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Query: UMLS:C0011854 (type 1 diabetes)
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Diabetic nephropathy is the main cause of the increased morbidity and mortality in patients with insulin dependent diabetes. The prevalence of microalbuminuria was determined in adults with insulin dependent diabetes of five or more years' duration that had started before the age of 41. All eligible patients (n = 982) attending a diabetes clinic were asked to collect a 24 hour urine sample for analysis of albumin excretion by radioimmunoassay; 957 patients complied. Normoalbuminuria was defined as urinary albumin excretion of less than or equal to 30 mg/24 h (n = 562), microalbuminuria as 31-299 mg/24 h (n = 215), and macroalbuminuria as greater than or equal to 300 mg/24 h (n = 180). The prevalence of microalbuminuria and macroalbuminuria was significantly higher in patients whose diabetes had developed before rather than after the age of 20. The prevalence of arterial hypertension increased with increased albuminuria, being 19%, 30%, and 65% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. The prevalence of proliferative retinopathy and blindness rose with increasing albuminuria, being 12% and 1.4%, respectively, in patients with normoalbuminuria, 28% and 5.6% in those with microalbuminuria and 58% and 10.6% in those with macroalbuminuria. An abnormal vibratory perception threshold was more common in patients with microalbuminuria (31%) and macroalbuminuria (50%) than in those with normoalbuminuria (21%). This study found a high prevalence (22%) of microalbuminuria, which is predictive of the later development of diabetic nephropathy. Microalbuminuria is also characterised by an increased prevalence of arterial hypertension, proliferative retinopathy, blindness, and peripheral neuropathy. Thus, urinary excretion of albumin should be monitored routinely in patients with insulin dependent diabetes.
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PMID:Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes. 312 80

Diabetic nephropathy, a rarely listed cause of end-stage renal failure (ESRF) among patients starting renal replacement therapy (RRT) in the early seventies, has progressively gained in importance and become one of the major reasons for the continuous growth of the patient population on RRT in most European countries. Amongst new patients commencing RRT in 1985, the acceptance rate varied between 3 and 12 per million population for type I diabetes mellitus and between one and four per million population for type II diabetes mellitus. Nordic countries, particularly Sweden and Finland, had the highest acceptance rate of young patients with type I diabetes mellitus whose median ages were 38-42 years. In most central and southern European countries the median age of patients with type I diabetes mellitus varied between 50 and 58 years. The high number of young patients with type I diabetes mellitus and ESRF in Nordic countries point to a different natural history of this disease. It cannot be excluded, however, that the higher median age in other countries might result from doctors mistakenly diagnosing type I disease in patients with type II disease who need insulin treatment. Patients with type II diabetes mellitus had a similar age distribution at start of RRT throughout Europe and their median ages clustered around 60 years in most countries. The contribution of haemodialysis, peritoneal dialysis and renal transplantation was analysed for diabetic compared to non-diabetic ESRF. Despite large geographical differences in the proportional use of methods of treatment, a general trend to apply CAPD more frequently in diabetic as compared to non-diabetic patients was observed, and this was true for countries with both predominant haemodialysis and predominant transplant programmes. Transplantation without prior dialysis was performed in 17% of Swedish and 30% of Norwegian patients with type I diabetes mellitus. In order to better explain the mortality of patients with diabetic ESRF, the proportional distribution of causes of death was analysed. Myocardial ischaemia and infarction was confirmed to be the leading cause of death in patients with diabetes mellitus on RRT. The coronary death rate was estimated to be 10 times greater in young patients with type I diabetes mellitus as compared to their non-diabetic counterparts. Other cardiovascular as well as infectious causes were recorded in a similar proportion of deaths in diabetics as in non-diabetics. Cancer deaths, however, appeared to be definitely less frequent in patients on RRT due to diabetic nephropathy.
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PMID:Renal replacement therapy in patients with diabetic nephropathy, 1980-1985. Report from the European Dialysis and Transplant Association Registry. 314 13

In 97 patients with type I diabetes mellitus, 155 patients with type II diabetes mellitus, and two matched control groups, serum concentrations of laminin P1, a non-collagenous component of basement membranes, were determined by radioimmunoassay to see whether laminin P1 might be a valuable indicator of microangiopathic complications in diabetics. Independent of the type of diabetes, serum laminin concentrations in patients without nephropathy or with early renal damage as assessed by microalbuminuria were comparable with those of the control subjects. Patients with macroproteinuria or with renal insufficiency had significantly increased serum laminin P1 concentrations. Diabetic retinopathy was not found to influence serum laminin P1 concentrations. These data indicate that serum laminin P1 concentrations are increased in advanced diabetic nephropathy.
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PMID:Serum concentrations of laminin P1 in diabetics with advanced nephropathy. 319 51

From August 1974 to January 1985, 53 patients (26 men; seven Maoris) mean age 45 (SD 15) years, with diabetes mellitus for a mean of 12 (SD nine) years had a renal biopsy and were followed. Indications for biopsy were nephrotic syndrome, proteinuria, renal impairment (five) and hematuria (one). Mean plasma creatinine concentration was 0.22 (SD 0.18) mmol/L and protein excretion 3.4 (SD 2.5) g/24 h. Diabetic nephropathy was demonstrated in 39 patients and significantly associated with retinopathy and insulin dependent diabetes mellitus (IDDM). Of the 39 patients followed for 25.7 (SD 22.8) months, 18 had died (nine myocardial infarction, six uremia, two sepsis, one stroke) and nine had begun dialysis. The five-year cumulative renal survival was 28%. The presence of the nephrotic syndrome and the plasma creatinine concentration at presentation were the best predictors of survival. Diabetics with IDDM of 20 years duration, retinopathy and heavy proteinuria, who survive the other complications of their disease, are likely to have diabetic nephropathy requiring renal replacement therapy.
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PMID:Renal disease in diabetics--which patients have diabetic nephropathy and what is their outcome? 324 62

The reasons for the presence of activated T-lymphocytes (ATL) in some long-standing insulin-dependent diabetic (IDDM) patients are unknown. These cells have been implicated in the genesis of proteinuria in some forms of immune-mediated renal disease. We measured ATL in 18 IDDM patients with diabetic nephropathy, 10 with nonnephrotic proteinuria (total urinary protein excretion rate greater than 0.5 and less than 3.5 g/24 h) and 8 with nephrotic proteinuria (total urinary protein excretion rate greater than 3.5 g/24 h), and in 17 age-, sex-, and duration-of-diabetes-matched diabetic control subjects without clinical proteinuria (total urinary protein less than 0.5 g/24 h). T-lymphocytes purified from peripheral blood were stained by direct immunofluorescence with the fluorescein-labeled monoclonal antibody anti-HLA-DR. Absolute number and percent of DR-positive T-lymphocytes were significantly higher in patients with nonnephrotic proteinuria (median and range 162 x 10(6)/ml, 40-320 x 10(6)/ml; 13.9%, 8.1-19.4%) compared with nonproteinuric control subjects (81 x 10(6)/ml, 2-240 x 10(6)/ml, P less than .05; 6.2%, 0-13.1%, P less than .01). In 8 patients with nephrotic proteinuria, absolute and percent DR-positive T-lymphocytes tended to be lower (36 x 10(6)/ml, 14-56 x 10(6)/ml; 3.4%, 1.1-5.4%) than in nonproteinuric control subjects. An increased number of activated T-lymphocytes may be part of an immune-mediated process associated with the development of proteinuria in diabetic nephropathy. In advanced renal disease with nephrotic proteinuria, this immune process may become exhausted.
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PMID:Proteinuria and activated T-lymphocytes in diabetic nephropathy. 325 34

Increases in kidney size and function are characteristic features of the early stages of Type I diabetes mellitus, and may contribute to the pathogenesis of diabetic nephropathy. Other studies have shown that the relative circulating concentrations of insulin and glucagon may be regulatory to renal growth and function. In order to elucidate the role of pancreatic glucagon in diabetic renal growth, subtotal pancreatectomy was performed prior to administration of streptozotocin to rats. Glycosuria and kidney weight were significantly reduced by subtotal pancreatectomy, although creatinine clearance and blood glucose levels were not different from diabetic controls. These data suggest that hyperglucagonemia may be an important mediator of renal growth in insulinopenic diabetes mellitus.
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PMID:The effects of subtotal pancreatectomy on renal growth in streptozotocin diabetic rats. 333 79

The state of the complement system was studied in 91 patients with insulin dependent and in 47 patients with non-insulin dependent diabetes. A study was made of the quantity of hemolytically effective molecules of some components C2, C4, C3, C5 of classic and factors B and D of alternative pathway of activation. Complement components were studied for control in 51 healthy blood donors. Antigens B8 and B18 of the HLA-histocompatibility system were studied in parallel in 24 patients and 21 donors. A significantly raised level of components C3 and C4, factors B and D was revealed in the patients with insulin dependent diabetes as compared to the controls (p less than 0.05). In non-insulin dependent diabetes C4, factors B and D were significantly raised and the level of C5 was lowered (p less than 0.05). In the patients with insulin dependent diabetes having antigens B18 the level of C3 was raised and the level of C4 was lowered as compared to the controls. The level of factors B and D was also lower than that in the diabetic patients. An analysis of the content of the complement components in 31 diabetic patients with diabetic nephropathy indicated a decrease in the levels of components C3 and C5 and an increase in the content of C4 (p less than 0.001) as compared to the normal. Diabetes was accompanied by considerable variations as compared to normal values characterizing the state of the complement system and reflecting, to a certain extent, the main features of the pathogenesis of disease.
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PMID:[Levels of various components of the classical and alternative pathways of complement activation in diabetes mellitus patients]. 347 6

Diabetes is associated with changes in plasma lipids and lipoproteins into atherogenic direction. In IDDM these changes are small or absent if good metabolic control can be maintained. Diabetic nephropathy is, however, associated with the appearance of dyslipoproteinemia. In NIDDM plasma total and VLDL triglyceride levels are elevated, and HDL-cholesterol level is decreased, and this pattern of dyslipoproteinemia does not always respond to improved control of hyperglycemia. Abnormalities of lipoprotein metabolism, not reflected in conventional plasma lipid and lipoprotein level measurements, and glucosylation of lipoproteins and resulting alterations in lipoprotein catabolism may be of importance in the enhanced atherogenesis in diabetes. Both IDDM and NIDDM are associated with an increased frequency of hypertension, but the underlying mechanisms appear to be different. In IDDM hypertension is usually associated with the development of diabetic nephropathy and thus with a long duration of the disease. In NIDDM hypertension is often present already at the time of diagnosis, and also in IGT, the precursor stage of NIDDM, the prevalence of hypertension is already increased. Obesity explains only in part the high prevalence of hypertension in patients with NIDDM. Diabetes is known to be associated with multiple abnormalities in hemostatic factors and, although these abnormalities may contribute importantly to the increased risk of ASVD in diabetic patients, information about their real role is scanty and conflicting. The impact of general major risk factors for ASVD, elevated plasma cholesterol, elevated blood pressure, and smoking, on the risk of ASVD appears to be similar in diabetics and nondiabetics. Only a relatively small proportion of the excessive occurrence of ASVD in diabetics can, however, be explained by the effects of diabetes on the levels of general risk factors for ASVD. This proportion mediated through the effects of diabetes on risk factors is larger in female diabetics than in male diabetics. The major proportion of the excess of ASVD in diabetics remains, however, unexplained and must be due to effects of diabetes itself through mechanisms that are incompletely understood.
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PMID:Diabetes and atherosclerosis: an epidemiologic view. 355 30

Hematuria of unknown origin occurs in 30% of patients with diabetic nephropathy. In nondiabetic persons, hematuria may be caused by hypercalciuria with or without nephrolithiasis. Eight children with type I diabetes mellitus, hematuria, and hypercalciuria were observed in our clinic during a 1-year period. Two of these also had evidence of renal papillary necrosis. To assess the importance of hypercalciuria in the pathogenesis of hematuria in children with diabetes mellitus, we measured urinary calcium excretion in a large population of such patients. The calcium to creatinine ratio in the urine of diabetic children (0.21 +/- 0.01) was greater than that of nondiabetic children (0.12 +/- 0.01). A calcium to creatinine ratio of 0.28 was established as the upper limit of normal in our nondiabetic population, and 27% of the diabetic children were hypercalciuric on this basis. The diabetic children with hypercalciuria also had hyperphosphaturia and a urinary CaHPO4 X 2H2O molar ion product three times that found in the nondiabetic control population. These data suggest that many children with diabetes are at risk for renal damage due to hypercalciuria. Because hypercalciuria is more common in diabetic than nondiabetic children, it may play a previously unrecognized role in the renal disease associated with diabetes mellitus.
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PMID:Hematuria and hypercalciuria in children with diabetes mellitus. 357 34

Fasting plasma zinc levels were determined in 45 IDDM and in 40 NIDDM patients. Mean values were similar in both groups, but diabetic men showed a significantly higher plasma zinc (p less than 0.05) than diabetic women. In patients with diabetic nephropathy a lower zinc level was associated with decreased plasma albumin as compared to patients without complications (p less than 0.001). Neuropathy and macro-angiopathy were also associated with lower zincemia (p less than 0.05) but in the presence of normal albumin levels. In IDDM without nephropathy a significant positive correlation was found between plasma zinc and plasma glucose, albumin, branched chain amino acids and glutamine, while in NIDDM without nephropathy a significant positive correlation exists between plasma zinc and the amino acids glutamine, valine, histidine and lysine.
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PMID:Plasma zinc levels in diabetes mellitus: relation to plasma albumin and amino acids. 375 14


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