Slower activation of insulin action in hypertension associated with obesity

Objective To determine whether kinetic abnormalities in the onset of insulin action contribute to the insulin resistance in obesity-associated hypertension. Design We monitored the rate of increase in glucose infusion during 6 h of hyperinsulinemic (40 mU/m(2) per min) euglycemic clamps in hypertensive and normotensive obese subjects. The two groups of hypertensive (n = 9) and normotensive (n = 9) subjects were matched for age (48 +/- 2 versus 45 +/- 5 years), sex (five males and four females versus four males and five females) and body mass index (42 +/- 3 versus 40 +/- 2 kg/m(2)). Results In all subjects, the glucose infusion rate required to maintain euglycemia increased progressively during the clamp studies to achieve maximal, steady-state values within the fifth hour. During the first 2 h of the clamp, mean glucose infusion rate, the traditional approach to assessing insulin sensitivity, was lower in the hypertensive than in the normotensive obese patients (2.04 +/- 0.13 versus 3.29 +/- 0.41 mg/kg per min, respectively; P< 0.05), In contrast, the maximal steady-state glucose infusion rate, calculated as the mean value during the sixth hour of clamping, was similar in the hypertensive and in the normotensive obese patients (4.48 +/- 0.43 Versus 4.81 +/- 0.45 mg/kg per min, respectively; NS). The time required to reach the half-maximal glucose infusion rate was greater in the hypertensive than normotensive obese patients (91 +/- 12 versus 38 +/- 5 min, respectively; P< 0.05). Conclusion In obesity, hypertension was associated with a slower rate of activation of the insulin effect on glucose metabolism, whereas the maximal steady-state insulin effects were not altered by elevated blood pressure. Thus, the link between obesity and hypertension may be associated with the kinetics of onset of insulin action, (C) 1998 Lippincott Williams & Wilkins.