title: Valsartan improves {beta}-cell function and insulin sensitivity in subjects with impaired glucose metabolism: a randomized controlled trial.
abstract: OBJECTIVE
  Recently, 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Valsartan 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).
  
  
  CONCLUSIONS
  Twenty-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.
authors.affiliation: Diabetes Center, Department of Internal Medicine, Vrije University Medical Center, Amsterdam, the Netherlands. nj.vdzijl@vumc.nl
authors.forename: Nynke J
authors.initials: NJ
authors.lastname: van der Zijl
authors.forename: Chantalle C M
authors.initials: CC
authors.lastname: Moors
authors.forename: Gijs H
authors.initials: GH
authors.lastname: Goossens
authors.forename: Marc M H
authors.initials: MM
authors.lastname: Hermans
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D001786:Blood Glucose; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine