Diabetes is an increasingly common diagnosis with the condition affecting around 1 in 15 people in the UK (Diabetes UK Data, 2019). As we are well aware, people with diabetes have increased risk of infectious diseases, including those affecting the skin. The reasons for this are probably multifactorial. Hyperglycaemia, altered immune cell function, vasculopathy and neuropathy can all play a part in the development of skin infection. Skin changes evident in diabetes include delayed wound healing, abnormal skin barrier repair and function along with changes in skin pH (1).
All of these changes may also affect the type of organisms present on the skin (or the “microbiome”). The organisms present on the skin play an important role in our skins natural defence, complementing normal skin homeostasis. For example, commensal organisms present on our epidermis by their sheer numbers can prevent the establishment of more virulent and opportunistic bacteria. Moreover, studies have shown how surface organisms interact to enhance the skins immune function (2). So, changes in the microbiome can potentially have a knock-on effect to the skins natural ability to defend itself from unwanted microbial invasion.
Studies of microbes living in diabetic foot ulcers have been undertaken, but less research has looked at the earlier stages - studying the changes to the types of organisms living on unbroken skin. In 2017, an Australian study highlighted how the skin on the feet of patients with diabetes was colonised by a range of bacteria. When compared to non-diabetic skin samples from other feet, it showed that the diversity was greatly reduced in diabetic subjects with a narrower range of bacteria present on the skin. The authors suggest that this could be related to the effects of diabetes on the skin such as increased pH and advanced glycation end products present in the dermis. Interestingly they go on to say the technique predict whether a subject has diabetes by the microbiome of the foot with an accuracy of 85%. Perhaps a test for the future with some refinement?
In 2019, a team of researchers in Korea has taken a slightly different approach to unravelling the complexity of it all by looking at the microbiome on the skin of the feet which included fungal microbes (3). Using 20 subjects with type 2 diabetes and 20 controls, confirmed by blood tests not to have diabetes, they used Polymerase Chain Reaction (PCR) for identifying DNA in order to recognise microbes within the skin samples. PCR has the advantage of being rapid and accurate when compared to traditional petri-dish cultures. The results concurred with the previous work, but most interestingly was the reduction of fungal diversity of the skin of patients with type 2 diabetes in favour of an increased presence of T rubrum. The research was limited in that it couldn’t explain the reasons but suggested that changes in skin physiology may have favoured its promotion.
From a clinical perspective, it is interesting to note as we know that fungal skin and nail infections are more prevalent in patients with diabetes (4, 5) with T rubrum being the most frequent offender. In consequence, this may lead to increased risk of other problems such as bacterial cellulitis (6). Antifungal management should be part of basic foot care for these patients but the big question which is still left unanswered is if and how fungi may play a part in the other complications such as ulceration in the diabetic foot syndrome. Previous studies have shown how fungi has been present in foot wounds of patients with diabetes (7, 8) but let’s hope further research can fully unravel this mystery.
References
1. Behm B, Schreml S, Landthaler M, Babilas P. Skin signs in diabetes mellitus. J Eur Acad Dermatol Venereol. 2012;26(10):1203-11.
2. Sherwani MA, Tufail S, Muzaffar AF, Yusuf N. The skin microbiome and immune system: Potential target for chemoprevention? 2018;34(1):25-34.
3. Han SH, Lee JS, Song K-H, Choe YB, Ahn KJ, Lee YW. Differences in Foot Skin Microbiomes Between Patients with Type 2 Diabetes and Healthy Individuals. Mycoses. 2020;n/a(n/a):early view.
4. Eckhard M, Lengler A, Liersch J, Bretzel RG, Mayser P. Fungal foot infections in patients with diabetes mellitus - results of two independent investigations. Mycoses. 2007;50(s2):14-9.
5. Gupta AK, Humke S. The prevalence and management of onychomycosis in diabetic patients. Eur J Dermatol. 2000;10(5):379-84.
6. Bristow IR, Spruce MC. Fungal foot infection, cellulitis and diabetes: a review. Diabet Med. 2009;26(5):548-51.
7. Mlinaric Missoni E, Vukelic M, de Soy D, Belicza M, Vazic Babic V, Missoni E. Fungal infection in diabetic foot ulcers. Diabet Med. 2005;22(8):1124-5.
8. Heald AH, O'Halloran DJ, Richards K, Webb F, Jenkins S, Hollis S, et al. Fungal infection of the diabetic foot: two distinct syndromes. Diabet Med. 2001;18(7):567-72.