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 patients with DM. However, the status of the permeability and antimicrobial barrier of the skin in DM remains unknown. This study aimed to elucidate skin barrier impairment in patients with type 2 DM and its pathomechanisms using classic animal models of type 2 DM. Functional studies of the skin barrier and an analysis of stratum corneum (SC) lipids were compared between patients with type 2 DM and age‐ and sex‐matched non‐diabetes controls. Also, functional studies on the skin barrier, epidermal lipid analyses, and electron microscopy and biomolecular studies were performed using type 2 DM animal models, db/db and ob/ob mice. Patients with type 2 DM 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 patients with type 2 DM compared with controls. Type 2 DM murine models presented with severe hyperglycaemia, impairment of skin barrier homeostasis, decreases in epidermal proliferation and epidermal lipid synthesis, decreases in lamellar body (LB) and epidermal antimicrobial peptides (AMPs), an increase in receptors for advanced glycation end‐product (AGE) in the epidermis and an increase in serum AGE. 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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The stratum corneum (SC) is the outermost layer of skin that functions as a barrier and protects against environmental influences and transepidermal water loss. Its unique morphology consists of keratin-enriched corneocytes embedded in a distinctive mixture of lipids containing mainly ceramides, free fatty acids, and cholesterol. Ceramides are sphingolipids consisting of sphingoid bases, which are linked to fatty acids by an amide bond. Typical sphingoid bases in the skin are composed of dihydrosphingosine (dS), sphingosine (S), phytosphingosine (P), and 6-hydroxysphingosine (H), and the fatty acid acyl chains are composed of non-hydroxy fatty acid (N), α-hydroxy fatty acid (A), ω-hydroxy fatty acid (O), and esterified ω-hydroxy fatty acid (E). The 16 ceramide classes include several combinations of sphingoid bases and fatty acid acyl chains. Among them, N-type ceramides are the most abundant in the SC. Mass spectrometry (MS)/MS analysis of N-type ceramides using chip-based direct infusion nanoelectrospray-ion trap mass spectrometry generated the characteristic fragmentation pattern of both acyl and sphingoid units, which could be applied to structural identification of ceramides. Based on the MS/MS fragmentation patterns of N-type ceramides, comprehensive fragmentation schemes were proposed. In addition, mass fragmentation patterns, which are specific to the sphingoid backbone of N-type ceramides, were found in higher m/z regions of tandem mass spectra. These characteristic and general fragmentation patterns were used to identify N-type ceramides in human SC. Based on established MS/MS fragmentation patterns of N-type ceramides, 52 ceramides (including different classes of NS, NdS, NP, and NH) were identified in human SC. The MS/MS fragmentation patterns of N-type ceramides were characterized by interpreting their product ion scan mass spectra. This information may be used to identify N-type ceramides in the SC of human, rat, and mouse skin.

These results suggested that FMP could be used as an alternative to antibiotics by enhancing growth performance and nutrient digestibility, and decreasing fecal noxious gas emission and early diarrhea score of weanling pigs.