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Query: UMLS:C0011854 (type 1 diabetes)
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Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.
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PMID:The management of diabetic proteinuria. Which antihypertensive agent? 150 44

Of the many information obtainable from the urine of diabetic patients, urinary C-peptide (CPR), albumin and anti-diuretic hormone (ADH) were representatively described using my clinical and experimental data. C-peptide excretion in 24h collection of urine is a good estimate of insulin secretion from the pancreas and thus low in IDDM patients and even in NIDDM patients at a later stage, but high in pathological conditions including Graves' disease, obesity, liver cirrhosis and Cushing's syndrome. Urinary albumin excretion in small amounts (microalbuminuria) is usually observed in diabetic patients who have been under a poor control state of diabetic hyperglycemia for over 5 years and provides a good tool for monitoring early diabetic nephropathy. The grade of microalbuminuria (30-300 mg/day) is positively correlated with the HbA1 level in diabetic patients, showing that microalbuminuria is reversible along with an improvement of diabetic control at least in an early phase of diabetic nephropathy. As the albumin level measured in a spot urine sample correlates well with the value in the 24h collection of urine, the albumin measurement is conveniently feasible with a spot urine sample at every patient's visit. The amount of ADH excreted in urine is 7-10% of that secreted from the posterior pituitary. The excretion of ADH in a day was in the urine of diabetic patients positively correlated with HbA1, urinary osmolarity and concentration of sodium in urine, although the pathological meaning of the observed ADH hypersecretion in the development of diabetic complications is currently unknown.
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PMID:[Pathophysiological analysis of diabetes mellitus and complications from the urine of diabetic patients]. 150 92

Heparan sulfate proteoglycans (HSPG) are negatively charged constituents of the renal extracellular matrix including the glomerular basement membrane (GBM) and mesangial matrix. Biochemical and functional studies of patients with type-1 insulin dependent diabetes mellitus (IDDM) suggest that alterations of HSPG may occur in diabetic nephropathy. We have utilized a specific cytochemical method and electron microscopy to quantitate the distribution of HSPG in the GBM of 10 normal people and in 16 IDDM patients with a spectrum of clinical and structural changes. Enzyme incubation studies of normal infant kidney demonstrated that heparitinase removed 94% of the stainable anionic sites in the lamina rara externa (LRE) and 77% of the sites in the lamina rara interna (LRI) of the GBM. In contrast, incubation in the enzyme chondroitinase ABC did not reduce the number of sites in the LRE but reduced the number of sites in the LRI by 26%. The HSPG anionic sites in normal subjects were distributed in the LRE as 20.9 +/- 1.3, and in the LRI as 13.1 +/- 2.2 per micron GBM length. Anionic sites were slightly reduced (19.6 +/- 1.3, P less than 0.04) in the LRE of IDDM patients with normal urinary albumin excretion rates (UAE), or microalbuminuria, and were reduced in both the LRE and LRI of IDDM patients with clinical proteinuria (13.1 +/- 2.3, P less than 0.001 and 8.9 +/- 2.1, P less than 0.001, respectively). The number of anionic sites in the LRE and LRI, respectively, correlated with UAE (r = +0.78, P less than 0.001, r = +0.58, P less than 0.02), with GBM thickness (LRE, r = +0.81, P less than 0.001; LRI, r = +0.67, P less than 0.01) and with the volume fraction of mesangium (LRE, r = +0.59, P less than 0.02; LRI, r = +0.58, P less than 0.03). These data confirm earlier biochemical findings of a reduction of HSPG in the GBM in advanced diabetic nephropathy but do not provide evidence for the loss of HSPG in the GBM as a mechanism for early microalbuminuria.
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PMID:Heparan sulfate proteoglycan in the glomerular basement membrane in type 1 diabetes mellitus. 151 88

Although hypertension is an important complication of diabetes it is unclear whether its association with other diabetic complications represents cause or consequence. Our study is a cross sectional evaluation of the relationship of blood pressure to renal structural and functional parameters. In 139 patients with insulin dependent diabetes for 18.9 +/- 7.4 years (mean +/- SD), we divided the patients into those with markedly increased mesangial volume fraction [Vv(mes/glom) greater than or equal to 0.37] and those with less [Vv(mes/glom) less than 0.37]. Hypertension (systolic BP greater than or equal to 160 and/or diastolic BP greater than 90 mm Hg or receiving BP medications) occurred in 29/40 with Vv(mes/glom) greater than or equal to 0.37. All 40 had clinical nephropathy with urinary albumin excretion (UAE) greater than 200 mg/24 hr. By two-way ANOVA creatinine clearance was lower and albuminuria was increased with both hypertension and the expanded mesangium. Also other measures of renal structure including filtration surface, index of interstitial fibrosis and index of arteriolar hyalinosis were increased by hypertension and mesangial expansion. Most patients with hypertension had other criteria for clinical nephropathy. Since, in these studies, we could not determine if hypertension contributed to or resulted from the renal lesions, we developed an estimate of the rate of mesangial expansion. We found that patients with normal BP (119 +/- 11/78 +/- 7 mm Hg) can be rapidly developing mesangial expansion. These studies support the view that the development of serious renal lesions can be independent of hypertension in IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of systemic blood pressure to nephropathology in insulin-dependent diabetes mellitus. 151 95

The relationship between glomerular and tubular dysfunction and metabolic control in type 1 diabetes was studied. To that end the urinary excretion rates of albumin and Tamm-Horsfall protein as well as HbA1c levels were measured in 58 patients with different degrees of diabetic nephropathy and in 76 apparently healthy subjects matched for sex and age. The urinary Tamm-Horsfall protein levels were measured by a simplified enzyme linked immunoassay. The intra- and interassay variations were 8.9% and 13.6%, respectively. The intraindividual variation was 41% and the sensitivity of the assay was 4 micrograms/l. The Tamm-Horsfall protein excretion rate was 42.1 x/2.0 micrograms/min (geometric mean x/tolerance factor) in the diabetic patients compared to 34 x/1.9 micrograms/min in the control subjects (NS). The diabetic patients had higher albumin excretion rate (38.5 x/7.3 micrograms/min) than the control subjects (4.7 x/2.3 micrograms/min; P less than 0.001). By using multivariate analysis of variance, HbA1c level was found to be the only independent variable associated with Tamm-Horsfall protein excretion rate in diabetic patients (r = -0.28; P = 0.04), while no relationship was found between Tamm-Horsfall protein excretion rate and age, age at onset and duration of diabetes, gender, serum creatinine, diuresis, urinary albumin excretion rate, systolic and diastolic blood pressure levels and antihypertensive treatment. The urinary albumin excretion rate was associated with diastolic blood pressure (r = 0.34; P = 0.02) but not with HbA1c levels when testing the above variables by multivariate analysis of variance. In conclusion, these results may indicate a lack of relationship between glomerular and tubular dysfunction. The former was influenced only by diastolic blood pressure levels and the latter only by the degree of metabolic control. However, the correlations were weak and do not provide any insight into what is actually responsible for glomerular and tubular dysfunction.
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PMID:Tubular secretion of Tamm-Horsfall protein in type 1 (insulin-dependent) diabetes mellitus using a simplified enzyme linked immunoassay. 152 39

The objective of this study was to examine the relationship between blood pressure, albumin excretion, and renal function in patients with type I diabetes mellitus. The study design was as follows: nonselected consecutive patients with type I diabetes mellitus were divided into three groups by level of albumin excretion rate (AER): less than 20 micrograms/min, 20 to 200 micrograms/min, and greater than 200 micrograms/min. The setting for the study was an outpatient diabetic clinic in a tertiary referral center. There were 166 patients studied: 53% men, 47% women, 86% white, 17% treated for hypertension. Seventy-six percent had an AER less than 20 micrograms/min, 18% had an AER of 20 to 200 micrograms/min, and 6% had an AER of greater than 200 micrograms/min. Glycosylated hemoglobin did not differ between groups. AER was increased with age and disease duration (P less than 0.005 by analysis of variance) after 10 yr of disease. Serum creatinine (P less than 0.005) and systolic (P less than 0.005) and diastolic (P less than 0.01) blood pressures were also increased with AER. Serum creatinine and blood pressure were found to be increased in parallel after 10 yr of disease, but both remained within the normal range overall. A comparison of individual blood pressures in patients not taking antihypertensive drugs (N = 138) with age-related blood pressures of nondiabetic subjects revealed increased systolic and diastolic blood pressures at all ages. Group comparison demonstrated a significant link between increased AER and serum creatinine (declining renal function) and increased blood pressure after a latent period of 10 yr. Blood pressure appears to be increased from the earliest age in diabetes compared with healthy populations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of disease duration and hypertension in albumin excretion of type I diabetes mellitus. 161 Sep 79

Urinary transferrin excretion was measured by radioimmunoassay in 74 children with Type 1 diabetes mellitus and in 40 normal children, and compared with urinary excretion of albumin, alpha-1-microglobulin, and N-acetyl-beta-D-glucosaminidase. Urinary transferrin excretion was significantly elevated in diabetic (median (range) 186 (18-1671) mg mol-creatinine-1) compared with normal (85 (27-668) mg mol-creatinine-1) children (p less than 0.001). Seventeen diabetic children had transferrin excretion above the 95th centile for normal children. In contrast there was no significant increase in urinary albumin excretion in the diabetic children although 8 had urinary albumin excretion which exceeded the 95th centile for normal children (6 of these 8 patients having coexistent urinary hyperexcretion of transferrin). Urinary transferrin excretion correlated significantly with urinary albumin excretion in both normal (rs = 0.62, p less than 0.001) and diabetic (rs = 0.61, p less than 0.001) children. The indices of proximal renal tubular function (urinary excretion of alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase) correlated significantly with transferrin excretion in both diabetic (rs = 0.43 and rs = 0.41, p less than 0.001) and normal (rs = 0.40, p less than 0.02 and rs = 0.53, p less than 0.001) children, but not with albumin excretion (rs = 0.20, p greater than 0.05 and rs = 0.22, p greater than 0.05). In addition urinary transferrin excretion significantly correlated with urinary glucose concentration (rs = 0.34, p less than 0.007) in Type 1 diabetic children. The discrepancy in urinary excretion of transferrin and albumin may reflect impaired proximal renal tubular reabsorption of transferrin and/or altered glomerular basement membrane selectivity for the two proteins.
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PMID:Increased urinary excretion of transferrin in children with type 1 diabetes mellitus. 168 49

Glomerular and tubular microproteinuria precede the development of overt nephropathy in Type 1 diabetes mellitus. However, in Type 2 diabetes urinary protein excretion and its relationship to diabetic nephropathy has not been clearly characterized. Twenty consecutive, newly diagnosed patients with Type 2 diabetes, whose urine was Albustix-negative and sterile on culture, were studied. Two timed overnight urine samples were collected at diagnosis, and after 2 months and 2 years, and excretion rates of albumin, alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase were calculated. HbA1c fell from 12.1 +/- 2.4% at diagnosis to 9.5 +/- 1.5% at 2 months and 9.6 +/- 2.2% at 2 years. Albumin excretion rate fell marginally from 6.5 (2.1-242.5) micrograms min-1 at diagnosis to 5.5 (1.7-274.0) micrograms min-1 at 2 months (p less than 0.05) rising again to 6.1 (1.9-201.7) micrograms min-1 at 2 years. alpha-1-Microglobulin excretion rate fell from 13.5 (3.6-59.9) micrograms min-1 at diagnosis to 8.4 (2.9-16.1) micrograms min-1 at 2 months and 8.8 (1.8-54.1) micrograms min-1 at 2 years (both p less than 0.05). Albumin excretion rate was found to correlate significantly with creatinine clearance at diagnosis (rs = 0.61, p less than 0.005), though not subsequently. In contrast, excretion rates of alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase correlated with HbA1c (rs = 0.68 and 0.66, respectively, p less than 0.005 at diagnosis and rs = 0.57 and 0.53, p less than 0.05 subsequently in both cases).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microproteinuria in type 2 diabetes mellitus from diagnosis. 169 21

Three hundred and fifty seven subjects (178 males and 179 females) with insulin dependent diabetes mellitus were evaluated for the presence of limited joint mobility of the interphalangeal joints. Sixty six subjects (19%) had stage 1 and 26 subjects (7%) had stage 2 involvement of their interphalangeal joints. The presence of contractures was significantly related to mean longitudinal glycated haemoglobin (HbA1) concentrations, duration of diabetes, age of onset, mean longitudinal cholesterol concentrations and blood pressure. Limited joint mobility was also significantly associated with early diabetic retinopathy and raised albumin excretion rates. Limited joint mobility remained a significant factor in the logistic regression model for albuminuria and grade of retinopathy when controlled for smoking, cholesterol concentrations, duration of diabetes, age, gender, and blood pressure. However, limited joint mobility was only significantly associated with diabetic retinopathy when the effect of HbA1 concentrations was included in the multivariate model.
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PMID:Limited joint mobility in subjects with insulin dependent diabetes mellitus: relationship with eye and kidney complications. 173 47

In 73 healthy (group I) and 32 children and juveniles with insulin dependent diabetes mellitus (IDDM, group II) urinary albumin excretion is determined by radioimmunoassay (RIA) and kinetic nephelometry. Intention of the study is to examine, if the kinetic nephelometry is--as observed in adults--a suitable method also in children and juveniles to detect microalbuminuria (greater than 30 mg/d). In both groups albumin excretion is observed in every urine sample when measured by RIA. Because of it's higher threshold kinetic nephelometry detects albumin excretion only in a part of the urine samples. The correlation between the two methods is very high (r = 0.905, p less than 0.001, n = 174). So kinetic nephelometry is not suitable to determine reference values. But as a faster and possibly more specific method than RIA nephelometry is a very effective way for a screening of microalbuminuria also in children and juveniles.
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PMID:[Comparative determination of microalbuminuria using radioimmunoassay and kinetic nephelometry in children and adolescent with and without Type-I diabetes mellitus (IDDM)]. 175 49


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