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)

The aim of the study was to analyze the etiology, the factors for progression of chronic renal failure to end-stage-renal disease (ESRD), and the influence of ESRD on the survival rate among a cohort of 59 heart transplant patients (HTP) referred for the management of chronic renal failure (CRF). At the time of the first nephrology consultation (6 +/- 4.25 years after cardiac transplantation) the mean creatininemia was 261.5 +/- 99 micromol/L and mean creatinine clearance (Cockcroft formula) was 32 +/- 15 mL/min. The cause of CRF were calcineurin inhibitor toxicity in 38.9% of patients, vascular events in 15.2%, hemolytic uremic syndrome in 5%, membranous glomerulopathy in 3.3%, diabetes in two patients, focal/segmental glomerulosclerosis in 3.3%, renal hypoplasia in 1.7%, and unknown in 27%. Evolution to ESRD occurred in 38.9% of patients: 17 patients started hemodialysis, three peritoneal dialysis, and two received a preemptive kidney transplantation. Creatininemia (micromol/L) at the time of nephrology referral was 229.2 +/- 72.6 versus 315.8 +/- 113.4 (P < .001) and creatinine clearance (mL/min) was 34.9 +/- 15.1 versus 27.3 +/- 13.7 (P = .049) for patients with CRF versus ESRD, respectively. Both proteinuria (g/24 hours) of 1 +/- 2.2 versus 2.3 +/- 1.8 (P = .02) and tobacco use in 35.1% versus 54.4% (P = .045) were significantly associated with progression of CRF, while age at the time of heart transplantation, cause of cardiac failure and renal failure, high blood pressure, type 2 diabetes, dyslipidemia, alcoholism, cirrhosis, and cerebral vascular accident were not. Death occurred in 18 HTP: 50% of patients with ESRD and 18.5% of patients with CRF-a 2.6 relative risk of of death in HTP patients with ESRD compared with HTP with CRF only (P < .01).
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PMID:Chronic renal failure and end-stage renal disease are associated with a high rate of mortality after heart transplantation. 1584 18

Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (> 396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.
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PMID:Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. 1593 41

Traditionally, microvascular disease resulting in a glomerulopathy and an increase in albumin excretion rate (AER) is believed to be the only significant mechanism by which diabetic renal disease develops. However, recent results have challenged the concept that a decline in renal function in patients with diabetes is always accompanied by an increased AER. This has led to the concept that subjects with diabetes, especially those with type 2 diabetes, can progress to renal impairment via either an albuminuric or non-albuminuric pathway. The natural history, renal morphological changes and exaggerated cardiovascular risk associated with the albuminuric-pathway to renal impairment have been well documented. Interventions to attenuate the progression of this pathway, especially inhibition of the renin-angiotensin system (RAS), are also a routine part of clinical practice. Subjects who follow the albuminuric pathway are detected by screening for the presence of microalbuminuria. The finding of microalbuminuria in this setting should provoke an intensified modification of the common risk factors for renal and cardiovascular disease, i.e. hyperglycemia, hypertension, dyslipidemia and smoking. In contrast, little is known about the natural history and structural basis of the non-albuminuric pathway to renal impairment and the best way to retard its progression is also not known. The prevalence of impaired renal function and normoalbuminuria is relatively common and in subjects with type 2 diabetes is at least 20% after accounting for the use of RAS inhibitors. It is therefore recommended that screening for diabetic renal disease should include an estimation of glomerular filtration rate (GFR) in addition to measuring AER. This will allow the detection of subjects following either an albuminuric or non-albuminuric pathway to renal impairment.
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PMID:Albuminuric and non-albuminuric pathways to renal impairment in diabetes. 1620 6

Diabetes mellitus and arterial hypertension are the leading causes of end-stage renal disease in industrialized countries. Although attention has focused on renal disease and insulin-dependent diabetes mellitus (type 1 diabetes), a silent epidemic of renal disease caused by type 2, noninsulin-dependent diabetes mellitus is rapidly developing. The course of renal function is heterogeneous in type 2 diabetic patients and reflects heterogeneous patterns of renal lesions. A subset of patients with microalbuminuria and proteinuria is characterized by the typical diabetic glomerulopathy usually observed in type 1 diabetic patients, with altered albumin excretion rate (AER), for example, glomerular basement membrane thickening and mesangial fractional volume expansion. These patients also have diabetic retinopathy and rapidly lose renal function despite tight blood pressure control. In contrast, a second subset of type 2 diabetic patients has normal or near-normal patterns of glomerular structure, despite abnormalities of AER comparable to those of the patients with diabetic glomerulopathy. Thus abnormalities of AER have a different renal prognostic value depending on the underlying renal structure. The patients with worse clinical prognosis and typical diabetic glomerulopathy also have diabetic retinopathy, whereas those with a better course of renal function quite often have no diabetic retinopathy. Several findings, albeit not unanimous, suggest that HbA1c levels above 7.5 to 8.0 % are closely associated with a rapid decay of renal function in type 2 diabetes. Tight blood pressure control plays a further important role in determining the progression of renal a damage in type 2 diabetes mellitus. Convincing evidence has been provided that drugs capable of inhibiting the renin-angiotensin hormonal system are quite effective in preventing and delaying the evolution of renal damage in both type 1 and 2 diabetes. Equally strong data support the view that other antihypertensive compounds such as beta-blockers and calcium antagonists also delay the progression of renal damage in diabetes mellitus. Whatever the drug used to treat hypertension, the majority of the authors conclude that blood pressure levels should be maintained below 130/85 mmHg in diabetic patients. While it is well established that uncontrolled diabetes underlies the development of diabetic nephropathy, newer evidence suggests that genetically determined susceptibility to hyperglycemia-caused glomerular injury is also necessary. More information on this issue will help to design new therapeutical approaches to treat hypertension and renal complications in type 2 diabetes.
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PMID:Hypertension and renal complications in type 2 diabetes. 1622 1

An 88-year-old man with a 30-year history of type 2 diabetes and a 3-year history of chronic renal failure was admitted for evaluation of anasarca. On admission, findings of nephrotic syndrome and microscopic hematuria were observed. During the course of therapy, rapid deterioration of renal function occurred with the appearance of pneumonia. Irrespective of the therapy with hemodialysis and antibiotics, he died of respiratory failure. The autopsy showed a rare case of rapidly progressive glomerulonephritis (crescentic glomerulonephritis) superimposed on membranous nephropathy. This experience highlighted the importance of the differential diagnosis of non-diabetic glomerulopathy even in elderly patients with diabetes mellitus.
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PMID:Diabetes mellitus complicated with rapidly progressive glomerulonephritis in an elderly patient. 1629 21

Diabetes is the most common cause of ESRD in Western countries. This article describes the impact of glycemic control in the various stages of the disease and considers the impact of tight glycemic control on the development and progression of diabetic nephropathy (DN). The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetic Study have demonstrated in type 1 and type 2 diabetes that intensive glycemic control significantly reduces the risk for development of microalbuminuria. Although observational studies suggest an impact of glycemia also on the progression of DN, fewer data are available on the impact of improved metabolic control in secondary prevention. The long-term follow-up of the patients who participated in the Diabetes Control and Complications Trial (Epidemiology of Diabetes Interventions and Complications Study) demonstrated a sustained effect of previous tight glycemic control on both development and progression of DN. Finally, long-term normoglycemia, achieved by pancreas transplantation, is able not only to prevent the development of early diabetic glomerulopathy in kidney transplant recipients but also to halt progression and induce regression of the established diabetic renal lesions in nonuremic patients. Taken together, these studies strongly demonstrate that improvement in glucose control is the most important therapeutic approach in primary prevention. Tight glycemic control also is important in slowing progression of DN, and if blood glucose is normalized, then regression of DN can be achieved. Therefore, a target of glycated hemoglobin levels <7% should be recommended in all patients with diabetes.
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PMID:Renal protection in diabetes: role of glycemic control. 1656 55

Glomerular injury plays a pivotal role in the development of diabetic nephropathy. To elucidate molecular mechanisms underlying diabetic glomerulopathy, we compared glomerular gene expression profiles of db/db mice with those of db/m control mice at a normoalbuminuric stage characterized by hyperglycemia and at an early stage of diabetic nephropathy with elevated albuminuria, using cDNA microarray. In db/db mice at the normoalbuminuric stage, hypoxia-inducible factor-1alpha (HIF-1alpha), ephrin B2, glomerular epithelial protein 1, and Pod-1, which play key roles in glomerulogenesis, were already upregulated in parallel with an alteration of genes related to glucose metabolism, lipid metabolism, and oxidative stress. Podocyte structure-related genes, actinin 4alpha and dystroglycan 1 (DG1), were also significantly upregulated at an early stage. The alteration in the expression of these genes was confirmed by quantitative RT-PCR. Through pioglitazone treatment, gene expression of ephrin B2, Pod-1, actinin 4alpha, and DG1, as well as that of oxidative stress and lipid metabolism, was restored concomitant with attenuation of albuminuria. In addition, HIF-1alpha protein expression was partially attenuated by pioglitazone. These results suggest that not only metabolic alteration and oxidative stress, but also the alteration of gene expression related to glomerulogenesis and podocyte structure, may be involved in the pathogenesis of early diabetic glomerulopathy in type 2 diabetes.
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PMID:Altered gene expression related to glomerulogenesis and podocyte structure in early diabetic nephropathy of db/db mice and its restoration by pioglitazone. 1700 39

Epidemiological studies have proven that obesity is a significant risk factor for type 2 diabetes. Long-term progression of diabetes leads to various microvascular complications, of which diabetic nephropathy has become of increasing importance, and is the main cause of end-stage renal failure in occidental countries. Microalbuminuria is the first marker of incipient diabetic nephropathy, an early stage glomerulopathy which can progress to renal failure and which historically has been treated with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists. We report a severely obese diabetic patient on treatment for diabetic nephropathy with ACE-inhibitors and poor results, which resolved after Roux-en-Y gastric bypass.
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PMID:Resolution of early stage diabetic nephropathy in an obese diabetic patient after gastric bypass. 1705 53

The activation of the poly(ADP-ribose) polymerase (PARP) plays an important role in the pathophysiology of various diseases associated with oxidative stress. We found increased amounts of poly(ADP) ribosylated proteins in diabetic kidneys of Lepr(db/db) (BKsJ) mice, suggesting increased PARP activity. Therefore, we examined the effects of two structurally unrelated PARP inhibitors (INO-1001 and PJ-34) on the development of diabetic nephropathy of Lepr(db/db) (BKsJ) mice, an experimental model of type 2 diabetes. INO-1001 and PJ-34 were administered in the drinking water to Lepr(db/db) mice. Both INO-1001 and PJ-34 treatment ameliorated diabetes-induced albumin excretion and mesangial expansion, which are hallmarks of diabetic nephropathy. PARP inhibitors decreased diabetes-induced podocyte depletion in vivo and blocked hyperglycemia-induced podocyte apoptosis in vitro. High glucose treatment of podocytes in vitro led to an early increase of poly(ADP) ribosylated modified protein levels. Reactive oxygen species (ROS) generation appears to be a downstream target of hyperglycemia-induced PARP activation, as PARP inhibitors blocked the hyperglycemia-induced ROS generation in podocytes. INO-1001 and PJ-34 also normalized the hyperglycemia-induced mitochondrial depolarization. PARP blockade by INO-1001 and PJ-34 prevented hyperglycemia-induced nuclear factor-kappaB (NFkappaB) activation of podocytes, and it was made evident by the inhibitor of kappaBalpha phosphorylation and NFkappaB p50 nuclear translocation. Our results indicate that hyperglycemia-induced PARP activation plays an important role in the pathogenesis of glomerulopathy associated with type 2 diabetes and could serve as a novel therapeutic target.
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PMID:Poly(ADP-ribose) polymerase inhibitors ameliorate nephropathy of type 2 diabetic Leprdb/db mice. 1706 36

Diabetic nephropathy is an important cause of morbidity and mortality in patients with either type 1 or type 2 diabetes mellitus. The pathogenesis and natural history of diabetic nephropathy, characterised by a progressive decline in glomerular function, were initially described in patients with type 1 diabetes. Reports that describe the glomerulopathy and progression of renal disease in patients with type 2 diabetes suggest that the disease process is similar to that observed in patients with type 1 diabetes with diabetic nephropathy. An emerging body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve pathobiochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic, reveal that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Clinical reports of the use of sulodexide, a preparation of low molecular weight glycosaminoglycan polysaccharides, have shown that proteinuria is significantly diminished in patients with diabetic nephropathy, even when these patients are receiving either an ACE inhibitor or angiotensin receptor antagonist.
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PMID:The role of sulodexide in the treatment of diabetic nephropathy. 1806 18


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