Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 24-h urine excretion and renal clearance of albumin, alpha I-acid glycoprotein, transferrin, IgG, IgA and haptoglobin were studied in 30 albustix-negative diabetics with no clinical data for diabetic nephropathy aiming at the precise characterization of proteinuria in patients with diabetes mellitus. The diabetic patients were divided into two groups - 15 patients with newly diagnosed diabetes and 15 - with a longer duration of diabetes. Thirteen healthy subjects, at the same mean age, served as a control group. The results reveal increase of the clearances and 24-h excretion of the proteins studied in the patients with diabetes mellitus, in those with a short duration of the disease including, with authentic difference for albumin, transferrin, IgG and haptoglobin among the patients with a longer duration of the disease and the healthy controls and authentic difference for albumin between those with the newly diagnosed diabetes and the healthy control. The possible prognostic significance of the indices studied is discussed as well as their importance for the early diagnosis of diabetic nephropathy.
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PMID:[Urinary excretion and renal clearance of several specific plasma proteins in diabetics]. 361 8

We prospectively investigated the evolution of proteinuria in 52 type I diabetics over 7.8 +/- 0.3 (mean +/- SE) yr and in 61 type II diabetics over 6.4 +/- 0.3 yr. Measurements of renal protein clearance were performed serially, and the time course of proteinuria was classified in each subject based on a threshold albumin clearance of 11 nl/s, equivalent to a urinary albumin excretion rate of 30 micrograms/min. The classification based on this threshold yielded four distinct patterns of albuminuria: minimal, intermittent, progressing, and established. These patterns occurred in both type I and type II diabetics independently of the duration of follow-up. This study has identified a pattern of intermittent microalbuminuria that is also associated with transient elevations of transferrin and IgG clearances. The relationship of clinical and biochemical parameters to proteinuria patterns was evaluated. No relationship was detected between proteinuria patterns and glycemic control in either type I or type II diabetics. In type I but not type II diabetics, established proteinuria was associated with higher systolic blood pressure and decreased creatinine clearance. The phase of intermittent proteinuria detected in this study may represent a reversible stage in the development of diabetic nephropathy, but the factors that trigger the transition to progressing proteinuria remain obscure.
Diabetes Care
PMID:Spectrum of proteinuria in type I and type II diabetes. 362 99

In vivo and in vitro studies were carried out to evaluate the clinical application of glycosylated hemoglobin and plasma proteins in the diagnosis and management of diabetes mellitus. Glycosylated hemoglobin registered an almost 80% fall in diabetic patients following controlled glycemia for two months while glycosylated plasma protein level registered an 80% fall in the patients after fifteen days of blood glucose homeostasis. Human serum proteins were glycosylated in vitro and glycosylation was linearly proportional to the glucose concentration and incubation time. Polyacrylamide gel electrophoresis of glycosylated serum proteins revealed that albumin and transferrin are the major proteins that are significantly glycosylated. Glycosylated hemoglobin and plasma protein levels were also increased in chronic renal failure patients without any history of diabetes.
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PMID:Retrospective glycemic status of diabetic patients: glycosylation of blood proteins in diabetes and chronic renal failure. 363 May 38

The urinary excretion of beta2-microglobulin, albumin, kappa light chains, transferrin, and IgG as well as their concentration ratios were assessed in 27 nondiabetic patients with proteinuria and in 72 IDDM patients, 41 with proliferative retinopathy (PR) and 31 without retinopathy, matched for age, duration of diabetes, and treatment. The mean excretions of albumin, transferrin, and IgG were similar in patients with nondiabetic proteinuria and in IDDM patients with PR and were significantly higher than in IDDM patients without retinopathy. Despite similar albumin excretion, the amount of excreted kappa light chains was significantly higher in IDDM patients than in patients with nondiabetic proteinuria, resulting in an elevated kappa chain/albumin ratio. Furthermore, diabetic subjects without microalbuminuria showed increased kappa chain/albumin ratio, indicating that increased urinary excretion of kappa chains may be an early sign of diabetic nephropathy. Determination of kappa light chain excretion may have clinical implications in the differentiation between proteinuria of diabetic and nondiabetic origin. The ratio kappa chain/albumin was independent of the excretion of beta2-microglobulin in patients with PR, suggesting that the reduced ability to reabsorb immunoglobulin light chains may occur earlier than that of beta2-microglobulin in the development of tubular dysfunction in insulin-dependent diabetes mellitus.
Diabetes 1985 Jun
PMID:Urinary excretion of plasma proteins in diabetic subjects. Increased excretion of kappa light chains in diabetic patients with and without proliferative retinopathy. 392 92

Peritoneal permeability to proteins was measured in diabetic and non-diabetic continuous ambulatory peritoneal dialysis patients during peritonitis and control periods. Clearances of albumin, transferrin, IgG, C3 and alpha 2-macroglobulin appeared to decrease as molecular weight increased. This relationship could be described by a power curve fit. The decrease was more than could be explained by differences in free diffusion only, indicating a size-selective barrier in the peritoneum. For all measured proteins clearances were higher in the diabetic patients. This may reflect a generally increased permeability due to their microangiopathy. The largest increase in protein loss and protein clearances was found during peritonitis. Our results do not suggest increased local production of any of the investigated proteins during the inflammation. Therefore, an increase in either peritoneal permeability or effective surface area or both is the most likely explanation. It is concluded in this study that peritoneal protein clearances are dependent on their molecular weight and that they are proportionally increased in patients with diabetes and during peritonitis.
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PMID:Peritoneal permeability to proteins in diabetic and non-diabetic continuous ambulatory peritoneal dialysis patients. 394 51

Recent studies have suggested a partial block in somatomedin (SM) production or growth hormone (GH) action in IDDM. Twelve well-nourished diabetic children (9 males and 3 females with a mean age of 11.2 +/- 3.3 yr), six with an HbA1c of 7.9-11.2% (group A) and six with an HbA1c of 12.5-15.6% (group B), were studied as follows: the GH response after 100 micrograms of oral clonidine and the SM generation capacity after i.m. administration of 0.2 U/kg/dose of human growth hormone (hGH) for 4 days. Group B diabetic subjects had a significantly higher mean +/- SD GH increase after clonidine than did group A patients (delta of 17.4 +/- 4.9 versus 5.7 +/- 6.0 ng/ml, P less than 0.01); the basal GH of both groups were similar (1.6 +/- 0.7 versus 2.3 +/- 1.4 ng/ml). In contrast, the SM response to hGH was significantly decreased in group B children as compared with those in group A (delta of 0.3 +/- 0.3 versus 1.2 +/- 0.4 U/ml, P less than 0.01). The basal SM levels of both groups were normal for age. GH and SM correlated with HbA1c levels (r = +0.80, P less than 0.01; r = -0.79, P less than 0.01, respectively); there was no correlation with plasma and urine glucose or serum cholesterol, cortisol, and transferrin. Our data indicate a blunted SM response to hGH in group B diabetic subjects; this defect in SM generation is apparently not present in group A subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Feb
PMID:Impaired somatomedin generation test in children with insulin-dependent diabetes mellitus. 396 1

A number of hormones and factors were found to stimulate growth of cultured rat islet tumor cells, the RIN-r cell line. A serum-free supplemented medium from RIN-r cells was formulated. It consisted of a 1:1 mixture of Ham's F12 and DME media with the addition of insulin, transferrin, triiodothyronine, prolactin, growth hormone, and an extract of proteose peptone (medium IM). The growth rate of RIN-r cells in this medium is as great as it is in 10% serum-supplemented medium. Up to 10 populations doublings occurred over a period of 20 days. Insulin is a very effective mitogen for RIN-r cells and has an effect on concentrations as low as 30 ng/ml. In addition, the insulin-like somatomedin, multiplication stimulating activity (MSA), is a growth factor at 50 ng/ml. It was found that RIN-r cells proliferate and continue to produce immunoreactive insulin in a hormonally and nutritionally defined medium. This medium is derived from medium IM, in which insulin is replaced with MSA and proteose peptone is omitted. Variations of this medium may prove useful in studies on the growth and function of the normal islets in long-term primary culture.
Diabetes 1981 Dec
PMID:Hormones and factors that stimulate growth of a rat islet tumor cell line in serum-free medium. 627 46

The relationship of early retinal changes and subclinical proteinuria to duration and metabolic regulation of insulin-dependent diabetes was studied in 67 children. Retinopathy was found in 25 patients and occurred almost exclusively (96%) in those with duration of disease longer than five years. Glomerular filtration rate was normal or increased in all patients. Urinary excretion of beta 2-microglobulin, albumin, transferrin, and IgG was significantly increased in patients, as compared with controls, whereas serum concentrations of these proteins were generally normal. The mechanisms responsible for the hyperexcretion of both large and small proteins are unclear but probably involve both glomerular and tubular dysfunction. Increased urinary protein excretion occurred independently of duration of disease. Retinopathy but not microproteinuria was more common in patients with glycosylated hemoglobin greater than 11% and in those with duration of disease longer than five years. Although a significant association was found between retinopathy and the hyperexcretion of one or more of the large molecular weight proteins, the weight of the evidence suggests that these two sequelae of diabetes differ in their pathogenesis. Long-term follow-up of these patients may provide insight as to their risk of developing more serious retinopathy or nephropathy, and whether good glycemic control may protect against these complications of insulin-dependent diabetes.
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PMID:Proteinuria in children with insulin-dependent diabetes: relationship to duration of disease, metabolic control, and retinal changes. 634 30

Modifications of plasma lipoprotein structure and function resulting from in vivo post-translational nonenzymatic glycosylation may play a role in the premature atherosclerosis of patients with diabetes mellitus. This report describes the generation and characterization of six unique murine monoclonal antibodies that bind glucosylated human plasma lipoproteins, but do not react with normal plasma lipoproteins. This was accomplished by immunizing mice with homologous glucosylated low density lipoprotein. In competitive inhibition radioimmunoassays, the dominant epitope recognized by these antibodies on glucosylated low density lipoprotein was identified as glucitollysine, the reduced hexose alcohol form of glucose conjugated to the epsilon amino group of lysine. Each of these antibodies was capable of identifying glucitollysine epitopes on all reduced glucosylated proteins studied, including high density lipoprotein, albumin, hemoglobin, and transferrin. These antibodies were also capable of identifying and quantitating glucitollysine residues on the total plasma proteins and isolated lipoproteins of normal and diabetic individuals after reduction of the proteins with NaBH4. Preliminary data suggest that diabetic total plasma proteins and isolated lipoproteins contain at least threefold more immunochemically detectable glucitollysine residues than nondiabetic plasma proteins and lipoproteins. The technique described in this report should allow production of region-specific antibodies to any immunogenic modification of a protein.
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PMID:A novel method for generating region-specific monoclonal antibodies to modified proteins. Application to the identification of human glucosylated low density lipoproteins. 641 10

Up until recently in clinical practice suspected hemochromatosis with a pathological iron-screening test (plasma iron, percentage transferrin saturation, serum ferritin, desferrioxamine-induced urinary iron excretion) made a liver biopsy necessary. Today, as a first step, the density of the liver parenchyma can be measured by means of computed tomography. Normal findings obviate the need for laparoscopy. Since the late forties weekly or twice weekly phlebotomy has been the sole form of treatment for manifest idiopathic hemochromatosis. In the mid-sixties the hopes placed in chelating substances (desferrioxamine) were not fulfilled, because the plasma half-life (only 7-10 minutes) of this drug was too short. Even with several daily injections only a small amount of iron was removed from the body tissue (10-25 mg daily urinary iron excretion). The introduction of portable infusion pumps in the late seventies offered us a new possibility of administering desferrioxamine by subcutaneous injection (Propper et al., 1976). Until that time such treatment was successfully used only in the field of pediatrics to treat secondary transfusion hemochromatosis in thalassemia. In one case of idiopathic hemochromatosis with severe organic involvement (right heart failure, repeated esophageal hemorrhage and bronzed diabetes) we had to achieve rapid iron elimination, and for this purpose we used continuous long-term desferrioxamine administration by means of a portable infusion pump (Autosyringe) in addition to phlebotomy. Since, particularly in the critical initial phase of treatment when heart failure was always threatening, great care had to be exercised in the use of phlebotomy, iron removal was achieved largely by desferrioxamine administration (daily up to 240 mg iron elimination in urine and stools).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New diagnostic and therapeutic possibilities in manifest idiopathic hemochromatosis. 651 41


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