Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of tissue advanced glycation end products (AGEs) that result from nonenzymatic reactions of glucose and proteins are high in both diabetic and aging people. Irreversible AGE formation is based on increases in AGE-derived protein-to-protein cross-linking and is considered to be a factor contributing to the complications of diabetes. A novel inhibitor of advanced glycation, OPB-9195, belongs to a group of thiazolidine derivatives, known as hypoglycemic drugs; however, they do not lower blood glucose levels. We did studies to determine if OPB-9195 would prevent the progression of nephropathy in spontaneous diabetic rats. In vitro inhibitory effects of OPB-9195 on AGE formation and AGE-derived cross-linking were examined by enzyme-linked immunosorbent assay (ELISA) and SDS-PAGE, respectively. Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of NIDDM, were used to evaluate the therapeutic effect of OPB-9195. Light microscopic findings by periodic acid-Schiff (PAS) staining, the extent of AGE accumulation detected by immunohistochemical staining in the kidneys, the levels of serum AGEs by AGE-specific ELISA, and urinary albumin excretion were examined. OPB-9195 effectively inhibited both AGE-derived cross-linking and the formation of AGEs, in a dose-dependent manner in vitro. In addition, the administration of OPB-9195 prevented the progression of glomerular sclerosis and AGE deposition in glomeruli. Elevation of circulating AGE levels and urinary albumin excretion were dramatically prevented in rats, even at 56 weeks of age and with persistent hyperglycemia. We concluded that a novel thiazolidine derivative, OPB-9195, prevented the progression of diabetic glomerular sclerosis in OLETF rats by lowering serum levels of AGEs and attenuating AGE deposition in the glomeruli.
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PMID:Progression of nephropathy in spontaneous diabetic rats is prevented by OPB-9195, a novel inhibitor of advanced glycation. 913 61

Non-insulin-dependent diabetes mellitus (NIDDM) and the renal disease attributable to it have been characterized extensively in the Pima Indians, a group of American Indians who form the Gila River Indian Community in Arizona. Both of these diseases are common in this community, and their onset and duration are known with greater certainty than in other populations because research examinations, which include oral glucose tolerance tests and measures of urinary protein excretion, have been performed frequently on most members of the population for the past 30 years. Studies of glomerular structure and hemodynamic function in diabetic Pima Indians indicate that glomerular hyperfiltration often develops at the onset of NIDDM and remains elevated until after overt nephropathy appears. Structurally, the glomeruli in subjects with microalbuminuria are not clearly distinguishable from those in subjects with normoalbuminuria, but macroalbuminuria is characterized by extensive glomerular sclerosis, mesangial expansion, and widening of epithelial cell foot processes that together lead to a rapid decline in the glomerular filtration rate. The decline in glomerular function in subjects with macroalbuminuria is due both to a loss of ultrafiltration surface area and to reduction in glomerular hydraulic permeability.
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PMID:Clinical and pathological course of renal disease in non-insulin-dependent diabetes mellitus: the Pima Indian experience. 914 78

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

We report the case of a patient with insulin-requiring type 2 diabetes who exhibited a rapid deterioration of his renal function leading to haemodialysis in a few months. Various diagnosis were considered to explain this rapid deterioration, excluding diabetic nephropathy as major etiology. The exploration, especially renal biopsy, demonstrated the presence of a glomerulonephritis due to the deposition of immune complexes associated to active hepatitis C rather than diabetic glomerulosclerosis. A treatment with interferon-alpha allowed to partially restore renal function, this recovery permitting the interruption of hemodialysis, with a current follow-up of more than 6 months.
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PMID:[Clinical case of the month. Galloping nephropathy in a patient with type 2 diabetes]. 964 Oct 9

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

The occurrence of immunoglobulin A nephropathy (IgAN) in patients with noninsulin dependent diabetes mellitus (NIDDM) is a rare event and of pathogenetic interest. It is not clear whether this is merely coincidence. We report here five patients with IgAN in NIDDM associated with or without diabetic glomerulosclerosis. All of the patients were Korean males. In three patients, diabetes mellitus was diagnosed at the same time with diagnosis of IgAN, and the known duration of the diabetes in the other two patients were three and seven years, respectively. There was no evidence of diabetic retinopathy in four patients, but it was found in one patient. In all cases, the diagnosis of IgAN was made by immunohistology.
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PMID:Immunoglobulin A nephropathy in patients with non-insulin dependent diabetes mellitus. 1057 58

The past three decades have seen enormous conceptual advances in understanding the pathogenesis of diabetic nephropathy. Increasing evidence points to important genetic determination of the renal risk, i.e. the propensity to develop diabetic nephropathy, in type 1 and type 2 diabetic patients. We are also further along the path to understanding the abnormalities of renal hemodynamics that underly these patients' propensity to develop diabetic glomerulosclerosis, i.e. afferent arterial vasodilation and increased glomerular pressure, identified in elegant experimental studies. Another important advance is the recognition that increased urinary albumin excretion is not only an extremely sensitive marker, but also an important player in the pathogenesis of diabetic nephropathy. Finally, the concept of the toxicity of hyperglycemia ("glucotoxicity") has been carried to the molecular level, so that pathomechanisms such as activation of protein kinase C and cellular damage by advanced glycation endproducts (AGE), to name only two, have been elucidated. Diabetic nephropathy has become the leading cause of endstage renal failure (ESRF) in Western countries, particularly in patients with type 2 diabetes. Three treatment modalities are available: (i) hemodialysis,(ii) CAPD and (iii) transplantation, meaning kidney transplantation, combined pancreas and kidney transplantation or - still in a very preliminary stage - islet cell transplantation. The ideal is to have all three modalities available to meet each patient's individual needs. Treatment outcome continues to be considerably worse, however, in diabetic than non-diabetic patients. This highlights the importance of prevention. Progression to ESRF in diabetic nephropathy is preventable, at least to a large extent.
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PMID:Diabetic nephropathy--what have we learned in the last three decades? 1068 11

Over a 4-yr period in the northeast region of Japan (Tohoku), 3643 patients for whom a renal biopsy was available were screened. In addition, 2370 biopsied patients for whom hepatitis C virus (HCV) serology was available were evaluated. The prevalence of HCV infection was investigated in the 2370 biopsied patients. The highest prevalence of HCV infection was found in type II diabetic-related glomerulosclerosis (II-DGS) (24 of 123; 19.5%). At renal biopsy, clinical and laboratory findings and histologic parameters were comparable between the HCV-positive and -negative II-DGS groups. After renal biopsy, the decline of renal function reflected by the slope of reciprocal serum creatinine (1/S(Cr)) was significantly greater in the HCV-positive group than in the HCV-negative group (P = 0.001). The log-rank test performed on the renal survival curves showed a significant difference in the two groups (P = 0.019). According to a multiple linear regression analysis adjusted for the effect of age, gender, BP, HbA1c, urinary protein excretion, and histologic parameters as covariates, urinary protein excretion (P = 0.011), severe arteriolar hyalinosis (P = 0.006), and HCV infection (P < 0.001) were significantly associated with 1/S(Cr) slope. Finally, HCV infection was randomly examined in 545 outpatients and inpatients with type II diabetes mellitus who did not undergo renal biopsy. Of these, 56 patients were positive for HCV antibody (10.3%), and their proteinuria was heavier than in 489 HCV-negative patients (P = 0.001). This study reveals that HCV infection is present at a high rate in type II diabetic-related nephropathy and may have an adverse effect on the progression of the disease.
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PMID:High prevalence and adverse effect of hepatitis C virus infection in type II diabetic-related nephropathy. 1075 28

The aim of this study was to examine the relationship between serum immunoglobulin A (IgA) levels and diabetic nephropathy in patients with type 2 diabetes mellitus, and to describe the role of IgA nephropathy superimposed on diabetes mellitus. A total of 127 type 2 diabetic patients were studied. Of these diabetics, 74 had no proteinuria, 35 had diabetic glomerulosclerosis confirmed by renal biopsy, 13 had superimposed IgA nephropathy, and five had superimposed non-IgA nephropathy. We also studied 93 non-diabetic patients with IgA nephropathy, 24 non-diabetic patients with non-IgA nephropathy, and 38 non-diabetic controls. Serum IgA levels were significantly higher in IgA nephropathy patients (350+/-130 mg/dl) than in non-diabetic controls (228+/-56 mg/dl) and diabetics without proteinuria (268+/-104 mg/dl). Serum IgA levels were also significantly higher in diabetics with superimposed IgA nephropathy (470+/-208 mg/dl) than in non-diabetic controls, non-IgA nephropathy patients (270+/-133 mg/dl), diabetics without proteinuria, diabetic glomerulosclerosis alone (302+/-126 mg/dl), and diabetics with superimposed non-IgA nephropathy (248+/-137 mg/dl). The prevalence of high serum IgA levels was significantly higher in diabetics with superimposed IgA nephropathy (76.9%) than in diabetic glomerulosclerosis alone (31.4%) and diabetics with superimposed non-IgA nephropathy (25.0%). In conclusion, our findings indicate that high serum IgA level is a sign of the existence of IgA nephropathy superimposed on diabetes mellitus.
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PMID:Serum IgA levels in patients with diabetic nephropathy and IgA nephropathy superimposed on diabetes mellitus. 1080 48

Emerging evidence suggests that transforming growth factor-beta (TGF-beta) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-beta antibody (alphaT) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-beta system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of alphaT prevents renal insufficiency and glomerulosclerosis in the db/db mouse, a model of type 2 diabetes that develops overt nephropathy. Diabetic db/db mice and nondiabetic db/m littermates were treated intraperitoneally with alphaT or control IgG, 300 microgram three times per week for 8 wk. Treatment with alphaT, but not with IgG, significantly decreased the plasma TGF-beta1 concentration without decreasing the plasma glucose concentration. The IgG-treated db/db mice developed albuminuria, renal insufficiency, and glomerular mesangial matrix expansion associated with increased renal mRNAs encoding alpha1(IV) collagen and fibronectin. On the other hand, treatment with alphaT completely prevented the increase in plasma creatinine concentration, the decrease in urinary creatinine clearance, and the expansion of mesangial matrix in db/db mice. The increase in renal matrix mRNAs was substantially attenuated, but the excretion of urinary albumin factored for creatinine clearance was not significantly affected by alphaT treatment. We conclude that chronic inhibition of the biologic actions of TGF-beta with a neutralizing monoclonal antibody in db/db mice prevents the glomerulosclerosis and renal insufficiency resulting from type 2 diabetes.
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PMID:Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. 1088 96


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