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)

Renin angiotensin system inhibitor therapy is seldom offered to individuals who have diabetes and advanced chronic kidney disease because of safety concerns. In this post hoc, secondary analysis of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, angiotensin antagonism risk/benefit profile was assessed in 1513 individuals with type 2 diabetes and overt nephropathy. Incidence of ESRD, hospitalizations for heart failure, withdrawals for adverse events, and proteinuria during losartan or conventional treatment were compared within three tertiles of baseline serum creatinine concentration (highest, 2.1 to 3.6 mg/dl; middle, 1.6 to 2.0 mg/dl; lowest, 0.9 to 1.6 mg/dl). Losartan decreased the risk of ESRD by 24.6, 26.3, and 35.3% in highest, middle, and lowest tertiles, respectively. For every 100 patients with serum creatinine >2.0, 1.6 to 2.0, or <1.6 mg/dl, respectively, 4 yr of losartan therapy was estimated to save 18.9, 8.4, and 2.9 ESRD events and US$1,502,855, US$1,021,770, and US$528,591 costs for renal replacement therapy. Losartan also decreased the hospitalizations for heart failure by 50.2 and 45.1, in the highest and middle tertile, respectively. Withdrawals for adverse events other than heart failure were comparable between tertiles and treatment groups. Proteinuria decreased more on losartan than on placebo in all tertiles (highest, 24 versus -8%; middle, 16 versus -8%; lowest, 15 versus -10%). In proteinuric individuals with type 2 diabetes, losartan therapy reduced ESRD and hospitalizations for heart failure and was well tolerated at all levels of renal function. Angiotensin II antagonism is a suitable and well-tolerated treatment for individuals with type 2 diabetes even with GFR levels approaching renal replacement therapy.
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PMID:Continuum of renoprotection with losartan at all stages of type 2 diabetic nephropathy: a post hoc analysis of the RENAAL trial results. 1557 15

A 59-year-old woman with chronic renal failure due to type 2 diabetes mellitus (DM) is presented. Her father and a brother had a history of brain tumor. Her blood urea nitrogen and serum creatinine levels were 102 mg/dl and 4.5 mg/dl, respectively. Her serum Ca(2+) and Pi were within the normal range (9.4 mg/dl and 5.4 mg/dl, respectively). Her intact parathyroid hormone (PTH) level was 1 730 000 pg/ml. A (99m)Tc-methoxy-isobutylisonitrile scintigraphy showed high uptake in three parathyroid glands. A magnetic resonance image showed microadenoma in the pituitary gland. The serum gastrin level was high. Genetic examination revealed a mutation of the MEN1 gene (894-9 G --> A). From these findings, she was diagnosed with multiple endocrine neoplasia (MEN) type 1. Subsequently, a parathyroidectomy was performed successfully, a parathyroid gland was transplanted to her right forearm, and her serum Ca(2+) level was controlled at 8.5-9.0 mg/dl. It is very important to identify MEN1 if an end-stage renal disease (ESRD) patient has hyperparathyroidism with multigland involvement. Examination of the MEN1 gene may be valuable to make an accurate diagnosis and choose the appropriate therapy in some ESRD patients with hyperparathyroidism.
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PMID:Multiple endocrine neoplasia type 1 in end-stage renal failure. 1561 41

The relationship between blood levels of N-carboxymethyl-lysine (CML) or pentosidine and the severity of microangiopathy was investigated in patients with type 2 diabetes. Blood CML and pentosidine levels were measured by ELISA in 97 type 2 diabetics (46 men and 51 women). CML and pentosidine levels were significantly higher in patients with chronic renal failure than in those with normoalbuminuria, microalbuminuria, or macroalbuminuria (all p < 0.05). Among the diabetics without nephropathy (n = 49), blood CML levels were significantly higher in the patients who had proliferative diabetic retinopathy than in those without retinopathy or those who had background retinopathy (both p < 0.01). In contrast, blood pentosidine levels showed no significant differences among the three retinopathy groups. These findings suggest that the blood level of CML is related to the severity of both nephropathy and retinopathy, while the pentosidine level is only related to the severity of nephropathy.
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PMID:Relationship between blood levels of N-carboxymethyl-lysine and pentosidine and the severity of microangiopathy in type 2 diabetes. 1564 71

It is no a secret that we are confronted by an alarmingly increasing number of patients with progressive renal disease. There is ample evidence for the notion that angiotensin II (Ang II) is a major culprit in progression. The vasopeptide Ang II turned out to have also multiple nonhemodynamic pathophysiologic actions on the kidney, including proinflammatory and profibrogenic effects. Diverse complex Ang II generating systems have been identified, including specifically local tissue-specific renin-angiotensin systems (RAS). For example, proximal tubular cells have all components required for a functional RAS capable of synthesizing Ang II. On the other hand, Ang II is not the only effector of the RAS and other peptides generated by the RAS influence renal function and structure as well. Moreover, the discoveries that Ang II can be generated by enzymes other than angiotensin-converting enzyme (ACE) and that Ang II and other RAS derived peptides bind to various receptors with different functional consequences have further added to the complexity of this system. Several major clinical trials have clearly shown that ACE inhibitor treatment slows the progression of renal diseases, including in diabetic nephropathy. Well-controlled studies demonstrated that this effect is in part independent of blood pressure control. More recently, with Ang II type 1 receptor (AT(1)) receptor antagonists a similarly protective effect on renal function was seen in patients with type 2 diabetes. Neither ACE inhibitor treatment nor AT(1) receptor blockade completely abrogate progression of renal disease. A recently introduced novel therapeutic approach is combination treatment comprising both ACE inhibitor and AT(1) receptor antagonists. The rationale for this approach is based on several considerations. Small-scale clinical studies, mainly of crossover design, documented that combination therapy is more potent in reducing proteinuria in patients with different chronic renal diseases. Blood pressure as an important confounder was, however, significantly lower in the majority of this studies in the combination treatment arms compared to the respective monotherapies. In a recent prospective study Japanese authors avoided this confounder and demonstrated that combination therapy reduced hard end-points (end stage renal failure or doubling of serum creatinine concentration) by 50% compared to the respective monotherapies. This effect could not be explained by a more pronounced reduction of blood pressure in the combination therapy group. Although these results are encouraging, administration of combination therapy should be reserved currently to special high risk groups. Further studies are necessary to confirm these promising results. It is possible that combination therapy may increase the risk of hyperkalemia, particularly when with coadministered with medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) or spironolactone. In our opinion patients with proteinuria >1 g/day despite optimal blood pressure control under RAS-blocking monotherapy are a high-risk group which will presumably benefit from combination therapy.
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PMID:Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. 1616 72

The first clinical evidence of nephropathy is the appearance of low, but abnormal, albumin levels in the urine (>30 mg/day or 20 mg/min), microalbuminuria. Without specific interventions, approximately 80% of type 1 diabetics have their urinary albumin excretion increase at a rate of 10-20%/yr to the stage of overt nephropathy or clinical albuminuria (>300 mg/24h or >200 mg/min) over 10-15 yrs, developing hypertension along the way. Approximately 30% of individuals with type 2 diabetes are found to have microalbuminuria or overt nephropathy shortly after the diagnosis of their illness, because diabetes is actually present for many years previously and because the presence of albuminuria can depend on other concomitant nephropathies, as shown by biopsy studies. Without specific intervention, 20-40% of type 2 diabetic patients with microalbuminuria progress to overt nephropathy, but 20 yrs after onset only 20% progress to end-stage renal failure (ESRD). The rates of decline in glomerular filtration rate (GFR) are highly variable from one individual to another, but they may not be substantially different between patients with type 1 and type 2 diabetes. As therapies and interventions for coronary artery disease continue to improve, more elderly type 2 diabetes patients can be expected to survive long enough to develop renal failure. The recently published Italian Society of Nephrology (SIN) guidelines for diagnosis and therapy of diabetic nephropathy present the route for the best strategies in prevention and therapy, from earlier onset to advanced ESRD.
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PMID:[Type 2 diabetic nephropathy: clinical course and prevention proposals 2004]. 1578 92

The major challenge for the treatment of hypertensive patients with type 2 diabetes is to achieve the uniformly recommended blood pressure goal of 130/80 mmHg, and 120/75 mmHg in proteinuric patients. Such low target blood pressure levels require the administration of multiple drugs. Angiotensin receptor blockers and the combination of angiotensin receptor blockers with diuretics fulfil the criteria to lower blood pressure effectively with a placebo-like side-effect profile. Beyond pressure control, clinical prospective trials have documented that it does matter what kind of antihypertensive agent is used to control blood pressure. Large-scale follow-up trials have documented blood pressure independent effects of angiotensin receptor blocker on cardiac [left-ventricular hypertrophy (LVH), congestive heart failure] and renal protection (proteinuria, chronic renal failure). Of note, in these trials, angiotensin receptor blockers have been combined with diuretics, and most of the included patients have been on combination therapy comprising two to four antihypertensive agents. In addition to the combination of an angiotensin receptor blocker with a diuretic, the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor appeared to be most effective in reducing proteinuria, attenuating chronic renal failure and treating congestive heart failure.
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PMID:Optimizing therapeutic strategies to achieve renal and cardiovascular risk reduction in diabetic patients with angiotensin receptor blockers. 1583 71

Calciphylaxis is an uncommon complication of end stage renal disease (ESRD) and secondary hyperparathyroidism. It characterized by cutaneous necrosis with mural calcifications and thrombosis in the small vessels of dermis. It is important to diagnose and treat, because of mortality rate from calciphylaxis is very high. We present the case of a patient with ESRD and type II diabetes mellitus developing calciphylaxis of the both upper and lower extremities had normal corrected calcium-phosphate product level. After amputation, necrosis was showed rapid progression resulting in death in one month.
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PMID:Calciphylaxis involving both the upper and lower extremities. 1584 9

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

Hypertension and proteinuria are risk factors for renal disease progression. There is clear evidence that pharmacological blockade of the RAS with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows down the progression of renal disease in diabetic and non diabetic nephropathies, a beneficial effect not related to blood pressure control. However, not all patients respond similarly to these treatments. Some patients exhibit a significant beneficial response while others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI, which are unable to block completely the formation of AII, some generation of AII is produced via other non ACE pathways. In the search of new alternatives that could improve the antiproteinuric and nephroprotective effects of RAS blockers, the association of ACEI and ARB might prove to be useful. ARB produces a complete blockade of the RAS and stimulates the vasodilating and non-proliferative actions of AII via the AT-2 receptor. Furthermore, ACE inhibitors but not ARB; inhibit the metabolism of kinins, which increases the level of bradykinin, a potent vasodilator. Recently, several authors have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone in spite of a similar effect on blood pressure. A recent study also has demonstrated that this more marked antiproteinuric effect is associated with a less progression of renal disease in primary, non diabetic nephropathies. Furthermore, at least two studies have shown that, treatment with ARB postpones end-stage renal disease and reduces the rate of decline in renal function in patients with type 2 diabetes and nephropathy, but until now, there is not any clear evidence of a superior beneficial effect of dual blockade versus maximal recommended dose of ARB regarding renal progression in type 2 diabetic nephropathy, which is the most frequent cause of end stage renal disease. Long-term clinical trials are needed and encouraged to further establish the significant role of dual blockade in renal protection particularly in diabetic nephropathy.
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PMID:The reno-protective effect of the dual blockade of the renin angiotensin system (RAS). 1585 85

A patient with a history of type II diabetes mellitus (DM), end stage renal disease (ESRD), and congestive heart failure (CHF) developed necrotizing fasciitis caused by Serratia marcescens after scraping his leg on rocks in a river while fishing. Aggressive management with surgical debridement, antibiotics, and pressure support was unsuccessful.
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PMID:A fatal case of necrotizing fasciitis caused by Serratia marcescens. 1586 38


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