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2021 AUG 21 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting based on a preprint abstract, our journalists obtained [...]

2020 AUG 29 (NewsRx) -- By a News Reporter-Staff News Editor at Obesity, Fitness & Wellness Week -- According to news reporting based on a preprint abstract, our journalists obtained [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.01.013 Byline: Anthony Barnett Keywords: Angiotensin-converting enzyme inhibitor; Angiotensin II receptor blocker; Antihypertensive therapy; Type 2 diabetes mellitus; Diabetic nephropathy; Telmisartan Abstract: Management of hypertension is the mainstay of prevention and treatment of diabetic renal disease; evidence suggests that tight blood pressure control slows renal disease progression in established diabetic nephropathy. Inhibition of the renin-angiotensin-aldosterone system (RAAS) has renoprotective effects over and above those achieved by lowering systemic blood pressure. To date, however, no long-term study using hard end points has directly compared current mechanisms for RAAS inhibition, angiotensin II receptor blockade (ARB) and angiotensin-converting enzyme (ACE) inhibition. This issue was addressed in the recently published Diabetics Exposed to Telmisartan and Enalapril (DETAIL) study, a head-to-head comparison of telmisartan and enalapril in 250 patients with hypertension and type 2 diabetes mellitus and early-stage nephropathy. After 5 years' treatment, change in glomerular filtration rate (GFR), the primary efficacy end point, was equivalent in the 2 treatment groups, as were all secondary end points. The expected steep decline in GFR in the first year was followed by a lesser decrease in the second year and then almost complete stabilization of renal function at [greater than or equal to]3 years. Over 5 years, no patient went into end-stage renal disease or required dialysis. There were also no increases in albumin excretion rate, nor was there an increase in creatinine beyond 200 [mu]mol/L. Incidence of cardiovascular morbidity and mortality was extremely low in both treatment groups, a remarkable outcome given that almost 50% of patients had evidence of cardiovascular disease at randomization. Inhibition of the RAAS should play a major part in management of patients with type 2 diabetes with nephropathy, for which both telmisartan and enalapril provide long-term renoprotection. Author Affiliation: Division of Medical Sciences, University of Birmingham and Birmingham Heartlands and Solihull National Health Service Trust, Birmingham, United Kingdom

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.01.008 Byline: Steven M. Haffner Keywords: Antihypertensive agents; Cardiovascular disease; Metabolic syndrome; Telmisartan; Type 2 diabetes mellitus Abstract: The prevalence of diabetes mellitus is increasing worldwide. Among other complications, diabetes is associated with the risk of coronary heart disease (CHD) that is thought to be equal to the risk of CHD in subjects without diabetes with previous myocardial infarction. Studies have shown that CHD risk factors start to increase long before the onset of clinical diabetes. Furthermore, the risk factors that are present in prediabetic individuals are also components of the highly prevalent metabolic syndrome. This suggests that treatment of CHD risk factors may effectively reduce the incidence of type 2 diabetes. Lifestyle interventions have proved effective in preventing the onset of type 2 diabetes in subjects with impaired glucose tolerance. A number of post hoc studies have reported consistent reductions in the incidence of type 2 diabetes in hypertensive patients treated with either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). As a result of these positive data, ongoing prospective studies are investigating whether antihypertensive agents prevent or delay the onset of diabetes in patients at risk. Telmisartan, a selective oral ARB that is indicated for first-line therapy of essential hypertension, may provide improved tolerability compared with ACE inhibitors. Therefore, the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) program is investigating the effectiveness of telmisartan in the prevention or delay of type 2 diabetes. The program comprises ONTARGET and the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND). Author Affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA Article Note: (footnote) This study was supported by a grant from Boehringer Ingelheim.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.01.011 Byline: Theodore W. Kurtz Keywords: Angiotensin II type 1 receptor blockers; Antihypertensive agents; The metabolic syndrome; Peroxisome proliferator-activated receptor-[gamma]; Telmisartan; Type 2 diabetes mellitus Abstract: The metabolic syndrome is characterized by the clustering of insulin resistance, dyslipidemia, and hypertension and is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. However, older antihypertensive agents such as thiazide diuretics and [beta]-blockers have potentially adverse effects on glucose and lipid metabolism and may even the exacerbate the metabolic syndrome and increase risk of type 2 diabetes. Recent clinical trials have suggested that antihypertensive agents that inhibit the renin-angiotensin system may reduce risk for new-onset type 2 diabetes, but only a few of these studies were placebo controlled, and in most cases, the absolute antidiabetic effects were relatively modest. Evidence is accumulating that telmisartan, in addition to blocking the angiotensin II type 1 receptor, activates the peroxisome proliferator-activated receptor (PPAR)-[gamma] a well-known target for treatment of the metabolic syndrome and diabetes. By contrast, other angiotensin-receptor blockers are largely devoid of activity on PPAR-[gamma]. Telmisartan is a partial agonist of PPAR-[gamma] and has a superior tolerability profile without causing the fluid retention and edema associated with full agonists of PPAR-[gamma] such as pioglitazone and rosiglitazone. Recent studies have indicated that in addition to antidiabetic properties, PPAR-[gamma] activators may also provide protection against atherosclerosis and coronary events. Thus, the ability of telmisartan both to activate PPAR-[gamma] and to block the angiotensin receptor may provide added value not only in the treatment of the metabolic syndrome and prevention of type 2 diabetes but also in prevention and treatment of atherosclerotic cardiovascular disease. Author Affiliation: Department of Laboratory Medicine, University of California, San Francisco, California, USA

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.01.010 Byline: Arya M. Sharma Keywords: Adipose tissue; Angiotensin receptor blockers; Diabetes mellitus; Obesity; Renin-angiotensin system; Telmisartan Abstract: Abdominal obesity is a recognized risk factor for both type 2 diabetes mellitus and cardiovascular disease. The metabolic consequences of obesity, such as insulin resistance and impaired glucose tolerance, are primarily attributable to visceral, rather than to subcutaneous, adipose tissue. As a result, liposuction, which mainly removes subcutaneous fat, has no significant effect on insulin sensitivity; by contrast, weight loss resulting from bariatric surgical procedures is associated with resolution of type 2 diabetes in almost 80% of patients. Even modest weight loss in overweight or obese individuals is associated with significant reductions in the risk of diabetes and increased survival. Recent studies have suggested that the renin-angiotensin system (RAS) functions in the regulation of adipogenesis. Activation of this system is increased in obese individuals and angiotensin II, acting via angiotensin type 1 receptors, inhibits the differentiation of preadipocytes into mature adipocytes. This might be expected to result in ectopic storage of fat in tissues such as skeletal muscle and liver, thereby decreasing insulin sensitivity. Evidence from animal studies suggests that angiotensin-receptor blockers can promote redistribution of excess fat from these ectopic sites to mature adipocytes, resulting in improved insulin sensitivity. Clinical trials with telmisartan are currently investigating the effects of RAS blockade on insulin sensitivity in humans. Author Affiliation: Michael G. deGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada