Effects of Ketone Bodies on Insulin Sensitivity

Condition(s) studied

Investigational drug(s) / intervention(s)

Growth Hormone, Human: Continuous intravenous infusion of growth hormone (30 ng·kg-¹·min-¹) for approximately 7 hours to induce physiological lipolysis.

Oral ketone supplement (KetoAid®, KE4): Oral administration of D-β-hydroxybutyrate ester (R-1,3-butanediol β-hydroxybutyrate).

Saline infusion (placebo): Continuous IV infusion of isotonic saline as placebo for growth hormone.

Oral placebo drink: Oral administration of an isocaloric placebo drink.

Study summary

KETO-SENSE is a clinical research study investigating how ketone bodies affect energy metabolism and insulin sensitivity in humans. Ketone bodies are naturally produced by the liver during fasting or prolonged exercise and can serve as an alternative fuel for the brain, heart, and muscles.

In this study, ten overweight but otherwise healthy adults aged 55-70 years will participate in four study days at Aarhus University Hospital. Participants will receive one of four interventions in a randomized crossover design: 1) growth hormone (GH) and a ketone supplement, 2) GH and placebo, 3) a saline infusion with the ketone supplement, or 4) placebo (saline infusion and placebo supplement). The study uses advanced PET/CT imaging, indirect calorimetry, and tissue biopsies to measure how ketones influence fat breakdown, glucose uptake, and energy expenditure.

By understanding these mechanisms, the study aims to clarify whether oral ketone supplementation can improve insulin sensitivity and energy metabolism - findings that could be relevant for common conditions such as overweight, insulin resistance, and type 2 diabetes.

Eligibility

Primary outcome measure(s)

• Insulin-stimulated glucose uptake in skeletal muscle and organs measured by [¹⁸F]-FDG PET — During four experimental study days conducted over approximately 12 weeks
  Quantification of insulin-stimulated glucose uptake rates in skeletal muscle and selected organs using dynamic \[¹⁸F\]-FDG PET during a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity.
• Tissue-specific uptake of β-hydroxybutyrate and palmitate measured by PET/CT imaging — During four experimental study days conducted over approximately 12 weeks
  Quantification of tissue-specific uptake of β-hydroxybutyrate (BHB) and palmitate in skeletal muscle, adipose tissue, and myocardium using dynamic PET/CT imaging with \[¹¹C\]-OHB and \[¹¹C\]-palmitate tracers.
• Tissue-specific oxidation of β-hydroxybutyrate and palmitate measured by PET/CT imaging — During four experimental study days conducted over approximately 12 weeks
  Quantification of oxidation rates of β-hydroxybutyrate (BHB) and palmitate in skeletal muscle, adipose tissue, and myocardium using dynamic PET/CT imaging with \[¹¹C\]-OHB and \[¹¹C\]-palmitate tracers to assess tissue-specific substrate utilization.
• Energy expenditure — During four experimental study days conducted over approximately 12 weeks
  Measurement of resting and insulin-stimulated energy expenditure using indirect calorimetry and analysis of respiratory exchange ratio (RER).
• Cardiac output measured by PET/CT imaging — During four experimental study days conducted over approximately 12 weeks
  Quantification of cardiac output in the basal state and during the hyperinsulinemic-euglycemic clamp using dynamic PET/CT imaging to evaluate hemodynamic effects of GH and β-hydroxybutyrate.
• Myocardial glucose and fatty acid uptake rates — During four experimental study days conducted over approximately 12 weeks
  Assessment of myocardial substrate metabolism using dynamic PET/CT imaging with \[¹⁸F\]-FDG and \[¹¹C\]-palmitate tracers during the basal period and the hyperinsulinemic-euglycemic clamp to quantify myocardial utilization of glucose and fatty acids.

Trial sites (1)

More University of Aarhus trials in Denmark

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