Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion

Abstract

Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 ± 11.5 v 22.1 ± 2.2 kg · m −2; mean ± SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 ± 3.8 v 2.4 ± 3.0 mU · L −1, P < .001) and remained elevated throughout infusion (F = 492, P < .001), as did C-peptide (F = 22.7, P < .001). Metabolic clearance rate for insulin (MCR I) at the highest infusion rate was similar (1,048 ± 425 v 1,018 ± 357 mL · m −2 · min −1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 ± 108 v 444 ± 68 μmol · m −2 · min −1, P < .01), as was the basal metabolic clearance rate for glucose (MCR G, 77 ± 26 v 108 ± 31 mL · m −2 · min −1, P < .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 ± 0.5 v 1.9 ± 0.5 mmol · L −1, P < .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL · m −2 · min −1/mU · L −1, P < .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were evevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations. Dose-response calculations suggested insulin resistance at physiological insulin concentrations in obesity for glucose, NEFA, glycerol, and ketones.