Glucocorticoids are known to impair skin function and wound healing which are also compromised in patients with type 2 diabetes. The enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates glucocorticoids in target tissues including skin. Pre-clinical data demonstrate that 11β-HSD1 inhibition improves skin function and wound healing but this has not been investigated in man.~Using the 11β-HSD1 inhibitor AZD4017, we will investigate if~Oral AZD4017 inhibits 11β-HSD1 activity in skin~AZD4017 is safe and well-tolerated in patient with T2DM~Oral AZD4017 regulates skin function~Systemic glucocorticoid levels and skin 11β-HSD1 activity, independently or in combination correlate with measures of skin function~Study feasibility will also be assessed; if successful, data from this pilot study will inform power calculations for a future trial to investigate the ability of 11β-HSD1 inhibition to promote foot ulcer healing in type 2 diabetes.
The study aims to investigate effects of inhibiting glucocorticoid activation on skin function and wound healing in patients with type 2 diabetes. Half of patients will be given a drug to inhibit glucocorticoid activation and the other half will be given a placebo.