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

Dysregulation of 11[beta]-hydroxysteroid dehydrogenase (11[beta]-HSD) enzyme activities are implicated in the pathogenesis of obesity and insulin resistance. The aim of the study was to determine whether hepatic 11[beta]-HSD type 1 (11[beta]-HSD-1) enzyme activity differs in people with and without obesity and type 2 diabetes. We measured hepatic 11[beta]-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-^sup 2^H^sub 3^]cortisol (D cortisol) and [4-^sup 13^C]cortisone ([^sup 13^C]cortisone) were ingested, while [1,2,6,7-^sup 3^H]cortisol ([^sup 3^H] cortisol) was infused intravenously to enable concurrent measurements of first-pass hepatic extraction of ingested D cortisol and hepatic conversion of ingested [^sup 13^C]cortisone to C13 cortisol derived from the ingested cortisone (a measure of 11[beta]-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. Plasma D cortisol and C13 cortisol concentrations were lower in OND than in LND (p