The Effect of Losartan on Insulin Resistance and Beta Cell Function in Chronic Hemodialysis Patients

Abstract

Insulin resistance (IR) is prevalent in hemodialysis patients. IR and hyperinsulinemia have an important role in the development of atherosclerosis, which is the most common cause of morbidity and mortality in hemodialysis patients. Thus, antihypertensive drugs that lower IR, may have an additional beneficial effect in the treatment of cardiovascular diseases in these patients. In this preliminary study we examined the effect of Losartan (an angiotensin II receptor antagonist) treatment on IR and beta cell function in five hypertensive non-diabetic chronic hemodialysis patients. All other known causes of IR in end stage renal failure were excluded. After a washout period of two weeks, Losartan 50 mg, was administered for 6 weeks. Fasting blood glucose (FBG) and insulin levels were measured before and after the treatment IR and beta cell function were calculated using the "homeostasis model assessment"-HOMA. Systolic and diastolic blood pressure (BP) have not changed significantly throughout the study. FBG increased significantly from 76 mg/dL +/- 1 to 89 mg/dL +/- 4 (p < 0.01), however, insulin levels have not changed significantly. Calculated IR values did not show a difference, but calculated beta cell function decreased significantly after Losartan treatment from 291% +/- 50 to 146% +/- 10, (p < 0.016). These preliminary results suggest that in chronic hemodialysis hypertensive non-diabetic patients short treatment with Losartan has deleterious effect on glucose homeostasis mediated via a decrease in beta cell function.

Effect of angiotensin II receptor blockers on insulin resistance in maintenance haemodialysis patients

“…Very little information regarding the effect of AT1‐subtype inhibition on insulin resistance in patients with MHD has been reported. One study did not demonstrate the effect of losartan on insulin sensitivity in peripheral insulin‐responsive tissues 10 . The discrepancy with the results from this study may be caused by significant differences among the PPARγ‐activating ARB from their physicochemical properties 20 .…”

“…Treatment with inhibition of the cellular actions of Ang II by the use of specific Ang II (AT1‐subtype) antagonists may be an effective intervention for insulin resistance. Although recent studies have demonstrated that ARB improved insulin action, 9 one previous study in patients with maintenance haemodialysis (MHD) suggested that ARB were not beneficiary to insulin resistance 10 . The role of a specific reduction in Ang II action on insulin responsiveness of MHD patients remains controversial.…”

The Losartan Intervention for Endpoint Reduction (LIFE) Trial—Have Angiotensin‐Receptor Blockers Come of Age?

“…In addition, in the LIFE trial the lower rate of new‐onset diabetes (difference of 25%) with losartan confirms findings from prior studies with the ACE inhibitors ramipril and captopril 13,14 . This finding could have related to a differential effect on insulin resistance—the precursor condition for overt diabetes—favoring losartan, although prior studies with losartan have not shown it to improve insulin resistance 15,16 . Likewise, the same was the case in the LIFE trial; therein, there was not a specific positive benefit of losartan on insulin resistance.…”

Effect of acute hyperinsulinaemia with and without angiotensin II type 1 receptor blockade on resistin and adiponectin concentrations and expressions in healthy subjects

“…Experimental and in vitro studies showed that ARB may improve insulin sensitivity via decreasing adipocyte size (14), promotion of adipocyte differentiation and preventing ectopic lipid deposition (15). Several randomized, placebo-controlled studies using the HEC technique have found little positive or no effect of ARB on insulin action in rodents (16,17) and humans (18,19). Clinical trials using ARB have provided indirect support for the possibility that ARB per se might improve insulin sensitivity and decrease incidence of type 2 diabetes (LIFE, CHARM and VALUE) (20).…”