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

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

Metabolic syndrome (MS), typified by hypertension, abdominal obesity, dyslipidaemia and impaired glucose metabolism, is a precursor of type 2 diabetes. Thiazide diuretics (TD) and beta-blockers are associated with increased risk of diabetes in patients with hypertension; however, the role of these agents in development of diabetes in MS patients is unknown. We reviewed the literature regarding risk factors for diabetes development and compared this with data from the Study of Trandolapril/Verapamil SR And Insulin Resistance (STAR), which investigated the effects of two fixed-dose combinations (FDCs) [trandolapril/verapamil SR and losartan/hydrochlorothiazide (L/H)] on glucose control and new diabetes in MS patients. In STAR, logistic regression modelling identified haemoglobin A1c [odds ratio (OR) 4.21 per 1% increment; p = 0.003), L/H treatment (OR 4.04; p = 0.002) and 2-h oral glucose tolerance test glucose levels (OR 1.39 per 10 mg/dl increments; p < 0.001) as baseline predictors of diabetes. These data support prior analyses and suggest that choice of antihypertensive agent is important. Patients with MS may be at lower risk of diabetes when using a FDC calcium channel blocker + angiotensin-converting enzyme inhibitor compared with an angiotensin receptor blocker + TD.
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PMID:Risk factor assessment for new onset diabetes: literature review. 1856 74

The immunological processes in type 1 diabetes and metabolic/inflammatory disorder in type 2 diabetes converge on common signaling pathway(s) leading to beta-cell death in these two diseases. The cytokine-mediated beta-cell death seems to be dependent on voltage-dependent calcium channel (VDCC)-mediated Ca2+ entry. The Ca2+ handling molecular networks control the homeostasis of [Ca2+]i in the beta-cell. The activity and membrane density of VDCC are regulated by several mechanisms including G protein-coupled receptors (GPCRs). CaR is a 123-kDa seven transmembrane extracellular Ca2+ sensing protein that belongs to GPCR family C. Tumor necrosis factor-alpha (TNF-alpha), is a cytokine widely known to activate nuclear factor-kappaB (NF-kappaB) transcription in beta-cells. To obtain a better understanding of TNF-alpha-induced molecular interactions between CaR and VDCC, confocal fluorescence measurements were performed on insulin-producing beta-cells exposed to varying concentrations of TNF-alpha and the results are discussed in the light of increased colocalization correlation coefficient. The insulin producing beta-cells were exposed to 5, 10, 20, 30, and 50 ng/ml TNF-alpha for 24 h at 37 degrees . The cells were then immunolabelled with antibodies directed against CaR, VDCC, and NF-kappaB. The confocal fluorescence imaging data showed enhancement in the colocalization correlation coefficient between CaR and VDCC in beta-cells exposed to TNF-alpha thereby indicating increased membrane delimited spatial interactions between these two membrane proteins. TNF-alpha-induced colocalization of VDCC with CaR was inhibited by nimodipine, an inhibitor of L-type VDCC thereby suggesting that VDCC activity is required for spatial interactions with CaR. The 3-D confocal fluorescence imaging data also demonstrated that addition of TNF-alpha to RIN cells led to the translocation of NF-kappaB from the cytoplasm to the nucleus. Such molecular interactions between CaR and VDCC in tissues possibly provide control over Ca2+ channel activity via direct protein-protein contact.
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PMID:Inflammatory cytokine signaling in insulin producing beta-cells enhances the colocalization correlation coefficient between L-type voltage-dependent calcium channel and calcium-sensing receptor. 1863 68

The great prevalence and incidence of non-insulin dependent diabetes mellitus (NIDDM) and hypertension in the elderly represent several therapeutic problems. Due to aged-related changes in glucose handling and cardiovascular functions which occur with advancing age, it is necessary to treat aged diabetic hypertensive patients with drugs lowering arterial blood pressure but without side effects on glucose metabolism. Non-pharmacological and pharmacological protocols can be taken into account. With regard to the non-pharmacological therapy, a decline in body fatness, an increase in body fitness and an appropriate dietary assumption of sodium, potassium, calcium and magnesium are the most important approach. As far as the therapeutic approach, calcium channel blockers and angiotensin converting enzyme (ACE)-inhibitors seem to be particularly useful in the treatment of aged diabetic hypertensive patients. Calcium channel blockers have no effects on glucose tolerance while they are very effective on heart beating and arterial blood pressure. ACE-inhibitors lowers arterial blood pressure, delay the progression of diabetic nephropathy to the renal failure and, have null or beneficial effects on glucose handling. In conclusion, in aged diabetic hypertensive patients non-pharmacological therapy should be combined to administration of calcium channel blockers and ACE-inhibitors.
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PMID:The therapy of aged diabetic hypertensives. 1865 44

The Shiga Microalbuminuria Reduction Trial (SMART) showed the advantage of ARB over CCB beyond the blood pressure (BP)-lowering effect in reducing microalbuminuria. To further assess the impact of BP control or renin-angiotensin system inhibition on microalbuminuria, the SMART patients were re-analyzed. Hypertensive patients with type 2 diabetes and microalbuminuria were randomly assigned to valsartan or amlodipine treatment groups for 24 weeks. Target blood pressure was set at <130/80 mmHg. Changes in the urinary albumin creatinine ratio (ACR) from baseline were assessed in the valsartan monotherapy (VM) group (n=33), the amlodipine monotherapy (AM) group (n=36), the concomitant valsartan and angiotensin-converting enzyme inhibitor group (VA) (n=33), and the concomitant amlodipine and angiotensin-converting enzyme inhibitor (AA) group (n=38). At the end of the study, mean BP was not different among the four treatment groups. The changes in ACR from baseline to the end of the treatment period in VM, AM, VA, and AA were -36%, +30%, -26%, and +8%, respectively. The dissociation between the anti-albuminuric and antihypertensive effects of valsartan or amlodipine was observed in the respective monotherapy groups. In the AA group, however, a significant positive relationship was found between the changes in ACR and those in systolic BP. In conclusion, RAS inhibitors may be necessary in order for calcium channel blockers to have an effect on microalbuminuria. Therefore, RAS inhibitors are first-line drugs for hypertensive patients with type 2 diabetes and microalbuminuria.
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PMID:Impact of renin-angiotensin system inhibition on microalbuminuria in type 2 diabetes: a post hoc analysis of the Shiga Microalbuminuria Reduction Trial (SMART). 2467 Oct 17

The metabolic syndrome considerably increases the risk of cardiovascular and renal events in hypertension. It has been associated with a wide range of classical and new cardiovascular risk factors as well as with early signs of subclinical cardiovascular and renal damage. Obesity and insulin resistance, beside a constellation of independent factors, which include molecules of hepatic, vascular, and immunologic origin with proinflammatory properties, have been implicated in the pathogenesis. The close relationships among the different components of the syndrome and their associated disturbances make it difficult to understand what the underlying causes and consequences are. At each of these key points, insulin resistance and obesity/proinflammatory molecules, interaction of demographics, lifestyle, genetic factors, and environmental fetal programming results in the final phenotype. High prevalence of end-organ damage and poor prognosis has been demonstrated in a large number of cross-sectional and a few number of prospective studies. The objective of treatment is both to reduce the high risk of a cardiovascular or a renal event and to prevent the much greater chance that metabolic syndrome patients have to develop type 2 diabetes or hypertension. Treatment consists in the opposition to the underlying mechanisms of the metabolic syndrome, adopting lifestyle interventions that effectively reduce visceral obesity with or without the use of drugs that oppose the development of insulin resistance or body weight gain. Treatment of the individual components of the syndrome is also necessary. Concerning blood pressure control, it should be based on lifestyle changes, diet, and physical exercise, which allows for weight reduction and improves muscular blood flow. When antihypertensive drugs are necessary, angiotensin-converting enzyme inhibitors, angiotensin II-AT1 receptor blockers, or even calcium channel blockers are preferable over diuretics and classical beta-blockers in monotherapy, if no compelling indications are present for its use. If a combination of drugs is required, low-dose diuretics can be used. A combination of thiazide diuretics and beta-blockers should be avoided.
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PMID:The metabolic syndrome in hypertension: European society of hypertension position statement. 1880 11

Although there have been increasing reports, which suggest that angiotensin receptor blockers (ARBs) may have anti-atherogenic actions, most of them are performed in vitro and there are a few reports about anti-atherogenic action in vivo. Especially, in humans, there have been no reports about effect of ARBs on atheroslocerosis. On the other hand, there have been several reports, including ours, which indicate that amlodipine, a calcium channel blocker, has a unique property to cause a reduction in the intima-media thickness (IMT) of common carotid artery, which is established to be an indicator of early atherosclerotic lesion, in humans. The present study investigated which of amlodipine and/or ARBs might have more profound effect on IMT progression. The study included 104 hypertensive patients with type 2 diabetes. They were divided into the two groups: the amlodipine group (n=58), who received amlodipine (2.5-5mg/day) and the ARB group (n=46), who received losartan (25-50mg/day), candesartan (4-8 mg/day), valsaratan (40-80 mg/day) or telmisartan (20-40 mg/day). IMT changes were examined during an average of 56.9 weeks. The amlodipine group showed a significant decrease in IMT compared to the ARB group (-0.046 [S.E. 0.161] mm vs. 0.080 [S.E. 0.255] mm, P<0.05). These results suggest that amlodipine has an inhibitory effect on early atherosclerotic process, and that ARBs do not have any effect on it in hypertensive patients with type 2 diabetes.
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PMID:Comparison of effects of amlodipine and angiotensin receptor blockers on the intima-media thickness of carotid arterial wall (AAA study: amlodipine vs. ARB in atherosclerosis study). 1907 Mar 83

In Western countries, chronic coronary artery disease (CAD) has a prevalence of 3-4%. The aims of treatment of chronic CAD are (1) improvement of quality of life by preventing anginal pain, by maintaining exercise capability, and by reducing anxiety; (2) decrease of cardiovascular morbidity, especially by avoiding myocardial infarction and development of heart failure; (3) reduction of mortality. These goals can be achieved by (a) cardiovascular risk reduction, especially management of risk factors, (b) optimal medical therapy, (c) coronary revascularization, (d) periods of rehabilitation, and (e) outpatient long-term observation and treatment. The patient has a good chance to improve the natural course of his disease by changing his lifestyle. In this regard, physical exercise, weight reduction and smoking cessation have to be mentioned first. Furthermore, the cardiovascular risk may significantly be diminished by adequate treatment of hyperlipoproteinemia: lowering of plasma LDL cholesterol levels in patients with chronic CAD is associated with a retarded progression of atherosclerosis as well as a decrease of cardiovascular events by 30-40% and lower mortality (by up to 34%). In patients with CAD and/or type 2 diabetes, statin therapy leads to a significant improvement of prognosis independent of the basal value of LDL cholesterol. Improved diet and adequate medical therapy may also result in diminished cardiovascular risk. By means of physical activity, mortality and morbidity of CAD can also be significantly reduced. The antianginal medication in patients with chronic CAD consists of nitrates, beta-blockers, and calcium channel blockers. In order to prevent myocardial infarction and death (secondary prevention), antiplatelet agents, renin-angiotensin-aldosterone system blockers, as well as cholesterol-lowering drugs are applied. In this paper, the guidelines of the American College of Cardiology/American Heart Association, the European Society of Cardiology and the NVL-KHK (German) guidelines regarding prevention, medical therapy and coronary artery revascularization procedures are summarized. Do the guidelines reflect daily practice? To answer this question, the following topics are discussed: (1) Management of risk factors with respect to available guidelines, (2) missing evidence from randomized controlled trials for medical therapy options widely used in clinical practice, (3) guideline-compliant use or underuse of diagnostic assessment, medical therapy and revascularization procedures, (4) gender bias in indications for percutaneous coronary interventions and in the use of investigations/evidence-based medical therapy, and (5) nonadherence to existing guidelines.
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PMID:Treatment of chronic CAD--do the guidelines (ESC, AHA) reflect daily practice? 1921 8

The diabetes epidemic continues to grow unabated, with a staggering toll in micro- and macrovascular complications, disability, and death. Diabetes causes a two- to fourfold increase in the risk of cardiovascular disease, and represents the first cause of dialysis treatment both in the UK and the US. Concomitant hypertension doubles total mortality and stroke risk, triples the risk of coronary heart disease and significantly hastens the progression of microvascular complications, including diabetic nephropathy. Therefore, blood pressure reduction is of particular importance in preventing cardiovascular and renal outcomes. Successful antihypertensive treatment will often require a combination therapy, either with separate drugs or with fixed-dose combinations. Angiotensin converting enzyme (ACE) inhibitor plus diuretic combination therapy improves blood pressure control, counterbalances renin-angiotensin system activation due to diuretic therapy and reduces the risk of electrolyte alterations, obtaining at the same time synergistic antiproteinuric effects. ACE inhibitor plus calcium channel blocker provides a significant additive effect on blood pressure reduction, may have favorable metabolic effects and synergistically reduce proteinuria and the rate of decline in glomerular filtration rate, as evidenced by the GUARD trial. Finally, the recently published ACCOMPLISH trial showed that an ACE inhibitor/calcium channel blocker combination may be particularly useful in reducing cardiovascular outcomes in high-risk patients. The present review will focus on different ACE inhibitor combinations in the treatment of patients with type 2 diabetes mellitus and hypertension, in the light of recent clinical trials, including GUARD and ACCOMPLISH.
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PMID:Choice of ACE inhibitor combinations in hypertensive patients with type 2 diabetes: update after recent clinical trials. 1947 78

A 3-year multicenter, prospective, randomized, open-label trial (ADVANCED-J) compared the effect of an increased dose of angiotensin-II receptor blocker (ARB) with that of a maintenance dose of ARB plus calcium channel blocker (amlodipine) on blood pressure (BP) control, nephropathy and atherosclerosis in patients with type 2 diabetes and hypertension in whom the usual ARB dose failed to control BP. A cross-sectional analysis using baseline data was conducted. Of 316 patients (recruited between September 2004 and December 2005), 228 patients were evaluated by multiple regression analysis using two models after randomization and exclusions. Model 1 assessed 13 baseline variables (age, sex, estimated diabetes duration, estimated hypertension duration, HbA1c, brain natriuretic peptide (BNP), high-sensitive C-reactive protein (hsCRP), triglycerides (TGs), total cholesterol (TCHO), diabetic retinopathy (DMR), systolic morning home BP (HBP), diastolic morning HBP and brachial-ankle pulse wave velocity (baPWV)) for correlation with the urinary albumin creatinine excretion rate (UACR). In model 2, systolic and diastolic morning HBP was replaced by systolic and diastolic office BP. The systolic morning HBP and systolic office BP or diastolic morning HBP and diastolic office BP correlations were weak, but significant (r=0.43 and 0.48, respectively). BNP, HbA1c, DMR and estimated diabetes duration were significantly correlated with UACR in both models 1 and 2. Although systolic office BP did not show a significant correlation with UACR in model 2, systolic morning HBP showed a significant correlation with UACR in model 1. Morning HBP, but not office BP, may be a significant marker of nephropathy in Japanese patients with type 2 diabetes.
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PMID:Morning home blood pressure may be a significant marker of nephropathy in Japanese patients with type 2 diabetes: ADVANCED-J study 1. 1955 3


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