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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is a multifactorial disorder leading to pathophysiologic changes in target organs over time through diverse mechanisms. In addition, hypertension frequently resists control with monotherapy, necessitating combination therapy with two or more antihypertensive agents. Many currently available fixed-dose antihypertensive combinations combine drugs with different, but complementary, mechanisms of action to improve overall efficacy and tolerability. In addition, it is possible to select drug combinations whereby one drug offsets the negative effects of the other drug. Fixed-dose antihypertensive combinations may provide significant advantages over high-dose monotherapy, such as improved BP-lowering efficacy, reduced adverse event frequency, improved patient compliance, potentially lower treatment costs, and shorter time to BP control. Combination therapy has been recommended as potential first-line therapy in recent consensus guideline statements, especially for higher-risk patients, such as those with stage 2 hypertension. The combination of a renin-angiotensin-aldosterone system-targeting agent, such as an ACE inhibitor or angiotensin II receptor antagonist (ARB), and a diuretic or calcium channel antagonist appears to provide synergy with regard to BP lowering. In addition, ACE inhibitors and ARBs have demonstrated beneficial effects beyond BP reduction, reducing cardiovascular morbidity and mortality, inhibiting development and progression of type 2 diabetes mellitus and the progression of renal disease. Preliminary studies of fixed-dose combinations have shown reductions in left ventricular hypertrophy and improvements in markers of renal function. Additional studies currently underway will compare the effects of available fixed-dose combinations on cardiovascular morbidity and mortality, and markers of renal dysfunction.
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PMID:Fixed-dose combination antihypertensives and reduction in target organ damage: are they all the same? 1807 8

Hyperglycemia, which is the biochemical hallmark of type 2 diabetes, mainly results from insulin resistance and beta-cell dysfunction. However, the latter is crucial in the development of the disease because diabetes cannot occur without an impairment of insulin secretion. Beta-cell failure is also responsible for progressive loss of metabolic control in type 2 diabetic patients and the eventual need for insulin treatment. An impairment of beta-cell function can be detected in several ways and can be observed already in pre-diabetic individuals. Histopathology studies documented that beta-cell volume is reduced in pre-diabetes and, to a greater extent, in type 2 diabetes mainly because the apoptotic rate of beta-cells is increased whereas neogenesis is intact. All anti-diabetic agents can improve, directly or indirectly, beta-cell function. However, only PPAR-gamma agonists and incretin-mimetic agents seem to have favorable effects on beta-cell morphology and volume. Many trials showed that type 2 diabetes can be prevented but few of them directly addressed the issue of beta-cell protection by the intervention used in the study. It is reasonable to conclude that in these trials diabetes prevention, which was based on the use of lifestyle changes (diet and/or exercise) or different drugs (tolbutamide, acarbose, metformin, glitazones, bezafibrate, orlistat, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers or pravastatin), depended also, or mainly, on a protection of the beta-cells but in most studies data on insulin secretion are not available or are insufficient to draw firm conclusions. The mechanisms of beta-cell protection in these trials, if any, remain unknown. They could be various and likely included reduced glucotoxicity, lipotoxicity, insulin resistance, inflammation, oxidant stress and/or apoptosis, an amelioration of islet blood flow and/or favorable changes in cation balance within the islets. Contrasting the decline and the eventual failure of beta-cells is crucial in preventing type 2 diabetes as well as in changing the natural history of the disease, when it occurs. The protection can be achieved in several ways but any strategy should include a change in lifestyle in order to generate a healthier islet milieu. Among anti-diabetic drugs, PPAR-gamma agonists and incretin-mimetic agents are the most promising in the protection. Among other drugs, inhibitors of the renin-angiotensin system might play a significant role. The increased worldwide diffusion of type 2 diabetes and the progressive loss of metabolic control in affected patients are clear demonstrations that the strategies to protect the beta-cells implemented so far, if any, were largely inadequate. Anti-diabetic agents targeting the intimate mechanisms of beta-cell damage might change the scenario in the near future.
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PMID:Protection of pancreatic beta-cells: is it feasible? 1809 75

The secondary analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) clinical trial investigated whether baseline demographic and clinical variables are predictive of different degrees of blood pressure reduction following an angiotensin II receptor blocker/diuretic treatment regimen. Irbesartan/hydrochlorothiazide and other angiotensin receptor blocker combinations with a diuretic have been shown to be effective in reducing systolic blood pressure in a diverse patient population previously uncontrolled on monotherapy. Ordinary least squares regression analysis was performed on the intent-to-treat population of the INCLUSIVE study to identify variables predictive of variations in blood pressure changes in response to irbesartan/hydrochlorothiazide combination therapy. Higher baseline systolic blood pressure, female sex, type 2 diabetes, and statin therapy were found to be predictive of additional blood pressure lowering with this combination. The impact of higher baseline systolic blood pressure and diabetic state on changes in systolic blood pressure were diminished in female patients compared with male patients. In conclusion, a significant correlation may exist between certain clinical/demographic characteristics and the extent of the therapeutic response with irbesartan/hydrochlorothiazide treatment.
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PMID:Predictors of blood pressure response to angiotensin receptor blocker/diuretic combination therapy: a secondary analysis of the irbesartan/hydrochlorothiazide blood pressure reductions in diverse patient populations (INCLUSIVE) study. 1817 68

Several factors have been incriminated in the genesis of diabetic nephropathy. To elucidate their interplay, we have used a hypertensive, obese, diabetic rat model with nephropathy (SHR/NDmcr-cp) that mimics human type 2 diabetes. This model is characterized by hypertension, obesity with the metabolic syndrome, diabetes with insulin resistance, and intrarenal advanced glycation end product (AGE) accumulation. In order to achieve renoprotection, which was evaluated by histology and albuminuria, various therapeutic approaches were used: caloric restriction, antihypertensive agents (angiotensin II receptor blocker [ARB] and calcium channel blocker), lipid- (bezafibrate) or glucose-lowering (insulin and pioglitazone) agents, and cobalt chloride (a hypoxia-inducible factor activator). Altogether, renoprotection is not necessarily associated with blood pressure or glycemic control. By contrast, it is almost always associated with decreased AGE formation, with the exception of insulin, which induces hyperinsulinemia, eventually leading to an overproduction of transforming growth factor-beta. AGE formation is reduced directly by in vitro active compounds (e.g., ARBs) or indirectly by in vitro inactive compounds (e.g., pioglitazone and cobalt). In the latter cases, AGE reduction may reflect a decreased oxidative stress as it is concomitant with a marked reduction of oxidative stress markers. It remains to be seen whether the renoprotection offered by these various approaches may be additive.
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PMID:Inhibition of advanced glycation end products: an implicit goal in clinical medicine for the treatment of diabetic nephropathy? 1844 8

The incidence of end-stage renal disease (ESRD) has been increasing, and within a 10-year period it is predicted that it will increase by 40 %. The main cause of death in this population of more than 50,000,000 individuals worldwide is cardiovascular disease. Increased urinary albumin is a predictor of renal failure, type 1 and type 2 diabetes; it correlates closely with mean arterial pressure in hypertensive subjects, predicts cardiovascular events and has a strong association with the metabolic syndrome. Treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers can reduce progressive renal damage, the beneficial effect being partially independent of the blood pressure lowering actions. Various therapies have proved effective in reducing microalbuminuria and progressive renal damage, demonstrating that the risk factor associated with a clinical outcome decreases with appropriate treatment. Cardiovascular events are the main cause of death in most patients with chronic renal disease. Diabetes, hypertension, obesity and smoking further increase the likelihood of vascular damage. Screening target populations of people with diabetes or hypertension is well recognized. Studies in several countries that have tested for albuminuria in unselected populations have demonstrated associations between microalbuminuria and deteriorating renal function, with the risk of developing ESRD and cardiovascular outcomes. There is some evidence for the use of urinary albumin as a marker of kidney involvement in unselected populations, but this needs to be strengthened and it may be cost effective compared with no screening. This has the potential to have a major impact in developing countries facing the challenges of chronic kidney disease, diabetes and cardiovascular disease.
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PMID:Evidence for the use of urinary albumin as marker of kidney involvement in unselected populations. 1856 65

The Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) study previously showed that treatment with telmisartan, an angiotensin II receptor blocker, effectively reduced the transition from incipient to overt nephropathy in Japanese type 2 diabetic patients. However, that large study included both normotensive and hypertensive patients. In the present post hoc analysis, we aimed to assess whether or not telmisartan elicits beneficial effects on the progression of microalbuminuria in normotensive patients. We randomized 163 microalbuminuric (urinary albumin-to-creatinine ratio: UACR of 100 to 300 mg/g creatinine) normotensive type 2 diabetic patients to treatment with telmisartan (40 or 80 mg once daily) or placebo over 52 weeks. The patients treated with either dose of telmisartan showed lower transition rates from microalbuminuria to overt nephropathy compared to the placebo group. In addition, more patients on telmisartan reverted to normoalbuminuria (UACR<30 mg/g creatinine): 15.5% of the 40 mg group, 19.6% of the 80 mg group, and 1.9% of the placebo group. In normotensive patients treated with telmisartan, changes in UACR were not significantly correlated with changes in blood pressure. Side effects did not differ among the groups. The present study demonstrates that telmisartan prevents the progression of microalbuminuria (in some cases induces remission of albuminuria) in normotensive Japanese patients with type 2 diabetes. Telmisartan is shown to be safe and well tolerated in these patients.
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PMID:Microalbuminuria reduction with telmisartan in normotensive and hypertensive Japanese patients with type 2 diabetes: a post-hoc analysis of The Incipient to Overt: Angiotensin II Blocker, Telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) study. 1863 77

The angiotensin II receptor blocker (ARB) telmisartan has a molecular structure that confers it partial agonist properties similar to those of peroxisome proliferators-activated receptor-gamma molecule, which is thought to modulate tissue response to insulin. In order to investigate the effects of telmisartan on insulin sensitivity and glucose metabolism, we enrolled 14 hypertensive patients under treatment with ARB other than telmisartan who had insulin resistance [homeostasis model for insulin resistance (HOMA-IR)>2.0] but no severe glucose tolerance (HbA1c<6.5%), and HOMA-IR was compared before and after the displacement by telmisartan. We also enrolled 27 obese (body mass index>25kg/m(2)) and hypertensive patients with type 2 diabetes under treatment with ARB other than telmisartan, and HbA1c was assessed before and after the displacement by telmisartan. The telmisartan significantly improved HOMA-IR in hypertensive patients and also significantly decreased HbA1c in type 2 diabetic patients especially in the patients with poor glycemic control (HbA1c>==8.0%). These results indicate that telmisartan improves insulin resistance and gives beneficial effects in hypertensive patients with type 2 diabetes and a poor glycemic control.
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PMID:The angiotensin II receptor blocker telmisartan improves insulin resistance and has beneficial effects in hypertensive patients with type 2 diabetes and poor glycemic control. 1869 32

Chronic kidney disease (CKD), a major worldwide public-health problem which affects about 10% of the population, has an increased annual incidence rate of about 5-8%. This increased incidence is mainly due to type 2 diabetes and hypertension and the increasing incidence of elderly patients with CKD. Although the progression to end-stage renal failure (ESRF) is mainly based upon the underlying disease, comorbid conditions such as an initial low renal function, severe proteinuria, and high levels of blood pressure also play important roles in the development of ESRF. Since experimental and clinical evidence suggest that angiotensin II plays a central role in the progression of CKD, pharmacological inhibition of the renin-angiotensin-aldosteron system (RAAS) with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists has been suggested as first-line treatment for hypertension and prevention of ESRF in these patients. Aliskiren, a novel renin inhibitor is also a promising medical intervention. However, independently of the category of the drugs used, low target blood pressure levels seem to be equally or more important for the delay or prevention of CKD. In this review the results of studies with pharmacological inhibition of the RAAS in patients with diabetic and nondiabetic nephropathy is discussed.
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PMID:Inhibition of the renin-angiotensin system and chronic kidney disease. 1880 6

Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P<or=0.01). Liver fat content was higher (P<0.05) following H than both P and C. The subcutaneous to visceral abdominal adipose tissue ratio was reduced following H versus C and P (P<0.01). Glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein levels were higher (P<0.05) after H, but not C, versus P. There were no changes in body fat, intramyocellular lipid, extramyocellular lipid, or first-phase insulin secretion. Blood pressure was reduced similarly by C and H versus P. In conclusion, visceral fat redistribution, liver fat accumulation, low-grade inflammation, and aggravated insulin resistance were demonstrated after hydrochlorothiazide but not candesartan treatment. These findings can partly explain the diabetogenic potential of thiazides.
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PMID:Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation: the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study. 1925 58

Hypertension has a worldwide high incidence in the general population and undoubtedly it is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries. In this Review we investigated the role of angiotensin II receptor antagonists (ARBs) therapy in the treatment of essential hypertension. We selected in the PubMed and in a list of selected sources the most significant clinical trials and meta-analysis carried out from 1999 to now, to assess, in adult patients populations, ARBs' efficacy, safety and tolerability profile, in comparison with the efficacy of the other common antihypertensive drugs, with particular regard to both the prevention of disabling consequences of hypertension (like cerebrovascular events, coronary events and heart failure) and the influence of an adequate antihypertensive therapy on comorbidities which strongly influence the outcome of hypertensive patients (like atherosclerosis, kidney damage, type II diabetes mellitus and arrhythmias). We also evaluated, in a detailed pharmacological and pharmaco-economic analysis, the basilar differences between ACE-inhibitors and ARBs in the control of the RAA system, and we assessed the possible benefits of their associated use, according to the new evidences concerning the treatment of arterial hypertension.
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PMID:Role of ARBs in the blood hypertension therapy and prevention of cardiovascular events. 1914 32


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