Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ras GTPases function as transducers of extracellular signals regulating many cell functions, and they appear to be involved in the development of hypertension. In the present study, we have investigated whether antihypertensive treatment with ARBs (angiotensin II receptor blockers), ACEi (angiotensin-converting enzyme inhibitors) and diuretics induce changes in Ras activation and in some of its effectors [ERK (extracellular-signal-regulated kinase) and Akt] in lymphocytes from patients with hypertension without or with diabetes. ACEi treatment transiently reduced Ras activation in the first month of treatment, but diuretics induced a sustained increase in Ras activation throughout the 3 months of the study. In patients with hypertension and diabetes, ARB, ACEi and diuretic treatment increased Ras activation only during the first week. ACEi treatment increased phospho-ERK expression during the first week and also in the last 2 months of the study; however, diuretic treatment reduced phospho-ERK expression during the last 2 months of the study. In patients with hypertension and diabetes, antihypertensive treatments did not induce changes in phospho-ERK expression in lymphocytes. ACEi treatment reduced phospho-Akt expression in patients with hypertension and diabetes only in the first month of treatment. In conclusion, these findings show that antihypertensive treatments with ACEi, and diuretics to a lesser extent, modify Ras activation and some of its signalling pathways, although in different directions, whereas ARBs do not appear to have any influence on Ras signalling pathways.
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PMID:Effect of different antihypertensive treatments on Ras, MAPK and Akt activation in hypertension and diabetes. 1858 12

Chronic kidney disease (CKD) is characterized by proteinuria and kidney dysfunction caused by multiple factors. Metabolic disorders such as diabetes, dyslipidemia and hypertension are involved in the underlying pathological mechanisms of CKD and cardiovascular disease (CVD). In patients with CKD, CVD is a major cause of morbidity and mortality. Recent clinical studies have revealed that intervention by angiotensin II blockade with ARB and ACEI reduces CKD and CVD. Accordingly, earlier intervention to metabolic disorders with blockers for angiotensin II and aldosterone may prevent CKD as well as CVD associated with CKD.
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PMID:[Prevention of CVD in patients with CKD]. 1878 4

In the last 30 years we have seen considerable progress in the management of patients with diabetes, in particular with diabetic renal disease. A number of paradigms have been broken down, namely the following, as a consequence, clinical care has improved dramatically. . Significant renal involvement and albuminuria is rare in patients with essential hypertension. 2. High GFR is good for prognosis. 3. Only proteinuric diabetic patients have a poor prognosis. 4. Microalbuminuria only predicts renal disease. 5. Reducing blood pressure may cause low perfusion in the kidney and other organs with long-term negative effect, especially on the glomerular filtration rate. 6. Only in the presence of high blood pressure, should microalbuminuric patients receive anti-hypertensive treatment, including blockade of the RAS. 7. Only reducing blood pressure by blocking RAS in diabetes is relevant and justified. 8. Normoalbuminuria as indicated in the present definition is 'normal'. 9. ACE-I or ARB can only be used separately. 10. Diastolic blood pressure and later systolic pulse pressure are the best parameters for blood pressure recording. 11. Microalbuminuria is the strongest risk marker in patients with type 1 diabetes. 12. Screening for microalbuminuria is relevant, but follow-up was not proposed (also regarding microalbuminuria). In the present situation, it is well-known that patients with essential hypertension may sometimes have microalbuminuria, and it is known that it predicts a poor prognosis. Interestingly, in type 1 diabetes, hyperfiltration is a marker for poor prognosis related to metabolic control. Thus hyperfiltration is a marker for bad development, but microalbuminuria (below the proteinuric level) is also associated with a poor prognosis. It was originally believed that microalbuminuria only predicts renal disease. However, surprisingly it predicts as well cardiovascular disease and early mortality. The story about blood pressure and progression of renal disease is interesting, because it was earlier believed that a certain high blood pressure was mandatory for preservation of the renal function. This appeared to be a completely wrong concept. The data regarding microalbuminuria suggest that patients with microalbuminuria should receive anti-hypertensive treatment, even patients with so-called normal blood pressure. This was confirmed in several trials and also included in the guidelines. Reducing blood pressure is important, but it appeared to be especially beneficial to block the renin-angiontensin system, and it is clear that albuminuria is a continuous variable and is also a risk factor. Earlier it was suggested to use ACE-inhibitors or ARBs. Now it is clear that it is possible to use a combination, with good theoretical background. In the history of hypertension, it was earlier believed that diastolic blood pressure was most important, but later on it was generally accepted that systolic is a better predictor and the goal for treatment and pulse pressure may be even better. Not only is microalbuminuria an important risk marker, but it is as well clear that regression of microalbuminuria is a good marker for a better prognosis in patients. Microalbuminuria is believed to be the strongest risk factor, but new studies actually suggest that a simple parameter such as self-rated health is crucial along with other factors. Regarding new developments, it is clear that new studies have led to several advancements in management in patients, for instance the Steno II study shows positive effect on mortality by multifactorial intervention. Similarly, the ADVANCE study also showed positive effect on mortality by more intensified anti-hypertensive treatment with an ACE-inhibitor. We are eagerly awaiting the results from glucose arm in the ADVANCE study, especially in the light of the ACCORD study showing increased mortality with too strict glycemic control with a goal of 6% in HbA1c.
Diabetes Res Clin Pract 2008 Nov 13
PMID:Twelve shifting paradigms in diabetic renal disease and hypertension. 1894 97

Men treated with hemodialysis (HD) have a very poor prognosis and an elevated risk of premature cardiovascular disease (CVD). In the general population, associations between low testosterone concentrations and cardiovascular risk have been suggested. We performed a prospective observational study involving a well characterized cohort of 126 men treated with HD to examine the relationship between testosterone concentration and subsequent mortality during a mean follow-up period of 41 mo. Independent of age, serum creatinine, and sexual hormone binding globulin (SHBG), testosterone levels inversely and strongly associated with the inflammatory markers IL-6 and CRP. Patients with a clinical history of CVD had significantly lower testosterone levels. During follow up, 65 deaths occurred, 58% of which were a result of CVD. Men with testosterone values in the lowest tertile had increased all-cause and CVD mortality (crude hazard ratios [HRs] 2.03 [95% CI 1.24 to 3.31] and 3.19 [1.49 to 6.83], respectively), which persisted after adjustment for age, SHBG, previous CVD, diabetes, ACEi/ARB treatment, albumin, and inflammatory markers, but was lost after adjustment for creatinine. In summary, among men treated with HD, testosterone concentrations inversely correlate with all-cause and CVD-related mortality, as well as with markers of inflammation. Hypogonadism may be an additional treatable risk factor for patients with chronic kidney disease.
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PMID:Low serum testosterone increases mortality risk among male dialysis patients. 1914 59

Diabetes is one of the most important risk factors for mortality along with hypertension. Recently, it has emerged that ARB is a suitable anti-hypertensive drug for diabetic patients, because ARB has some features to prevent the progression of atherosclerosis in diabetic patients. Here, we summarize the evidences suggesting that ARB couldprevent not only macroangiopathy but also microangiopathy in diabetic patients. We conclude that ARB might be an ideal anti-hypertensive drug for diabetic patients.
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PMID:[ARB as a drug for diabetic microangiopathy]. 1934 42

The documentation for the beneficial effects of antihypertensive treatment in patients with diabetes is overwhelming. Most patients will require three or four antihypertensive drugs to achieve blood pressure (BP) goals. The regime should include an agent that blocks the renin angiotensin aldosterone system. Reduction in albuminuria during antihypertensive treatment is indicative of renal and cardiovascular protection. Thus, if the level of albuminuria remains high, the treatment should be intensified, even in the light of achieved BP goals. Options for intensification are dual blockade, supramaximal doses of ACE-I or ARB, or addition of aldosterone or renin-blocking agents. Long-term data are awaited regarding the optimal strategy for combination therapy. Patients on intensive antihypertensive treatment should be monitored regularly.
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PMID:[Hypertension in patients with diabetes]. 1952 70

Losartan/hydrochlorothiazide (HCTZ) [Hyzaar(R)] is a fixed-dose combination of the angiotensin II receptor antagonist (angiotensin receptor blocker [ARB]) losartan and the thiazide diuretic HCTZ. It is indicated for the treatment of hypertension (including as initial therapy in severe hypertension) and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy (LVH). Losartan/HCTZ is an effective combination therapy, lowering blood pressure (BP) to a greater extent than losartan or HCTZ alone in patients with hypertension. Other ARB/HCTZ fixed-dose combinations generally lowered BP to a greater extent than losartan/HCTZ in patients with hypertension, although whether this translates into improvements in cardiovascular outcomes is not known. In the LIFE study, losartan-based therapy was associated with a lower incidence of cardiovascular morbidity and mortality than atenolol-based therapy, mainly as a result of a reduced risk of stroke; the incidence of new-onset diabetes mellitus was also lower with losartan-based therapy. Losartan/HCTZ is a well tolerated combination therapy. Thus, losartan/HCTZ remains an important option in the treatment of hypertension, as well as being indicated to reduce stroke risk in patients with hypertension and LVH.
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PMID:Losartan/Hydrochlorothiazide: a review of its use in the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy. 1953 40

Whether the use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker inhibitor (ACEI/ARB) is beneficial in renal transplant recipients remains controversial. In this retrospective study on 505 renal transplant recipients, we analyzed blood pressure and graft survival according to antihypertensive treatment with ACE-I/ARB and/or calcium channel blockers (CCB) over a period of 10 years. Patients were stratified according to their blood pressure 1 year after transplantation [controlled (<or=130/80 mmHg; CTR, 181 patients) and noncontrolled (>130/80 mmHg; non-CTR, 324 patients)] and according to antihypertensive treatment (ACE-I/ARB and/or CCB taken for at least 2 years). One year after transplantation, 88.4% of CTR and 96.6% of non-CTR received antihypertensive treatment (P < 0.05). Graft survival was longer in CTR than in non-CTR (P < 0.05). Importantly, graft survival was longer in patients who received long-term treatment with ACEI/ARB, CCB, or a combination of ACEI/ARB and CCB (P < 0.001). The beneficial effect of ACEI/ARB therapy was more pronounced in non-CTR compared with that of CTR. We conclude that blood pressure control is a key target for long-term graft survival in renal transplant patients. Long-term ACEI/ARB and CCB therapy is beneficial for graft survival, especially in patients with diabetes and/or albuminuria.
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PMID:Blood pressure, antihypertensive treatment, and graft survival in kidney transplant patients. 1962 95

The 2005 American Heart Association/American College of Cardiology heart failure (HF) guidelines contributed to a renewed focus on "at-risk" patients and emphasized HF as a progressive disease. Patient categorization by stages focused attention on customization of therapy to achieve optimal, evidence-based treatments across the HF continuum. Therapy for risk factors that predispose patients to left ventricular dysfunction or other symptoms may help reduce HF development. beta-Blockers are valuable for treatment of HF; however, the class is heterogeneous, and proper beta-blocker selection for each HF stage is important. beta-Blockers have been used routinely to treat patients with stage A HF with hypertension. Recent controversy regarding the detrimental effects that some beta-blockers have on metabolic parameters has raised inappropriate concerns about the use of any beta-blocker for diabetes. beta-Blockade is standard therapy for the patient with stage B HF who has had a myocardial infarction, but few data are available concerning use in asymptomatic patients with left ventricular dysfunction. Additionally, beta-blockers are part of the core therapy for stage C HF and selected patients with stage D HF. This review examines the role and use of beta-blockers in each HF stage through an evidence-based approach to provide better understanding of their importance in this progressive disease. PubMed searches (1980-2008) identified large clinical trials that evaluated cardiovascular events and outcomes in any HF stage or hypertension. Search terms were heart failure, hypertension, beta-blocker, ACEI, ARB, and calcium channel blocker AND blood pressure coronary artery disease, diabetes, efficacy, left ventricular dysfunction, metabolism, mortality, myocardial infarction, or stroke.
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PMID:Beta-blocker use for the stages of heart failure. 1964 89

Insulin-like growth factor-I (IGF-I) is an important cardioprotective substance. We previously reported that sensory neuron stimulation increases IGF-I production by releasing calcitonin gene-related peptide (CGRP) in spontaneously hypertensive rats (SHRs). Because angiotensin II (Ang II) inhibits sensory neuron activation by interacting with Ang II type 1 (AT(1)) receptors, it is possible that AT(1) receptor blockers (ARBs) increase IGF-I production in SHRs. We examined this possibility in the current study, using the ARBs olmesartan, valsartan, losartan, and telmisartan. Plasma, renal, and cardiac levels of CGRP and IGF-I in SHRs were significantly lower than those in normotensive Wistar Kyoto rats (WKYs) (P < 0.01), which increased to levels found in WKYs after the administration of ARBs. These ARB-induced increases in SHRs were completely reversed by pretreatment with capsazepine (CPZ), which is a specific vanilloid receptor-1 (VR-1) antagonist. The mean arterial blood pressure (MABP) was decreased after administration of ARBs in SHRs, and those decreases were reversed by pretreatment with CPZ. The administration of nifedipine decreased MABP but did not increase CGRP or IGF-I levels in SHRs. Baseline CGRP release and cellular cyclic adenosine 3',5'-monophosphate (cAMP) levels in dorsal root ganglion neurons (DRG) isolated from SHRs were significantly lower than those in DRG isolated from WKYs (P < 0.01). Although ARBs reversed decreases in CGRP release and cAMP levels in the presence of Ang II in DRG isolated from WKYs, they increased CGRP release and cAMP levels in the absence of Ang II in DRG isolated from SHRs. Cellular levels of Ang II were not detected in DRG isolated from WKYs or SHRs, but messenger RNA (mRNA) levels for angiotensin-converting enzyme in DRG were significantly higher in SHRs than in WKYs (P < 0.01). The expression of AT(1) receptors in DRG was not different between WKYs and SHRs. Thus, it is likely that decreases in CGRP release and cAMP levels in DRG isolated from SHRs are mainly caused by AT(1) receptor activation by Ang II through an autocrine mechanism. These observations suggest that ARBs might increase CGRP release from sensory neurons by sensitizing VR-1 activation through increases in cAMP levels, which thereby increased the production of IGF-I in SHRs. These activities of ARBs might at least partly explain their therapeutic effects in areas such as improving insulin resistance in patients with diabetes and hypertension.
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PMID:AT(1) receptor blockers increase insulin-like growth factor-I production by stimulating sensory neurons in spontaneously hypertensive rats. 1966 90


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