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.


METHODS
We monitored the rate of increase in glucose infusion during 6 h of hyperinsulinemic (40 mU/m2 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/m2).


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).


CONCLUSIONS
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.
Biolo
G
G
Istituto di Clinica Medica, University of Trieste, Italy. gianni.biolo@clmed.univ.trieste.it
Toigo
G
G
Ciocchi
B
B
Situlin
R
R
Guarnieri
G
G
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D005947:Glucose / Q000009:adverse effects; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000139:chemically induced; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology
D007328:Insulin; D005947:Glucose