Obesity and insulin resistance in humans: A dose-response study

Riccardo C. Bonadonna, Groop Leif, Nancy Kraemer, Eleuterio Ferrannini, Stefano Del Prato, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

278 Scopus citations

Abstract

Insulin-mediated glucose metabolism (euglycemic insulin clamp at plasma insulin concentration of 100 μU/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 μU/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 < .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 < .01) and was inversely related to the rate of glucose uptake during the insulin clamp (r = -.438, P < .05), but was still unable to normalize glucose disposal (P < .05). In conclusion, our results indicate that insulin resistance is a common accompaniment of obesity and can by 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.

Original languageEnglish (US)
Pages (from-to)452-459
Number of pages8
JournalMetabolism
Volume39
Issue number5
DOIs
StatePublished - May 1990

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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