Impaired permeability and antimicrobial barriers in type 2 diabetes skin are linked to increased serum levels of advanced glycation end-product

Abstract

Background

The incidence of type 2 diabetes mellitus (DM) has been increasing rapidly, and the disease has become a serious sociomedical problem. Many skin problems, such as xerosis, pruritus, skin infections, and delayed wound healing, that might be related to chronic impairment of skin barrier function decrease the quality of life in DM patients. However, the status of the permeability and antimicrobial barrier of the skin in DM remains unknown.

Objective

This study aimed to elucidate skin barrier impairment in type 2 DM patients and its patho-mechanisms using classic animal models of type 2 DM.

Methods

Functional studies of the skin barrier and an analysis of stratum corneum (SC) lipids were compared between type 2 DM patients and age- and sex-matched non-diabetes controls. Also, functional studies on the skin barrier, epidermal lipid analyses, and electron microscopy and bio-molecular studies were performed using type 2 DM animal models, db/db and ob/ob mice.

Results

Type 2 DM patients presented with epidermal barrier impairments, including SC hydration, which was 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 compared with controls. Type 2 DM murine models presented with severe hyperglycemia, impairment of skin barrier homeostasis, decreases in epidermal proliferation and epidermal lipid synthesis, decreases in lamellar body (LB) and epidermal anti-microbial peptides (AMPs), an increase in receptors for advanced glycation end-product (AGE) in the epidermis, and an increase in serum AGE.

Conclusion

Impairment of the skin barrier was observed in type 2 DM, which results in part from a decrease in epidermal proliferation. Serum AGE and its epidermal receptors were increased in type 2 diabetic mice which display impaired skin barrier parameters such as epidermal lipid synthesis, LB production, epidermal AMP, and SC lipids.

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