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)

Impaired renal function and albuminuria, common among people with type 2 diabetes, are strong predictors of atherosclerotic cardiovascular events. However, the relationships among albuminuria and measures of calcified atherosclerotic plaque are unknown. Coronary and carotid artery calcified plaque were measured using fast-gated helical computed tomography, and B-mode ultrasonography measured common carotid artery intima-medial thickness (IMT) in 588 white participants with type 2 diabetes from 325 families ascertained for the presence of multiple siblings with type 2 diabetes. Measured risk factors included age, gender, BP, body mass index, GFR, glycosylated hemoglobin, LDL cholesterol, HDL cholesterol, smoking, and medications that affect urine albumin:creatinine ratio (ACR). Generalized estimating equations with exchangeable correlation and the sandwich estimator of the variance were used to test for an association among coronary artery calcified plaque, carotid artery calcified plaque, carotid IMT, and ACR while adjusting for measured risk factors. Participants had a mean +/- SD (median) age of 61.2 +/- 9.2 yr (61.0 yr), ACR of 106.2 +/- 590 mg/g (12.9 mg/g), GFR of 93.3 +/- 33.2 ml/min (87.4 ml/min), coronary artery calcium mass score of 1394 +/- 2685 (323), carotid artery calcium mass score of 295 +/- 652 (51), and IMT of 0.66 +/- 0.12 mm (0.65 mm). Adjusting for the measured covariates, ACR was strongly and positively associated with coronary artery calcium (P = 0.004) and carotid artery calcium (P = 0.0004). Albuminuria is strongly associated with calcified plaque in the coronary and carotid arteries in white individuals with type 2 diabetes and relatively preserved renal function.
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PMID:Relationship between albuminuria and cardiovascular disease in Type 2 diabetes. 1594 32

We describe a case of a 58-year-old male with longstanding hypertension and Type 2 diabetes mellitus who developed sudden onset renal impairment. The first clue to the possible presence of amyloidosis in this case was provided by the radionuclide renal cortical scan performed with trivalent dimercapto succinic acid (Tc99m-DMSA-3), which revealed intense tracer uptake in the spleen suggesting amyloid deposit. Further workup to ascertain the cause of amyloidosis led to the diagnosis of multiple myeloma. We conclude that in cases of extra-renal or splenic accumulation of Tc99m-DMSA-3, a diagnosis of amyloidosis should be considered, in an appropriate clinical setting.
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PMID:Accumulation of Tc99m-DMSA-3 in the spleen in a case of multiple myeloma with associated amyloidosis. 1600 4

Proteinuria is a graded marker for kidney damage, as well as the risk for future cardiovascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) reduce urinary protein excretion and slow progression of renal impairment, independent of blood pressure lowering. Both the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction in Endpoints in NIDDM with the Angiotensin Antagonist Losartan (RENAAL) study were large, randomized, prospective studies in type 2 diabetic patients with proteinuria. There was no reduction in the incidence of myocardial infarction or stroke with the ARBs compared to placebo in either trial. A broader overview of clinical trials comparing ACEIs and ARBs with other antihypertensive drugs fails to show any substantive blood pressure-independent effects on stroke or myocardial infarction with these classes of drugs. Therefore, for cardiovascular end points (as opposed to renal end points), it may be more important that the blood pressure is reduced, rather than how the process is started.
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PMID:Antihypertensive, antiproteinuric therapy and myocardial infarction and stroke prevention. 1615 81

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

Metformin is an effective anti-hyperglycaemic and cardioprotective agent, but a long list of contraindications precludes millions of patients with type 2 diabetes from using it. This is largely due to the historical experience of lactic acidosis with phenformin, despite the fact that metformin does not predispose to this when compared with other therapies. Contraindications such as old age, renal impairment and cardiac insufficiency are increasingly disregarded in clinical practice, yet there is no evidence that the incidence of lactic acidosis has changed. Metformin has been shown to improve metabolic control without causing lactic acidosis in elderly patients with multiple comorbidities, including explicit contraindications, and its use in patients with type 2 diabetes over the age of 70 with mild renal impairment did not produce a clinically relevant increase in plasma lactate. There is no correlation between levels of metformin and lactate in patients with lactic acidosis, and its prognosis is mainly related to the causal hypoxic underlying disease and comorbidities. These findings raise doubts about the pathogenetic significance of metformin in lactic acidosis. We propose that advanced age per se, mild renal impairment and compensated heart failure can no longer be upheld as contraindications for metformin. A clear re-definition of contraindications to metformin will enable more physicians to prescribe within guidelines.
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PMID:Contraindications can damage your health--is metformin a case in point? 1656 48

Telmisartan (Micardis, Pritor), a highly selective angiotensin II (AII) type 1 (AT1) receptor antagonist, is approved for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents. The long elimination half-life of telmisartan ensures the drug provides effective reductions in blood pressure (BP) across the entire 24-hour dosage interval. Extensive evidence from well designed clinical trials and the clinical practice setting indicates that telmisartan, either as monotherapy or in combination with other antihypertensive agents, provides long-term antihypertensive efficacy and is well tolerated in a broad spectrum of hypertensive patients, including the elderly and those with coexisting type 2 diabetes mellitus, metabolic syndrome and/or renal impairment. Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 6 hours of this period. Independent of its effect on BP, telmisartan displays favourable effects on insulin resistance, lipid levels, left ventricular hypertrophy (LVH) and renal function. The consistent antihypertensive efficacy during the entire 24-hour dosage interval and sustained BP-lowering effect in the long term, combined with its favourable tolerability profile, mean that telmisartan is a valuable first-line treatment option for the management of essential hypertension.
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PMID:Telmisartan: a review of its use in the management of hypertension. 1639 68

For fear of lactic acidosis the currently listed contraindications to the use of metformin exclude a large number of people with type 2 diabetes from efficacious anti-hyperglycemic and cardioprotective treatment. Yet recent data call the traditional contraindications to metformin into question. As the incidence of lactic acidosis in patients with type 2 diabetes is the same with or without metformin therapy (about 9 per 100,000 patient years) there is no evidence that metformin therapy is associated with an increased risk of lactic acidosis. Similarly, despite disregard internationally of major metformin contraindications, there has been no corresponding increase in the incidence of lactic acidosis. Metformin treatment of elderly diabetics with multiple comorbidities and explicit contraindications has led to significantly better clinical parameters in them than in the control group without metformin; and there were no cases of lactic acidosis. The two groups did not differ with regard to progression of renal failure, patient-oriented endpoints or overall mortality. Compared with its predecessors phenformin and buformin, metformin is considerably less lipophilic and has a shorter plasma half-life; it is eliminated renally in unchanged form. In type 2 diabetics treated with metformin -- even those over 70 years of age and those in mild renal failure -- no relevant increases in lactate levels were found. In patients with lactic acidosis there was no correlation between the levels of metformin and lactate. The prognosis of lactic acidosis is determined less by the serum concentrations of metformin and lactate than by the hypoxia caused by the underlying disease and comorbidities. These findings raise doubts about the significance of metformin in the pathogenesis of lactic acidosis. On the basis of the current data, advanced age per se, mild renal impairment and stable heart failure can no longer be upheld as contraindications to the use of metformin. It should be safe to withdraw metformin the evening before radiological examinations with intravenous contrast media or surgical procedures under general anaesthesia in diabetics with normal renal function.
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PMID:[Traditional contraindications to the use of metformin -- more harmful than beneficial?]. 1641 51

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.
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PMID:Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. 1648 81

The metabolic syndrome, which is characterized by obesity, serum lipid profile alterations, hypertension, and fasting hyperglycemia, is very common in developed countries, and its prevalence is likely to increase. Chronic kidney disease (CKD) also has become a significant public health problem because it affects a considerable proportion of the adult population and is a major risk factor for cardiovascular disease and premature death. Although it is widely known that the metabolic syndrome is a major risk factor for the development of type 2 diabetes and cardiovascular disease, its precise relationship with the risk for renal impairment only recently has been clarified: Patients with the metabolic syndrome are at significantly higher risk for microalbuminuria and/or CKD, and the level of risk is related to the number of components of the syndrome itself. Although it is difficult to discriminate the detrimental renal effects of the metabolic syndrome from those of hypertension and impaired glucose metabolism, its other aspects (particularly obesity) may favor independently the development of renal abnormalities and may be considered new modifiable risk factors for CKD. These observations provide a rationale for intervention studies that aim to verify whether treating the many components of the metabolic syndrome can effectively prevent the development and progression of renal damage.
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PMID:Renal manifestations in the metabolic syndrome. 1656 54

Endothelial dysfunction, characterized by impaired nitric oxide activity, constitutes an early step in the pathogenesis of atherosclerotic disease. Prospective studies have shown that impaired endothelium-dependent vasorelaxation and the vasodilatory response of coronary arteries to acetylcholine predict cardiovascular events. Microalbuminuria and estimated glomerular filtration rate, which are both deeply influenced by renal nitric oxide activity, are predictors of cardiovascular outcome and total mortality but develop at a later stage of renal impairment. Endothelial dysfunction reflects early stage renal involvement in the atherosclerotic processes. The Telmisartan versus Ramipril in renal ENdothelium DYsfunction (TRENDY) trial examined endothelial function of the renal vasculature as a therapeutic target in patients with hypertension and type 2 diabetes, but without albuminuria. The rationale was that blockade of the renin-angiotensin system (RAS) is cardio- and renoprotective at later stages of the disease, but the impact of blockade of the RAS at earlier stages of disease is unknown. The results of TRENDY indicate that the endothelial function, as assessed by basal nitric oxide activity, can be improved after RAS blockade. These data complement the results of the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) trial, which demonstrated that telmisartan and enalapril similarly decelerate the progression of overt diabetic nephropathy. The results of TRENDY are in accordance with the observed changes in peripheral circulation. Endothelium-dependent vasorelaxation could be improved with angiotensin II receptor blockers, but not with diuretics or beta-blockers, in hypertensive patients. Intervention at the beginning of the renal and cardiovascular continuum offers the opportunity to prevent the fatal development towards renal and cardiac failure.
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PMID:Endothelial dysfunction: how can one intervene at the beginning of the cardiovascular continuum? 1660 59


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