Acute effects of valsartan on insulin sensitivity in obese, non-hypertensive subjects with and without type 2 diabetes.
BACKGROUND
Two studies were designed to determine whether a single dose (80 mg) of the angiotensin II receptor blocker (ARB), valsartan, alters insulin sensitivity in obese, non-hypertensive subjects with and without Type 2 diabetes.


METHODS
Insulin sensitivity (S(I)), glucose effectiveness (S(G)), and acute insulin response (AIR(0-10 min)) were measured by means of a 3-hour insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT) before and after a single dose of valsartan. Study 1: obese, normotensive non-diabetic male subjects (n = 12), mean (SD) age 37.2 +/- 11.2 years, BMI 32.8 +/- 6.8 kg/m (2); Study 2: obese, normotensive Type 2 diabetic patients (n = 12), mean age 55.7 +/- 6.9 years, BMI 35.0 +/- 6.8 kg/m (2)/l. Both studies were randomised, double-blind, placebo-controlled, single-dose crossover group studies involving subjects in two study days, two weeks apart. After fasting samples were taken, a 300 mg/kg iv glucose bolus was injected at 0 min, and 0.05 U/kg iv insulin was given 20 min later. Blood samples for analysis of glucose and insulin were taken throughout the 3-hour study period.


RESULTS
Study 1 (non-diabetic subjects) S(I) 2.81 vs. 2.63 x 10 (-4) min (-1) per microU/ml (p = 0.54), S(G) 0.020 vs. 0.020 min (-1) (p = 0.90), AIR(0-10) min 3305 vs. 3450 microU/min/ml (p = 0.71); Study 2 (patients with type 2 diabetes) S(I) 0.59 vs. 0.85 x 10 (-4) min (-1) per microU/ml (p = 0.15), S(G) 0.013 vs. 0.014 min (-1) (p = 0.71), AIR(0-10) min 65 vs. 119 microU/min/ml (p = 0.14), placebo vs. valsartan, respectively.


CONCLUSIONS
In obese, non-hypertensive non-diabetic and Type 2 diabetic subjects a single dose of valsartan does not alter insulin sensitivity.
Luzio
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SD
Diabetes Research Unit, Llandough Hospital, Penlan Road, Penarth, S. Glam. CF64 2XX, Wales, UK. luzio@cf.ac.uk
Dunseath
G
G
Owens
D R
DR
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects*; D018592:Cross-Over Studies; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D013777:Tetrazoles / Q000009:adverse effects*; D014633:Valine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D000068756:Valsartan
D000959:Antihypertensive Agents; D007328:Insulin; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine