Crowley RK, et al. - Given that increasing adiposity, aging, and tissue-specific cortisol regeneration through the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have been associated with deterioration in glucose tolerance, researchers determined whether alterations in local glucocorticoid metabolism track with changes in glucose tolerance. For this investigation, 65 individuals who were overweight/obese were subjected to oral glucose tolerance testing, body composition assessment, subcutaneous tissue biopsy and urinary steroid metabolite analysis for up to 5 years each year. They categorized participants into those with deteriorating (“deteriorators”) or improved (“improvers”) glucose tolerance. The results obtained from the longitudinal cohort study indicate that deteriorating glucose tolerance was linked to increased total and trunk fat mass and increased lipogenic gene expression of subcutaneous adipose tissue. Longitudinal deterioration in metabolic phenotype was not related to increased 11β-HSD1 activity but with decreased expression of the subcutaneous adipose tissue gene. These changes can represent a compensatory mechanism in the face of an adverse metabolic phenotype to decrease local glucocorticoid exposure.