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Query: UMLS:C0011860 (type 2 diabetes)
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Placebo-controlled clinical trials have shown that atorvastatin is beneficial in patients with myocardial ischemia, established coronary artery disease, hypertension and 3 other cardiovascular risk factors (e.g. left-ventricular hypertrophy, type 2 diabetes, smoking), and in diabetes, but not in patients with calcific aortic stenosis. Recently, intensive low density lipoprotein (LDL)-cholesterol lowering with atorvastatin 80 mg/day has been shown to have a greater clinical benefit than atorvastatin 10 mg/day in patients with coronary heart disease and one other high-risk factor (previous myocardial infarction, coronary revascularization or angina), and to be superior to moderate lipid lowering with pravastatin (40 mg/day) in patients with an acute coronary syndrome. However, a smaller study comparing lovastatin 5 mg/day with atorvastatin 80 mg/day was unable to detect any difference in outcomes in patients with stable coronary disease, despite the greater LDL-cholesterol lowering with the atorvastatin, possibly because it was not powered to do so. In a retrospective cohort study, atorvastatin 10 mg/day, pravastatin 20 mg/day, simvastatin 20 mg/day, lovastatin 20 mg/day and fluvastatin 20 mg/day had similar efficacy as secondary prevention after acute myocardial infarction. At present, the evidence from clinical trials is favouring the intensity of the effect on LDL-cholesterol and/or C-reactive protein (CRP) with atorvastatin 80 mg, rather than the use of atorvastatin per se, when greater benefits are observed with the 80 mg dose of atorvastatin compared to other statins. Thus, at present, it is not clear whether atorvastatin is superior to other statins in some indications (coronary heart disease, acute coronary syndromes) or whether it is the intensive lipid lowering that is responsible for the superiority. Atorvastatin has little or no ability to increase high density lipoprotein (HDL)-cholesterol, and this may be a disadvantage in patients with metabolic syndrome or diabetes, where low HDL-cholesterol is a key feature. Thus, other statins should probably be preferred to atorvastatin in patients with diabetes/metabolic syndrome. Alternatively, atorvastatin can be used in combination with a fibrate to increase HDL-cholesterol in patients with diabetes/metabolic syndrome.
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PMID:Is atorvastatin superior to other statins? Analysis of the clinical trials with atorvastatin having cardiovascular endpoints. 1847 65

Type 2 diabetes mellitus (DM) is associated with increased risk for developing heart failure (HF) and worse outcomes once HF is present. While the exact mechanisms underpinning these observations remain poorly understood, several metabolic perturbations associated with DM have been implicated as contributors to the HF risk, including alterations of cardiomyocyte metabolic substrate switching between free fatty acid (FFA) and glucose metabolism; increased FFA exposure and cellular accumulation; and alterations in peroxisome proliferator-activated receptor-(PPAR-)alpha activity, among others. The commonly coincident conditions of left ventricular hypertrophy and ischemic heart disease likely confound the metabolic derangements further increasing HF risk. Continued investigation into these mechanistic connections is necessary to better understand the pathophysiology and ideally inform the pursuit of novel therapeutic targets and strategies to intervene on the HF associated with DM.
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PMID:Cardiomyopathy in type 2 diabetes: update on pathophysiological mechanisms. 1856 12

This study was conducted to find out the prevalence of hypertension in newly diagnosed patients with type 2 diabetes mellitus. Five hundred patients (229 men and 271 women) with type 2 diabetes mellitus diagnosed in the last 6 months were evaluated for hypertension and presence of various diabetes related complications. Overall 42% (210/500) of the patients had hypertension; more women (46.1%) than men (37.1%) were affected. Patients with hypertension were older, had higher body mass index and plasma triglyceride levels, and evidence of ventricular hypertrophy on electrocardiogram. Female sex, higher age, family history of hypertension or diabetes, history of neuropathic pains, higher body mass index, presence of albuminuria, dyslipidaemia or cardiac hypertrophy were found to affect prevalence of hypertension in newly diagnosed patients with type 2 diabetes mellitus.
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PMID:Prevalence of hypertension in patients with new onset type 2 diabetes mellitus. 1870 51

TREATMENT OF ARTERIAL HYPERTENSION - Blood pressure (BP) should be regularly measured in all patients with CKD (Strength of Recommendation C). - BP control and proteinuria reduction delay progression of CKD (Strength of Recommendation A) and reduce cardiovascular risk (Strength of Recommendation C). Thus, control of both factors should be the treatment objective. - The BP target in patients with CKD should be < 130/80 mmHg, and 125/75 mmHg if proteinuria is > 1 g/24 hours (Strength of Recommendation A). - Lifestyle changes should be made: low-sodium diet (less than 100 mEq/day of sodium or 2.4 g/day of salt); weight reduction if patient is overweight (body mass index 20-25 kg/m2); regular aerobic physical exercise and moderate alcohol intake for BP control and prevention of cardiovascular risk (Strength of Recommendation A). - The choice of the antihypertensive drug in patients with CKD depends on the etiology of CKD, cardiovascular risk, or presence of clinical or subclinical cardiovascular disease (Strength of Recommendation A). - Two or more antihypertensive drugs are usually required to control blood pressure in patients with CKD (Strength of Recommendation B), and will frequently include a diuretic, which in stages 4-5 should be a loop diuretic (Strength of Recommendation B). - Renin-angiotensin-aldosterone system (RAAS) inhibitors are first choice drugs in patients with diabetic nephropathy, patients with non-diabetic nephropathy with a protein/creatinine ratio higher than 200 mg/g, and patients with heart failure (Strength of Recommendation A). The combination of ACEIs and ARBs is indicated for reducing proteinuria that remains high despite treatment with a RAAS inhibitor, provided potassium levels do not exceed 5.5 mEq/L (Strength of Recommendation B). - When RAAS blockers are started or their dose is changed in patients with advanced CKD, kidney function and serum potassium levels should be monitored at least after 1-2 weeks. DIAGNOSIS AND TREATMENT OF DYSLIPIDEMIA - A complete evaluation of the lipid profile including total cholesterol, LDL-C, HDL-C, and triglycerides should be performed in any patient with CKD at baseline and at least annually (Strength of Recommendation B). - In patients with stage 4-5 CKD and LDL-C >or= 100 mg/dL, treatment to decrease levels to < 100 mg/dL should be considered because of their high CV risk. This reduction is recommended in secondary prevention and in primary prevention in diabetic patients. Lipid-lowering treatment is recommended in all other patients, although no evidence showing its benefits is available yet (Strength of Recommendation C). - In patients with stage 4-5 CKD and triglyceride levels >or= 500 mg/dL which are not corrected by treating the underlying cases, treatment with triglyceride-lowering drugs may be considered to reduce the risk of pancreatitis. However, treatment with fibrates should be used with caution, and these drugs should not be associated to statins due to the risk of rhabdomyolysis (Strength of Recommendation C). There is little experience on the efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in patients with grade 4-5 CRF, but they may be considered a possibly safer alternative to fibrates (Strength of Recommendation C). SMOKING - Smoking is a cardiovascular risk factor and a risk factor for progression of kidney disease in patients with CRF (Strength of Recommendation B). - Use of active measures to achieve smoking cessation is recommended in patients with CRF (Strength of Recommendation C). HOMOCYSTEINE - Hyperhomocysteinemia has been postulated as a cardiovascular risk factor in the general population and in kidney patients, but the available evidence is not consistent. - There is no evidence that vitamin therapy decreases cardiovascular risk in patients with CRF, and recommendation of routine vitamin measurement and start of vitamin therapy to reduce cardiovascular risk in these patients is therefore questionable (Strength of Recommendation B). LEFT VENTRICULAR HYPERTROPHY - Left ventricular hypertrophy (LVH) is a cardiovascular risk factor in patients with CRF (Strength of Recommendation B). - It is advisable to perform an echocardiogram at baseline and every 12-24 months and to consider treatments allowing for LVH regression (Strength of Recommendation C). The approach to LVH should be early and multifactorial because its reversibility is limited once established (Strength of Recommendation C). - RAAS blockade with ACEIs or ARBs partially reverts LVH in patients with CRF (Strength of Recommendation B). ANTI-PLATELET AGGREGATION - Because of the high cardiovascular risk in patients with CKD, anti-platelet aggregant therapy, especially low-dose aspirin, would be indicated in patients with type 2 diabetes as primary prevention, and in all patients with CKD as secondary prevention. There is however no evidence of the benefits of anti-platelet aggregant therapy in primary prevention in patients with CKD, particularly in stages 4-5; indication for treatment in this situation should therefore be individualised because of its greater risk of bleeding. - Adequate good blood pressure control should previously be achieved to minimise the risk of haemorrhagic stroke (Strength of Recommendation C).
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PMID:[Arterial hypertension and dyslipidemia in patients with chronic kidney disease (CKD). Anti-platelet aggregation. Goal oriented treatment]. 1901 37

To investigate the value of ultrasound speckle tracking imaging (STI) in the assessment of the short-axis and long-axis systolic function of the left ventricle (LV) in patients with type 2 diabetes mellitus (DM), 100 subjects with normal ejection fraction were studied, including 41 patients with DM only (DM group), 22 patients with both DM and left ventricular hypertrophy (DH group), and 37 healthy subjects (control group). Left ventricle systolic function in the long axis defined as longitudinal strain, and that in the short axis defined as radial strain, apical and basal LV rotations, and LV twist were assessed respectively. The results showed that average peak strain in the long axis at basal, middle and apical levels, and global peak strain were significantly decreased in the patient groups when compared with the control group (P<0.001 for each). The parameters in DH group were significantly lower than those in DM group (P<0.01 for each). There were no significant differences in average radial peak strain in the short axis at different levels, and global peak strain among the three groups (P>0.05). Apical and basal LV rotations, and LV twist were greater in the patient groups than in the control group (P<0.01 for each). Basal LV rotation and LV twist were greater in DH group than those in DM group (P<0.01). It was concluded that STI may be used to identify early abnormalities in patients with type 2 DM that have normal left ventricular systolic function.
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PMID:Ultrasound speckle tracking imaging contributes to early diagnosis of impaired left ventricular systolic function in patients with type 2 diabetes mellitus. 1910 75

Various guidelines for hypertension specify that the target blood pressure (BP) should be below 140/90 mm Hg and that strict control is recommended for patients with cardiovascular risk factors. We examined the relationship between the achieved BP and the incidence of cardiovascular events in hypertensive patients with complications as a sub-analysis of the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial. A total of 4703 patients were evaluated for efficacy in the CASE-J trial. In this sub-analysis, 4553 patients had at least one follow-up visit without any cardiovascular events. We examined the relationship between the achieved BP and cardiovascular events in hypertensive patients with type II diabetes mellitus (DM), chronic kidney disease (CKD) or left ventricular hypertrophy (LVH) at baseline. Possible baseline confounders were adjusted by using the multiple Cox regression model. A higher achieved BP was associated with an increased risk of cardiovascular events in hypertensive patients with complications (DM, CKD or LVH). In patients with LVH, who achieved systolic/diastolic BP (SBP/DBP) <130/75-79 mm Hg, the risk of cardiovascular events was reduced to the same level of SBP/DBP <130/75-79 mm Hg in those without LVH. However, the risks of cardiovascular events in patients with DM or CKD, who achieved SBP/DBP <130/75-79 mm Hg, were still significantly higher than in those without DM or CKD. In conclusion, this study extended the significance of BP control in hypertensive patients especially with complications. Further investigation in a large-scale clinical trial is needed to determine the optimal target BP for LVH patients.
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PMID:Relationship between the achieved blood pressure and the incidence of cardiovascular events in Japanese hypertensive patients with complications: a sub-analysis of the CASE-J trial. 1934 33

Blood pressure (BP) is one of the most important and common vascular risk factors but it is often poorly controlled. Inhibition of the renin-angiotensin-aldosterone system (RAAS) provides beneficial effects in hypertensives. The association of low-dosed diuretics in combination with RAAS blocking agents allows maximum benefit from potassium depletion and control of compensatory increase in renin secretion, so increasing the efficacy and safety of RAAS blockers. Irbesartan is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy. Once-daily irbesartan administration provides 24h control of BP. In patients with mild-to-moderate hypertension, irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than losartan and valsartan in terms of absolute reduction in BP and response rate. Irbesartan also induced regression of left ventricular hypertrophy. Moreover, irbesartan 300 mg/day exerts a significant renoprotective effect in hypertensive type 2 diabetic patients. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo. Irbesartan was also effective in non-diabetic nephropatic patients. Moreover, irbesartan has peroxisome proliferator-activated receptor agonistic effects in in vitro studies, and it also demonstrated beneficial effects on inflammatory markers of atherosclerosis and endothelial function. The overall incidence of adverse events is similar to that of placebo. A fixed dose of hydrochlorothiazide (HCTZ) and irbesartan shows additive antihypertensive effect in a dose dependent manner up to HCTZ 25 mg and irbesartan 300 mg with high tolerability in diverse patient groups. Combination effects on end organ protection must be evaluated by broad spectrum studies. Ongoing trials about irbesartan and its combination with diuretics may provide necessary data to interpret the value of this association among others.
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PMID:Irbesartan and hydrochlorothiazide association in the treatment of hypertension. 1986 79

Obesity, especially upper body fat distribution, has become an increasingly important medical problem in children and adolescents. Outcomes related to childhood obesity include, as in adult population, hypertension, type 2 diabetes mellitus, dyslipidemia, left ventricular hypertrophy, obstructive sleep apnea, orthopedic and socio-psychological problems. Obese children are at approximately 3-fold higher risk for hypertension from non-obese ones. Obesity-hypertension appears to be characterized by a preponderance of isolated systolic hypertension, increased heart rate and blood pressure variability, increased levels of plasma catecholamine and aldosterone, and salt-sensitivity. Lifestyle changes of weight loss, healthier diet and regular physical exercise are effective in obesity-hypertension control, though pharmacological treatment is frequently necessary. Screening for dyslipidemia and impaired glucose tolerance should be performed in paediatric patients with obese hypertension on regular basis, at least once annually or semiannually to discover metabolic syndrome and to prevent its increased cardiovascular risk. Of course, prevention of obesity is the primary goal.
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PMID:[Hypertension in obese children and adolescents]. 1937 Sep 74

Cardiovascular disease is responsible for 70% of all mortality among patients with type 2 diabetes and is also a major contributor to diabetes-related healthcare costs. The ADVANCE trial clearly demonstrated that a simple and easily applicable pharmacological strategy based on perindopril/indapamide fixed combination could substantially reduce total and cardiovascular mortality (-14% and -18%, respectively). The observed benefits were largely caused by a substantial decrease in systolic blood pressure (SBP), confirming the need to have ambitious therapeutic goals in such high-risk patients. This point is of importance because most of the patients included in the trial were being treated for hypertension, and baseline brachial SBP and diastolic blood pressure at inclusion were very close to normal. Previous mechanistic studies have highlighted the positive effect of perindopril/indapamide fixed combination on large artery function as well as on microvascular structure. For example, in the REASON trial, in patients treated with perindopril/indapamide, the decrease in central aortic SBP, which closely correlated with the decrease in left ventricular hypertrophy, reflected a significant improvement in large artery function and a changing pattern in both peripheral reflection coefficients and structural arteriolar network. These data are supported by those from other studies, which show increases in coronary blood flow reserve with perindopril/indapamide treatment. In conclusion, normalization of SBP, pulse pressure, arterial function and myocardial perfusion, a haemodynamic profile known to improve survival in the hypertensive populations at high cardiovascular risk, seems to be more easily achieved when a strategy based on the perindopril/indapamide combination is applied.
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PMID:Heart protection: a key target in the management of patients with diabetes. 1948 6

Aliskiren is the first direct renin inhibitor for the treatment of hypertension. Clinical experience from studies in over 14,000 patients has shown that aliskiren, alone or in combination with other antihypertensive therapies, provides effective blood pressure lowering with a good safety and tolerability profile.The ultimate aim of antihypertensive therapy, however, is to reduce the risk of adverse cardiovascular and renal outcomes.The effect of aliskiren on surrogate markers of organ damage and clinical outcomes is being assessed in the ongoing ASPIRE HIGHER programme, the largest clinical trials programme in the cardio-renal disease area. Results from the ALOFT, AVOID and ALLAY studies suggest that aliskiren has positive effects on markers of cardiovascular and renal damage in patients with type 2 diabetes and nephropathy, heart failure and left ventricular hypertrophy.ASPIRE HIGHER also includes four large-scale studies assessing the potential outcome benefits of aliskiren, and the results of these trials will help define the clinical utility of aliskiren in the treatment of cardiovascular and renal diseases. In this article, we review the antihypertensive efficacy of aliskiren and explore its potential in the management of cardiovascular and renal risk.
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PMID:Managing cardiovascular and renal risk: the potential of direct renin inhibition. 1950 53

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