Crowley RK, et al. - Deterioration in glucose tolerance has been linked to increased adiposity, aging and tissue-specific cortisol regeneration via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity, so researchers determined whether changes in local glucocorticoid metabolism mirror changes in glucose tolerance. Sixty-five people who were overweight/obese had oral glucose tolerance testing, body composition assessment, subcutaneous tissue biopsy and metabolite analysis of urinary steroids annually for up to five years. In this longitudinal, prospective clinical study, participants were classified into those who deteriorated ("deteriorators") or improved ("improvers") with regard to glucose tolerance. Increased total and trunk fat mass and increased lipogenic gene expression of subcutaneous adipose tissue were linked to deteriorating glucose tolerance. There was no change in global 11β-HSD1 activity and it did not differ between baseline or follow-up in deteriorators or improvers. Findings suggested that longitudinal deterioration in metabolic phenotype was not related to higher activity of 11β-HSD1, but lower expression of the subcutaneous gene of adipose tissue. These changes may be a compensatory mechanism in the face of an adverse metabolic phenotype to decrease local glucocorticoid exposure.