Metabolic phenotype in Darier disease: a cross-sectional clinical study

BACKGROUND: Human data supporting a role for endoplasmic reticulum (ER) stress and calcium dyshomeostasis in diabetes is scarce. Darier disease (DD) is a hereditary skin disease caused by mutations in the ATP2A2 gene encoding the sarcoendoplasmic-reticulum ATPase 2 (SERCA2) calcium pump, which causes calcium dyshomeostasis and ER stress. We hypothesize that DD patients have a diabetes-like metabolic phenotype and the objective of this study was to examine the association between DD with impaired glucose tolerance and diabetes. METHODS: Cross-sectional clinical study on 25 DD patients and 25 matched controls. Metabolic status was assessed primarily by fasting blood glucose, oral glucose tolerance test, HOMA2-%S (insulin resistence) and HOMA2-%B (beta cell function). RESULTS: DD subjects showed normal oral glucose tolerance test and HOMA2-%S, while fasting blood glucose was lower and c-peptide as well as HOMA2-%B was higher. CONCLUSION: Increased HOMA2-%B values are indicative of increased basal insulin secretion which is a type of beta cell dysfunction associated to diabetes development. These results supports a role of ER stress in diabetes pathophysiology and contribute to the understanding of DD as a multi-organ syndrome.