THE RISK OF DEVELOPING DIABETES IN HYPERTENSION : -Insulin sensitivity, AT-1 receptor blockade and sympathetic activity
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AbstractPatients with hypertension have a high risk of developing diabetes mellitus. We investigated predictors of diabetes development among 15245 high risk hypertensive patients included the VALUE trial and blood glucose and BMI were the most important predictors. The patients who developed diabetes mellitus during the average 4.2 year of the trial had increased cardiac morbidity (myocardial infarction and heart failure) compared with patients that did not develop diabetes mellitus.
Antihypertensive treatment with additional Angiotensin II AT1-receptor blockade improved insulin sensitivity measured with the hyperinsulinaemic isoglycaemic glucose clamp compared to treatment with calcium channel blocker alone in a double-bind, randomised crossover study of 21 patients with hypertension and other cardiovascular risk factors. No significant differences were found in adipokines, inflammatory variables and whole blood viscosity, but a significant reduction in plasma noradrenaline was found. One possible mechanism for the improved insulin sensitivity by AT1-receptor blockade may be effects on the sympathetic nervous system.
List of papers
Paper I: Aksnes TA, Kjeldsen SE, Rostrup M, Størset Ø, Hua TA, Julius S. Predictors of new-onset diabetes mellitus in hypertensive patients: the VALUE trial. J Hum Hypertens 2008; 22(8):520-7
Paper II: Aksnes TA, Reims HM, Guptha S, Moan A, Os I, Kjeldsen SE. Improved insulin sensitivity with the angiotensin II-receptor blocker losartan in patients with hypertension and other cardiovascular risk factors. J Hum Hypertens 2006; 20(11):860-866
Paper III: Aksnes TA, Seljeflot I, Torjesen PA, Høieggen A, Moan A, Kjeldsen SE. Improved insulin sensitivity by the angiotensin II-receptor blocker losartan is not explained by adipokines, inflammatory markers or whole blood viscosity. Metabolism 2007; 56(11):1470-7
Paper IV: Aksnes TA, Flaa A, Sevre K, Mundal HH, Rostrup M, Kjeldsen SE. Effect on plasma noradrenaline may explain some of the improved insulin sensitivity seen by AT-1 receptor blockade. Blood Pressure 2008; 17(3):156-63
Paper V: Aksnes TA, Kjeldsen SE, Rostrup M, Omvik P, Hua TA, Julius S. The impact of new-onset diabetes mellitus on cardiac outcomes in the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial population. Hypertension 2007; 50(3): 467-73