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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two kidneys were removed from a cadaveric donor with 17-year history of type 1 diabetes. At the time of death the donor had proteinuria but normal serum creatinine, and on histological examination the kidneys showed features of established diabetic nephropathy including diffuse glomerulosclerosis and thickening of mesangial matrix and capillary basement membranes. After transplantation into non-diabetic recipients (cold ischaemia times 46 h and 52 h) the kidneys functioned well with standard immunosuppression. Renal biopsy specimens taken 7 months after transplantation showed almost complete resolution of the nephropathy and both patients remain free from proteinuria after a further 7 months. As well as indicating that longstanding type 1 diabetes need not always contraindicate kidney donation, these observations are relevant to the pathogenesis and management of diabetic nephropathy.
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PMID:Reversal of diabetic nephropathy in human cadaveric kidneys after transplantation into non-diabetic recipients. 613 20

Already at the time of diagnosis of juvenile onset diabetes mellitus, there are morphological and functional changes in the kidney. The kidneys and the individual glomeruli are considerably enlarged, and the glomerular filtration increased. In experimental diabetes mellitus the metabolism of the glomerular basement membrane is increased. These abnormalities are reversible by meticulous metabolic control. Their relationship to the diabetic glomerulosclerosis that causes uremia twenty to thirty years later is not clear. Carefully analyzed extensive clinical experience confirms that good metabolic control delays the onset of symptomatic diabetic renal disease, as expected from experimental studies. Normalization of even a slightly elevated blood pressure may be important to slow the progression of the renal insufficiency. Better methods for the management of the diabetic state and better education of the patients may be important to postpone the heroic endeavours of renal or pancreatic transplantation or dialysis.
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PMID:Diabetic nephropathy. Pathogenesis and prevention. 693 19

One proposed role of glomerular mesangial cells is the regulation of glomerular blood flow by contraction. Alterations in the contractile activity of mesangial cells could lead to alterations in glomerular hemodynamics and then to glomerular injury. In this study, the effects of glucose and insulin on the contractile response of cloned homogeneous cultures of rat glomerular mesangial cells to angiotensin II were examined. Cells were cultured in normal-glucose medium (D-glucose at 200 mg/dl) and normal-glucose medium with added insulin (4 microgram/ml). To mimic the diabetic state, cells were cultured in high-glucose medium (D-glucose at 550 mg/dl) and high-glucose medium with added insulin. The media contained 20% fetal calf serum. Cells were grown for at least 1 wk in medium prior to contraction experiments. All clones of mesangial cells grown in the presence of additional insulin, in either normal- or high-glucose media, underwent contraction when treated with angiotensin II (0.001-10 microM). Seventy-five percent of the cells contracted. Not one contracted cell was seen in cultures grown without insulin in the medium, even when exposed to 10 microM angiotensin II. From these data, it appears that insulin may be required for the contractile response of mesangial cells to angiotensin II. Loss of contractile activity by mesangial cells in low- or no-insulin conditions (e.g., juvenile diabetes mellitus) could lead to a marked increase in glomerular blood flow, ultimately resulting in glomerulosclerosis.
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PMID:Insulin requirement for contraction of cultured rat glomerular mesangial cells in response to angiotensin II: possible role for insulin in modulating glomerular hemodynamics. 705 Oct 7

Diabetic nephropathy can be regarded mainly as a type of microangiopathy, but is a disease that may also include aspects of macroangiopathy. This is especially true of renal disease in non-insulin dependent diabetes mellitus (NIDDM), which is characterized not only by diabetic glomerulosclerosis, but also by atherosclerosis. We performed morphological studies on the kidney, using computed tomography (CT), focusing on such points as: (1) abdominal aortic calcifications at the level of kidney, (2) calcifications in the renal artery, and (3) wedge-shaped defects on the renal surface. We noted that these findings became more prominent in NIDDM patients during end-stage renal failure than during normal renal function, and were significantly more common in those two NIDDM groups than in age-matched nondiabetic patients without hypertension, hyperlipidemia or gout. NIDDM patients exhibited these features more frequently than IDDM patients.
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PMID:[Computed tomographical evaluation of diabetic nephropathy]. 875 67

The histologic diagnosis of diabetic glomerulosclerosis was made in 14 renal transplant recipients. All 14 had insulin-dependent diabetes mellitus, which was the original cause of end-stage renal disease in 12; one patient had membranoproliferative glomerulonephritis and another patient had membranous nephropathy as the cause of end-stage renal disease. Insulin-dependent diabetes mellitus was diagnosed at an average age of 18.5 years (range, 8-41 years), and the mean duration of diabetes prior to transplantation was 15 years (range, 2-25 years). All patients were recipients of first kidney transplants (six living related donors and eight cadavers). The histologic diagnosis of diabetic glomerulosclerosis was made on average, 97 months after transplantation (range 41-154 months). All 14 patients had proteinuria (mean 5.3 g/24 hr; range 1.1-12 g/24 hr) and renal dysfunction (mean serum creatinine level, 2.8 mg/dl). Patient and graft survival rates at 1 year, 5 years, and 10 years after transplantation were 100%, 92%, and 59%, and 100%, 92%, and 34%, respectively. Graft failure was due to diabetic nephropathy in seven patients, diabetic nephropathy and membranous nephropathy in one patient, and death due to a cerebrovascular accident in one patient. A total of five patients are alive with a functioning kidney. Of the eight patients who returned to dialysis, four are alive, three remain on dialysis, and 1 had a combined kidney and pancreas transplant. Histologic findings were as follows: 9/14 had moderate or severe diffuse glomerular basement membrane thickening and 2/14 had nodular glomerulosclerosis. Arteriolar lesions were prominent in all cases and was graded moderate or severe in 11 cases. The development of allograft diabetic nephropathy is associated with a high rate of allograft failure.
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PMID:Diabetic nephropathy after renal transplantation. Clinical and pathologic features. 883 Aug 28

Microalbuminuria predicts overt nephropathy in non-insulin-dependent diabetic (NIDDM) patients; however, the structural basis for this functional abnormality is unknown. In this study we evaluated renal structure and function in a cohort of 34 unselected microalbuminuric NIDDM patients (26 male/8 female, age: 58 +/- 7 years, known diabetes duration: 11 +/- 6 years, HbA1c: 8.5 +/- 1.6%). Systemic hypertension was present in all but 3. Glomerular filtration rate (GFR) was 101 +/- 27 ml.min-1.1.73 m-2 and albumin excretion rate (AER) 44 (20-199) micrograms/ min. Light microscopic slides were categorized as: C I) normal or near normal renal structure; C II) changes "typical" of diabetic nephropathology in insulin-dependent diabetes (IDDM) (glomerular, tubulo-interstitial and arteriolar changes occurring in parallel); C III) "atypical" patterns of injury, with absent or only mild diabetic glomerular changes associated with disproportionately severe renal structural changes including: important tubulo-interstitial with or without arteriolar hyalinosis with or without global glomerular sclerosis. Ten patients (29.4%) were classified as C I, 10 as C II (29.4%) and 14 as C III (41.2%); none of these patients had any definable non-diabetic renal disease. GFR, AER and blood pressure were similar in the three groups, while HbA1c was higher in C II and C III than in C I patients. Diabetic retinopathy was present in all C II patients (background in 50% and proliferative in 50%). None of the patients in C I and C III had proliferative retinopathy, while background retinopathy was observed in 50% of C I and 57% of C III patients. In summary, microalbuminuric NIDDM patients are structurally heterogeneous with less than one third having "typical" diabetic nephropathology. The presence of both "typical" and "atypical" patterns of renal pathology was associated with worse metabolic control, suggesting that hyperglycaemia may cause different patterns of renal injury in older NIDDM compared to younger IDDM patients.
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PMID:Patterns of renal injury in NIDDM patients with microalbuminuria. 896 Aug 44

To characterize the molecular mechanism of cardiac and renal complications in non-insulin-dependent diabetes mellitus (NIDDM), we examined the gene expression of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new animal model for human NIDDM, at the ages of 14 weeks (prediabetic stage), 30 weeks (NIDDM stage), and 54 weeks (IDDM stage). Tissue mRNA levels were measured by Northern blot analysis. In 14-week-old OLETF rats, cardiac mRNAs for transforming growth factor-beta1 (TGF-beta1) and extracellular matrix, including collagen types I, III, and IV and laminin, were significantly increased compared with control rats (Long-Evans Tokushima Otsuka rats). Cardiac beta-myosin heavy chain (MHC) mRNA of OLETF was increased at 30 and 54 weeks of age, whereas alpha-MHC mRNA of OLETF was inversely decreased at 54 weeks. Marked perivascular fibrosis was seen in the hearts of OLETF rats from 30 weeks of age. In the kidney of OLETF rats, glomerular TGF-beta1 expression was temporally increased at 30 weeks of age, followed by glomerulosclerosis characterized by mesangial proliferation, thickening of the basement membrane, and nodular lesions. Blood pressure of OLETF rats remained higher than that of control rats from the prediabetic stage to the IDDM stage. Thus, in OLETF rats, cardiac fibrosis-related gene expressions were already enhanced at the prediabetic stage, which supports the involvement of these gene expressions in cardiac perivascular fibrosis. The antithetical change in beta- and alpha-MHC expressions seems to participate in the decreased cardiac contractility seen in diabetes. Furthermore, TGF-beta1 may also contribute to glomerulosclerosis of OLETF rats. OLETF rats seem to be a useful model to study the mechanism of hypertension and cardiac and renal complications in NIDDM.
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PMID:Characteristics of diabetes, blood pressure, and cardiac and renal complications in Otsuka Long-Evans Tokushima Fatty rats. 905 88

We have recently described heterogeneity in renal structure in non-insulin-dependent diabetic patients (NIDDM) with microalbuminuria (MA; defined as albumin excretion rate from 20 to 200 micrograms/min). Thus, at variance with IDDM patients, "typical" diabetic glomerulopathy by light microscopy is observed only in a third of NIDDM with MA (Category II, CII). Further, despite persistent MA, 30% of NIDDM have normal or near normal renal structure (Category I, CI). Another one-third shows "atypical" patterns of renal injury with absent or mild diabetic glomerular changes, associated with disproportionately severe tubulointerstitial lesions and/or arteriolar hyalinosis and global glomerular sclerosis (Category III, CIII). The aims of this study were to evaluate whether similar patterns of renal lesions could be confirmed in a larger group of NIDDM with MA and to investigate tubular function in order to understand the mechanisms underlying MA in NIDDM patients. Renal biopsies were performed in 53 NIDDM with MA. Categories I, II and III were found in 41%, 26% and 33% of NIDDM with MA, respectively. All 8 patients with proliferative diabetic retinopathy were in CII. We also studied the urinary daily excretion rate of alpha 1-microglobulin (alpha 1 m), a low molecular weight protein, which is a useful indicator of tubular function. alpha 1 m was markedly increased only in CII patients (CI vs. CII vs. CIII: 6.2 +/- 1.2 vs. 13.7 +/- 2.1 vs. 7.3 +/- 0.9 mg/day, ANOVA, P < 0.01). In conclusion, we confirm that there is heterogeneity in renal structure in NIDDM patients with MA. This heterogeneity is not due to renal diseases other than diabetes. Increased alpha 1 m and proliferative retinopathy are useful indicators of the subgroup of MA NIDDM patients with typical diabetic glomerulopathy. It is suggested that diabetic microangiopathy explains the simultaneous occurrence of typical diabetic glomerulopathy, proliferative retinopathy and tubular dysfunction in a subgroup of NIDDM patients with MA.
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PMID:Renal structure and function in non-insulin dependent diabetic patients with microalbuminuria. 940 19

End-stage renal failure (ESRF) in diabetic patients, mostly type 2, has become the most frequent cause of renal replacement therapy in western Europe. The majority of patients with type 2 diabetes and renal failure suffer from diabetic glomerulosclerosis, but nondiabetic renal disease and atypical presentations, e.g. as irreversible acute renal failure or ischaemic nephropathy, play an increasingly important role. Known risk factors for the onset of diabetic nephropathy include (1) genetic predisposition (indicated by a history of hypertension and cardiovascular events in first-degree relatives), (2) quality of glycaemic control, (3) level of blood pressure, and (4) smoking. At the time when type 2 diabetes is diagnosed, an abnormal blood pressure profile is found in approximately 80%. In patients with established diabetic nephropathy, hypertension is the most important factor which promotes progression, and this is susceptible to intervention. Although less data are available for type 2 diabetes (compared with type 1 diabetes), ACE inhibitors appear to be the antihypertensive agent of first choice, but monotherapy is rarely sufficient to achieve the blood pressure goal. Although, at least in principle, diabetic nephropathy is a preventable condition, currently only a minority of type 2 diabetic patients in western Europe receives adequate medical treatment to prevent onset or progression of diabetic nephropathy. Consequently, novel approaches to patient management and interdisciplinary interaction are necessary to fulfil the postulate of the St Vincent declaration concerning prevention of diabetic complications.
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PMID:Nephropathy in type 2 diabetes. 1008 14

Hyperglycemia causes capillary vasodilation and high glomerular capillary hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene can modulate risk of nephropathy due to hyperglycemia, and the II genotype (producing low plasma ACE concentrations and probably reduced renal angiotensin II generation and kinin inactivation) may protect against diabetic nephropathy. We tested the possible interaction between ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia ( approximately 5 mmol/L) and hyperglycemia ( approximately 15 mmol/L) in 9 normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and 18 matched controls with the ID or DD genotype. Baseline GFR (145+/-22 mL/min per 1.73 m2) and ERPF (636+/-69 mL/min per 1.73 m2) of II subjects declined by 8+/-10% and 10+/-9%, respectively, during hyperglycemia; whereas baseline GFR (138+/-16 mL/min per 1.73 m2) and ERPF (607+/-93 mL/min per 1.73 m2) increased by 4+/-7% and 6+/-11%, respectively, in ID and DD subjects (II versus ID or DD subjects: P=0.0007 and P=0.0005, for GFR and ERPF, respectively). The changes in renal hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE concentration (P=0.024); this was not observed in subjects with the II genotype. Thus, type 1 diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy.
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PMID:Renal changes on hyperglycemia and angiotensin-converting enzyme in type 1 diabetes. 1008 86


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