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)

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.
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PMID:Proteinuria: clinical signficance and basis for therapy. 1176 58

SOME FIGURES: Terminal renal failure (TRF) is a major public health problem in France in view of its increasing incidence (110 pmi/year), prevalence (700 pmi) and the costs of treatments supplied. In France, more than 6,500 new patients started treatment for TRF in 2001; around 42,000 patients with renal failure have been treated. The mean cost of treatment per patient is estimated to be of 350 KF per annum for dialysis, 450 KF for transplantation the first year and 50 KF per annum thereafter. Hence, more than 10 billion francs are spent every year on treating TRF, i.e., 1.5% of the Health Scheme. However, these costs do not include expensive treatments (erythropoietin), transport or hospitalisation. RECENT TENDENCIES: Our information system concerning TRF is fragmented and not coordinated. Identification of the cases is incomplete, their declaration is not always systematic and the quality control of the data has not been formalized. Nonetheless, major tendencies can be identified. The notable facts of the last 10 years are an aging TRF population and an increase in associated comorbidity. The diseases leading to TRF are changing. Vascular nephropathies predominate; ischemic renal diseases have become the first cause of TRF in elderly patients. The incidence of type 2 diabetes is increasing and strangely in the French overseas territories. Glomerular nephropathies are the third cause of TRF, particularly in the young. However, compared with other causes, their prevalence is decreasing. INSUFFICIENCIES: The morbidity and mortality with dialysis is dominated by cardiac and vascular causes. Renal transplantation has stagnated; the waiting lists increase and donations are insufficient. Conversely, transplantation survival is progressing. In a second part, we will examine the elements of health strategy necessary to adapt the supply of care and the organization of preventive measures.
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PMID:[Epidemiology of care demands]. 1186 26

Diabetes mellitus has reached epidemic proportions worldwide as we enter the new millennium. The World Health Organization (WHO) has commented there is 'an apparent epidemic of diabetes which is strongly related to lifestyle and economic change'. Over the next decade the projected number will exceed 200 million, possibly reaching 250 million persons. Most will have type 2 diabetes and all are at risk of the development of complications. Better education, improved nutrition, more exercise, early diagnosis and prompt treatment are imperative. Diabetes is a serious disease, subject to the development of many complications affecting large vessels (heart, cerebral and peripheral), small vessels (kidney and retina), nerves and other organs. In type 2 diabetes these complications may precede diagnosis of the disease by many years. The process continues inexorably, with premature mortality and morbidity mainly from the development of vascular disease. Data from the WHO confirm the principal role of non-communicable disease on mortality in developed countries, while mortality in developing countries is rising rapidly, now often exceeding communicable disease. The non-communicable diseases are divided into cancer and degenerative diseases. In the developed world, degenerative diseases are grouped to include ischaemic heart disease, stroke, renal failure, hypertension and other macro- and microvascular diseases. The major complications of diabetes encountered most frequently and with the greatest impact are: 1. Neuropathy, both peripheral and autonomic, with principal manifestations in the lower limbs 2. Microvascular disease, mainly affecting the retina and kidney, resulting in blindness and renal failure 3. Macrovascular disease, presenting with atherosclerosis in the coronary arteries causing ischaemic heart disease, cerebrovascular disease causing stroke and peripheral vascular disease contributing to diabetic gangrene.
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PMID:The economic burden of insulin resistance. 1196 27

Overexpression of the renin-angiotensin system is important in the pathogenesis of macroangiopathy (MA). Patients with diabetes with end-stage renal failure have elevated serum angiotensin-converting enzyme (ACE) activity compared with their nonuremic counterparts. Because their major cause of death is MA, the significance of serum ACE activity on outcome of this group of patients is studied. We performed a prospective cohort study of 49 patients with type 2 diabetes on continuous ambulatory peritoneal dialysis (CAPD) therapy. Baseline serum ACE activity was determined by a modified spectrophotometric method and followed up at a median of 34 months. The prevalence of MA (defined as ischemic heart disease, sudden cardiac arrest, stroke, or peripheral vascular disease) and all-cause mortality rates were studied. Risk for MA is associated with serum ACE activity (median with MA, 69.0 U/L [range, 46.0 to 100.1 U/L] versus without MA, 57.2 U/L [range, 36.3 to 81.0 U/L]; P = 0.02). At the end of follow-up, 48% of patients (24 of 49 patients) died, 70% of MA. The group that died had increased baseline serum ACE activity (nonsurvivors, 65.0 U/L [range, 33.5 to 100.0 U/L] versus survivors, 49.4 U/L [range, 36.4 to 86.5 U/L]; P < 0.05) and MA rates (nonsurvivors, 77% versus survivors, 36%; P < 0.01). Cox regression analysis performed with age, sex, mean blood pressure, body mass index, metabolic control, Kt/V, residual renal function, serum albumin level, and ACE activity showed that baseline serum ACE activity (P = 0.033) is an independent predictor for mortality in patients with type 2 diabetes on CAPD therapy. Among patients with type 2 diabetes on CAPD therapy, serum ACE activity is associated with risk for MA and is an independent predictor for mortality. Whether ACE inhibition will have a beneficial effect on the outcome of these patients needs further investigation.
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PMID:Prognostic role of serum ACE activity on outcome of type 2 diabetic patients on chronic ambulatory peritoneal dialysis. 1197 50

There is a unique relationship between the kidney and blood pressure (BP): on the one hand, renal dysfunction and particularly renal disease cause an increase in BP, while on the other hand, high BP accelerates loss of function of the diseased kidney. Transplantation studies, both in experimental animals and humans, documented that "blood pressure goes with the kidney," a normotensive recipient of a kidney genetically programmed for hypertension (HT) will develop HT, while conversely hypertensive patients with renal failure receiving the kidney of a normotensive donor may develop normotension. Family studies showed higher BP values and more frequent HT in first degree relatives of patients with primary glomerulonephritis or diabetic nephropathy, both type 1 and type 2. The notion that HT accelerates the loss of renal function has been proposed at the turn of the century, but definite evidence by observational and interventional studies has only been provided in the last two decades. The issue has been much confounded by the mistaken believe that damaged kidneys require higher BP values in order to function properly. The mechanisms of BP increase in renal disease comprise: salt retention, inappropriate activity of the renin-angiotensin system (RAS) and of the sympathetic nerve system as well as impaired endothelial cell-mediated vasodilatation. There is ample evidence both in primary renal disease (AIPRI and REIN trials) and in nephropathy of type 1 and type 2 diabetes (IDNT, RENAAL) that pharmacological blockade of the RAS by angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers has BP-independent renoprotective effects. More recently, it has also been shown that blockade of the sympathetic nerve system has BP-independent effects on albuminuria and on glomerulosclerosis.
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PMID:Kidney and hypertension. 1198 15

Mutations in the hepatocyte nuclear factor - 1 beta (HNF-1 beta) gene cause maturity onset diabetes of the young type 5 (MODY 5). A clinical feature of the resulting phenotype besides impaired glucose tolerance is a variety of renal abnormalities, ranging from renal cysts to end-stage renal failure. Using a candidate gene approach we investigated the prevalence of mutations in the HNF-1 beta gene in a group of 63 patients from two different European populations (33 Germans, 30 Czechs) with type 2 diabetes mellitus and diabetic nephropathy diagnosed by increased albuminuria (39 patients) or end-stage renal failure (24 patients). No mutations were found in any of the 9 exons or in a minimal promoter region. Three intronic variants (single nucleotide polymorphisms - SNPs) were detected. The frequencies of these variants showed no difference between the two studied populations and were comparable to data reported from healthy subjects. No association between SNPs or formed haplotypes and any clinical parameters (like age of disease onset, BMI and severity of renal failure) was found. The results confirm that the genetic variations in the HNF-1 beta gene would be a very uncommon cause of progressive nephropathy in patients with type 2 diabetes mellitus.
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PMID:Mutations and intronic variants in the HNF-1 beta gene in a group of German and Czech Caucasians with type 2 diabetes mellitus and progressive diabetic nephropathy. 1201 76

Factors were studied that may initiate macroangiopathy or enhance or aggravate its pathogenesis in patients with type 2 diabetes mellitus. A total of 151 diabetics were compared with healthy controls (n=50); all patients and subjects were normotensive and without renal failure. Plasma endothelin-1 and free radical levels were measured. In addition, plasma prostacyclin levels were assessed by assaying its stable, spontaneous, breakdown product 6-keto-prostaglandin-F1a. Diabetics were divided into three groups: those with clinically evident macroangiopathy and those with early or without atherosclerosis (as determined by the carotid intima-media thickness. Plasma endothelin-1 levels were increased in all diabetics with atherosclerosis. Plasma free radical levels were increased in diabetics with macroangiopathy when compared with control subjects. The plasma levels of 6-keto-prostaglandin-F1a were slightly, but significantly, decreased in the diabetics with macroangiopathy when compared with control subjects. The carotid intima-media thickness was significantly greater in diabetics without macroangiopathy when compared with the controls. Furthermore, the intima-media thickness increased significantly in this group of diabetics but not in the controls over a 30-month follow-up period. Several factors may contribute to atherogenesis in diabetics. These include increased plasma endothelin-1 and free radical levels as well as a deficiency of prostacyclin. These factors may become targets for intervention as well as markers of disease progression.
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PMID:Carotid atherosclerosis in type 2 diabetes mellitus: potential role of endothelin-1, lipoperoxides, and prostacyclin. 1202 15

Diabetes is the leading cause of blindness, end-stage renal failure, non-traumatic limb amputations, and cardiovascular morbidity and mortality. The vast majority of patients with diabetes receive routine care from primary care providers who are not endocrinologists. Primary care providers, including internists, family practice physicians, and physician extenders with advanced skills, face the important task of implementing standards of care recommendations for persons with diabetes. These recommendations draw upon an emerging body of compelling evidence regarding the prevention and management diabetes and its complications. The challenge of diabetes must be tackled on three fronts: Primary prevention, secondary prevention (of diabetes complications), and tertiary prevention (of morbidity and mortality from established complications). There is now abundant evidence that type 2 diabetes, which accounts for greater than 90% of diabetes world-wide, is preventable. Moreover, the complications of diabetes are preventable by a policy of tight glycemic control and comprehensive risk reduction. Even after complications have set in, intensive glucose control dramatically reduces the risk of progression of complications. The challenge, therefore, is the identification of strategies that enable translation of existing scientific data to pragmatic benefits. This article proposes 10 strategies for preventing or reducing diabetes-related morbidity and mortality at the primary care level. These strategies include provider education; patient empowerment through promotion of lifestyle and self-care practices; surveillance for microvascular complications; cardiovascular risk reduction; efficient use of medications; goal setting; and stratification of patients and triaging of those with poor glycemic control for more intensive management.
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PMID:Preventing diabetes-related morbidity and mortality in the primary care setting. 1251 Jul 10

The Pro12Ala polymorphism of the gene encoding the peroxisome proliferator-activated receptor (PPAR)-gamma2 has recently been shown to be associated with type 2 diabetes. In the present analysis, we investigated whether PPAR-gamma2 Pro12Ala was associated with microvascular complications of type 2 diabetes, such as albuminuria, end-stage renal failure (ESRF), or retinopathy. A total of 445 patients with type 2 diabetes who were enrolled in the Berlin Diabetes Mellitus Study and in whom we determined albuminuria and the presence of ESRF and retinopathy were genotyped for the PPAR-gamma2 Pro12Ala polymorphism. We also measured potentially important covariables, such as blood pressure, BMI, duration of diabetes, glycosylated hemoglobin, serum creatinine, and serum lipids. Among 445 patients with type 2 diabetes (mean age 59.3 years), the Pro12Ala genotype distribution was in Hardy-Weinberg equilibrium (P = 0.42). The Ala12 allele frequency was 0.14. With adjustment for covariables, the 118 Ala12 allele carriers had significantly lower urinary albumin excretion (UAE) than the 327 noncarriers (17.1 vs. 25.8 mg/d; P = 0.01). The percentage decrease in UAE observed in PPAR-gamma Ala12 allele carriers relative to noncarriers (P = 0.003) rose from 0.2% (P = 0.99) to 54% (P = 0.008) and to 70% (P = 0.01) when the duration of diabetes increased from <10 years to 10-19 years and to >or=20 years, respectively. Similarly, the odds ratios of having albuminuria decreased from 1.22 (P = 0.54) to 0.61 (P = 0.23) and to 0.11 (P = 0.007), respectively. Among patients with type 2 diabetes, PPAR-gamma2 Ala12 allele carriers had significantly lower UAE and tended to develop overt proteinuria less frequently. These observations suggest a protective effect of the Ala12 allele in relation to diabetic nephropathy.
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PMID:Peroxisome proliferator-activated receptor-gamma2 polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes: The Berlin Diabetes Mellitus (BeDiaM) Study. 1214 84

The incidence of end-stage renal disease (ESRD) in the US is rising at an alarming rate, with the largest increase among African-American populations. The key risk factors for kidney disease are hypertension and diabetes, which are both becoming more prevalent in the US, and particularly in African Americans. Although African Americans make up 12.6% of the US population, the incidence of diabetes-related ESRD is four times higher than for whites, and the prevalence of ESRD due to hypertension is twice that of white patients. Approximately 30 to 40% of all patients with diabetes will develop nephropathy and many will progress to ESRD, necessitating dialysis or kidney transplantation. Recent studies in patients with type 2 diabetes indicate a significant delay in progression or development of diabetic nephropathy following blockade of the renin-angiotensin-aldosterone system with the use of angiotensin receptor antagonists. Early intervention in patients with hypertension is necessary to prevent kidney damage, and data from the African American Study of Kidney Disease and Hypertension suggest that angiotensin-converting enzyme inhibitors are effective in this population. Although African-American patients receiving hemodialysis appear to have increased survival compared with whites, racial factors and poor access to medical care contribute to the increased risk of kidney disease in minorities. A concerted effort is necessary to raise awareness in minority populations and provide strategies for prevention and early treatment thereby attenuating the increasing prevalence of kidney failure in these groups.
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PMID:Diabetes mellitus and hypertension: key risk factors for kidney disease. 1215 17


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