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. Over a 5-year period, they evaluated 65 overweight/obese people for oral glucose tolerance, body composition, biopsy of subcutaneous adipose tissue, and urinary steroid metabolites annually. They categorized participants into those with deteriorating (“deteriorators”) or improved (“improvers”) glucose tolerance. According to results, deteriorating glucose tolerance was correlated with increased total and trunk fat mass and increased subcutaneous adipose tissue expression of lipogenic genes. 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 be a compensatory mechanism to reduce local glucocorticoid exposure to an adverse metabolic phenotype.