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 this study was to assess the prevalence of long-term complications in a large sample of French NIDDM patients. Therefore, 427 NIDDM patients 35-74 years old were recruited in ten centers. Standardized clinical criteria and central reading for retinal and electrocardiographic changes were used to assess the presence of complications. The prevalence rates of complications were 29.7% and 3.3% for background and proliferative retinopathy; 21.8%, 6.1%, and 2.8% for microalbuminuria, proteinuria, and renal insufficiency; 19.9 and 11.7% for asymptomatic and symptomatic pheripheral neuropathy; 8.2% for orthostatic hypotension; 10.1% and 8.4% for angina pectoris and myocardial infarction; and 13.1% and 6.3% for mild and moderate to severe peripheral vascular disease, respectively. In conclusion, prevalence rates in this study were lower than in most studies from other countries.
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PMID:Low prevalence of long-term complications in non-insulin-dependent diabetes mellitus in France: a multicenter study. CODIAB-INSERM-ZENECA Pharma Study Group. 955 86

The prevalence of abnormally elevated albumin excretion rate (> 30 mg/24 h) is approximately 40% in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. Diabetes has become the leading cause of end-stage renal failure in the US, Japan and Europe. Approximately 90% of the direct and indirect cost of caring for diabetic patients are spent on the complications of diabetes. Identification of patients at high risk of developing diabetic nephropathy is possible by screening for microalbuminuria (30-300 mg/24 h). Elevated urinary albumin excretion rate indicates a substantially increased mortality risk in diabetic patients. Randomised controlled trials in normotensive IDDM and NIDDM patients with persistent microalbuminuria indicate that ACE inhibitors diminish urinary albumin excretion rate, postpone it and may even prevent progression to clinical overt nephropathy. These findings indicate that screening and intervention programs are likely to have life saving effects and lead to considerable economic savings. Systemic blood pressure elevation to a hypertensive level is an early and frequent phenomenon in diabetic nephropathy. Furthermore, nocturnal blood pressure elevation (non-dippers) occurs more frequently in patients with nephropathy. Systemic blood pressure elevation and to a lesser degree albuminuria accelerate the progression of diabetic nephropathy. Effective blood pressure reduction with non-ACE-inhibitors and/or ACE-inhibitors frequently in combination with diuretics: (a) reduces albuminuria; (b) delays the progression of nephropathy; (c) postpones renal insufficiency; and (d) improves survival in IDDM and NIDDM patients with diabetic nephropathy. A specific renal protective effect of ACE-inhibitors in diabetic nephropathy has been demonstrated in IDDM patients with moderately reduced kidney function (s-creatinine > 133 mumol/l) while the data conflict with NIDDM patients. Antihypertensive treatment for diabetic nephropathy simultaneously extends life and saves money. Finally, reduced risk of fatal and non-fatal cardiovascular events have been demonstrated when diabetic patients with isolated systolic hypertension are treated with blood pressure lowering agents. Absolute risk reduction with active treatment compared to placebo was twice as great for the diabetic versus non-diabetic patients (101/1000 versus 51/1000 randomised participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. In conclusion, early detection and aggressive treatment of arterial hypertension with ACE-inhibitors, long acting calcium antagonist and low dose diuretics as first line drugs are highly warranted in diabetic patients with or without diabetic renal disease.
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PMID:Is antihypertensive treatment the same for NIDDM and IDDM patients? 964 59

The biological checkup of asymptomatic patients but presenting various risk factors is justified in the hope of detecting and correcting premorbid pathological abnormalities early and treating various silent but threatening diseases effectively. The author considers type 2 diabetes mellitus, hypercholesterolemia, thyroid diseases, renal insufficiency, prostate and colorectal cancer, sexually transmitted diseases, and prenatal work up.
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PMID:[Routine screening of asymptomatic patients at risk, without warning signs: a necessity]. 980 55

Diabetic nephropathy (DN) appears in about 30% of patients with type 1 diabetes (D1) and 15 to 60% of patients with type 2 diabetes (D2). It is preceded by microalbuminuria. Microalbuminuria is defined as an albumin excretion rate between 30 and 300 mg/24 h (on a 24-hour urine collection) or between 20 and 200 micrograms/min (on an overnight collection) in at least two out of three consecutive collections made within a 6-month period. Alternative screening techniques use either dipstick (Micral-Test II) or the albumin to creatinine ratio on an early morning urine sample (30-300 mg/g creatinine). Once persistent microalbuminuria is confirmed, 80% of type 1 diabetic patients and 20 to 50% of type 2 diabetic patients will progress to DN. In D2, microalbuminuria also represents a powerful predictor of early mortality from cardiovascular disease. Macroalbuminuria (AER > 300 mg/24 h, corresponding to a total protein excretion > 500 mg/24 h) will eventually lead to a end-stage renal insufficiency within 10 to 20 years. In D2, numerous patients will die from cardiovascular disease before reaching end-stage renal failure. Angiotensin-converting enzyme inhibitors can slow down the evolution toward DN when prescribed when microalbuminuria appears. Screening for microalbuminuria should therefore be a part of the annual clinical assessment in every diabetic patient.
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PMID:[How I evaluate...diabetic nephropathy. First part: micro- and macroalbuminuria]. 981 Feb 12

Protein alteration resulting from a nonenzymatic reaction between ambient glucose and primary amino groups on proteins to form glycated residues called Amadori products is termed the Maillard reaction. By dehydration and fragmentation reactions, Amadori products are transformed to stable covalent adducts called advanced glycosylation end products (AGEs). In diabetes, accelerated synthesis and tissue deposition of AGEs is proposed as a contributing mechanism in the pathogenesis of clinical complications. Uremia in diabetes is associated with both a high serum level of AGEs and accelerated macro- and microvasculopathy. Diabetic uremic patients accumulate advanced glycosylated end products in "toxic" amounts that are not decreased to normal by hemodialysis or peritoneal dialysis but fall sharply to within the normal range within 8 h of restoration of half-normal glomerular filtration by renal transplantation. It follows that the higher mortality of hemodialysis-treated diabetic patients compared with those given a renal transplant may relate, in part, to persistent AGE toxicity. Pharmacologic prevention of AGE formation is an attractive means of preempting diabetic microvascular complications because it bypasses the necessity of having to attain euglycemia, an often unattainable goal. Pimagidine (aminoguanidine) interferes with nonenzymatic glycosylation and reduces measured AGE levels leading to its investigation as a potential treatment. The mechanism by which pimagidine prevents renal, eye, nerve, and other microvascular complications in animal models of diabetes is under investigation. Separate multicenter clinical trials of pimagidine in type 1 and type 2 diabetes, where proteinuria is attributable to diabetic nephropathy, are in progress. The effect of treatment on the amount of proteinuria, progression of renal insufficiency, and the course of retinopathy will be monitored.
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PMID:Advanced glycosylated end products and hyperglycemia in the pathogenesis of diabetic complications. 1009 2

Recent epidemiological data have reaffirmed that elevated plasma triglyceride and low HDL-cholesterol levels are important risk factors for atherosclerotic vascular disease. The rationale for the clinical use of fibric acid derivatives, which are designed to correct this metabolic nexus, is now on firmer ground. The mechanism of action of fibrates on lipoprotein metabolism has recently been elucidated at the molecular level and involves the activation of peroxisome proliferator-activated receptor-alpha 1 in the liver, with the net effect of improving the plasma transport rates of several lipoproteins. Other potential anti-atherothrombotic effects include the inhibition of coagulation and enhancement of fibrinolysis, as well as the inhibition of inflammatory mediators involved in atherogenesis. These consequences probably underpin the favourable effects of fibrates seen in recent angiographic and clinical trials. Two important clinical trials on the effect of gemfibrozil (Veterans Administration-HDL-Cholesterol Intervention Trial) and bezafibrate (Bezafibrate Infarction Prevention Study) have recently been completed in subjects with elevated triglyceride, low HDL and normal or near-normal LDL-cholesterol levels. The results testify to the efficacy of these agents in decreasing the incidence of cardiovascular events, particularly in patients with multiple risk factors and plasma triglyceride levels of over 2.2 mmol/l. The findings of these trials are compared with the statin-based Air Force/Texas Coronary Atherosclerosis Prevention Study, with a recommendation that future studies in appropriately selected patients should examine the synergistic effect of the fibrate/statin combination. The absolute risk reduction in the incidence of coronary events in the Veterans Administration-HDL-Cholesterol Intervention Trial compares favourably with the statin trials. The therapeutic aspects of the efficacy and safety of fibrates are reviewed. Besides primary mixed hyperlipidaemias, particular indications for the clinical use of fibrates include type 2 diabetes, the metabolic syndrome and renal insufficiency. The St Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study has suggested that fibrates may decrease the incidence of coronary events in type 2 diabetes, but this hypothesis will be more extensively tested in the Diabetes Atherosclerosis Intervention Study, Fenofibrate in Event Lowering in Diabetes Study and Lipids in Diabetes Study projects. Although significant new knowledge has accrued over the past few years concerning the fundamental and clinical aspects of fibrates, the success of these agents in clinical practice depends on the availability of methods for assessing cardiovascular risk as well as on treatment guidelines, which as presently designed and recommended may be inaccurate and suboptimal.
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PMID:Fibrates, dyslipoproteinaemia and cardiovascular disease. 1068 50

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

Amadori-glycated albumin in diabetic nephropathy: Pathophysiologic connections. Nonenzymatic glycation of proteins represents a major mechanism by which hyperglycemia leads to diabetic renal disease. Recent research has shown that Amadori-modified albumin, the principal glycated protein in plasma, elicits pathobiologic effects in cultured renal cells that are identical to those of high ambient glucose. When added to the incubation media of glomerular mesangial and endothelial cells, glycated albumin stimulates protein kinase C (PKC) activity, increases transforming growth factor-beta (TGF-beta) bioactivity, and induces gene overexpression and enhanced production of extracellular matrix proteins. These cellular events, whereby PKC-mediated TGF-beta activation leads to increased matrix expression, are inextricably linked, and they form the central tenets of a pathophysiologic connection between glycated proteins and diabetic nephropathy. In vivo studies further corroborate the role of glycated proteins in the pathogenesis of diabetic nephropathy. Reduction or neutralization of glycated albumin in the db/db mouse model of type 2 diabetes significantly ameliorates the proteinuria, renal insufficiency, mesangial expansion, and overexpression of matrix proteins. In human type 1 diabetes, the plasma-glycated albumin concentration is independently associated with the presence of nephropathy. Abrogating the biologic effects of increased glycated albumin has novel therapeutic potential in the management of renal complications in diabetes.
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PMID:Amadori-glycated albumin in diabetic nephropathy: pathophysiologic connections. 1099 89

Activation of the renal transforming growth factor-beta (TGF-beta) system likely mediates the excess production of extracellular matrix in the diabetic kidney. To establish the role of the TGF-beta system in type 2 diabetic nephropathy, we examined the intrarenal localization and expression of the TGF-beta1 isoform, the TGF-beta type II receptor, and the Smad signaling pathway in the 16-week-old db/db mouse, a genetic model of type 2 diabetes that exhibits mesangial matrix expansion, glomerular basement membrane thickening, and renal insufficiency that closely resemble the human disease. Compared with its nondiabetic db/m littermate, the db/db mouse showed significantly increased TGF-beta1 mRNA expression by in situ hybridization in both glomerular and tubular compartments. Likewise, TGF-beta1 protein, by immunohistochemical staining, was increased in both renal compartments, but the fractional expression of TGF-beta1 protein was less than that of the mRNA in the glomerulus. In situ hybridization and immunohistochemical staining for the TGF-beta type II receptor revealed concordant and significant increases of both mRNA and protein in the glomerular and tubular compartments of diabetic animals. Finally, immunohistochemistry showed preferential accumulation of Smad3 in the nuclei of glomerular and tubular cells in diabetes. The complementary technique of Southwestern histochemistry using a labeled Smad-binding element demonstrated increased binding of nuclear proteins to Smad-binding element, indicating active signaling downstream of the TGF-beta stimulus. We therefore propose that the TGF-beta system is up-regulated at the ligand, receptor, and signaling levels throughout the renal cortex in this animal model of type 2 diabetes. Our findings suggest that the profibrotic effects of TGF-beta may underlie the progression to glomerulosclerosis and tubulointerstitial fibrosis that characterize diabetic nephropathy.
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PMID:Increased glomerular and tubular expression of transforming growth factor-beta1, its type II receptor, and activation of the Smad signaling pathway in the db/db mouse. 1133 63

Metformin is an oral hypoglycemic agent belonging to the class of biguanides that are commonly used in the treatment of type II diabetes mellitus. Lactic acidosis is a rare but severe adverse reaction that occurs primarily in patients with contraindications such as renal failure. The case of a 71-year-old woman with type II diabetes, in whom severe metformin-associated lactic acidosis was precipitated by acute renal failure in the absence of pre-existing chronic renal failure or other absolute contraindications to biguanide use, is presented. Aggressive correction of the acidosis and prolonged dialysis resulted in a favourable outcome despite severe acidosis. The present case report shows that metformin-associated lactic acidosis can occur in patients without pre-existing renal insufficiency. Metformin should be temporarily stopped when acute renal failure occurs or is anticipated.
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PMID:Metformin-associated lactic acidosis in a low risk patient. 1149 39


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