Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The female patient initially showed the acquired type of total lipoatrophy at about 8 years of age. At 12 years of age, the onset of diabetes mellitus was speculated from advanced pyodermia and dedentition. At 29 years of age, glucosuria was found, and she developed proteinuria, ascites, and pretibial edema. The physical examination revealed: hepatosplenomegaly, complete absence of subcutanous fat, cutaneous xanthomas, and emaciated facies with pronounced zygomatic arches. Diabetic retinopathy was revealed in the ophthalmological examination, and nephropathy was evident in renal biopsy specimens. She also had peripheral diabetic neuropathy. No adipose tissue was found in the mesenterium under peritoneoscopy. The hepatic biopsy specimen revealed advanced portal liver cirrhosis. Laboratory findings included: hyperlipidemia, elevation of BMR without evidence of hyperthyroidism, impaired renal function, and undetected anti-insulin antibodies and anti-insulin antibodies. Endocrinological examinations revealed normal value, except for an impaired hGH response in the arginine test. C-peptide immunoreactivity was high. Her condition was fairly well controlled by 140 units of insulin injection daily.
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PMID:Lipoatrophic diabetes. Report of a case. 15 92

The evidence of sorbitol excess in the crystalline lens of alloxan-diabetic rats has led to anticipate the role of the enzyme aldose-reductase in the pathogenesis of the diabetic cataract. In addition, a number of experimental works have more recently shown the involvement of myoinositol deficiency, which probably results from the sorbitol accumulation. These metabolic pathways are most likely implicated in the pathogenesis of diabetic neuropathy and perhaps additionally in that of microangiopathy. The synthesis of several aldose-reductase inhibitors (AR inhibitors) confirmed experimentally these hypothesis. By reducing the activity of the enzyme aldose-reductase, these substances suppress the adverse metabolic consequences of polyol accumulation, myositol deficiency and dysfunction of the Na+/K+ ATPase dependent sodium activity. Although different experimentations showed that the AR inhibitors could prevent in animals the development of experimental cataract as well as the early functional or later anatomic abnormalities of the diabetic retinopathy and nephropathy, the clinical trials did not clearly support these experimental results in humans. On the other hand, the AR inhibitors were proved to exhibit some efficacy in the early stage of diabetic neuropathy and in incipient nephropathy where they delay the development of albustix positive proteinuria. However, the benefit of an early treatment with AR inhibitors should be confirmed by long term prospective studies, which could also assess the safety of these drugs in chronic administration.
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PMID:[Role of polyols in the development of diabetic complications. Value of aldose-reductase inhibitors]. 141 Aug 79

A personal series of 6780 patients with diabetes mellitus is reported. Of these 1410 were thought to have insulin-dependent (Type 1) diabetes and 4926 non-insulin-dependent (Type 2) diabetes. Among the former, 128 patients were only diagnosed when in severe ketoacidosis or coma. In 116 patients the diabetes was diagnosed in pregnancy. Chronic alcoholism was an aetiological factor in 75 patients; in 52 it led to the diagnosis being made, and it complicated treatment in 129 additional patients. In the patients with Type 2 diabetes whose treatment was stabilized 23.5% were having insulin injections, 44.5% tablets, and 32.0% diet only. Sight-threatening retinopathy developed in 21.3% of patients with Type 1 and 7.9% of those with Type 2 diabetes. The rate of developing sight-threatening retinopathy was 1.1% of patients per year. Blindness occurred in 0.28% of patients with Type 1 diabetes per year and 0.097% per year in Type 2 diabetes. If the mean survival of patients with retinopathy going blind is 7.5 years, this would mean 7500 people in the UK blind from diabetic retinopathy. There was a striking drop in the annual incidence of blindness after 1970 coinciding with the introduction of specific treatment for diabetic retinopathy. Juvenile cataract developed in 1.7% of patients who developed Type 1 diabetes before 30 years of age. Clinically important diabetic neuropathy developed in 17.4% of patients with Type 1 and 11.6% of those with Type 2 diabetes. The main features were paraesthesiae and numbness (49%), neuropathic ulceration (37%), pain (5%), autonomic symptoms (5%), and amyotrophy (4%). Oculomotor palsies and mononeuropathies were noted. Foot ulceration occurred in 81 patients with Type 1 and 279 of those with Type 2 diabetes. Charcot changes in the feet were noted in 21 patients. Major amputations were needed in 18 patients with Type 1 and 60 with Type 2 diabetes. Proteinuria believed to be due to diabetic nephropathy developed in 12.8% of patients with Type 1 and 4.7% of those with Type 2 diabetes. The prevalence of early renal failure was 4.6% and 1.4%, respectively. Coronary artery disease was noted in 9% of patients with Type 1 diabetes, and was more common in those who developed diabetes after 20 years of age. Myocardial infarction was as common in women as in men. In Type 2 diabetes coronary artery disease gave rise to symptoms in 19.1%, and myocardial infarction was more common in men.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diabetes in the United Kingdom: a personal series. 182 47

Diabetic neuropathy is an intriguing problem both for the patient and the clinician, however the clinical characteristics of type-II (non insulin-dependent) diabetics with peripheral neuropathy with special reference to gender differences is not paid much attention. We studied peripheral neuropathy and related complications in 179 type-II diabetics. Peripheral neuropathy was noted in 46 of 111 men and in 46 of 68 women. The age group of subjects did not differ significantly. Duration of diabetes differed between the groups with (n = 46) and without (n = 65) peripheral neuropathy (expressed in years and as mean +/- S.E: 7.7 +/- 0.7 vs 5.5 +/- 0.7; t = 2.2; P less than 0.05) in men, whereas in women it was not significant. Higher proportion (62.5% of 24) of men with proteinuria had neuropathy. Similar findings in women were not different. We conclude i) a large percent (51.4%) of the type-II diabetics had peripheral neuropathy than realised ii) duration of diabetes and proteinuria are important risk factors associated with neuropathy especially in men and iii) the gender differences need further clinicopathologic evaluation.
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PMID:Gender differences in the associated complications among type-II diabetics with peripheral neuropathy. 226 9

Neuropathy and retinopathy are two potentially serious late complications of diabetes. There is accumulating evidence that the development of these conditions is closely related to increased activity of the polyol pathway, which occurs in certain tissues as a consequence of long term hyperglycaemia. Symptomatic diabetic neuropathy may appear as one of many forms and is frequently accompanied by pain. Diabetic retinopathy is a progressive degeneration of the retina that represents one of the major causes of blindness in the developed world. A good prognosis for either of these conditions is believed to rely on early diagnosis and optimisation of glycaemic control as they become less reversible with progression of cellular damage. A new approach to the treatment of these and other late complications of diabetes may be offered by recently developed drugs, such as sorbinil, that inhibit the enzyme aldose reductase. In various animal models of late complications of diabetes sorbinil and other aldose reductase inhibitors have been shown to reverse some of the biochemical and physiological changes believed to underlie these complications. These include prevention or reversal of the accumulation of sorbitol and depletion of myo-inositol in nerve, lens and renal glomeruli. Sorbinil also counteracts the slowing of nerve conduction velocities, reverses the structural changes of Sipple stages I and II cataracts and prevents proteinuria in diabetic rats. Orally administered sorbinil is absorbed rapidly and reaches steady state plasma concentrations after 6 to 10 days' administration. Its elimination half-life is long (38-52 hours) and much greater than that of another aldose reductase inhibitor, tolrestat (10-12 hours). Within the dose range 50-250 mg about one-third of administered sorbinil appears in the urine as unchanged drug. In the small number of clinical studies of diabetic patients with neuropathies sorbinil has demonstrated limited therapeutic effects. There is now a requirement for studies of its prophylactic use and its therapeutic use in patients with diabetic neuropathy in the early stages of development.
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PMID:Aldose reductase inhibitors and late complications of diabetes. 309 44

To evaluate the diagnostic usefulness of gallium 67 scintigraphy in glomerular disease, 45 patients with various glomerulopathies, excluding lupus nephritis and renal vasculitis, were studied. Persistent renal visualization 48 hours after the gallium injection, a positive scintigram, was graded as + (less than), ++ (equal to), and +++ (greater than) the hepatic uptake. Positive scintigrams were seen in ten of 16 cases of focal segmental glomerulosclerosis, six of 11 cases of proliferative glomerulonephritis, and one case of minimal change, and one of two cases of membranous nephropathy; also in three of six cases of sickle glomerulopathy, two cases of diabetic neuropathy, one of two cases of amyloidosis, and one case of mild chronic allograft rejection. The 25 patients with positive scans were younger than the 20 with negative scans (31 +/- 12 v 42 +/- 17 years; P less than 0.01), and exhibited greater proteinuria (8.19 +/- 7.96 v 2.9 +/- 2.3 S/d; P less than 0.01) and lower serum creatinine values (2 +/- 2 v 4.1 +/- 2.8 mg/dL; P less than 0.01). The amount of proteinuria correlated directly with the intensity grade of the gallium image (P less than 0.02), but there was no correlation between the biopsy diagnosis and the outcome of the gallium scan. It was concluded that gallium scintigraphy is not useful in the differential diagnosis of the glomerular diseases under discussion. Younger patients with good renal function and heavy proteinuria are likely to have a positive renal scintigram regardless of the underlying glomerulopathy.
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PMID:Gallium 67 scintigraphy in glomerular disease. 319 76

In order to define genetic, immunological and metabolic risk factors and markers associated with diabetic neuropathy (DN) 47 insulin-dependent diabetic patients with neuropathy were compared to 30 age-matched insulin-dependent diabetes mellitus (IDDM) patients without neuropathy. Patients with diabetic neuropathy more often had proliferative retinopathy and Albustix positive proteinuria than patients without neuropathy. Judged by haemoglobin A1 (HbA1) concentrations measured during the preceding two years glycaemic control was worse in patients with than without diabetic neuropathy. The frequency of HLA-antigens DR3, DR4, DR3/DR4, B8, and B15 were increased and those of DR2 and B7 decreased in the diabetic patients. The frequency of any of these HLA-antigens did not differ in patients with or without diabetic neuropathy. There were no significant differences in the frequencies of insulin antibodies or proliferative responses to insulin antigens between patients with or without diabetic neuropathy. However, patients who were HLA-DR3/DR4 heterozygotes and had diabetic neuropathy responded to insulin antigens more often by proliferation than DR3/DR4 positive patients without diabetic neuropathy. Thus poor glycaemic control is associated with an increased risk for diabetic neuropathy. Patients with DR3/DR4 heterozygocity and failing to respond to insulin antigens by proliferation seem to be less prone to develop diabetic neuropathy.
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PMID:HLA-antigens and immunity to insulin in insulin-dependent diabetics with or without diabetic neuropathy. 323 12

We quantitatively assessed peripheral and autonomic nerve function in diabetic patients and compared them with various parameters of their diabetic status. Motor and sensory nerve conduction velocity (MCV, SCV), vibratory perception threshold (VPT) and the coefficient of variation of the ECG R-R interval (CV R-R) were measured in 85 diabetic patients aged 20-59 years. These values were compared with those of age-matched healthy subjects. Moreover, in 53 patients, MCV, SCV, VPT and CV R-R were investigated by multivariate analysis in relation to clinical parameters. In diabetics, MCV, SCV and CV R-R were significantly lower and VPT was higher than in age-matched healthy controls. The prevalence of impaired values in diabetics was 70% for VPT in the toe, 60% for SCV, and 55% for MCV, CV R-R and VPT in the finger. Impairments of MCV, SCV, CV R-R and VPT were closely correlated with diabetic retinopathy, proteinuria and duration of disease. Categorical regression analysis (multivariate analysis) revealed that the impairment of conduction velocity was closely related to diabetic retinopathy and to hypo- or areflexia, that the impairment of the vibratory perception threshold was related to ischemic changes in ECG and to hypo- or areflexia, and that the reduction of CV R-R was related to orthostatic hypotension and to proteinuria. These findings suggest that diabetic neuropathy progresses in parallel with other complications, and that it is a heterogeneous syndrome rather than a single entity.
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PMID:Diabetic neuropathy as a heterogeneous syndrome: multivariate analysis of clinical and neurological findings. 335 22

Fifty-five patients with chronic peripheral neuropathy, 31 with and 24 without retinopathy, had albumin excretion rates determined on 2-h supine urine collections on three occasions by a radioimmunoassay method. Four patients with retinopathy had albustix-positive proteinuria and were excluded from subsequent analysis. Microalbuminuria was found in 20 of the 27 patients with retinopathy compared with 10 of the 24 patients with neuropathy alone. The mean albumin excretion rate (AER) was higher in neuropathic patients with retinopathy than in those patients with neuropathy alone (41.2 +/- 40.3 vs 18.8 +/- 33.2 micrograms/min, P less than 0.01). Multivariate analysis of the data was performed and this revealed a correlation coefficient of R2 = 0.33 (P less than 0.01) for AER as the dependent variable with respect to the independent variables HbA1, systolic blood pressure and known duration of diabetes. There was, however, no significant contribution separately of these individual variables to the regression equation. Microalbuminuria was significantly associated with retinopathy although almost half of the patients with neuropathy alone had microalbuminuria. The association between microalbuminuria and neuropathy even in the absence of retinopathy provides support for a microvascular element in the pathogenesis of diabetic neuropathy.
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PMID:Microalbuminuria in diabetic subjects with chronic peripheral neuropathy. 340 31

Motor nerve conduction velocity and H. reflex parameters were studied in 85 insulin-treated diabetics classified in groups I to VI, according to the duration of the disease, in 32 maturity-onset diabetics (groupe V) and in 92 healthy control subjects. Each diabetic subject was examined prior to testing for clinical evidence of neuropathy and also had funduscopic examination, fluorescein angiography and an estimation of renal status by serum creatinine measurement and proteinuria. Electrical parameters were significantly different in all groups of diabetics from results in the control group. Neuropathy, as judged by these electrical studies, was frequently present in the absence of clinical expression, worsened with the duration of the disease in groups I to IV and preceeded other degenerative changes of diabetes. H. reflex parameters are an earlier index of neuropathy than motor nerve conduction velocity and may be used as a monitor of diabetic neuropathy.
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PMID:[Contribution of motor nerve conduction velocity and Hoffmann reflex in early detection of neuropathy in diabetics. Results and correlations with duration and other long-term complications in 117 patients (author's transl)]. 740 94


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