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

Tara Ahanian; Philip Curman; Ivone U S Leong; Kerstin Brismar; Etty Bachar-Wikstrom; Martin Cederlöf; Jakob D Wikstrom

doi:10.1186/s13098-020-0520-0

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

Diabetol Metab Syndr. 2020 Feb 5:12:12. doi: 10.1186/s13098-020-0520-0. eCollection 2020.

Authors

Tara Ahanian^#^{1

2}, Philip Curman^#^{1

2}, Ivone U S Leong¹, Kerstin Brismar³, Etty Bachar-Wikstrom¹, Martin Cederlöf⁴, Jakob D Wikstrom^{1

2}

Affiliations

¹ 1Dermatology and Venereology Division, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden.
² 2Dermato-Venereology Clinic, Karolinska University Hospital, Stockholm, Sweden.
³ 3The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
⁴ 4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

^# Contributed equally.

Abstract

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.

Keywords: Calcium; Darier disease; Diabetes; ER stress; Endoplasmic reticulum; Glucose; Insulin; Sarcoendoplasmic-reticulum ATPase 2 (SERCA2).