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Updated: Jun 24, 2026

Randomized Controlled Trial to Study the Acute Effects of Strength Exercise on Insulin Sensitivity in Obese Adults
Published on: December 1, 2023
Effects of insulin on ketogenesis following fasting in lean and obese men
Maarten R Soeters1, Hans P Sauerwein, Linda Faas
1Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.r.soeters@amc.uva.nl
Abstract:
The ketone bodies (KBs) D-3-hydroxybutyrate (D-3HB) and acetoacetate (AcAc) play a role in starvation and have been associated with insulin resistance. The dose-response relationship between insulin and KBs was demonstrated to be shifted to the right in type 2 diabetes patients. However, KB levels have also been reported to be decreased in obesity. We investigated the metabolic adaptation to fasting with respect to glucose and KB metabolism in lean and obese men without type 2 diabetes using stable glucose and D-3HB isotopes in a two-step pancreatic clamp after 38 h of fasting. We found that D-3HB fluxes in the basal state were higher in lean compared to obese men: 15.2 (10.7-27.1) vs. 7.0 (3.5-15.1) micromol/kg lean body mass (LBM) x min, respectively, P < 0.01. No differences were found in KB fluxes between lean and obese volunteers during the pancreatic clamp (step 1: 6.9 (1.8-12.0) vs. 7.4 (4.2-17.8) micromol/kg LBM x min, respectively; and step 2: 2.9 (0-7.2) vs. 3.4 (0.85-18.7) micromol/kg LBM x min, respectively), despite similar plasma insulin levels. Meanwhile, peripheral glucose uptake was higher in lean compared to obese men (step 1: 15.2 (12.3-25.6) vs. 14.7 (11.9-22.7) micromol/kg LBM x min, respectively, P < or = 0.05; and step 2: 12.5 (7.0-17.3) vs. 10.8 (5.2-15.0) micromol/kg LBM x min, respectively, P < or = 0.01). These data show that obese subjects who display insulin resistance on insulin-mediated peripheral glucose uptake have the same sensitivity for the insulin-mediated suppression of ketogenesis. This implies differential insulin sensitivity of intermediary metabolism in obesity.
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