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

The potential pathogenic role of angiotensin-II (AII) in early progressive diabetic and renal ablation-induced glomerulosclerosis was explored and compared in the Sprague-Dawley (SD) rat and the mongrel dog. Male SD rats were divided into control and streptozotocin-treated (65 mg/kg, iv) groups. Unilateral surgical nephrectomy (Nx) was performed in half of each group. Enalapril (E; 50 mg/liter in the drinking water) was administered to half of each subgroup. Enalapril (high E; 250 mg/liter) was given to another 13 streptozotocin rats. All diabetic rats were treated with sc NPH insulin (4 U/day), and blood glucose was 520 +/- 124 mg/dl (mean +/- SD). Microalbuminuria was measured by RIA in 24-h urine collections; wet kidney weights were compared. [125I]AII binding assays were performed on isolated glomeruli. In control rats the high affinity binding dissociation constant (Kd) was 0.59 +/- 0.15 nM (n = 26; mean +/- SD) and receptor number (Ro) was 732 +/- 195 fmol/mg glomerular protein. At 3 weeks, the diabetic glomerular AII receptor Kd was 0.38 +/- 0.07 nM (n = 6; P less than 0.02 vs. control) and Ro was 784 +/- 97 fmol/mg protein (P = NS vs. control); diabetic high E Kd was 0.39 +/- 0.06 nM (n = 6; P less than 0.02 vs. control), and Ro was 873 +/- 105 fmol/mg protein (P = NS vs. diabetes without E). By 10 weeks, a Kd of 0.49 +/- 0.12 nM (n = 32; P less than 0.01 vs. control) and a Ro of 780 +/- 174 fmol/mg protein (P = NS vs. control) were observed when all of the diabetic group data were pooled. Neither Nx nor low or high dose E altered Ro. This is evidence that intraglomerular AII levels are normal or reduced after diabetes, Nx, or both. In the diabetic group, low dose E partially prevented, and high E abolished, Nx-enhanced microalbuminuria and renal hypertrophy. In nine pancreatectomized insulin-treated mongrel dogs over a 12- to 24-month period, despite moderately poor glucose control (300 +/- 75 mg/dl) and combined unilateral Nx in five dogs (12 months), elevated microalbuminuria was not observed. [125I]AII binding to isolated normal and diabetic dog glomeruli revealed the Kd to be of low affinity (1.86 +/- 0.28 to 13.80 +/- 1.88 nM), identifying the presence of type B receptors. Hence, the SD rat and mongrel dog differ in susceptibility to glomerular AII receptor type and progressive diabetic glomerulopathy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of angiotensin-II in progressive diabetic glomerulopathy in the rat. 255 33

The microvascular complications of diabetes mellitus may be caused, in part, by poor glycemic control. Diabetic patients who have received renal allografts may have new glomerular lesions that are manifested structurally by increases in mesangial and glomerular volume. Successful pancreas transplantation produces long-term normoglycemia and provides a unique opportunity to evaluate the impact of the normalization of the blood glucose level on the development of the renal lesions typical of diabetes mellitus in transplanted kidneys. We obtained biopsy specimens from the functioning renal allografts of 12 patients with insulin-dependent (Type I) diabetes before successful pancreas transplantation (performed one to seven years after renal transplantation) and repeated the biopsy at least 1.9 years later. In renal biopsy specimens obtained before pancreas transplantation, the mesangial volume was normal or modestly increased and the glomerular basement membrane was moderately thickened. At follow-up, no progression could be detected in any structural measure in the glomerulus. Furthermore, the recipients of pancreas transplants had smaller glomerular volumes than 13 matched diabetic patients who were recipients of renal allografts but who did not undergo pancreas transplantation (mean +/- SD, 1.80 +/- 0.55 vs. 2.47 +/- 0.73 x 10(6) microns 3; P = 0.02) and showed markedly less mesangial expansion (mesangial-volume fraction, 0.19 +/- 0.07 vs. 0.31 +/- 0.10 microns 3 per cubic micrometer; P = 0.004). We conclude that successful pancreas transplantation is associated with significantly less severe diabetic glomerulopathy in kidneys previously transplanted into diabetic patients. These data support the hypothesis that normoglycemia can prevent the progression of diabetic glomerulopathy in humans.
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PMID:The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. 265 96

Approximately 5.8 million people in the United States have been diagnosed by a physician as being diabetic, and an additional 4 to 5 million people have undiagnosed diabetes. Although the incidence of diabetes appears to be declining from a peak of 300 per 100,000 population in 1973, to 230 per 100,000 in 1981, its prevalence continues to rise, due to a 19 percent decline since 1970 in deaths caused by diabetes. In 1982, 34, 583 deaths were attributed to diabetes, resulting in diabetes being ranked as the seventh leading underlying cause of death. Medical and surgical complications of diabetes due to macro- and microvascular disease result in 5,800 new cases of blindness, 4,500 perinatal deaths, 40,000 lower extremity amputations and 3,000 deaths due to diabetic coma (ketotic and hyperosmolar) and at least 4,000 new cases of end-stage renal disease. Hyperglycemia is a major if not sole determinant of diabetic glomerulopathy. The exact mechanism underlying diabetic vasculopathy is under intensive study. Experiments in the induced-diabetic rat and dog suggest that small vessel injury may--under defined circumstances--be associated with the polyol (sorbitol) pathway of glucose metabolism, myoinositol deficiency, capillary hypertension, plasma hyperviscosity, stiff erythrocytes, elevated circulating thromboxane, and platelet-derived growth factor(s). As yet, no single hypothesis fits these seemingly disparate pieces together into a unified formulation of the genesis of diabetic complications. Clinical experience sustains the contention that a functioning kidney transplant proffers the uremic diabetic younger than age 60 a higher probability for survival with good rehabilitation than does either peritoneal dialysis or maintenance hemodialysis. Diabetics treated by kidney transplantation require more than the routine preoperative and postoperative attention afforded to nondiabetic ESRD patients. During initial nephrologic evaluation, concurrent extrarenal vascular disease--especially ophthalmic, cardiovascular, cerebrovascular and in the extremities, often demands immediate attention. Inventory of co-morbid risk factors pre-transplant facilitates their management post-transplant, thereby improving chances for rehabilitation. Consultations with an ophthalmologist and podiatrist familiar with management of the uremic diabetic should be obtained prior to transplant surgery. When performed as a component of pre-transplant evaluation, coronary angiography permits identification and correction, in many patients, of potentially fatal coronary artery disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Renal failure in diabetes: a substantive problem in provision of health care. 267 7

Renal changes similar to those considered diagnostic for diabetes in humans are infrequently observed in spontaneous noninsulin-dependent (NID) diabetic monkeys. In the current study, renal cortical tissue blocks are rendered acellular to demonstrate glomerular basement membrane (GBM) and mesangial matrix (MM) changes in a naturally occurring NID diabetic rhesus monkey (Macaca mulatta). Transmission electron micrographs of these specimens show axial MM accumulations with numerous striated collagen fibrils that frequently extend onto internal (endothelial) surfaces of peripheral GBM. The outer (epithelial) component, although compact, appears bilaminar due to folded external surfaces not coinciding with similar irregularities on internal surfaces. By scanning electron microscopy, external surfaces of sclerotic GBMs are extensively wrinkled and, following cryofracture, show congestion and expanded MM. A fenestrated meshwork of MM, which appears less dense and compact than epithelial BM, extends from axial regions onto GBM internal surfaces. The true thickness of randomly sampled peripheral GBM thickness (approximately 400 nm) is approximately double that of normal rhesus GBM. Diabetic GBMs exhibit ruthenium red positivity for surface polyanions with linear site densities not significantly different from normal. These observations indicate that sclerotic GBMs in diabetic rhesus monkeys closely resemble those seen in human end-stage diabetic glomerulopathy and suggest that this nonhuman primate may offer an excellent model for studies of chronic diabetic BM disease.
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PMID:Ultrastructural analyses of acellular glomerular basement membranes and mesangial matrix in a spontaneously diabetic rhesus monkey. 275 Apr 66

Dogs were randomly assigned to experimental galactosemia or diabetes, or to a normal untreated group, and diabetic animals were then randomly assigned to either poor or good glycemic control. At five years duration, kidneys from the animals were compared by quantitative stereology. Glomerulopathy appeared in the poor control diabetes group, and the thickness of glomerular capillary basement membrane, the glomerular tuft volume, and the fraction of glomerulus occupied by mesangium were each significantly greater than normal. The capillary filtering surface area per glomerulus was supranormal also, but nonetheless was subnormal relative to glomerular volume. The development of glomerulopathy was significantly inhibited in dogs assigned to good glycemic control. In galactosemic animals, the basement membrane thickness was greater than normal, but the glomerular volume, fractional and absolute volumes of mesangium, and capillary filtering surface area remained normal. The polyol concentration in renal cortex seemed elevated by galactosemia no less than by diabetes, and was highest in galactosemia. The galactosemic animals are known to have developed a retinopathy morphologically comparable to that of diabetic patients and diabetic dogs. Thus, sequelae of hyperglycemia sufficient to produce glomerular basement membrane thickening and retinopathy proved not necessarily sufficient to produce the mesangial expansion and glomerular hypertrophy typical of diabetes.
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PMID:Hyperglycemia and development of glomerular pathology: diabetes compared with galactosemia. 281 Oct 56

To study the relationship between retinal and renal microangiopathy, the albumin excretion rate (AER) was measured by radioimmunoassay in 111 insulin-dependent diabetics and compared to their stages of retinopathy, as assessed by ophthalmoscopic examination and fluorescein angiography. The prevalence of pathological AER differed from that of diabetic retinopathy. The stage of retinopathy was related to the duration of diabetes (r = 0.59; P = 0.001), which was not the case for AER (r = 0.06; ns). Half of patients with proliferative retinopathy (11/22) had a normal AER, while 12% of those without retinopathy had a pathological AER (microalbuminuria). No relationship was found between glycaemic control and AER. The highest prevalence of hypertension was found in patients with macroalbuminuria (greater than 500 mg/24 h) and/or severe retinopathy. The mean AER was higher in hypertensive diabetics than in non-hypertensive diabetics (P less than 0.005). These results suggest that the risk of retinopathy is dissociated from the risk of glomerulopathy in diabetics, and that hypertension associates with diabetes mellitus in a greater risk of pathological AER.
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PMID:[Relation between urinary albumin excretion and retinopathy in insulin-dependent diabetics]. 294 9

Two groups of adult male Munich-Wistar rats and a third group of nondiabetic age-matched and weight-matched normal control rats underwent micropuncture study 1 mo, and morphologic studies 14 mo, after induction of streptozotocin diabetes or sham treatment. All animals were fed standard rat chow. Diabetic rats received daily ultralente insulin to maintain stable moderate hyperglycemia (approximately 350 mg/dl). In addition, one group of diabetic rats was treated with the angiotensin I converting enzyme inhibitor, enalapril, 15 mg/liter of drinking water. Average kidney weight, whole kidney and single-nephron glomerular filtration rate, and glomerular plasma flow rate were elevated to similar values in both groups of diabetic rats, relative to normal control rats. Non-enalapril-treated diabetic rats exhibited significant elevations in mean glomerular capillary hydraulic pressure and transcapillary hydraulic pressure gradient, compared with the other groups studied, and only this group eventually developed marked and progressive albuminuria. Likewise, histological examination of the kidneys at 14 mo disclosed a high incidence of glomerular structural abnormalities only in non-enalapril-treated diabetic rats. These findings indicate that prevention of glomerular capillary hypertension in rats with diabetes mellitus effectively protects against the subsequent development of glomerular structural injury and proteinuria. This protection is afforded despite pronounced hyperglycemia and elevated levels of glucosylated hemoglobin, further supporting our view that hemodynamic rather than metabolic factors predominate in the pathogenesis of diabetic glomerulopathy.
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PMID:Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. 301 62

Hyperfiltration is a very characteristic feature in insulin-dependent diabetes. Hyperfiltration is to some extent associated with long-term glycemic control but the correlation is not very strong. Long-term hyperfiltration may play a role in the genesis of late diabetic nephropathy, but it is difficult to distinguish effects of hyperfiltration per se from effects of poor metabolic control. Long-term hyperfiltration without diabetes does not produce nephropathy. It is hypothesized that IDDM patients who do not show considerable hyperfiltration in spite of poor metabolic control may be those who are to some extent protected against late diabetic nephropathy, but other mechanisms may also be involved in the renal protection of these patients, who survive long-term diabetes without nephropathy. On the other hand, those with poor metabolic control combined with hyperfiltration are likely to develop nephropathy. In addition, it is suggested that the metabolic aberrations in diabetes, with the subsequent changes in the biochemistry of the glomerular wall, are permissive and absolutely required for the development of diabetic nephropathy. Of note, diabetic glomerulopathy in NIDDM occurs without significant hyperfiltration and extreme hyperfiltration in the one-kidney-model (without diabetes) does not produce nephropathy. Nonglycemic modalities of intervention, resulting in reduced hyperfiltration, e.g., low-protein diet or administration of somatostatin analogues, deserves interest as new potential ways of preventing or postponing diabetic nephropathy. Also intervention with aldose-reductase inhibitors may be an important therapeutic modality for those patients in whom good metabolic control is not obtainable. It is now well-established that antihypertensive treatment, including ACE-inhibition, reduces rate of decline in GFR in patients with already established nephropathy. In addition, protein excretion is diminished in IDDM patients with incipient diabetic nephropathy by antihypertensive treatment where GFR is well-preserved during treatment. No data are available for NIDDM.
Diabetes Metab Rev 1988 Aug
PMID:Comparative renal pathophysiology relevant to IDDM and NIDDM patients. 306 56

A 41-year-old male with a 25-year history of diabetes mellitus requiring 25 to 30 units of neutral protamine hagedorn (NPH) insulin daily was found dead at home. Recent history revealed that he was well until the last four days of life when he had the onset of nausea, vomiting, and anorexia coinciding with procurement of a new bottle of insulin from his pharmacist. Pertinent autopsy findings included coronary and aortic atherosclerosis, a peptic ulcer, and diabetic glomerulopathy. Chemical analysis of the vitreous humor, including glucose (813 mg/dL) and acetone (40 mg/dL), revealed that he died of diabetic ketoacidosis. Further investigation revealed that the pharmacist had accidentally substituted regular insulin, with a duration of action of up to 6 h as opposed to 24 to 28 h, for NPH. Cultures of blood and of the regular insulin yielded no growth. Analysis of this case emphasizes the importance of obtaining a careful medical and medication history and the usefulness of vitreous electrolytes when investigating a sudden death in a diabetic.
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PMID:Pharmaceutical error resulting in fatal diabetic ketoacidosis. 308 89

Three hundred and twenty outpatients with diabetes mellitus (DM) were studied to evaluate the prevalence, origin (glomerular or nonglomerular), significance and possible association of glomerular hematuria (GH) with other clinical and laboratory features. In patients with 24 h proteinuria equal or superior to 500 mg, hematuria was seen in 16 out of 22 (72.7%); for those with 24 h proteinuria between 150 and 500 mg 5 out of 23 (21.7%) had hematuria, and in the general population of diabetics studied hematuria was present in 47 patients (14.7%). It was glomerular in 43 (13.4%) patients and nonglomerular in 4 (1.3%). Red blood cell casts were observed in 15 (34.9%) out of the 43 patients with GH. Ten out of 31 patients (32.3%) with GH, for whom 24 h proteinuria was available, had negative proteinuria in a 24 h urine when analyzed by routine methods. In 18 patients with GH, clinical and laboratory findings that could suggest a second form of glomerulopathy--nondiabetic--were negative. Renal biopsy in 9 of them showed only diabetic glomerulosclerosis. We have observed a significant association between GH and the male sex (p less than 0.001), high serum creatinine levels (p = 0.0002) and 24 h proteinuria greater than 150 mg (p less than 0.001). GH was more frequent among males with DM lasting more than 10 years (p less than 0.001) and among those with retinopathy (p less than 0.001). There was no association between GH and age, type of DM, insulin requirement or hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glomerular hematuria in diabetics. 326 36


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