Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

Abstract

OBJECTIVERecently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes.RESEARCH DESIGN AND METHODSIn this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex.RESULTSValsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P < 0.001). BMI remained unchanged in both treatment groups (P = 0.89).CONCLUSIONSTwenty-six weeks of valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes.

A Comparison of the effects of fixed dose Valsartan/Hydrochlorothiazide and Atenolol/Chlorthalidone on Blood Lipid Profile in Hypertensive Patients

“…This could be because valsartan improves pancreatic β-cell function. This is supported by the findings of van der Zijl et al (2011) who demonstrated that this drug increased glucose stimulated insulin release and sensitivity in normotensive patients with impaired glucose metabolism.…”

A Comparative Study of Olmesartan and Valsartan on Insulin Sensitivity in Hypertensive Patients with Diabetes Mellitus or Impaired Glucose Tolerance (OVIS Study)

“…Telmisartan and irbesartan have a partial agonist action of PPARγ [30] and are expected to have beneficial effects on insulin resistance by increasing adiponectin levels than the other ARBs without such action. However, supportive data were published in 6 of 12 clinical studies using telmisartan [11,13,15,17,22,23,[37][38][39][40][41][42] and in 1 of 2 studies using irbesartan [11,16], indicating almost same rates comparing with those using other ARBs [9,10,12,14,17,23,32,33].…”

“…In a crossover study using olmesartan (20 mg/day) and telmisartan (40 mg/day) for 8 weeks, there was no difference between the groups in metabolic parameters (HbA1c and HOMA-IR) and adiponectin levels in Japanese early stage type 2 diabetics with hypertension [31]. On the other hand, 3 studies using valsartan showed an effect of improving insulin sensitivity in maintenance hemodialysis patients (n=10) for 12 weeks treatment [12], in obese patients with impaired glucose tolerance (n=13) for 4 weeks treatment [14], and in normotensive subjects with impaired glucose tolerance (n=40) for 26 weeks therapy [32]. However, in a trial using 80 mg/day valsartan, it did not improve insulin sensitivity in 91 patients with diabetes and mild-to-moderate hypertension [33].…”

Τhe role of sacubitril/valsartan therapy on renal function and glucose metabolism in chronic heart failure patients

“…In high-fat-fed neprilysin deficient mice, the improvement in glycaemic status was associated with elevated active GLP-1 concentrations, reduced plasma dipeptidyl peptidase 4 (DPP-4) activity and improved beta cell function, suggesting beneficial metabolic effects of neprilysin inhibition. Inhibition of the reninangiotensin system also benefit glycaemic control, as angiotensin II promotes insulin resistance [45]. Nevertheless, the improvement of glucose metabolism by renin-angiotensin system inhibition alone is most likely to be modest.…”

“…Neprilysin is known to promote lipid mobilization from adipose tissue, increase postprandial lipid oxidation, promote adiponectin release, and enhance muscular oxidative capacity. Furthermore, blood glucose concentrations have been shown to decrease after infusion of B-type natriuretic peptide [37,45,46]. In the Atherosclerosis Risk in Communities study in a population of 7822 individuals, with a median follow-up of 12 years, higher concentrations of N-terminal proBNP were associated with a significantly decreased risk of diabetes, even after adjustment for traditional risk factors and fasting glucose.…”