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Query: UMLS:C0011854 (type 1 diabetes)
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Type 2 diabetes mellitus has emerged as an important condition of older patients in which both microvascular and macrovascular complications are a common cause of morbidity and mortality. In contrast to type 1 diabetes mellitus, this endocrinopathy is clustered in minority populations and has both strong genetic and environmental factors that influence disease manifestation. A number of physiological alterations of glucose metabolism including hepatic overproduction of glucose, and reduced glucose utilization by peripheral tissues as a result of insulin resistance contribute to the development of the metabolic manifestations of this disease. Ultimately, pancreatic failure and reduced insulin secretion lead to hyperglycemia and the diabetic state. Frequently, many of these metabolic manifestations, or what has been termed Syndrome X, antecede the development of overt diabetes by many years. This syndrome is manifest clinically by such cardiovascular risk factors as hypertension, dyslipidemia, and coagulation abnormalities. This abnormal metabolic milieu contributes to the high prevalence of macrovascular complications including coronary artery disease as well as more generalized atherosclerosis. Microvascular complications have only more recently been recognized as an important and frequent complication of type 2 diabetes. Among the elderly and minority populations, this has become the single most important cause of end-stage renal failure that necessitates renal replacement therapies. The outcome for these patients on hemodialysis, the modality most frequently selected, is poor, with the majority of these patients dying of cardiovascular causes. Unfortunately, interventional strategies to reduce or prevent the microvascular and macrovascular complications have only recently received the needed attention and will require considerable effort and resources to improve the clinical outcomes and life expectancies for these patients.
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PMID:Diabetes in the elderly population. 1067 16

Increased circulating growth hormone (GH) levels and aberrant response to different stimuli characterize both type 1 diabetes mellitus and chronic uremia and are associated with severe retinal, kidney and heart complications. Combined kidney and pancreas transplantation is a therapy that restores the endogenous, closed-loop, insulin secretion in diabetes and cure uremia. To evaluate if combined transplantation can restore a normal secretion and response of GH to growth hormone releasing hormone (GH-RH), we studied four groups of subjects: (1) seven type 1 diabetic patients with end-stage renal failure who had received pancreas and kidney transplantation (KPTx); (2) six diabetic uremic subjects, candidates for combined transplantation (IDDUP); (3) nine patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients, six of whom treated only with prednisone (UVEST), while three (4) were treated with both prednisone and cyclosporin (UVESTCY). All subjects underwent a GH-RH test (50 microg intravenously, i.v., at 13:00 h). Serum insulin levels were significantly higher in IDDUP compared to UVEST (P=0.05) both at baseline and post GH-RH stimulus, while were similar to KPTx (P=0.2) and UVESTCY (P=0.7). In contrast, plasma free fatty acids were similar in all groups. In IDDUP baseline plasma glycerol was higher than in KPTx (P=0.04) and UVEST (P=0.02) and similar to UVESTCY (P=0.36); glycerol concentration did not change after GH-RH (P=0.08). Before and after GH-RH, serum GH levels tended to be higher in IDDUP (P=0.5) and KPTx (P=0.2) compared to UVEST and UVESTCY. Our results indicate that: 1) kidney-pancreas transplantation does not normalize the GH response to GH-RH; 2) GH abnormalities are not due either to the chronic immunosuppressive therapy or to the insulin effect on GH release; 3) GH abnormalities are probably secondary to functional and/or organic complications of the hypothalamus and/or pituitary as a sequela of diabetes mellitus.
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PMID:Persistence of anomalies in the growth hormone-releasing hormone-stimulated growth hormone response in diabetic-uremic patients after combined kidney-pancreas transplantation. 1083 Feb 43

Diabetic nephropathy is the most common single cause of end-stage renal failure (ESRF) in the Western world, recorded as the cause of renal failure in up to 40% to 45% of those entering renal replacement therapy (RRT) programs. However, marked differences exist between countries; the percentage of patients entering RRT in Norway because of diabetic nephropathy is 10% of the incident RRT population. The percentage in the United States is approximately 40%; therefore, the purpose of the present study was to compare data from Norway with data from the United States in an attempt to detect factors that might explain some of the differences. To make the comparisons as valid as possible, an attempt has been made to focus on populations of similar genetic make-up. The incidence of type 1 diabetes is a little higher in Norway than in the United States, whereas the prevalence of type 2 diabetes may be twice as high in the United States as in Norway; marked differences in the prevalence of obesity is probably a significant causative factor. There seems to be no striking difference in the prevalence of microalbuminuria in people with diabetes in the two populations, whereas there are insufficient data to compare the prevalence of overt proteinuria. The incidence of patients with a diagnosis of diabetic nephropathy as the cause of ESRF entering RRT in the two study populations showed marked differences; the incidence for 1997 was 8.9/million population in Norway and 113/million population in the United States. The proportion of type 2 diabetes was 46% in Norway and 64% in the US (1997). It is unlikely that the marked difference in incidence of RRT can be explained by differences in type 2 diabetes prevalence alone. The populations may not be directly comparable, and differences in the size of study populations and in the choice of renal diagnosis in patients with diabetes as a comorbid factor at the beginning of RRT may introduce uncertainties. Further, data on other factors--such as incidence of death before RRT is indicated, quality of care, and health care delivery, expressed as degree of blood pressure and metabolic control--were not available. Differences in acceptance of diabetes patients into RRT programs are not believed to contribute significantly. Norway is seeing a development toward increasing body weight and a change toward a more sedentary lifestyle, together with an increasing prevalence of type 2 diabetes earlier in life than has previously been the case. An increase in diabetic nephropathy and need for RRT because of type 2 diabetes must therefore be expected in Norway. To understand differences and to best design preventive programs, further comparative studies of the two populations seem warranted.
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PMID:Diabetic nephropathy and end-stage renal failure: the Norwegian story. 1117 23

In developed countries diabetics patients are the most numerous group with renal replacement therapy (USA 34%). The main and diagnostically irreplaceable criterion of incipient diabetic nephropathy is microalbuminuria which is usually associated with hypertension and poor glycaemic compensation. With advancing microalbuminuria progresses diabetic retinopathy and neuropathy. The increased transcapillary albumin escape rate and changes of some haemocoagulation factors in diabetics patients with microalbuminuria indicate that endothelial dysfunction is involved. In type 1 diabetes microalbuminuria is an indicator of increased mortality in which participate in particular cardiovascular diseases and to a minor extent renal failure. In type 2 diabetes microalbuminuria is an independent risk of generalized vascular disease. Microalbuminuria is also in non-diabetic subjects with hypertension associated with abnormalities such as impaired glucose tolerance and insulin resistance, an unflavourable lipidogram and altered diurnal blood pressure rhythm. The results of a coronarographic investigation revealed that the risk of severe coronary artery disease is more than double in subjects with microalbuminuria. Hypertension and hypercholesterolaemia are causal risk factors of cardiovascular diseases and concurrent microalbuminuria implies a higher expression of already existing microvascular damage in hormonal and metabolic disorders with an atherogenic potential.
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PMID:[Microalbuminuria--a risk factor for diabetic nephropathy and cardiovascular disease]. 1139 74

We report the case of a 52-year-old woman with long-term type 1 diabetes mellitus, complicated with proliferative retinopathy, autonomic neuropathy and microalbuminuria and moderate renal failure. A normochromic, normocytic are generative anaemia had been diagnosed for three years. Clinical and biological investigations for the aetiology of anaemia remained normal or negative. Anaemia was associated with a concentration of erythropoietin (EPO) in the normal range, but inappropriately low regarding anaemia. Treatment with recombinant EPO induced a rapid increase in haemoglobin level and improved the patient's quality of life. The role of diabetic neuropathy in the genesis of anaemia, in conjunction with a modest renal impairment is discussed.
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PMID:Erythropoietin-dependent anaemia: a possible complication of diabetic neuropathy. 1143 5

Diabetic Nephropathy (DN) is the commonest cause of end-stage renal failure (ESRF) in the Western world. Diabetic nephropathy follows a well outline clinical course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRF. Before the onset of overt proteinuria, there are various renal functional changes including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetes. It has been postulated that DN occurs as a result of the interplay of metabolic and hemodynamic factors in the renal microcirculation. There is no doubt that there is a positive relationship between hyperglycaemia, which is necessary but not sufficient, and microvascular complications. The accumulation of advanced glycosylated end-products (AGEs), the activation of isoform(s) of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycemia damages tissue. PKC is one of the key signaling molecules in the induction of the vascular pathology of diabetes. The balance between extracellular matrix production and degradation is important in this context. Transforming growth factor-beta (TGF-beta) appears to play a pivotal role in accumulation in the diabetic kidney. Hemodynamic disturbances are believed to be directly responsible for the development of glomerulosclerosis and its attendant proteinuria. There is familial clustering of diabetic kidney disease. A number of gene loci have been investigated to try to explain the genetic susceptibility to diabetic nephropathy. The genes coding for components of renin-angiotensin system have drawn special attention, due to the central role that this system plays in the regulation of blood pressure, sodium metabolism, and renal hemodynamics. Endothelial dysfunction is closely associated with the development of diabetic retinopathy, nephropathy and atherosclerosis, both in IDDM and in NIDDM. The pathogenesis of diabetic nephropathy is not clarified completely yet.
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PMID:Pathogenesis of diabetic nephropathy. 1146 May 89

Uncontrolled hypertension leads to an increased risk of cardiovascular disease and stroke. Hypertensive patients with concomitant type 2 diabetes are at even greater risk of cardiovascular complications; also, this high-risk patient population is at increased risk of renal disease and, ultimately, renal failure. Prospective morbidity and mortality trials have demonstrated that tight blood pressure control improves the cardiovascular prognosis and provides target organ protection. Current treatment guidelines recommend a target blood pressure of < 130/85 mm Hg for patients with hypertension and diabetes. Angiotensin II (A-II), a major component of the renin-angiotensin system, plays an essential role in the pathophysiology of hypertension and diabetes-related renal disease. Currently, the treatment of choice for hypertensive patients with diabetes is angiotensin-converting enzyme (ACE) inhibition, but most of the data are limited to patients with type 1 diabetes. Although ACE inhibition is clearly a mechanism for blocking A-II formation, inhibition at this site may not be complete, as alternate pathways exist for A-II formation. Thus, for interrupting the renin-angiotensin system, A-II receptor antagonists theoretically provide advantages over ACE inhibitors in that they directly inhibit A-II by binding to the AT(1) receptor subtype. The objectives of this review are to: 1) provide an overview of the associated risk of cardiovascular complications with concomitant hypertension and diabetes; 2) demonstrate the cardiovascular benefits of effective blood pressure control in this patient population; 3) review the current treatment guidelines for managing high-risk hypertensive patients; and 4) discuss major, ongoing clinical studies with A-II receptor antagonists in patients with concomitant hypertension, type 2 diabetes, and renal disease. (c)2001 Le Jacq Communications, Inc.
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PMID:Management of high-risk hypertensive patients with diabetes: potential role of angiotensin II receptor antagonists. 1149 50

The prevalence of type 2 diabetes is rising in all Westernized societies. Presumably as a consequence of diminishing cardiovascular mortality, end-stage renal failure (ESRF) in patients with diabetes (mostly type 2) as a co-morbid condition has risen dramatically in the past decade. This constellation has become the single most common cause of ESRF in most countries. Such an epidemiological trend is particularly regrettable, since in uraemic diabetic patients, medical rehabilitation and survival are remarkably poor. Recent studies indicate that an interplay between genetic predisposition and factors, some of them susceptible to intervention, such as hyperglycaemia, blood pressure, smoking, age, gender and ethnicity, predispose to the development and progression of nephropathy. It has also become clear that trace albuminuria ('microalbuminuria') provides unique opportunities to recognize incipient renal involvement early on, although it is less specific in type 2 as compared with type 1 diabetes. Factors that promote progression include hypertension, proteinuria, smoking, glycaemic control and, less certainly, dietary protein intake and hyperlipidaemia. Cumulating evidence indicates that early intervention delays progression of nephropathy. The most important strategies to combat the medical catastrophe of increasing numbers of diabetic patients with ESRF include: (i) prevention of diabetes (mainly type 2); (ii) glycaemic control to prevent onset of renal involvement; and (iii) meticulous antihypertensive treatment to avoid progression of nephropathy.
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PMID:Renal disease in type 2 diabetes. 1150 79

While there is progress in management of newly-diagnosed diabetic patients, treatment of diabetes and prevention of comorbid conditions, nephrologists are progressively confronted with the picture of fully established micro- and macrovascular disease. Experience with CAPD in patients with diabetes mellitus in the hospital Vienna-Lainz from 1982 to 8/1999 was analyzed and outcome data are presented. During this period 139 patients were treated with CAPD as primary renal replacement therapy, 41 with diabetes Type 1 and 47 with diabetes Type 2. Survival rate after 10 years of treatment (including transplantation and change to hemodialysis due to technical failure of CAPD) was 50% in type 1 diabetes and 8% in type 2 diabetes. In 73% of patients with type 1 diabetes a kidney or kidney-pancreas transplantation was performed. In contrast, only 11% of type 2 diabetic patients were eligible for kidney transplantation. These long-term data implicate further attempts in reducing the incidence of diabetic nephropathy and later on renal failure. Furthermore, screening and aggressive treatment for atherosclerotic complications are necessary to improve the prognosis in this patient cohort.
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PMID:[CAPD (continuous ambulatory peritoneal dialysis) in diabetic nephropathy: overview and general practice in the Lainz Hospital since 1982]. 1151 92

Diabetic nephropathy can develop in up to one-third of patients with type 1 diabetes and approximately 25% of patients with type 2 diabetes. This complication is important as it not only leads to renal failure but is associated with a high risk of coronary artery disease and other vascular complications. Although hyperglycaemia is necessary for the development of diabetic nephropathy, it is not sufficient, genetic factors also being important. This is evidenced by studies showing that only a subgroup of patients are at risk of nephropathy and that nephropathy clusters in families. The genes involved in susceptibility to diabetic nephropathy have yet to be identified. Most studies to date have been case-control in design, and there have been conflicting results. Genes suggested as having a role include those encoding angiotensin-1 converting enzyme, apolipoprotein E, heparan sulphate and aldose reductase. In order to clarify the role of these and other candidate genes in nephropathy, association studies in families are necessary. Because of the large number required, this will require international collaboration. A genetic marker for nephropathy would enable the earlier detection of this complication, thus facilitating screening and targeted intervention. An understanding of the role of susceptibility genes will ultimately allow the development of novel therapeutic strategies.
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PMID:Genetics of diabetic nephropathy. 1155 75


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