Comparing skin characteristics and molecular markers of xerotic foot skin between diabetic and non-diabetic subjects: An exploratory study
Introduction
Xerosis cutis is one of the most common skin conditions among patients with type 2 diabetes mellitus [[1], [2], [3], [4]]. About 25% of diabetic patients are affected by xerosis and associated pruritus [5]. Scaling, roughness, redness and fissures are the main clinical signs of skin dryness [6]. There are many factors, which may cause dry skin. An imbalance of natural moisturizing factors (NMFs) and intercellular lipids are common reasons [7,8]. Intercellular lipids like ceramides play an important physicochemical role in maintaining the barrier function and determining the water permeability of the stratum corneum (SC) [9], whereas NMFs, which are produced by proteolysis of filaggrin, are important for maintaining the hydration of the SC [10]. Low hydration of the SC triggers the de novo synthesis of NMF. Especially at the foot, where the stratum corneum (SC) is thickest, dry skin is prone to develop fissures. This facilitates the entry of germs and foreign substances into the skin, leading to increased risks of infections and ulceration [4,[11], [12], [13], [14]]. Foot ulcers are one of the most serious complications in the course of diabetes mellitus [3,[15], [16], [17]]. Diabetes mellitus induces microvascular changes which result in impaired blood circulation of the foot and delayed wound healing. Up to 15% of patients with diabetes mellitus are affected by non-healing ulcers [3,15], often leading to some form of lower extremity amputation [15,[18], [19], [20], [21]].
Type 2 diabetes mellitus is characterized by increased insulin resistance and beta cell failure, finally resulting in hyperglycemia [22], which in the long-term leads to glycation of proteins, lipids and nucleic acids [1,5,23]. These so called ‘Advanced Glycation Endproducts’ (AGEs) are associated with many dysfunctions and damages of organs, including the retina, the kidney, the nervous system and also the skin [1,22]. The accumulation of AGEs is considered to cause skin alterations, which promotes xerosis cutis, delays wound healing and increases the susceptibility for infections [1,5,18]. As AGEs alter collagen properties the skin also becomes stiffer [1,24]. Furthermore, high glucose levels impair the proliferation and migration of keratinocytes [1,5,23].
However, there are only few studies investigating the properties of diabetic skin [5,[25], [26], [27], [28]] and results are partially inconsistent [5]. For example, while dry skin in the context of atopic dermatitis is well-differentiated from other forms of dry skin (e.g. ‘senile xerosis’), it is unclear whether xerotic foot skin in diabetic patients also show different signs and patterns compared to dry foot skin of non-diabetics. Therefore, the aim of this study was to compare the structure, function and biomarkers of dry to very dry foot skin between diabetic and non-diabetic subjects.
Section snippets
Study design
A descriptive, exploratory study was conducted to compare diabetic and non-diabetic dry foot skin.
Participants and setting
The study took place at the Department of Dermatology and Allergy, Charité‐Universitätsmedizin Berlin between September 2016 and April 2017. Eligible for inclusion were patients affected by diabetes mellitus type 2 for at least 2 years and non-diabetics. The participants had to be between 40 and 75 years and affected by moderate or severe skin dryness at their feet (see Appendix A) with comparable
Participants
More than 200 subjects were contacted, of which 71 were screened. In total 60 participants took part, comprising 40 diabetics and 20 non-diabetics. Based on the clinical evaluation, 20 diabetics were allocated to the group with moderate skin dryness and 20 diabetics to the groups with severe skin dryness at feet. Regarding non-diabetics this applies to 7 (moderate) and 13 (severe). Demographic characteristics for non-diabetics and diabetics are shown in Table 1. Diabetics were older (63.5 (SD
Clinical parameters
Overall, the clinical signs of skin dryness between both groups as well as the mean numbers of deep fissures were comparable. However, there were much more superficial fissures in the diabetic group. The underlying reason is unclear. Oe et al. (2012) proposed different etiologies of superficial and deep fissures in diabetic subjects and described a correlation between autonomic neuropathy and the presence of superficial fissures, while deep fissures were additionally correlated with angiopathy [
Conclusion
Most clinical signs and skin barrier characteristics of xerotic foot skin in diabetics and non-diabetics are similar. However, dry diabetic foot skin is much stiffer and the number of superficial fissures is noticeable higher, indicating a higher risk for superficial wounding. The reason for the high number of superficial fissures may be because of the differences in molecular concentrations together with the increased stiffness.
Funding
Galderma S.A., La Tour-de-Peilz, Switzerland provided financial support for the performance of this study. This had no influence on analyses, interpretation of data or writing of the report.
Ethical approval
An ethical approval by the responsible Ethics Committee of the Charité - Universitätsmedizin Berlin has been obtained (EA1/207/16). The study was carried out in accordance with the principles of the Declaration of Helsinki and the guidelines of Good Clinical Practice (ICH GCP). Written informed consent was received before inclusion.
Declaration of competing interest
The authors AL, MA, TT, TB, AM, UBP and JK declare that they have no competing interests. NL is employed by Galderma S.A.
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