Slower activation of insulin action in hypertension associated with obesity

Objective To determine whether kinetic abnormalities in the onset of insuli n action contribute to the insulin resistance in obesity-associated hyperte nsion. 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 no rmotensive (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 eug lycemia increased progressively during the clamp studies to achieve maximal , steady-state values within the fifth hour. During the first 2 h of the cl amp, mean glucose infusion rate, the traditional approach to assessing insu lin sensitivity, was lower in the hypertensive than in the normotensive obe se 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, ca lculated as the mean value during the sixth hour of clamping, was similar i n the hypertensive and in the normotensive obese patients (4.48 +/- 0.43 Ve rsus 4.81 +/- 0.45 mg/kg per min, respectively; NS). The time required to r each the half-maximal glucose infusion rate was greater in the hypertensive than normotensive obese patients (91 +/- 12 versus 38 +/- 5 min, respectiv ely; P< 0.05). Conclusion In obesity, hypertension was associated with a slower rate of ac tivation of the insulin effect on glucose metabolism, whereas the maximal s teady-state insulin effects were not altered by elevated blood pressure. Th us, the link between obesity and hypertension may be associated with the ki netics of onset of insulin action, (C) 1998 Lippincott Williams & Wilkins.