Hepatic 11β-hydroxysteroid dehydrogenase type 1 activity in obesity and type 2 diabetes using a novel triple tracer cortisol technique

Aims/hypothesis Dysregulation of 11β-hydroxysteroid dehydrogenase (11β-HSD) enzyme activities are implicated in the pathogenesis of obesity and insulin resistance. The aim of the study was to determine whether hepatic 11β-HSD type 1 (11β-HSD-1) enzyme activity differs in people with and without obesity and type 2 diabetes. Methods We measured hepatic 11β-HSD-1 activity in the overnight fasted state in 20 lean non-diabetic participants (LND), 21 overweight/obese non-diabetic participants (OND) and 20 overweight/obese participants with type 2 diabetes (ODM) using a non-invasive approach. One mg doses of [9,12,12- 2 H 3 ]cortisol (D cortisol) and [4- 13 C]cortisone ([ 13 C]cortisone) were ingested, while [1,2,6,7- 3 H]cortisol ([ 3 H] cortisol) was infused intravenously to enable concurrent measurements of first-pass hepatic extraction of ingested D cortisol and hepatic conversion of ingested [ 13 C]cortisone to C13 cortisol derived from the ingested cortisone (a measure of 11β-HSD-1 activity in the liver) using an isotope dilution technique. One-way ANOVA models and Kruskal–Wallis tests were used to test the hypothesis. Results Plasma D cortisol and C13 cortisol concentrations were lower in OND than in LND ( p