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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic glomerulopathy continues as a major problem in the management of the patient with diabetes mellitus; however, evidence in man and in animals underlines the fact that good control of diabetes favorably alters the course of this complication. Islet transplantation in the diabetic rat returns plasma glucose and insulin levels to normal. In parallel mesangial matrix thickening, mesangial deposition of immunoglobulin and urinary excretion of albumin markedly improve following islet transplantation. Although amelioration of diabetes affects the course of glomerulopathy, other factors (most notably measures that increase glomerular capillary pressure) enhance the development of the diabetic renal lesions. Following uninephrectomy or clipping of a renal artery, the remaining (in the case of uninephrectomy) or unclipped diabetic kidney develops the morphologic and functional changes of diabetic nephropathy at a rate greater than in kidneys in an intact diabetic rat. The clipped kidney demonstrates diminished diabetic changes, suggesting a protective effect with decreased glomerular capillary pressures. In addition to measures improving the control of diabetes, procedures reducing factors accelerating diabetic complications may improve the prognosis in diabetic glomerulopathy.
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PMID:The development, enhancement, and reversal of the secondary complications of diabetes mellitus. 11 28

Kidney disease, characterized by proteinuria and glomerular lesions, is a common complication of spontaneous diabetes mellitus in many animal species. It occurs in animals with hypoinsulinemia, hyperinsulinemia, or impaired glucose tolerance. The renal functional and structural abnormalities in spontaneously diabetic animals resemble human diabetic nephropathy in many respects. Mesangial expansion and glomerular basement membrane thickening, two structural hallmarks of diabetic glomerulopathy in humans, are the most frequently encountered lesions in animals. In addition, a nodular form of mesangial expansion that resembles but is not identical with human nodular glomerulosclerosis or the Kimmelstiel-Wilson lesion has been observed in some animal models. Other abnormalities, such as exudative hyaline lesions and arteriolar hyalinosis, have also been noted occasionally in other models. Although diabetic animals may develop kidney disease that resembles human diabetic nephropathy, no single animal model develops renal changes identical to those seen in humans. Nonetheless, animal models with spontaneous diabetic kidney disease may be useful for investigating the mechanisms of development of diabetic nephropathy and the effects of various treatment modalities on the progression of renal disease.
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PMID:Animal models of spontaneous diabetic kidney disease. 219 83

Diabetic glomerulopathy is characterized by a very slow development of basement membrane (BM) accumulation, manifested as thickening of the peripheral BM and increased volume of the mesangial BM-like material (BMLM) with mesangial expansion. The initiation of the process is probably at the onset of diabetes since the BM thickening is detectable after a few years. The BM accumulations at the two sites (PBM and BMLM) in the glomerular tuft are considered as two different expressions of a fundamental BM abnormality. The two locations present different conditions for quantitation, may have a different biochemical make-up, and immediate functional implications of the abnormalities may differ as well. In the long run, however, the two in concert lead to the ultimate solidification of the glomerular tuft with loss of capillary surface. The end-stage is glomerular closure, with elimination of glomerular function. A very close correlation has been found between the total remnant surface area of the glomerular capillaries and the level of GFR. Along with the classical changes of the diabetic glomerulopathy, changes in glomerular size are detectable. In early diabetes during the stages of glomerular hyperfunction, hypertrophy develops acutely at the onset of diabetes, leading to an increase in capillary surface corresponding to the increase in filtration rate. In the advanced stages when glomerular closure involves a proportion of the nephrons compensatory hypertrophy develops, thereby probably helping to preserve capillary surface for a period of time. The exact mechanisms that may influence these developments are not known, but underlying them all are the metabolic abnormalities of diabetes.
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PMID:Structural changes in the diabetic kidney. 353 98

Phagocytic function of polymorphonuclear leukocytes was studied in patients with insulin-dependent and insulin-independent diabetes. A total of 52 patients were examined; the patients were mainly young, suffering from insulin-dependent diabetes with or without angiopathies. The leukocyte phagocytic activity was studied with the use of the direct method developed by G. I. Podoprigora and V. N. Andreev in 1976. All phagocytosis parameters were shown to be reduced, the relationship between these parameters distorted, and digestion impaired, especially in patients with diabetic functional angiopathy and with the Kimmelstiel-Wilson syndrome. A trial is described of correcting phagocytosis disorders by means of a Biostator apparatus (an artificial pancreas, functioning according to the feedblack principle). Such investigation was the first attempted in this country, no data on the leukocyte phagocytic activity before and after treatment with the use of an artificial pancreas apparatus were reported in foreign literature. Clinical application of the method is described.
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PMID:[Indicators of phagocytic activity of neutrophils in patients with diabetes mellitus before and after treatment using the "Biostator"]. 651 80

A 24-year-old woman had insulin-dependent juvenile diabetes for 15 years. She developed Sheehan's syndrome (postpartum pituitary necrosis) and diabetic nephropathy at 20 years of age. She had multiple sessions of argon laser photocoagulation for proliferative diabetic retinopathy. Histologically, loss of outer retina and pigmented epithelium occurred at the laser sites. Trypsin retinal digest preparations revealed microaneurysms and markedly decreased numbers of pericytes. The kidneys displayed nodular glomerulosclerosis (Kimmelstiel-Wilson syndrome). The anterior pituitary showed cystic degeneration and old hemorrhage.
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PMID:Histopathology of argon laser photocoagulation in juvenile diabetic retinopathy. 668 74

Diabetic glomerulopathy develops in a subset only of patients with insulin-dependent diabetes (IDDM) and early, in its course, is characterized by cell hypertrophy and by excessive extracellular matrix production. These observations suggest that an alteration in the control of cell growth processes may contribute to its pathogenesis and be related to the susceptibility to kidney disease. We therefore investigated whether the development of diabetic nephropathy is associated with abnormalities of cell growth and morphology. Cultured skin fibroblasts from 14 IDDM patients with nephropathy (DN) were compared with those of 10 IDDM patients without nephropathy (D) and of 14 control non-diabetic subjects (C). Cell volume (in arbitrary units) and total protein content (microgram/10, 000 cells) were increased in serially passaged skin fibroblasts of IDDM patients with nephropathy (DN = 809.5 +/- 33.1 and 1.93 +/- 0.38 vs. D = 764.4 +/- 31.5 and 1.5 +/- 0.37, P = 0.005 and P = 0.03, respectively; vs. C = 756.2 +/- 36.3 and 1.5 +/- 0.38, P = 0.0006 and P = 0.03, respectively). These hypertrophic cells had a tendency to a slower duplication rate and exhibited a dissociation of the DNA and cytoplasmic cell-cycles, resulting in a higher proportion of tetraploid cells (DN = 25 +/- 15% vs. D = 6 +/- 4%, P = 0.005; and vs. C = 10 +/- 8%, P = 0.04). The frequency of terminally differentiated post-mitotic fibrocytes, cells specialized for extracellular matrix production, was higher in patients with nephropathy compared to that of patients without nephropathy and normal controls (DN = 34 +/- 14% vs. D = 21 +/- 10%, P = 0.02; and vs. C = 19 +/- 12%, P = 0.008). That early differentiation was a specific feature of cells derived from patients with diabetic nephropathy was confirmed by the study of cell life-span which demonstrated that these cells aged prematurely (log rank test, chi 2 = 10,012; P = 0.0067). We conclude that an acceleration of cell aging is a peculiar feature of diabetic kidney disease and may contribute to its pathological tissue changes.
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PMID:Premature senescence of skin fibroblasts from insulin-dependent diabetic patients with kidney disease. 880 95

Structural changes underlying diabetic nephropathy in Type 1 diabetes are prodominant in the glomerulus [thickening of glomerular basement membrane (GBM) and mesangial expansion], but also include arteriolar, tubular and interstitial lesions. The structural measure that correlates best with all renal functional parameters in Type 1 diabetes is mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion. Structural-functional relationships in Type 2 diabetes are much less known. These studies investigated renal structure in the early stages of nephropathy [microalbuminuria (MA)] in patients with Type 1 and Type 2 diabetes. Diabetic glomerulopathy was quite advanced in Type 1 diabetic patients with MA, and both Vv (mes/glom) and GBM width were increased as compared to normoalbuminuric (NA) patients when the albumin excretion rate (AER) was > 30 microgram/min. Serial renal biopsies were performed 5 years apart in 11 Type 1 diabetic patients to evaluate whether glomerular and interstitial lesions progress jointly. AER increased significantly in 5 years, while the glomerular filtration rate remained unchanged. All structural parameters were initially abnormal. Vv(mes/glom) and mean glomerular volume increased significantly, whereas GBM width and the interstitial volume fraction were unchanged. Moreover, the change in Vv (mes/glom) was correlated with the change in AER (r =0.64, p <0.05). Thus, at the disease stage during which some patients progress to MA or proteinuria, continuing mesangial expansion is the main variable, whereas further interstitial expansion does not occur. A large number of Type 2 patients were also studied. Early diabetic glomerulopathy was detected by electron microscopy in NA patients and found to be more advanced in those with MA and proteinuria. However, lesions were milder than in Type 1 diabetic patients, and there was considerable overlap between groups. Morphometric results by electron microscopy were similar to those by light microscopy, demonstrating the heterogeneity of renal structure in Type 2 diabetic patients. In fact, only 30% of MA patients had typical diabetic glomerulopathy, while 40% had more advanced tubulo-interstitial and/or vascular lesions and 30% had normal renal structure.
Diabetes Metab 2000 Jul
PMID:Structural involvement in type 1 and type 2 diabetic nephropathy. 1092 68

Diabetic glomerulopathy is a well-recognized consequence of both type I and type II diabetes. Occasionally, pathologic diagnosis may be challenging for the pathologist. These circumstances include atypical light microscopy or diabetic change with a second superimposed glomerulopathy (dual disease). We have compiled a selection of 12 renal biopsies from diabetic patients that show either an unusual pattern of nephropathy or "dual disease," as well as 2 cases in which the patient had no history of diabetes but had renal biopsies exhibiting changes consistent with diabetic nephropathy. The salient diagnostic features are discussed. To accurately assess these biopsies, immunofluorescence and electron microscopy become essential, and a broadened differential diagnosis must be considered.
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PMID:Diabetic glomerulopathy: unusual patterns and dual disease. 1218 Jun 36

Diabetic glomerulopathy has been linked to shifts in balance between the synthetic and degradative pathways of the glomerular basement membrane (GBM), a key player in the permselectivity properties of the glomerular wall. The goal of this study was to trace the expression and localization of membrane type-1 metalloprotease (MT1-MMP) and its activating enzyme furin, key proteins involved in basement membrane turnover, in short- and long-term diabetic rat renal tissues. Quantitative immunogold was carried out for MT1-MMP and furin and their expression was evaluated in renal tissues of young and old, control and diabetic rats. To corroborate immunocytochemical findings, Western blots were performed on glomerular lysates. Electron microscopy revealed that the overall expression of MT1-MMP and furin is reduced in plasma membranes of all glomerular cell types of old normoglycemic animals, a phenomenon that is exacerbated in long-term diabetic animals. This observation supports the prevailing theory that diabetes fosters acceleration in the aging process. Interestingly, while biochemical results confirmed a decrease in MT1-MMP expression, an increase in furin was observed. Immunocytochemical studies resolved this discrepancy by tracing the increased furin expression in endoplasmic reticulum and Golgi membranes of podocytes, indicating that furin is retained in the secretory pathway in a diabetic environment. Disturbances at the molecular level of the otherwise tightly regulated MT1-MMP/furin interactions found at the cell surface must account for a lack in extracellular matrix remodeling, increased deposition of GBM material, and loss of glomerular filtration integrity.
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PMID:Expression and localization of MT1-MMP and furin in the glomerular wall of short- and long-term diabetic rats. 1654 Oct 18

Diabetic nodular glomerulosclerosis, also known as Kimmelstiel-Wilson syndrome, is a specific pathological variant of diabetic nephropathy ; however, histological findings similar to diabetic nephropathy are observed occasionally without glucose intolerance. Therefore, such nodular glomerulosclerosis is called idiopathic nodular glomerulosclerosis. Several case reports that have been published recently indicate that smoking and hypertension, which are classical renal risk factors, may be attributed to this form of glomerular degeneration. Accordingly smoking- and hypertension-associated nodular glomerulosclerosis has been considered to be different from the idiopathic form. This novel form of nodular glomerulosclerosis is associated with a history of long-term smoking and hypertension, and the age of onset of this disease is more than 60 years. We present the case of a 27-year-old Japanese male who was admitted to our hospital with nephrotic syndrome, hypertension, and renal impairment. He had a smoking history of at least 13 years, and had been exposed to passive smoking for several years because his parents were smokers. Renal biopsy revealed diffuse and global nodular glomerulosclerosis, although the patient did not have any primary diseases such as diabetes mellitus or paraproteinemia, that can cause this condition. We diagnosed smoking- and hypertension-associated nodular glomerulosclerosis. Cessation of smoking and the administration of an angiotensin II receptor blocker decreased his proteinuria and showed recovery of kidney function. This case report suggests that long-term smoking is closely associated with nodular glomerulosclerosis. Further, in our case, the age of the patient was lower than that of patients with the same disease among cases that have been reported previously.
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PMID:[Association between long-term smoking and hypertension and early-onset nodular glomerulosclerosis]. 2107 48


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