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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II receptor blockers (ARBs) have been shown to decrease insulin resistance in obese diabetic animal models and reduce the risk of new-onset diabetes in hypertensive patients. In the present study, we studied whether candesartan, an ARB, can exert a direct effect against fatty acid-induced oxidative stress in pancreatic beta-cells. The effect of candesartan on lipotoxicity was evaluated using mouse insulin-secreting clonal cell, MIN6 and isolated mouse pancreatic islets. Intracellular insulin and triglyceride content, uncoupling protein-2 (UCP-2) mRNA expression, reactive oxygen species, protein kinase C (PKC) and NAD(P)H oxidase activity were examined. Candesartan recovered decreased insulin content in MIN6 exposed to 25mM glucose with 0.5mM palmitate (P<0.01). Candesartan tended to decrease intracellular triglyceride accumulation in cells exposed to 25mM glucose with 0.5mM palmitate. Palmitate-induced up-regulation of UCP-2 mRNA levels was suppressed by candesartan in a dose-dependent manner. Candesartan decreased palmitate-induced reactive oxygen species accumulation in MIN6 cells by 23% and in mouse islets by 59%. Candesartan also decreased palmitate-induced PKC activity by 21% and NAD(P)H oxidase activity by 37% in MIN6 cells. These findings indicated that candesartan attenuated fatty acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells.
Diabetes Res Clin Pract 2010 Oct
PMID:Candesartan attenuates fatty acid-induced oxidative stress and NAD(P)H oxidase activity in pancreatic beta-cells. 2066 13

The prevalence of proteinuria in patients presenting acutely with oedema due to heart failure has not been studied extensively. Recent evidence from the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) trial suggests that there is a high prevalence of albuminuria in chronic heart failure patients. We set out to investigate the prevalence of proteinuria in patients presenting with fluid retention secondary to heart failure. A random collection of urine albumin-creatinine ratios (ACRs) in successive patients was used to quantify proteinuria. Out of a sample of 19 patients, seven had no detectable albuminuria, eight had microalbuminuria and four had macroalbuminuria. We did not find any relation between urine ACR and age, serum urea or serum creatinine. Moreover, we did not find a higher prevalence of albuminuria with increasing age or the presence of diabetes mellitus. In conclusion, the clinical significance of this common finding in patients presenting with fluid retention is not clear, and further research is warranted to clarify its prognostic value.
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PMID:The prevalence of proteinuria in patients presenting with fluid retention due to heart failure. 2113 34

Merging data from existing electronic patient records, and electronic hospital discharge and cause of death registers, is a fast and relatively inexpensive method for comparing different treatments with regard to clinical outcome. This study compared the effects of antihypertensive treatment with candesartan or losartan on cardiovascular disease (CVD) using Swedish registers. Patients without previous CVD who were prescribed candesartan (n=7329) or losartan (n=6771) for hypertension during 1999-2007 at 72 Swedish primary care centers were followed for up to 9 years. Both medications were given according to current recommendations, and there was no difference observed in achieved blood pressures. The authors have previously shown that candesartan lowered the risk of all CVD (primary composite end point) more so than losartan (adjusted hazard ratio, 0.86; 95% confidence interval, 0.77-0.96). Candesartan also had a significantly better effect with regards to reducing the development of heart failure, cardiac arrhythmias, and peripheral arterial disease. In the present analysis, the authors found that candesartan, compared with losartan, reduced the risk of all CVD, irrespective of sex, age, previous antihypertensive treatment, baseline blood pressure, and presence of diabetes. These clinical findings may reflect differences between candesartan and losartan in their binding characteristics to the angiotensin type 1 receptor.
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PMID:Cardiovascular events in subgroups of patients during primary treatment of hypertension with candesartan or losartan. 2136 50

In the Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial, comparable efficacy was noted between candesartan and amlodipine in the incidence of cardiovascular (CV) morbidity and mortality during 3.2 years of follow up. Candesartan suppressed new-onset diabetes more effectively than amlodipine. In this observational study, we investigated whether or not the efficacy of the two drugs is sustainable for another 3 years beyond the experimental period of the CASE-J trial. Of the 4728 high-risk hypertensive patients initially enrolled in the CASE-J trial, 2232 agreed to further follow up. The primary endpoint was a composite of CV morbidity and mortality. The distribution of demographic characteristics for the 2232 patients in the CASE-J extension was similar to that in the initial 4703 patients in the CASE-J trial. Both drugs controlled blood pressure well over the relatively long period of time. The incidence of CV events was 15.5/1000 patient years in the candesartan group and 16.3/1000 patient years in the amlodipine group (Hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.77-1.18; P=0.650). The incidence of new-onset diabetes was significantly lower in the candesartan group (9.5/1000 patient years) than in the amlodipine group (13.3/1000 patient years), representing a 29% risk reduction for new-onset diabetes (HR=0.71, 95% CI=0.51-1.00, P=0.0495). In conclusion, candesartan and amlodipine showed comparable efficacy against CV events beyond the experimental period of the CASE-J trial in high-risk hypertensive patients. In addition, the effects of candesartan on new-onset diabetes observed during the CASE-J trial were sustained in the CASE-J extension. The CASE-J extension, which covered a 3-year extension of follow-up from the original trial, corroborated the results of the CASE-J trial.
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PMID:Long-term effects of candesartan and amlodipine on cardiovascular morbidity and mortality in Japanese high-risk hypertensive patients: the Candesartan Antihypertensive Survival Evaluation in Japan Extension Study (CASE-J Ex). 2183

We have shown previously that stimulation of the angiotensin II type 2 receptor (AT(2)R) results in nerve facilitation. In this study, we determined the capacity of candesartan to correct expression patterns characteristic of neuropathy and AT(2)R-mediated neurite outgrowth in the fructose-induced insulin-resistant rat, which is one of the human hyperinsulinemia models. Wistar rats received a 15% (w/v) fructose solution in their drinking water for 4 weeks (fructose-drinking rats [FDRs]), with or without candesartan (5 mg/kg/day). We evaluated physiological and behavioral parameters and performed immunohistochemical studies. We found that the FDR developed insulin resistance and downregulated both AT(2)R neuronal function and phosphorylated Akt expression in dorsal root ganglia (DRG) neurons. Candesartan improved neurite outgrowth in the FDR, which was associated with the restoration of AT(2)R and phosphorylated Akt expression. Furthermore, downregulation of phosphoinositide 3-kinase (PI3K) inhibited AT(2)R-mediated neurite outgrowth in control DRG cells. PI3K activation increased AT(2)R-mediated neurite outgrowth and phosphorylated Akt expression in FDR DRG cells. These results suggest that the decrease of AT(2)R-mediated neurite outgrowth in FDRs is likely to be the result of decreased PI3K-dependent Akt activation. Candesartan improved AT(2)R neuronal function and Akt phosphorylation, which were associated with sensory nerve defects and insulin sensitivity in the FDR.
Diabetes 2012 Apr
PMID:Candesartan cilexetil improves angiotensin II type 2 receptor-mediated neurite outgrowth via the PI3K-Akt pathway in fructose-induced insulin-resistant rats. 2235 59

The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial was conducted to compare the effects of the angiotensin II receptor blocker (ARB) candesartan and the calcium channel blocker (CCB) amlodipine on the incidence of cardiovascular events in Japanese high-risk hypertensive patients. The CASE-J Extension (CASE-J Ex) was an observational study designed to evaluate the long-term effects of ARB candesartan and CCB amlodipine, incorporating an additional 3-year follow-up of the CASE-J trial. As in the CASE-J trial, no statistically significant difference was observed in the incidence of primary cardiovascular events, all-cause mortality, or cardiovascular death between the two groups. The superiority of candesartan over amlodipine in reducing new-onset diabetes was sustained in the three-year-long CASE-J Ex, thereby corroborating the results of the CASE-J trial.
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PMID:[Clinical implications from the results of the CASE-J extension]. 2251 36

Examination of patients with reduced and preserved ejection fraction in the DIG (Digitalis Investigation Group) trials and the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) trials provides comparisons of outcomes in each of these types of heart failure. Comparison of the patients in these trials, along with the I-PRESERVE (Irbesartan in Heart Failure with Preserved Systolic Function Trial), with patients of similar age, sex distribution, and comorbidity in trials of hypertension, diabetes mellitus, angina pectoris, and atrial fibrillation provides even more interesting insights into the relation between phenotype and rates of death and heart failure hospitalization. The poor clinical outcomes in patients with heart failure and preserved ejection fraction do not seem easily explained on the basis of age, sex, comorbidity, blood pressure, or left ventricular structural remodeling but do seem to be explained by the presence of the syndrome of heart failure.
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PMID:What have we learned about patients with heart failure and preserved ejection fraction from DIG-PEF, CHARM-preserved, and I-PRESERVE? 2350 Feb 53

Increased angiotensin II (ANG II) or adenosine can potentiate each other in the regulation of renal hemodynamics and tubular function. Diabetes is characterized by hyperfiltration, yet the roles of ANG II and adenosine receptors for controlling baseline renal blood flow (RBF) or tubular Na(+) handling in diabetes is presently unknown. Accordingly, the changes in their functions were investigated in control and 2-wk streptozotocin-diabetic rats after intrarenal infusion of the ANG II AT1 receptor antagonist candesartan, the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or their combination. Compared with controls, the baseline blood pressure, RBF, and renal vascular resistance (RVR) were similar in diabetics, whereas the glomerular filtration rate (GFR) and filtration fraction (FF) were increased. Candesartan, DPCPX, or the combination increased RBF and decreased RVR similarly in all groups. In controls, the GFR was increased by DPCPX, but in diabetics, it was decreased by candesartan. The FF was decreased by candesartan and DPCPX, independently. DPCPX caused the most pronounced increase in fractional Na(+) excretion in both controls and diabetics, whereas candesartan or the combination only affected fractional Li(+) excretion in diabetics. These results suggest that RBF, via a unifying mechanism, and tubular function are under strict tonic control of both ANG II and adenosine in both control and diabetic kidneys. Furthermore, increased vascular AT1 receptor activity is a contribution to diabetes-induced hyperfiltration independent of any effect of adenosine A1 receptors.
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PMID:Angiotensin II contributes to glomerular hyperfiltration in diabetic rats independently of adenosine type I receptors. 2328 98

Circulating microRNAs (miRNAs) have emerged as novel biomarkers of diabetes. The current study focuses on the role of circulating miRNAs in patients with type 1 diabetes and their association with diabetic retinopathy. A total of 29 miRNAs were quantified in serum samples (n = 300) using a nested case-control study design in two prospective cohorts of the DIabetic REtinopathy Candesartan Trial (DIRECT): PROTECT-1 and PREVENT-1. The PREVENT-1 trial included patients without retinopathy at baseline; the PROTECT-1 trial included patients with nonproliferative retinopathy at baseline. Two miRNAs previously implicated in angiogenesis, miR-27b and miR-320a, were associated with incidence and with progression of retinopathy: the odds ratio per SD higher miR-27b was 0.57 (95% CI 0.40, 0.82; P = 0.002) in PREVENT-1, 0.78 (0.57, 1.07; P = 0.124) in PROTECT-1, and 0.67 (0.50, 0.92; P = 0.012) combined. The respective odds ratios for higher miR-320a were 1.57 (1.07, 2.31; P = 0.020), 1.43 (1.05, 1.94; P = 0.021), and 1.48 (1.17, 1.88; P = 0.001). Proteomics analyses in endothelial cells returned the antiangiogenic protein thrombospondin-1 as a common target of both miRNAs. Our study identifies two angiogenic miRNAs, miR-320a and miR-27b, as potential biomarkers for diabetic retinopathy.
Diabetes 2016 Jan
PMID:Angiogenic microRNAs Linked to Incidence and Progression of Diabetic Retinopathy in Type 1 Diabetes. 2669 37

Skin is constantly subjected to pressure at different levels. Pressure-induced vasodilation (PIV) is one of the response mechanisms to low pressure that maintains the homeostasis of the skin. PIV results from the interaction of primary afferent nerves and vascular endothelium of skin vessels. Thanks to this cutaneous neuro-vascular interaction, the cutaneous blood flow increase allows the maintenance of an optimal level of oxygenation and minimizes the lack of vascularization of the skin tissue under low pressure. It seems to be associated with the cutaneous protection mechanisms to prevent pressure ulcers. In some contexts, where microangiopathy and neuropathy can occur, such as aging and diabetes, PIV is impaired, leading to a dramatic early decrease in local skin blood flow when low pressure is applied. In aging, PIV alteration is due to endothelial dysfunction, essentially from an alteration of the nitric oxide pathway. In the inflamm-aging context, oxidative stress increases leading to endothelial cell and nerve damages. An age-related sensory neuropathy will exacerbate the alteration of PIV during the aging process. In diabetes, non-controlled hyperglycaemia leads to an increase in several pathological biochemical pathways that involve oxidative stress and can affect PIV. Sorbinil, alagebrium and alpha-lipoic acid are able individually to restore PIV through a possible oxidative stress reduction. Candesartan, an angiotensin II type 1 receptor blocker, is also able to restore PIV and prevent pressure ulcer formation. The possibility of preventing pressure ulcer associated to diabetes and/or aging with the restoration of PIV seems to be a promising research path.
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PMID:Alteration of Pressure-Induced Vasodilation in Aging and Diabetes, a Neuro-Vascular Damage. 3133 1


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