Obesity and insulin resistance in humans: a dose-response study.
Insulin-mediated glucose metabolism (euglycemic insulin clamp at plasma insulin concentration of 100 microU/mL) and glucose-stimulated insulin secretion (hyperglycemic clamp) were examined in 42 obese subjects (ideal body weight [IBW], 158 +/- 4%) with normal glucose tolerance and in 36 normal weight (IBW, 102% +/- 1%) age-matched controls. In 10 obese and eight control subjects, insulin was infused at six rates to increase plasma insulin concentration by approximately 10, 20, 40, 80, 2,000, and 20,000 microU/mL. Throughout the physiologic range of plasma insulin concentrations, both the increase in total body glucose uptake and the suppression of hepatic glucose production (HGP) were significantly impaired in the obese group (P less than .001 to .01). At the two highest plasma insulin concentrations, inhibition of HGP and the stimulation of glucose disposal were similar in both the obese and control groups. Insulin secretion during the hyperglycemic (+/- 125 mg/dL) clamp was twofold greater in obese subjects than in controls (P less than .01) and was inversely related to the rate of glucose uptake during the insulin clamp (r = -.438, P less than .05), but was still unable to normalize glucose disposal (P less than .05). In conclusion, our results indicate that insulin resistance is a common accompaniment of obesity and can be overcome at supraphysiological insulin concentrations. Both in the basal state and following a hyperglycemic stimulus obese people display hyperinsulinemia, which correlates with the degree of insulin resistance. However, endogenous hyperinsulinemia fails to fully compensate for the insulin resistance.
Division of Diabetes, University of Texas Health Science Center, San Antonio 78284.
R C
RC
Bonadonna
L
L
Groop
N
N
Kraemer
E
E
Ferrannini
S
S
Del Prato
R A
RA
DeFronzo
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000097:blood*
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose