this marker might therefore characterise the stage of overt nephropathy. Computerized nephelometry can be considered as a prompt, reproducible and high sensitive approach in the clinical evaluation of proteinuria and tubular function in diabetic renal disease.
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PMID:Nephelometry in the clinical assessment of glomerular proteinuria and tubular function in diabetic nephropathy. 934 86

Combined pancreas-kidney transplantation has been introduced in the treatment of patients with type 1 diabetes and renal failure 20 years ago. By 1985 374 combined pancreas-kidney transplantations had been reported to the International Pancreas Transplant Registries. Surgical drainage of the transplanted exocrine pancreas into the urinary bladder solves most of the postoperative problems encountered with the exocrine secretions. Furthermore, monitoring of pancreatic enzyme (amylase) activity in urine has been shown to be useful in diagnosis of rejection of the pancreatic graft. However, little attention has been paid to the biochemical consequences of high activities of proteolytic pancreatic enzymes on the determination of urinary proteins. The present case illustrates the difficulties in interpreting proteinuria in patients with combined pancreas-renal transplant with pancreaticocystostomia. In the propositus, interpretation of the urinary protein electrophoresis is hampered by the presence of pancreatic juice proteins and peptides originating from digestion of proteins by activated pancreatic enzymes. Results of immunochemically determined marker proteins ([micro]albumin, transferrin, beta 2-microglobulin) are unreliable due to digestion by pancreatic enzymes.
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PMID:Difficulties in evaluating urinalysis following combined pancreas-kidney transplantation. 936 5

Renal disease is a frequent late complication of type I diabetes mellitus, occurring almost entirely in adult patients. Typical diabetic nephropathy is characterized by proteinuria, and by the histological lesions of mesangial expansion and basement membrane thickening. We report an interesting case of a 3-year-old boy who developed immune complex glomerulonephritis with nephrotic syndrome 2 months after the onset of insulin-dependent diabetes mellitus.
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PMID:Appearance of immune complex glomerulonephritis following the onset of type I diabetes mellitus in a child. 937 Jan 89

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

Approximately 30% of patients with type 1 and type 2 diabetes develop diabetic nephropathy. Apart from metabolic control, genetic predisposition plays an important role in its genesis. Analysis of intermediate phenotypic markers showed that the activity of Na/Li- and Na+/H(+)-countertransport is increased in patients with diabetic nephropathy. The renin-angiotensin system is of crucial importance as a system for therapeutic intervention and as genetic marker for susceptibility to renal disease. Consequently, the analysis of molecular genetic markers has focused on a polymorphism in the gene for the angiotensin II converting enzyme (ACE). However, the analysis of the I/D-polymorphism with respect to development of diabetic nephropathy in type 1 and type 2 diabetes has yielded conflicting results, at least in type 1 diabetes. These discrepant results may be due to differences in definition, sample size and ethnic background of the patients. In IgA glomerulonephritis it has been shown that the DD genotype (which is correlated with higher serum and tissue ACE activity compared to II genotype) is associated with a more rapid deterioration of renal function. The same adverse effect of the DD genotype could also be demonstrated in patients with diabetic nephropathy. Two studies examined the response to treatment according to the different genotypes, with contradictory results. A Japanese study showed a more pronounced reduction in proteinuria under ACE inhibitor treatment in patients with DD genotype, whereas a Danish study showed that patients with the DD genotype exhibited a steeper decline in renal function despite ACE inhibitor treatment. The data available for other candidate genes are fragmentary and negative throughout.
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PMID:Genetic determinants of diabetic renal disease and their impact on therapeutic interventions. 940 16


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