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Query: UMLS:C0011881 (diabetic nephropathy)
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The Danish study group for metabolic studies after transplantation of the pancreas. Development of combined pancreatic and renal transplantation and transplantation of islet cells in the treatment of insulin-dependent diabetes mellitus is reviewed. Transplantation of the pancreas is undertaken in Denmark on the indication of diabetes mellitus complicated by terminal diabetic nephropathy in patients who are considered, in advance, as candidates for renal transplantation. During recent years, improved results have been obtained by combined pancreatic renal transplantation with patient survival of up to 96% and graft survival of up to 84% after two years. Despite normal HbA1C, the intermediate metabolism is abnormal after combined pancreatic and renal transplantation. At present, it does not appear to prevent or arrest development of diabetic retinopathy while the results indicate that progression of diabetic nephropathy and neuropathy can be halted. Development in islet cell transplantation is promising. As yet, there has only been limited success with transplantation of foetal islet cells and this also involves great ethical problems. Xenographic transplantation of foetal islet cells may be of current value in the future. During recent years, 20% of islet cell transplantations from adult human donors have resulted in insulin independence for briefer periods (maximal 24 months, January 1992). Improved methods have been developed in immune modulation, immune isolation and cryopreservation and these make purification and harvesting of adequate quantities of islet cell mass possible to obtain exogenic insulin independence. Development of new immune suppressives has not improved the results. In the future, islet cell transplantation will possibly become part of the treatment of insulin-dependent diabetes mellitus.
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PMID:[Transplantation of pancreas and islet cells in insulin dependent diabetes mellitus--status after 25 years]. 150 46

Insulin-dependent diabetics may manifest evidence of autoimmune diseases involving endocrine or other organs. Rare cases of a peculiar fibrous and inflammatory lesion of the breast in diabetic patients have been previously described; however, the pathologic and clinical features that uniquely characterize these cases have not been defined or distinguished from other chronic inflammatory and fibrosing conditions in the breast. We studied eight patients with breast masses and longstanding insulin-dependent diabetes and compared them with 36 nondiabetic or short-duration diabetic patients with fibrosis and chronic mastitis. The longstanding diabetic patients presented with clinical breast masses ranging in size from 2 to 6 cm. Six of the eight patients had documented diabetic nephropathy, retinopathy, or neuropathy. Pathologically, these lesions showed lymphocytic lobulitis and ductitis, lymphocytic vasculitis (predominantly B cell), and dense keloid-like fibrosis that in many cases (six of eight) contained peculiar epithelioid cells embedded in dense fibrous stroma. We have provisionally labeled these cells "epithelioid fibroblasts" (EFBs). Although the features of lymphocytic lobulitis, ductitis, and/or vasculitis may occasionally be encountered in nondiabetic breast biopsies, EFBs appear to be unique to the diabetic condition. Control cases of chronic mastitis in nondiabetic or short-duration diabetes patients failed to show the complete constellation of lymphocytic lobulitis and ductitis, vasculitis, keloidal fibrosis, and EFBs. Diabetic mastopathy may represent an immune reaction to abnormal matrix accumulation. A hypothesis is presented.
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PMID:Diabetic mastopathy: a distinctive clinicopathologic entity. 161 78

In long-term diabetes mellitus, thickening of basement membrane in capillaries and small vessels is a characteristic lesion and plays an important role in the progression of diabetic microangiopathy. We have developed a sandwich enzyme immunoassay for human serum type IV collagen peptide with monoclonal antibodies. Previous studies suggested that collagen levels reflect the activity of fibrogenesis in basement membrane. Serum type IV collagen levels were measured in 137 non-insulin-dependent diabetic patients (aged 50-75 yr) with or without clinical signs of retinopathy, nephropathy, and/or neuropathy and 110 healthy subjects (aged 50-75 yr) without serological abnormality. Serum concentrations of type IV collagen were significantly higher (P less than 0.01) in diabetic patients (mean +/- SE 124.1 +/- 4.1 ng/ml) than in healthy subjects (73.9 +/- 2.2 ng/ml) and were increased with the prevalence or incidence of diabetic complications. In the patients with diabetic microangiopathy, serum type IV collagen levels became higher as clinical signs worsened. Especially in the patients with diabetic nephropathy, serum type IV collagen levels became higher with elevation of blood urea nitrogen, serum creatinine, and serum beta 2-microglobulin but not urinary excretion of beta 2-microglobulin and N-acetyl-beta-glucosaminidase. These observations indicated that elevation of serum type IV collagen in diabetic nephropathy was related to glomerular filtration dysfunction rather than renal tubular dysfunction. However, the antigen, which can be detected by our assay system, did not exist in urine specimens of healthy subjects, and an intimate relationship was not observed between serum type IV collagen level and serum creatinine level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum type IV collagen concentrations in diabetic patients with microangiopathy as determined by enzyme immunoassay with monoclonal antibodies. 169 88

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.
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PMID:The future of calcium channel blocker therapy in diabetes mellitus. 172 50

Late complications of diabetes mellitus include a variety of clinical pictures, mainly related to the involvement of the arterial wall both of large vessels (macroangiopathy) and small vessels (microangiopathy), and of the peripheral nervous system (neuropathy). Their presence in almost all types of diabetes indicates that there is a common pathogenetic mechanism, which can be substantially identified in high blood glucose levels and related alterations. Hyperglycemia, in fact, leads to some metabolic abnormalities, i.e. non-enzymatic glycosylation of proteins and polyol pathway activity; moreover it can negatively affect the pattern of some hormones, especially GH and sex steroids, and normal rheological and clotting properties of blood. These abnormalities, confirmed by experimental models, play a key role in the development of late diabetic complications. However some evidence indicates that a genetic background may predispose to their development or protect from their onset. The two main forms of diabetic retinopathy, non-proliferative and proliferative, show an incidence which increases with age and duration of diabetes, reaching 100% when diabetes lasts for more than 20 years. The risk of blindness, which is very high for the proliferative form, has been dramatically reduced by laser-photocoagulation. Diabetic nephropathy affects a lesser number of diabetics but, after a silent or preclinical stage, leads to renal failure and subsequent replacement therapy. Strict metabolic control in the silent stage and later rigid anti-hypertensive treatment can prevent or retard the evolution of this complication. A close association has been observed between diabetes and hypertension, which can directly affect the onset and evolution of diabetic nephropathy, probably through a common genetic mechanism. Diabetic neuropathy has a wide variety of clinical manifestations, at somatic, autonomic and central levels and can greatly modify the quality and expectancy of life. However, the major cause of death in diabetic subjects is large vessel disease or macroangiopathy, which is similar to non-diabetic atherosclerosis regarding the main histopathological and clinical manifestations but has a much higher prevalence and severity. Finally, a specific cardiomyopathy has also been described in diabetes mellitus and can account for the high rate of heart failure observed in these patients.
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PMID:The late complications of diabetes mellitus. 174 48

Estimates of the cost of diabetes should take into account the development of complications. Patient records identified from the 1987 National Hospital Discharge Survey were used to evaluate the risk of hospitalization due to late complications. Hospitalization for diabetic nephropathy reached a peak of 6.74/1000 between the ages of 45 and 54 years, compared to 0.14 to 1.80/1000 in controls. Diabetic patients less than or equal to 45 years of age were 46 times more likely to be hospitalized due to neuropathy. The risk of cardiovascular complications is high, with a greater incidence of arterial than venous disorders. Diabetic patients were 22 times more likely to be admitted for skin ulcers/gangrene, 15 times more likely due to peripheral vascular disease, and 10 times due to atherosclerosis. The risk of cerebrovascular accident and heart disease was 6 to 10 times greater in diabetic patients. Seventy-five per cent of diabetic cardiovascular disorders are myocardial infarction or chronic ischaemia. Hospitalization from renal complications occurs at younger ages than in the general population. Ophthalmic complications increase with age. Diabetic complications account for 2% of the total hospital admissions in the US in 1987. The total cost of the treatment of late diabetic complications was estimated at +5091 million (cardiovascular 74%; renal diseases 10%; nephropathy 3.6%; ophthalmic disorders 1.5%; other unspecified diseases 10%).
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PMID:The cost of hospitalization for the late complications of diabetes in the United States. 182 50

We performed a retrospective study on 1,019 patients with noninsulin-dependent diabetes who were followed for the past 20 years in our Diabetic Unit in order to determine the prevalence of overt diabetic nephropathy in relation to the other known complications of diabetes. In comparison with neuropathy, retinopathy and peripheral vascular disease, whose prevalence was 23.4%, 28.0%, and 27.4% respectively, the prevalence of macroproteinuria was significantly lower (7.0%). The prevalence of complications was correlated directly with patient age and duration of diabetes, and inversely with the degree of metabolic control. The reasons for the low prevalence of overt diabetic nephropathy in our population of noninsulin-dependent diabetics may be related to genetic factors, diet, other unknown environmental factors, or higher mortality rates in patients with renal disease.
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PMID:Prevalence of overt diabetic nephropathy in patients with noninsulin-dependent diabetes mellitus. 201 50

Since the late 1970s patients with diabetic nephropathy have formed an increasing proportion of new entrants to the Hospital renal dialysis and transplantation programme, reaching 28% for the three year period to December 1988. Between 1 January 1975 and 31 December 1988, 87 diabetic patients were accepted for treatment. Fifty-one per cent were European, predominantly type I diabetics. Maori (9% of the total reference population) accounted for a disproportionately high 47% due to an over-representation by type II diabetic patients (34 of 41 Maori). These findings cannot be explained by the higher prevalence in Maori of type II diabetes but appear to be due to a more prevalent and/or aggressive diabetic renal lesion in this group. On commencing treatment, nearly all patients had retinopathy and the majority had evidence of peripheral vascular disease, hypertension and neuropathy. CAPD was the initial mode of renal replacement therapy in 70% of patients. Overall patient survival was 77% at one year and 42% at three years, and survival on CAPD was 76% and 37% at one and three years, respectively. Patient survival on transplantation was 63% at one year and 58% at three years. Graft survival was 51% at one year and 46% at three years. Although the short term outlook for diabetic patients on renal replacement therapy is encouraging, longer term survival compared to non-diabetic patients is poor. Vascular disease is the major cause of death and an important factor in patient morbidity.
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PMID:Diabetic end stage renal failure--the Wellington experience 1975-1988. 203 73

Eighty-eight type I diabetics were subjected to neurological and myographic examination and tests were performed assessing the condition of the vegetative nervous system. Forty-four patients (50% of the group) suffered from diabetic nephropathy with different expression in the stage of chronic renal failure. The authors revealed significant positive correlation between the results of tests of vegetative neuropathy and all evaluated parameters of the neurological and electromyographic finding. In patients with a S-creatinine level above 125 mumol/l in both tests of vegetative neuropathy and in all examined parameters of peripheral nerves highly significantly lower values were recorded than in diabetic patients with normal renal function. In diabetics without renal insufficiency, however, the correlations between the findings on the autonomous and peripheral nervous system were also statistically significant.
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PMID:[The relation between peripheral and autonomic neuropathies in insulin-dependent diabetics]. 216 Mar 29

Increasing prevalence of insulin-dependent diabetes in associated with a rise in organ complications, markedly increasing morbidity and mortality, especially those of young and middle-aged people. The key role in the etiopathogenesis of diabetic nephropathy, retinopathy and neuropathy is played by a metabolic disorder. The only procedure capable of restoring normal metabolism is replacement of damaged endocrine tissue, i.e., pancreas transplantation. A look back into the history, and a review of current concepts in experimental and clinical pancreases transplantation, highlight some questions to be solved, yet including prevention of the adverse effect of pancreatic hydrolytic enzymes, inhibition of the onset of thrombosis, and timely diagnosis of rejection. The currently employed techniques--pancreatic duct obliteration with polymer, intestinal and urinary bladder drainage of pancreatic secretion--yield approximately similar results. The technique of pancreas transplantation has not been refined to such an extent so as to enable its performance in the early stage of diabetes in a effort to prevent the onset of complications. Patients deriving most benefit from the technique are mainly uremic diabetics undergoing it in combination with renal transplantation which yields optimal results. While a renal graft allows improved detection of pancreas rejection, a pancreatic graft confers protection against recurrence of diabetic nephropathy. Simultaneous transplantation of both organs represents not only a life-saving procedure, it also offers appreciable improvement of the quality of life of the diabetic patient.
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PMID:Current concepts in pancreas transplantation. 219 14


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