Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in patients with hypertension and other cardiovascular risk factors

Abstract

We aimed to compare the effects of two different vasodilating principles, angiotensin II-receptor blockade and calcium channel blockade, on peripheral insulinmediated glucose uptake in patients with hypertension and other cardiovascular risk factors. Twenty-one hypertensive patients (11 women and 10 men) with mean age 58.6 years (range 46-75 years), body mass index 29.271.0 kg/m 2 and blood pressure 16073/ 9672 mm Hg entered a 4-week run-in period with open-label amlodipine 5 mg. Thereafter they were randomized double-blindly to additional treatment with amlodipine 5 mg or losartan 100 mg. After 8 weeks of treatment, all patients underwent clinical examination and laboratory testing, and 17 of them underwent a hyperinsulinaemic isoglycaemic glucose clamp. After a 4-week open-label wash-out phase, the participants crossed over to the opposite treatment regimen and final examinations with hyperinsulinaemic isoglycaemic glucose clamp after another 8 weeks. Blood pressure was lowered to the same level in both treatment periods. The glucose disposal rate was significantly higher after treatment with losartan 100 mg þ amlodipine 5 mg compared to amlodipine 10 mg (4.970.4 vs 4.270.5 mg/kg/ min, P ¼ 0.039). Thus our data suggest that angiotensin II-receptor blockade with losartan improves glucose metabolism at the cellular level beyond what can be expected by the vasodilatation and blood pressure reduction alone.

Chronic Treatment With Losartan Results in Sufficient Serum Levels of the Metabolite EXP3179 for PPARγ Activation

“…1,2 Indeed, the losartan metabolite EXP3179 exhibits a variety of beneficial pleiotropic effects in vitro that may also account for antiinflammatory, antiaggregatory, and antidiabetic actions of losartan observed in clinical trials. 1,18,19 The underlying molecular mechanism of these actions is unknown. PPAR␥ activation by EXP3179 demonstrated in the present study may provide a potential molecular explanation for these clinical findings.…”

Myocardial Insulin Resistance: An Overview of Its Causes, Effects, and Potential Therapy

“…As discussed previously in this chapter, the most compelling evidence for a role for the RAS in the aetiology of insulin resistance comes from studies using ACE inhibitors and AT receptor antagonists to control blood pressure. Both these therapies are associated with reduced risk of developing insulin resistance and type-2 diabetes in patients [119,122,[263][264][265][266] and in rodent models of obesity and insulin resistance [127,128]. Although these antihypertensives are not prescribed for the treatment of abnormal RAS activity, they potentially improve insulin sensitivity in a patient population that is at high risk of cardiovascular disease due to their hypertension.…”

Dipeptidyl peptidase-4 inhibitor sitagliptin improves pancreatic β-cell function in hypertensive diabetic patients treated with angiotensin receptor blockers

“…14,15 In addition, ARBs have recently been reported not only to improve insulin sensitivity, but also to preserve pancreatic β-cell function in both animal experiments and clinical studies. [16][17][18][19] Therefore, it is clinically relevant to investigate whether the beneficial effect of DDP-4 inhibitors could be exerted in ARB-treated T2DM patients.…”