Impaired permeability and antimicrobial barriers in type 2 diabetes mellitus is linked to altered advanced glycation end product expression

Abstract

Type 2 diabetes mellitus (DM) has been rapidly increasing and became a serious sociomedical problem. Many skin problems such as xerosis, pruritus, skin infections and delayed wound healing that could be related with chronic impairment of skin barrier function lead to decreased quality of life in DM patients. But the status of the permeability and antimicrobial barrier in DM remains unknown. This study was designed to elucidate the skin barrier impairment in type 2 DM patients and its patho-mechanism by using classic animal models of type 2 DM. Functional studies on the skin barrier and analysis of stratum corneum (SC) lipids were compared between type 2 DM patients and the age and sex-matched non-diabetes controls. Also, functional studies on skin barrier, epidermal lipid analysis, electron microscope and bio-molecular studies were performed using type 2 DM animal models, db/db and ob/ob mice. Type 2 DM patients presented epidermal barrier impairment, among which SC hydration defining dry skin was more influenced by blood glucose control (HbA1c level). In the lipid analysis of SC, ceramides, fatty acids and cholesterol were significantly decreased in type 2 DM patients. Type 2 DM murine models presented severe hyperglycemic condition, impairment of skin barrier homeostasis, decrease of epidermal proliferation and epidermal lipid synthesis, decrease of lamellar body and epidermal anti-microbial peptides, and increase of receptor for advanced glycation end product (AGE) in epidermis as well as serum AGE. In conclusion, impairment of skin barrier was observed in type 2 DM, which could be contributed by the decrease of epidermal proliferation induced by increased interaction of serum AGE and epidermal receptor for AGE. In order, the decrease of epidermal proliferation decrease epidermal lipid synthesis, LB production, epidermal AMP and SC lipids.