Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microalbuminuria (MA) is associated with microangiopathy (renal and retinal lesions) in insulin-dependent diabetic (IDDM) patients. In contrast MA does not reflect microvascular damage in a substantial number of non-insulin-dependent diabetic (NIDDM) patients. MA predicts cardiovascular disease in NIDDM patients with increased von Willebrand factor (vWF) plasma levels which are hypothesized to reflect endothelial dysfunction. However, it is not known whether MA is consequent to generalised endothelial dysfunction or to renal injury. Thus, this study evaluated vWF plasma levels in relation to renal and retinal structural abnormalities in NIDDM patients with MA. Kidney biopsies, fundoscopy and measures of vWF plasma levels were performed in 32 NIDDM patients with MA. These patients were allocated to two renal structural categories: A) Without renal structural abnormalities (C I, n = 10): normal or near-normal renal structure, and B) With renal structural abnormalities (n = 22), further divided into: C II (n = 12) with typical diabetic nephropathology, predominantly glomerulopathy, and C III (n = 10) with atypical patterns of renal injury (more advanced tubulo-interstitial and arteriolar than glomerular changes). vWF plasma levels were significantly higher in category B (C II: 195+/-49% and C III: 161+/-46%) than in category A (C I: 119+/-42%), (chi-square, p < 0.05). Diabetic retinopathy was also related to vWF plasma levels (ANOVA, p < 0.05). These data suggest that there are two types of MA in NIDDM: one associated with increased vWF levels, established renal injury and frequently retinopathy, and the other characterized by normal vWF levels, normal renal structure and absent or mild diabetic retinopathy. We propose that vWF plasma levels in NIDDM patients with MA may help to identify patients with important renal structural changes, increased retinopathy risk and, perhaps, generalised endothelial dysfunction. Whether vWF plasma levels predict end-stage renal disease and cardiovascular events deserves longitudinal studies.
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PMID:Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure. 949 59

We report on a 33-year-old male patient with generalized acquired lipodystrophy, insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome). First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous fatty tissue, and loss of muscular strength) became evident three years ago, with the onset of diabetes mellitus occurring about six months later. The patient suffered from the following clinical symptoms: IDDM with increasing insulin-requirement, extreme reduction of fatty tissue, fatty liver hepatitis with elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well as hypertriglyceridaemia. A basal C-peptide concentration is rather high. Definitely, the endogenous insulin secretion is increased. In other words, insulin resistance is documented. In an effort to identify the pathogenetic mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a therapeutic strategy, antibodies against different tissues and endocrinologic regulation were investigated. It was possible to demonstrate the presence of serum autoantibodies against lipocytes of the subcutis and other tissues, against hepatic stellate cells, together with autoantibodies against different endocrine organs. By studying the basis of diabetic abnormalities relating to the growth hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e. reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3, were detected. An immunosuppressive treatment strategy was not beneficial.
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PMID:Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes. 951 65

The large interindividual variation in diabetes duration until the onset of nephropathy is partly unexplained. This study was performed to compare renal structure in insulin-dependent (IDDM) patients who had developed signs of nephropathy after a short or long duration of diabetes. Renal biopsies were obtained from 17 IDDM patients, with albumin excretion rate 20-300 microg/min and normal blood pressure. Six patients had <25 years duration ("short-term", early onset of microalbuminuria) and eight patients had duration >30 years ("long-term", late onset of microalbuminuria). Biopsies were obtained 18 months after entry into a study testing the effect of low-dose antihypertensives. Parameters characterizing diabetic glomerulopathy were significantly increased in IDDM patients compared with those in 17 living donors: Basement membrane thickness, mean and (CV): 591 nm (0.17) vs 320 nm (0.12), mesangial volume fraction per glomerulus 0.27 (0.19) vs 0.19 (0.10), matrix volume fraction per glomerulus 0.16 (0.20) vs 0.097 (0.22), matrix star volume 38.5 microm3 (0.43) vs 13.9 microm3 (0.31), (p<10(-4) for each). Comparison of short vs long-term patients showed no significant differences in glomerulopathy parameters, glomerular volume or extracellular material per glomerulus, whereas the fraction of occluded glomeruli was significantly increased in long-term patients. A close correlation obtained between fraction of occluded glomeruli and glomerular filtration rate (r=0.72, p= 0.001). Glomerular occlusion occurred unrelated to the severity of diabetic glomerulopathy. It is suggested that diabetic macroangiopathy and arteriolar hyalinization may play an important role in the renal function of patients with slow development of nephropathy.
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PMID:Renal structural changes in insulin-dependent diabetic patients with albuminuria. Comparison of cases with onset of albuminuria after short or long duration. 954 24

Pathological changes in the urine sodium dodecyl sulphate gel electrophoresis (SDS PAGE) patterns often precede the occurrence of any sign of renal involvement in diabetes. However, data concerning the most frequent SDS PAGE pattern of the urine in early stages of type I diabetes mellitus are controversial. In the present study an SDS PAGE technique has been used that provides an adequate sensitivity for the detection of the abnormal pattern. Urinary proteins have been analyzed by SDS PAGE in twenty two diabetic adolescents and twenty four age matched controls. Albumin concentration, and N acetyl-beta-D-glucosaminidase (NAG) activity were also measured in the same samples. There was no significant difference in urine albumin concentration and NAG activity between diabetic children and controls. However twelve patients showed an electrophoretic pattern characteristic for glomerulopathy, two had a pattern indicating tubular dysfunction and another two patients had a mixed pattern. Among the twenty four controls only three showed abnormal electrophoretic patterns. The results support the view that early stages of diabetic nephropathy may involve both glomerular and tubular dysfunction. However the exact clinical and prognostic significance of the information provided by SDS PAGE analysis remains to be elucidated.
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PMID:Electrophoretic analysis of urinary proteins in diabetic adolescents. 1143 99

Glomerulopathy, characterized by thickening of the glomerular basement membrane (GBM) and mesangial expansion, is the most important renal structural change in type 1 diabetic patients with diabetic nephropathy. Morphological lesions develop concomitantly in the arterioles, tubules and interstitium. Mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion, is the structural parameter that best correlates with glomerular filtration rate (GFR) and it is also closely related to the presence of proteinuria and hypertension. Diabetic glomerulopathy has also been described in type 2 diabetic patients, but glomerular lesions are milder than in type 1 diabetic patients. In type 2 diabetes glomerular structural parameters are, on average, altered. However, despite persistent microalbuminuria or proteinuria, several patients have normal glomerular structure. Renal structure is, in fact, heterogeneous in type 2 diabetic patients: only a subset has typical diabetic glomerulopathy, while a substantial proportion has more advanced tubulo-interstitial and vascular rather than glomerular lesions, or has normal or near normal renal structure. Also in type 2 diabetes mesangial expansion is related to renal functional parameters, but although significant, these structural-functional relationships are less precise than in type 1 diabetes. Thus, both in type 1 and in type 2 diabetes, mesangial expansion is the most important structural change. Finally, we have recently demonstrated that, the lesions of diabetic glomerulopathy can be reversed in humans. This amelioration in glomerular structure was observed after long-term normoglycemia obtained by pancreas transplantation. This is a new concept in nephrology, and the understanding of the mechanisms involved in the glomerular architectural remodelling might have important clinical and therapeutic implications.
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PMID:Role of mesangial expansion in the pathogenesis of diabetic nephropathy. 1179 46

This study was designed to elucidate the cellular basis of risk of or protection from nephropathy in patients with type 1 diabetes. Entry criteria included diabetes duration of > or =8 years (mean duration, 22.5 years) and glomerular filtration rate (GFR) >30 ml x min(-1) x 1.73 m(-2). Patients were classified, on the basis of the estimated rate of mesangial expansion, as "fast-track" (upper quintile) or "slow-track" (lower quintile). A total of 88 patients were normoalbuminuric, 17 were microalbuminuric, and 19 were proteinuric. All three groups had increased glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(Mes/glom)], with increasing severity from normoalbuminuria to microalbuminuria to proteinuria but with considerable overlap among groups. Vv(Mes/glom) (r = 0.75, P < 0.001) and GBM width (r = 0.63, P < 0.001) correlated with albumin excretion rate (AER), whereas surface density of peripheral GBM per glomerulus [Sv(PGBM/glom)] (r = 0.50, P < 0.001) and Vv(Mes/glom) (r = -0.48, P < 0.001) correlated with GFR. Vv(Mes/glom) and GBM width together explained 59% of AER variability. GFR was predicted by Sv(PGBM/glom), AER, and sex. Fast-track patients had worse glycemic control, higher AER, lower GFR, more hypertension and retinopathy, and, as expected, worse glomerular lesions than slow-track patients. Thus, there are strong relationships between glomerular structure and renal function across the spectrum of AER, but there is considerable structural overlap among AER categories. Given that normoalbuminuric patients may have advanced glomerulopathy, the selection of slow-track patients based on glomerular structure may better identify protected patients than AER alone.
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PMID:Cellular basis of diabetic nephropathy: 1. Study design and renal structural-functional relationships in patients with long-standing type 1 diabetes. 1181 62

Criteria for renal biopsy in proteinuric type 2 diabetes mellitus (T2DM) patients have been not defined. Usually criteria for renal biopsy in type 1 diabetes mellitus (T1DM) are used (microhaematuria, absence of diabetic retinopathy (DR), uncharacteristic change in renal function or immunological abnormalities). The aim of this study was to reconsider the indications for renal biopsy in T2DM using T1DM criteria, to determine whether they are useful in identifying patients with potentially treatable lesions. We studied 127 proteinuric patients with T2DM. Renal biopsy was performed in 35 who met the criteria for biopsy. Biopsy revealed diabetic glomerulopathy (DG) in 29 (83%) (in three associated with nondiabetic renal disease), immunoglobulin A (IgA) glomerulonephritis in three, focal glomerulosclerosis in one and normal glomeruli in two. DG was diagnosed in 17 (74%) of the patients without DR, in 18 (78%) of the patients with microhaematuria and in 10 (67%) of the patients with microhaematuria and without DR. All patients with DR had DG alone, except three with sudden unexpected changes in renal function. We conclude that DG is the most commonly found renal lesion in T2DM patients with proteinuria biopsied according to T1DM criteria, even in patients with microhaematuria or without retinopathy. Thus, these biopsy criteria are not useful in identifying patients with potentially treatable other renal diseases.
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PMID:Is there a need for changes in renal biopsy criteria in proteinuria in type 2 diabetes? 1221 57

To describe gene expression changes that characterize the development of diabetic nephropathy, we performed microarray and phenotype analysis on kidneys from db/db mice (a model of type 2 diabetes), streptozotocin-induced diabetic C57BL/6J mice (a model of type 1 diabetes), and nondiabetic controls. Statistical comparisons were implemented based on phenotypic outcome characteristics of the animals. We used weighted vote-based supervised analytical methods to find genes whose expression can classify samples based on the presence or absence of mesangial matrix expansion, the best indicator for the development of end-stage renal disease in humans. We identified hydroxysteroid dehydrogenase-3beta isotype 4 and osteopontin as lead classifier genes in relation to the mesangial matrix expansion phenotype. We used the expression levels of these genes in the kidney to classify a separate group of animals for the absence or presence of diabetic glomerulopathy with a high degree of precision. Immunohistochemical analysis of murine and human diabetic kidney samples showed that both markers were expressed in podocytes in the glomeruli and followed regulation similar to that observed in the microarray. The application of phenotype-based statistical modeling approaches has led to the identification of new markers for the development of diabetic kidney disease.
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PMID:Molecular profiling of diabetic mouse kidney reveals novel genes linked to glomerular disease. 1498 65

To study the development of diabetic glomerulopathy, we performed two kidney biopsies after 10.5 and 17 years of type 1 diabetes in 19 normoalbuminuric, normotensive adolescents (10 males). The biopsies were examined with light and electron microscopy. The glomerular filtration rate and effective renal plasma flow, determined with inulin and para-aminohippuric acid clearances, respectively, and ambulatory blood pressure were studied. Between the biopsies, significant increases occurred in glomerular volume, foot process width, mesangial matrix, and mesangial volume fraction/glomerulus. The metabolic control affected the basement membrane thickness, mesangial matrix, and mesangial volume fraction/glomerulus. The mesangial matrix and mesangial volume fraction/glomerulus were higher in female patients on the first biopsy, but on the second biopsy, the levels in males increased to those in females. The night-time systolic and mean arterial blood pressures from the first biopsy seemed to predict the mesangial matrix and mesangial volume fraction/glomerulus, foot process width, and slit pore length on the second biopsy. Despite normoalbuminuria and normal blood pressure, patients with type 1 diabetes have morphological changes of diabetic glomerulopathy that progress. The night-time blood pressure can be used to predict morphological changes of diabetic nephropathy in adolescents who are normoalbuminuric and normotensive.
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PMID:Follow-up of kidney biopsies in normoalbuminuric patients with type 1 diabetes. 1522 26

We report the case of a 46-yr-old man with a 16-yr history of type I diabetes mellitus who developed rapid onset of nephrotic syndrome. Renal biopsy revealed diabetic nephropathy, characterized by thickened glomerular basement membranes (GBM), mild nodular glomerulosclerosis, and focal arteriolar hyalinization. Immunofluorescent (IF) studies showed strong granular IgM staining along glomerular loops, with subepithelial and intramembranous immune complex deposits along glomerular capillary loops demonstrated by electron microscopy (EM). These findings are consistent with membranous glomerulopathy with IgM as the predominant immunoglobulin. In addition, there were large aggregates of electron-dense material composed of numerous ring or spherical particles, ranging from 200 to 400 nm, in Bowman's space, which corresponded to eosinophilic aggregates on light microscopy (LM) and strong IgM stained materials by IF studies.
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PMID:Case report: IgM type of membranous glomerulopathy in a diabetic patient. 1594 83


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