C:\Users\JURNAL FKUSAKTI\Docume 188 *Department of Parasitology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia **Department of Dermatology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia ***School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia Correspondence : Sem Samuel Surja Department of Parasitology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia Jalan Pluit Raya 2 Jakarta Utara 14440 Phone : +6221-6694366, 6693168 Fax : +62216606123 Email : semsurja@gmail.com ORCID ID: orcid.org/0000-0001- 5981-0014 Date of first submission, April 25, 2018 Date of final revised submission, October 26, 2018 Date of acceptance, October 26, 2018 This open access article is distributed under a Creative Commons Attribution- Non Commercial-Share Alike 4.0 International License ABSTRACT UNIVERSA MEDICINA Uncontrolled blood sugar tends to increase prevalence of dermatomycosis in diabetic type 2 patients Sem Samuel Surja*, Melyawati Hermawan**, Meiliyana Wijaya*, Pramanta***, and Hanna Yolanda* BACKGROUND The prevalence of type 2 diabetes mellitus (DM) is increasing. Diabetic patients have a higher risk of getting dermatomycosis. Dermatomycoses, although a common health problem amongst DM, is often misdiagnosed and consequently undertreated. Studies on the association between dermatomycosis and type 2 diabetes are lacking, especially in Indonesia. Therefore, the aim of this study was to determine the prevalence, etiology, and association of dermatomycosis with diabetic control of type 2 DM. METHODS A cross-sectional study was performed involving 87 subjects with type 2 DM. Demographic and clinical data, including age, sex, and blood glucose level, were collected. If a dermatomycosis lesion was found, a specimen would be taken for identification. Determination of serum glucose level was conducted using Roche c111 analyzer®. Statistical analysis was performed with the chi-square test and Kolmogorov-Smirnov two- independent sample test. RESULTS Seventeen (19.55%) subjects had dermatomycosis. The predominant age group affected was 51 - 60 years (42.4%). The number of clinically apparent dermatomycosis was greater in the uncontrolled than in the controlled blood sugar group, but the difference was statistically not significant (p > 0.05). The lesions were mostly found on the nails (74%) and the most common etiology was candida (50%) followed by dermatophyte (25%) and non-dermatophyte molds (25%). CONCLUSION Uncontrolled blood sugar tends to increase the risk of dermatomycosis in type 2 DM patients. Fungal skin infections are common in type-2 DM patients, especially in those with poor glycemic control. Keywords: Candida, dermatomycosis, dermatophytes, diabetes mellitus type 2 DOI: http://dx.doi.org/10.18051/UnivMed.2018.v37.188-194 ORIGINAL ARTICLE pISSN: 1907-3062 / eISSN: 2407-2230 Cite this article as: Surja SS, Hermawan M, Wijaya M, et al. Uncontrolled blood sugar tends to increase prevalence of dermatomycosis in diabetic type 2 pa- tients. Univ Med 2018;37:184-94. doi: 10.18051/UnivMed.2018.v37.188-194 September-December, 2018 Vol.37 No.3 189 Univ Med Vol.37 No.3 INTRODUCTION Diabetes mellitus (DM) describes a group of metabolic disorders characterized by high blood glucose level.(1) In type 2 DM, this condition is caused by both insulin resistance and insulin s e c r e ti o n d e f e c t t ha t a f f e ct gl uc os e metabolism.(2) The International Diabetes Federation (IDF) estimated that there were 451 million people (age 18-99 years) with diabetes in the world in 2017. This number is predicted to increase to 693 million by 2045. Nearly 9.9% of the population aged 20-79 years is estimated to have DM in 2045. (1) The World Health Organization (WHO) predicted that there will be an increase from 8.43 million in 2000 to 21.3 million patients in 2030 in Indonesia.(2) Dermatomycosis is a skin disease caused by fungi. It might appear under various clinical pictures, such as dermatophytosis, candidiasis, piedra, pytir ia sis versicolor, tinea nigra, onyc homycosis, a nd paronychia. (3 ) Dermatomycosis affects more than 20-25% of the world population.(3,4) These numbers continue to increase along with demographic and social economic changes, and the emerging of comorbid diseases and treatment options. The causative agents of dermatomycosis are dermatophytes, yeasts, and non-dermatophyte molds (NDM).(5,6) People with type 2 DM might be more susceptible to dermatomycosis because of the state of their immune system.(5,7,8) One study showed that patients with type 2 DM tended to have a higher prevalence of dermatomycosis than patients with type 1 DM, which could be possibly explained by the delay in the disease detection and following glycemic control.(9) A chronic hyperglycemic condition affects cellular immunity and disrupts the function of phagocytes throughout the body, including the skin. This is one of the reasons why the skin becomes more easily colonized by the fungi.(10) Most of the dermatomycosis features found in people with type 2 DM are dermatophytosis (66%) and candidiasis (24.1%).(11) The agents causing the clinical manifestations are changing according to time and place.(3) And the fact that these skin infections are more prevalent in people with uncontrolled type 2 DM raises the need of attention to their presence.(12) Specifically, onychomycosis is one of the most frequent form of dermatomycosis found in Asia.(13) This condition is more prevalent in people with DM, about 1.9 – 2.8 times higher than in normal people.(14) The most common agents causing onychomycosis are the dermatophytes, chiefly Trichophyton rubrum. (5) Ninety percent of onychomycosis in toenails is caused by d e r ma t op hyt e s , wh i l e on yc h omyc o si s in fingernails is caused by yeasts, especially Candida albicans.(15,16) In the last two decades, t he r e h a s b e e n a n i nc r e a s i ng tr e n d o f nondermatophyte molds (NDM). Some species s uc h a s S c op u la r i op s is bre v i c a ul i s , Aspergillus spp., Fusarium spp., Scytalidium spp, Alternaria alternata, and many more were found to be the cause of onychomycosis. (17-19) This may be the result of an increasing population with an immunocompromized state, peripheral vascular disorders, and other conditions.(20) Dat a re late d to the epid emio logy of dermatomycosis in diabetic patients in our country are scarce. This study was developed in order to find the prevalence and the most frequent causative agents of dermatomycosis in people with type 2 DM. Therefore, the aim of this study was to determine the prevalence, etiology, and association of dermatomycosis with the diabetic control of type 2 DM patients. METHODS Research design The design of this study was cross-sectional. This study was conducted in the Inte rnal Medicine wards and the Parasitology Laboratory, School of Medicine and Health Sciences, Atma J a ya Ca t h ol i c Un i ve r s it y o f In do ne si a , from October 2016 - March 2017. 190 Study subjects Patients with type 2 DM who underwent hospitalization were included in the study. The inclusion criterion was type 2 DM patients who were hospitalized in the Internal Medicine wards of Atma Jaya Hospital from October 2016 until January 2017. A total of 91 patients were hospitalized during that period. Of these, 4 patients were excluded due to insufficient data or because they had been admitted twice to the hospital, leaving 87 patients included in this study. Data collecting Demographic and clinical data such as age, sex, patient’s diagnosis, blood glucose level and microbiological test results were collected. Age and sex were collecte d f rom the medical records. The diagnosis of type 2 DM was made b y a n i n t er n i st , wh i l e t he dia gn os i s of dermatomycosis was made by a dermatologist. The blood glucose level was collected from the medical records (collection of blood glucose samples was described below). Mycological tests were conducted in all patients suffering from dermatomycosis. Laboratory analysis A venous blood sample was collected from each patient. Serum was then separeated from other blood components. Determination of blood glucose level was conducted on serum using a Roche c111 analyzer®. The patient’s blood glucose level was grouped into uncontrolled and uncontrollable blood glucose. Controlled blood glucose was defined by fasting blood glucose (FBG) <130 mg/dl and postprandial blood glucose (PBG) <180 mg/dl.(2) Isolation and identification of isolates Each patient underwent a thorough skin examination by a dermatologist to determine the presence of dermatomycosis clinical lesions. Dermatomycosis lesions were wiped with alcohol swabs then scraped with sterile glass slides. The samples from skin and nail scrapings were inoculated onto three types of media, i.e. Sabouraud Dextrose Agar ( SDA) (Oxoid, Ha mp s hi r e , E n gl a nd) , SDA c on t a i n in g c h l or a mp he ni c o l ( Ind of a r ma , J a ka r t a , Indonesia), and SDA containing 0.4 mg/ml chloramphenicol and 0.5 mg/ml cycloheximide (Amresco, Ohio, USA).(21,22) If pytiriasis was suspected, the sample would be inoculated onto SDA containing chloramphenicol and overlaid with 2% olive oil. (23) Inoculated samples were incubated at 25°C - 30°C. The onychomycosis samples were inoculated at 16 points in those media. If no dermatophyte or candida was detected, the cause of dermatomycosis was determined from the most-growing colonies.(24) The cultures were examined daily until the growth of the fungus was observed and was declared negative if there was no growth within 4 weeks. If the isolates formed mold colonies, the samples were continued in slide culture with SDA. But, if the isolates formed yeast colonies, the samples were continued in slide culture with rice cream and culture on Hi-Chrom Agar (HiMedia Laboratories, Mumbai, India) for identification.(22) Statistical analysis The statistical tests used were chi-square and Kolmogorov-Smirnov 2-independent sample test, to analyze the relationship between several variables, such as gender, age, blood glucose level, and dermatomycosis case. The software used was SPSS for Windows version 17. Ethical clearance This study has obtained ethical approval from the Institute of Ethics Studies of Atma Jaya and has received permission from Atma Jaya Hospital. The number of ethical clearance was 01/02/KEP-FKUAJ-2016. RESULTS Of the 87 diabetic patients, 50 (57.5%) were female and the predominant age group affected was 51 - 60 years (42.4%) (Table 1). From the clinical examination, 17 (19.55%) Surja, Herwaman, Wijaya, et al Dermatomycoses in type-2 DM patients 191 Univ Med Vol.37 No.3 patients had dermatomycosis, and no significant difference between dermatomycosis and sex or a ge ( Ta b le 2 ) . T he n umbe r of c l i ni c a l dermatomycosis was greater in uncontrolled FBG or PBG than in controlled FBG or PBG, but the difference was statistically not significant (p=0.394 and p=0.658 respectively) (Table 2). Of t h e bo dy s i te s a f f e c t e d wi t h dermatomycosis 74% were nails and out of all d e rma t omyc os is c a se s 50% we re d ue t o candida. Candida glabrata was the most commonly found candida species (40%) and the most common dermatophyte was Trichophyton rubrum (75%), followed by Trichophyton mentagrophytes (25%). Other fungi that have been isolated were NDM and Rhodotorulla glutinis. The NDMs found were aspergillus, Ony ch oc o la c ana de ns is, Neo scy ta li diu m dimidiatum, and geotrichum. DISCUSSION This study showed that the prevalence of dermatomycosis in females was higher than in males, but the difference was statistically not significant. Other studies showed that men are more likely have dermatomycosis than women, b ut t h e d if f e r e nc e wa s n ot s t at i st i c a l l y confirmed.(8,9,25) Dermatomycosis is associated with the physical activities and habits of the patient, such as water-related work, and physical activities that cause injuries.(12,25,26) The hyperglycemic state disrupts skin h ome o st a s is by i nh i bi t i ng ker a t i no c yte proliferation or migration, protein biosynthesis, inducing apoptosis, reducing nitric oxide synthesis, disturbing phagocytosis and cell Characteristic n (%) Sex Male 37 (42.5) Female 50 (57.5) Age (years) 57.93 ± 9.14 40 4 (5) 41 - 50 15 (17.1) 51 - 60 37 (42.4) >60 31 (35.5) Dermatomycosis Yes 17 (19.55) No 70 (80.05) Type of dermatomycosis* Onychomycosis 13 (72.22) Tinea 2 (11.11) Candidiasis 3 (16.67) Blood glucose (mg/dL) Fasting 169.59 ± 69.66 Controlled 103.63 ± 11.5 Uncontrolled 184.45 ± 68.66 2 h-Postprandial 217.84 ± 104.37 Controlled 127.94 ± 24.99 Uncontrolled 238.09 ± 104.81 Table 1. Distribution of features characteristic of research subjects (n=87) *Based on clinical diagnosis by dermatologist (1 patient could have more than 1 diagnosis) Variables Dermatomycoses p value Yes No Sex Male Female Age group (years) 40 41–50 51–60 >60 FBG Uncontrolled Controlled PBG Uncontrolled Controlled 6 (16.2%) 11 (22%) 0 (0%) 3 (20%) 9 (24.3%) 5 (16.1%) 13 (22%) 4 (14.3%) 10 (21.3%) 7 (17.5%) 31 (83.8%) 39 (78%) 4 (100%) 12 (80%) 28 (75.7%) 26 (83.9%) 46 (78%) 24 (85.7%) 37 (78.7%) 33 (82.5%) 0.472* 1.000# 0.394* 0.658* Table 2. The relationship between dermatomycoses and sex, age, and blood glucose control *: Chi-square test; #: Kolmogorov-Smirnov 2-independent sample test; FBG: fasting blood glucose; PBG: 2-h postprandial blood glucose 192 chemotaxis. These conditions promote skin disorders in diabetes, including skin fungal infection.(27) The results of our study showed that the prevalence of dermatomycosis tends to be higher in uncontrolled diabetic patients than in controlled ones. This result is in concordance with Sugandhi et al.(28) in that poor glycemic control was significantly associated with fungal infection. Type 2 diabetes was previously known as p re d isp os ing fa c t or f or f un ga l i nfe c t io n especi al l y Ca ndi da i n f e c t i o n a n d dermatophytosis of the foot and nail.(7,9,29) Akkus et al.(12) stated that tinea pedis and o nyc h omyc os i s w e re mo r e f r e q ue nt i n uncontrolled diabetic patients and patients with vascular disturbance. Tzar et al.(30) also found that the most frequent fungal infection is onychomycosis. Uncontrolled blood glucose level is also associated with onychomycosis.(7) The result of the present study is in concordance with other previous studies, in that the most frequent dermatomycosis was onychomycosis. This study found that candida was the most common cause of dermatomycosis, followed by dermatophytes, NDM, and R. glutinis. The high prevalence of candida infection was supported by many studies stating that the most frequent etiology of dermatomycosis in DM was candida infection, followed by dermatophytes, especially in nails and their surroundings.(31,32) Candida is part of the normal flora in humans that is a potential opportunistic pathogen. In the diabetic condition, there are an increased blood glucose level and an impaired immune system. The high blood glucose level provides the optimal condition for fungal growth. The impaired immune system results in the incapability of the host immune s ys t e m t o c ou nt e r ca nd i da i n c ut a ne ou s invasion.(32) Different results were obtained by Nenoff et al.(7) who found that the most common etiology of dermatomycosis was dermatophytes, rather than candida. The most common dermatophyte found in this study was T. rubrum, followed by T. mentagrophytes. This result is in concordance with previous knowledge that dermatophytosis is commonly caused by T. rubrum and T. mentagrophytes.(7) Studies in Asian countries such as India and Japan, as reviewed by Hayette et al.,(5) also confirmed that these species are the main agents causing dermatophytosis. Parada et al.(9) a lso found that T. rubrum and T. me nt a grop hy te s we r e t he c a us e o f dermatomycosis in the lower limb of patients with type 2 diabetes. Reddy et al.(25) stated that the high incidence of T. rubrum is related to its a b i li t y t o f or m col o n ies i n h ar d ke ra t i n structures. It is also known that T. rubrum more commonly affects people with predisposing factors such as DM.(7) Of the 30% sample in this study it was found that the etiological agents were non- dermatophyte and non-candida fungi, such as Aspergillus, R. glutinis, O. canadensis, N. dimidiatum, and Geotrichum, the most common b e ing As p e rgi l l us . Be si d e s c a n di d a a n d dermatophytes, the other fungi have also been kno wn a s t h e c a us a t i ve age n t s of o nyc h omyc os is, s uc h a s S c op u la r i op s is brevicaulis, Aspergillus spp., Fusarium spp., Scytalidium spp, Alternaria alternata, and many more.(17-19) Nondermatophyte molds may invade nails damaged by occupational trauma, such as in young persons, immunocompromized individuals, those with impaired peripheral c i r c ul a t i on , a n d th o se wi t h p e r i ph e r a l neuropathy.(20) However, NDM may also present as contaminants that grow saprophytically in nails. To diagnose NDM as the etiology of onychomycosis, is challenging. There are several methods that may be u se d t o de c i de ND M a s t he et i o lo gy of onychomycosis cases. In this study, samples have been cultured on 16 spots in media. If candida or dermatophytes appeared, they would be decided as the etiology of onychomycosis. But, if they did not, the etiology would have been decided from the most populous colony of fungi that grew in the media.(23 ) Gupta et al.(2 4) suggested 6 criteria for diagnosing NDM as the etiology of onychomycosis cases accurately: Surja, Herwaman, Wijaya, et al Dermatomycoses in type-2 DM patients 193 Univ Med Vol.37 No.3 d e t e c t i ng N DM b y d i r e c t mi c r os c o p ic examination from clinical samples with potassium hydroxide (KOH), positive culture of NDM, re- positive culture of NDM (at different points in ti me) , the den sity of c olony, abse nce of dermatophytes, and histologic examination. Minimally 3 of those criteria have to be obtained. It is important to bear in mind some limitations of this study. First, the true frequency of onychomycosis in the group of patients might have been underestimated due to negative cultures for fungi. Second, the cross-sectional design of this study prevents the finding of the t r u e c a us a l r e l a t i on s hi p be t w e e n dermatomycosis and poor blood glucose control. Since dermatomycosis is common in DM patients, the management of type 2 DM should also address this problem to improve the patient’s quality of life. Future research studies with similar objectives should be designed as cohort studies with larger sample sizes to find a more precise causal relationship between dermatomycosis and diabetic control. CONCLUSIONS Uncontrolled blood sugar tends to increase dermatomycosis in patients with type 2 diabetes me l l it u s . T he mos t c o mmo n c a s e s of dermatomycosis are the onychomycoses and the most common etiology is candida. CONFLICT OF INTEREST The authors declare they have no conflict of interest. FUNDING DISCLOSURE This study was funded by Atma Jaya Catholic University of Indonesia. ACKNOWLEDGEMENT The authors thank Vilia Budi Prasetio, K e yn e Chr is t a M on i n tj a , An ge l a M e i ke Indrayani, Josephine, Richard Firmansyah, Ivon Setiawan, and Linda Widyawati for the ir contribution during this study. CONTRIBUTORS SSS contributed to conceiving and presenting the research idea, conducting laboratory work, conducting statistical analysis, constructing article. MH contributed to collecting research data, constructing article. MW contributed to collecting research data, conducting laboratory work, conducting statistical analysis, constructing article. P contributed to collecting research data. HY contributed to finding research grant, conducting statistical analysis, constructing article. All authors have read and approved the final manuscript. REFERENCES 1. Cho NH, Shaw JE, Karuranga S, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018;138:271–81. doi: 10.1016/j.diabres.2018.02.023. 2. Soelistijo SA, Novida H, Rudijanto A, et al. Konsensus: pengelolaan dan pencegahan diabetes melitus tipe 2 di Indonesia. 1st ed. Jakarta: PB Perkeni; 2015. 3. Schieke SM, Garg A. Fitzpatrick’s dermatology in general medicine. 8th ed. New York: McGraw Hill; 2012. 4. Havlickova B, Czaika VA, Fredrich M. Epidemiological trends in skin mycosis worldwide. Mycosis 2008;51:2-15. doi: 10.1111/j.1439-0507. 2008.01606. 5. Hayette MP, Sacheli R. Dermatophytosis, trends in epidemiology and diagnostic approach. Curr Fungal Infect Rep 2015;9:164-79. doi: 10.1007/ s12281-015-0231-4. 6. Mehlig L, Garve C, Ritschel A, et al. Clinical evaluation of a novel commercial multiplex-based PCR diagnostic test for differential diagnosis of dermatomycoses. Mycoses 2014;57:27-34. doi: 10.1111/myc.12097. 7. Nenoff P, Kruger C, Ginter-Hanselmayer G, et al. Mycology - an update. Part 1: dermatomycoses: causative agents, epidemiology and pathogenesis. J Dtsch Dermatol Ges 2014;12:188- 212. doi: 10.1111/ddg.12245. 194 8. Qadim HH, Golforoushan F, Azimi H, et al. Factors leading to dermatophytosis. Ann Parasitol 2013; 59:99-102. 9. Parada H, Verissimo C, Brandao J, et al. Dermatomycosis in lower limbs of diabetic patients followed by podiatry consultation. Rev Iberoam Micol 2013;30:103–8. doi: 10.1016/j.riam. 2012.09.007. 10. Powers AC. Diabetes mellitus. In: Jameson JL, editor. Harrison’s endocrinology. 2nd ed. New York: McGraw Hill;2010.p.267-313. 11. Ngwogu A, Ngwogu K, Mba I, et al. Pattern of presentation of dermatomycosis in diabetic patients in Aba, South-eastern, Nigeria. J Med Investigations Pract 2014;9:10-3. doi: 10.4103/ 9783-1230.139164. 12. Akkus G, Evran M, Gungor D, et al. Tinea pedis and onychomycosis frequency in diabetes mellitus patients and diabetic foot ulcers: a cross sectional - observational study. Pakistan J Med Sci 2016;32:891-5. doi: 10.12669/pjms.324.10027. 13. Ghannoum M, Isham N. Fungal nail infections (onychomycosis): a never-ending story? PLoS Pathog 2014;10:e1004105. doi: 10.1371/journal. ppat.1004105. 14. Westerberg DP, Voyack MJ. Onychomycosis: current trends in diagnosis and treatment. Am Fam Physician 2013;88:762–70. 15. Mayser P, Freund V, Budihardja D. Toenail onychomycosis in diabetic patients: issues and management. Am J Clin Dermatol 2009;10:211-20. doi: 10.2165/00128071-200910040-00001. 16. Thomas J, Jacobson GA, Narkowicz CK, et al. Toenail onychomycosis: an important global disease burden. J Clin Pharm Ther 2010;35:497- 519. doi: 10.1111/j.1365-2710.2009.01107.x. 17. Moreno G, Arenas R. Other fungi causing onychomycosis. Clin Dermatol 2010;28:160-3. doi: 10.1016/j.clindermatol.2009.12.009. 18. Baudraz-Rosselet F, Ruffieux C, Lurati M, et al. Onychomycosis insensitive to systemic terbinafine and azole treatments reveals non- dermatophyte moulds as infectious agents. Dermatology 2010;220:164-8. doi: 10.1159/ 000277762. 19. Hashemi SJ, Gerami M, Zibafar E, et al. Onychomycosis in Tehran: mycological study of 504 patients. Mycoses 2010;53:251-5. doi: 10.2165/00128071-200910040-00001. 20. Farwa U, Abbasi SA, Mirza IA, et al. Non- dermatophyte moulds as pathogens of onychomycosis. J Coll Physicians Surg Pakistan 2011;21:597-600. doi: 10.2011/JCPSP.597600. 21. Cappuccino JG. Welsh C. Microbiology, a laboratory manual. 11th ed. Harlow: Pearson; 2017. 22. Klaassen KM, Dulak MG, van de Kerkhof PC, et al. The prevalence of onychomycosis in psoriatic patients: a systematic review. J Eur Acad Dermatol Venereol 2014;28:533-41. doi: 10.1111/jdv.12239. 23. Archana BR, Beena PM, Kumar S. Study of the distribution of malassezia species in patients with pityriasis versicolor in Kolar Region, Karnataka. Indian J Dermatol 2015; 60:321. doi: 10.4103/0019- 5154.156436. 24. Gupta AK, Drummond-Main C, Cooper EA, et al. Systematic review of nondermatophyte mold onychomycosis: diagnosis, clinical types, epidemiology, and treatment. J Am Acad Dermatol 2012;66:494-502. doi: 10.1016/j.jaad.2011.02.038. 25. Reddy KN, Srikanth BA, Sharan TR, et al. Epidemiological, clinical and cultural study of onychomycosis. Am J Dermatology Venereol 2012;1:35-40. doi: 10.5923/j.ajdv.20120103.01. 26. Neupane S, Pokhrel DB, Pokhrel BM. Onychomycosis: a clinico-epidemiological study. Nepal Med Coll J 2009;11:92-5. 27. de Macedo GMC, Nunes S, Barreto T. Skin disorders in diabetes mellitus: an epidemiology and physiopathology review. Diabetol Metab Syndr 2016;8:63. doi: 10.1186/s13098-016-0176-y. 28. Sugandhi P, Prasanth DA. Prevalence of yeast in diabetic foot infections. Int J Diabetes Dev Ctries 2017;37:50-7. doi: 10.1007/s13410-016-0491-8. 29. Lima AL, Illing T, Schliemann S, et al. Cutaneous manifestations of diabetes mellitus: a review. Am J Clin Dermatol 2017;18:541-53. doi: 10.1007/ s40257-017-0275-z. 30. Tzar M, Zetti Z, Ramliza R. Dermatomycoses in Kuala Lumpur, Malaysia. Sains Malaysiana 2014;43:1737-42. 31. Thilak S, Anbumalar M, Sneha PM. Cutaneous fungal infections in subjects with diabetes mellitus. Int J Res Dermatol 2017;3:55-8. DOI: http://dx.doi.org/10.18203/issn.2455-4529. Int J Res Dermatol 2016;44:12. 32. Santhosh Y, Ramanath K, Naveen M. Fungal infections in diabetes mellitus: an overview. Int J Pharm Sci Rev Res 2011;7:221-5. Surja, Herwaman, Wijaya, et al Dermatomycoses in type-2 DM patients