Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Na+,K(+)-ATPase is an ubiquitous membrane enzyme that allows the extrusion of three sodium ions from the cell and two potassium ions from the extracellular fluid. Its activity is decreased in many tissues of streptozotocin-induced diabetic animals. This impairment could be at least partly responsible for the development of diabetic complications. Na+,K(+)-ATPase activity is decreased in the red blood cell membranes of type 1 diabetic individuals, irrespective of the degree of diabetic control. It is less impaired or even normal in those of type 2 diabetic patients. The authors have shown that in the red blood cells of type 2 diabetic patients, Na+,K(+)-ATPase activity was strongly related to blood C-peptide levels in non-insulin-treated patients (in whom C-peptide concentration reflects that of insulin) as well as in insulin-treated patients. Furthermore, a gene-environment relationship has been observed. The alpha-1 isoform of the enzyme predominant in red blood cells and nerve tissue is encoded by the ATP1A1 gene. A polymorphism in the intron 1 of this gene is associated with lower enzyme activity in patients with C-peptide deficiency either with type 1 or type 2 diabetes, but not in normal individuals. There are several lines of evidence for a low C-peptide level being responsible for low Na+,K(+)-ATPase activity in the red blood cells. Short-term C-peptide infusion to type 1 diabetic patients restores normal Na+,K(+)-ATPase activity. Islet transplantation, which restores endogenous C-peptide secretion, enhances Na+,K(+)-ATPase activity proportionally to the rise in C-peptide. This C-peptide effect is not indirect. In fact, incubation of diabetic red blood cells with C-peptide at physiological concentration leads to an increase of Na+,K(+)-ATPase activity. In isolated proximal tubules of rats or in the medullary thick ascending limb of the kidney, C-peptide stimulates in a dose-dependent manner Na+,K(+)-ATPase activity. This impairment in Na+,K(+)-ATPase activity, mainly secondary to the lack of C-peptide, plays probably a role in the development of diabetic complications. Arguments have been developed showing that the diabetes-induced decrease in Na+,K(+)-ATPase activity compromises microvascular blood flow by two mechanisms: by affecting microvascular regulation and by decreasing red blood cell deformability, which leads to an increase in blood viscosity. C-peptide infusion restores red blood cell deformability and microvascular blood flow concomitantly with Na+,K(+)-ATPase activity. The defect in ATPase is strongly related to diabetic neuropathy. Patients with neuropathy have lower ATPase activity than those without. The diabetes-induced impairment in Na+,K(+)-ATPase activity is identical in red blood cells and neural tissue. Red blood cell ATPase activity is related to nerve conduction velocity in the peroneal and the tibial nerve of diabetic patients. C-peptide infusion to diabetic rats increases endoneural ATPase activity in rat. Because the defect in Na+,K(+)-ATPase activity is also probably involved in the development of diabetic nephropathy and cardiomyopathy, physiological C-peptide infusion could be beneficial for the prevention of diabetic complications.
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PMID:C-peptide, Na+,K(+)-ATPase, and diabetes. 1519 70

In the history of diabetes, chlorpropamide alcohol flushing test (CPAF) was a big topic in the 1970s to 1980s. Alcohol tolerance after chlorpropamide has prognostic significance, with the intolerant group (CPAF-positive group) being less prone to develop vascular complication than the tolerant group (CPAF-negative group). A mechanism of CPAF has been regarded as the inhibition of aldehyde dehydrogenase 2 (ALDH2) by an N-alkyl-substituted derivative of chlorpropamide, and the expression of these mutations of ALDH2 and alcohol dehydrogenase 2 (ADH2) could determine the alcohol tolerance among the Japanese population. Therefore, we hypothesized that expression of different ALDH2 and ADH2 polymorphisms may induce differences in vascular complications in diabetes and conducted two studies. The first study (study 1) was to determine the association of ALDH2/AHD2 polymorphism with diabetic complications. To know the association of ALDH2/AHD2 polymorphism with diabetic vasculopathy and neuropathy, a total of 158 patients with type 2 diabetes were divided into four groups on the basis of ALDH2 "activity" and ADH2 "superactivity." The frequency of proteinuria and the percentage of proliferative retinopathy among the patients with retinopathy was higher in those with active ALDH2 and superactive ADH2. We speculated that protein kinase C isoforms up-regulated by 4-hydroxynonenal that was detoxified by ALDH2 and ADH2 may account for the long-term development of diabetic nephropathy and severe retinopathy. As for neuropathy, the frequency of symptomatic neuropathy was higher in patients with inactive ALDH2 and usual ADH2. We speculate that increased tissue levels of toxic aldehyde could result from inactive ALDH2 and usual ADH2 expression, which results in the increased level of reactive aldehyde in sensory neuron pathway, thereby causing symptomatic polyneuropathy.
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PMID:ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes. 1531 96

Non-insulin dependent diabetes mellitus is often associated with some complications such as nephropathy, retinopathy and neuropathy. Genes of the renin angiotensin system are potential candidate genes for diabetic complications. We investigated the relationship between angiotensin converting enzyme (ACE) gene polymorphism in type 2 diabetic patients with and without diabetic nephropathy. Seventy five patients (25 type 2 diabetic patients with nephropathy, 50 type 2 diabetic patients without nephropathy) and 37 healthy controls were studied. Gene polymorphism of ACE was determined by PCR (polymerase chain reaction) amplification using allele-spesific primers. The frequencies of ACE DD, ID and II genoypes among the patients with type 2 diabetic patients were found 48%, 42%, 10% whereas in control subjects, 27%, 60%, 13% respectively. Type 2 diabetic patients carrying DD genotype without nephropathy increased 1.77 fold than control subjects (P < 0.05). There is no significant correlation between diabetic nephropathy and ACE gene polymorphism. But we found that ACE DD genotype increased significantly in type 2 diabetic patients compared to control subjects (P <.05).
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PMID:Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients. 1536 53

Urotensin II (UII) is the most potent vasoconstrictor peptide ever identified. In order to clarify the pathophysiological role of UII in diabetes mellitus, we examined plasma immunoreactive UII levels and urinary excretion of immunoreactive UII in 10 control subjects and 48 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to the renal function: Group I with Ccr > or = 70 ml/min, group II with 30 < or = Ccr <70 ml/min and group III with Ccr <30 ml/min. Plasma immunoreactive UII levels were elevated in the three diabetic groups compared with normal controls (P <0.05). Group III patients had significantly higher plasma immunoreactive UII levels (15.9 +/- 2.2 fmol/ml, mean +/- S.E.M., n=6) by approximately 1.6-fold than did group I (10.9 +/- 0.9 fmol/ml, n=17) and group II (10.8 +/- 0.8 fmol/ml, n=25) (P <0.05). Urinary excretion of immunoreactive UII was significantly increased in group III patients (52.4 +/- 14.8 pmol/day) by more than 1.8-fold compared with control subjects, groups I and II (P <0.005). Fractional excretion of immunoreactive UII significantly increased as renal function decreased. Presence of diabetic retinopathy or neuropathy had negligible effects on plasma immunoreactive UII levels and urinary immunoreactive UII excretion. Reverse phase HPLC analyses showed three immunoreactive peaks in normal plasma extracts and multiple immunoreactive peaks in normal urine extracts. Thus, Type 2 diabetes mellitus itself is a factor to elevate plasma immunoreactive UII levels, and accompanying renal failure is another independent factor for the increased plasma immunoreactive UII levels in Type 2 diabetic patients. Increased urinary immunoreactive UII excretion in Type 2 diabetic patients with advanced diabetic nephropathy may be due not only to the elevated plasma immunoreactive UII levels but also to increased UII production and/or decreased UII degradation in the diseased kidney.
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PMID:Elevated plasma levels of immunoreactive urotensin II and its increased urinary excretion in patients with Type 2 diabetes mellitus: association with progress of diabetic nephropathy. 1547 50

Osteopontin (OPN) is thought to play multiple roles in the progression of atherosclerotic plaque including diabetic vascular complications. However, it still remains unclear whether the level of OPN in vivo is indeed clinically associated with the progression of diabetic complications. This study evaluated whether the levels of OPN in plasma and urine are correlated with the progression of diabetic complications, such as retinopathy, neuropathy, and nephropathy in patients with type 2 diabetes. In 229 patients with type 2 diabetes, OPN level in plasma and urine was evaluated by both the severity of diabetic complications, such as retinopathy, neuropathy, and nephropathy, and the clinical characteristics and the substantial laboratory findings. Plasma OPN level increased significantly with aging and the progression of diabetic nephropathy, especially at the stage of renal failure (p<0.05). However, the level was not related to the progression of retinopathy or neuropathy, or to laboratory findings, such as HbA1c or serum lipids. In contrast, urinary OPN level was not associated with diabetic complications in any of the subjects. There was no correlation between the plasma and urinary values of OPN. The results established that the plasma OPN was elevated in proportion to the progression of diabetic nephropathy, indicating that the plasma concentration may be a potential diagnostic predictor of diabetic end-stage renal disease.
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PMID:Progression of diabetic nephropathy enhances the plasma osteopontin level in type 2 diabetic patients. 1551 85

Diabetes mellitus (DM) is a complex multifaceted metabolic disorder characterised by chronic disease processes of hyperglycaemia and changes in the metabolism of carbohydrates, fats and proteins. It holds no boundaries with age, gender, culture or social strata. It is a life long disease process, which belongs to the individual, impacting on physical, social, psychosocial and spiritual life experiences. Diabetes is a worldwide burden to healthcare providers. In the United Kingdom (UK) 1.4 million people are affected with a suspected million people undiagnosed. A significant subgroup of patients with DM are predisposed to developing diabetic nephropathy, and it is now the single commonest cause of end-stage renal failure, accounting for 16% of new patients taken on to renal replacement therapy each year. It is in this subgroup that other diabetes related complications such as retinopathy, neuropathy and peripheral vascular disease are also concentrated. Microalbuminuria is an early indicator of renal disease in diabetes, and also predictive of total mortality, cardiovascular mortality and cardiovascular morbidity. These associated macro and microvascular complications can result in high personal, social and financial costs of managing complications associated with diabetic nephropathy and end-stage renal disease (ESRD). Some ethnic groups are particularly vulnerable--in the UK, the incidence of ESRD in South Asians and African Caribbean's is three times higher than in White Caucasians, in part due to the high prevalence of diabetic nephropathy.
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PMID:Patient and professional partnership in diabetic nephropathy. 1571 23

Macro- and microvascular disease are the most common causes of morbidity and mortality in patients with diabetes mellitus. Diabetic cardiovascular dysfunction represents a problem of great clinical importance underlying the development of various severe complications including retinopathy, nephropathy, neuropathy and increase the risk of stroke, hypertension and myocardial infarction. Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, are closely associated with increased oxidative and nitrosative stress, which can trigger the development of diabetic complications. Hyperglycemia stimulates the production of advanced glycosylated end products, activates protein kinase C, and enhances the polyol pathway leading to increased superoxide anion formation. Superoxide anion interacts with nitric oxide, forming the potent cytotoxin peroxynitrite, which attacks various biomolecules in the vascular endothelium, vascular smooth muscle and myocardium, leading to cardiovascular dysfunction. The pathogenetic role of nitrosative stress and peroxynitrite, and downstream mechanisms including poly(ADP-ribose) polymerase (PARP) activation, is not limited to the diabetes-induced cardiovascular dysfunction, but also contributes to the development and progression of diabetic nephropathy, retinopathy and neuropathy. Accordingly, neutralization of peroxynitrite or pharmacological inhibition of PARP is a promising new approach in the therapy and prevention of diabetic complications. This review focuses on the role of nitrosative stress and downstream mechanisms including activation of PARP in diabetic complications and on novel emerging therapeutical strategies offered by neutralization of peroxynitrite and inhibition of PARP.
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PMID:Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies. 1572 18

Foot lesions in postrenal transplant diabetics are often overlooked and hence underestimated. An audit of patients attending the authors' department was done. They reviewed the case notes to assess the presentation, clinical profiles, and outcomes of foot infections in patients with diabetes mellitus who received renal transplants at their center. Medical records of 192 diabetic foot patients were assessed, of which 8.8% (n = 17) had a history of previous renal transplantation for diabetic nephropathy. All 17 patients had noninsulin-dependent diabetes of mean duration of 16.2 years (range 7-27 years). Common complications and risk factors were studied. Mean duration to development of foot lesions in renal allograft recipients was 19.7 months (range 6-84 months). The big toe was the most common site of infection. Neuropathy and poor foot care appear to be important factors in the development of these foot lesions. Escherichia coli was the predominant organism on pus culture. Thirty-eight percent of patients needed major amputations; absence of an intact distal vascular tree was associated with a high major amputation rate. Two patients expired due to foot-related septicemia, and healing occurred in the remainder. Mean hospitalization time was 32.7 days. Most patients required more than one admission. The study emphasizes the need for greater attention to lower extremity complications in this patient group.
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PMID:An audit of foot infections in patients with diabetes mellitus following renal transplantation. 1586 7

Diabetes mellitus is a major and increasing health problem worldwide. One of the most serious consequences of diabetes is the development of diabetic angiopathy, which includes cardiovascular disease, neuropathy, retinopathy and nephropathy. Diabetic nephropathy alone affects 15-25% of patients with type 1 diabetes and 30-40% of patients with type 2 diabetes and is the single-most important cause of end-stage renal failure in the Western World. Existing research has demonstrated the involvement of glycation factors, growth factors/cytokines, hemodynamic factors and intracellular changes in the pathogenesis of diabetic kidney disease. An emerging amount of recent data suggests that the complement system, especially the MBL pathway, plays an important role in the pathogenesis of diabetic vascular complications. Although the numerous therapeutic interventions available today may delay the development and progression of diabetes vascular complications, there is an ongoing need for new therapeutic strategies. In this article the evidence for a connection between the complement system and vascular dysfunction will be reviewed, with a special focus on the relation to diabetic kidney disease. Several ways of specifically manipulating the complement system already exist. However, whether or not these drugs provide new targets for intervention on diabetic vascular complications is still unknown.
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PMID:Complement activation and diabetic vascular complications. 1599 50

The high sensitivity C-reactive protein (hsCRP) is known to be a sensitive predictor of coronary heart disease and type 2 diabetes. This study evaluated the association between the serum hsCRP and the components of metabolic syndrome (MS) and microvascular complications in type 2 diabetes. Two hundred and sixty-nine patients with type 2 diabetes were enrolled. All the subjects underwent measurement of MS and carotid intima-media thickness (IMT). The serum hsCRP concentrations and the 24 h urine albumin excretion amounts were measured. Ophthalmoscope examinations and nerve conduction velocity tests were performed to evaluate microvascular complications. The hsCRP was significantly higher in the patients with MS than in those without (p=0.019). The serum hsCRP was significantly correlated with all the components of MS. There were no differences between the serum hsCRP levels of those with and without retinopathy and neuropathy. The serum hsCRP was correlated with the 24 h urine albumin excretion amount. Serum hsCRP level has a significant correlation with MS and might be used as the future criteria of MS. Among microvascular complications, only diabetic nephropathy is associated with the serum hsCRP level. It suggests that the inflammatory process plays a role in nephropathy in type 2 diabetes.
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PMID:Relationship of serum high sensitivity C-reactive protein to metabolic syndrome and microvascular complications in type 2 diabetes. 1600 64


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