Topical Corticosteroid use and risk of Type 2 Diabetes: A Nationwide Population-Based Cohort Study in Korea

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Data may be preliminary. 16 March 2025 V1 Latest version Share on Topical Corticosteroid use and risk of Type 2 Diabetes: A Nationwide Population-Based Cohort Study in Korea Authors : Seungwoo Kim , Ji hui An , In Sun Ryou , and Yongho Jee 0000-0003-0365-8302 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174215714.49752623/v1 631 views 140 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Purpose : Steroid-induced diabetes mellitus (SIDM) is a well-known side effect of corticosteroid agents. While diabetes induced by systemic corticosteroids has been extensively studied for over 60 years, evidence regarding the association between topical corticosteroids and type 2 diabetes remains limited. This study aimed to investigate the relationship between topical corticosteroid use and the risk of type 2 diabetes. Methods : A nationwide, population-based cohort study was conducted using data from the Korea National Health Insurance Service National Sample Cohort Database (NHIS-NSC2). A total of 186,057 adults with new-onset type 2 diabetes were identified as case subjects. Among these, 171,113 adults who had been treated with topical corticosteroids and 14,944 adults with no history of topical corticosteroid use were included and followed prospectively for approximately 9 years. The primary outcome was the incidence of type 2 diabetes following topical corticosteroid use, with additional analyses by frequency and potency of corticosteroid use. Kaplan-Meier curves and Cox proportional hazard models were used to estimate hazard ratios (HR) for type 2 diabetes. Results : The use of topical corticosteroids was significantly associated with an increased risk of type 2 diabetes (adjusted hazard ratio [aHR] 1.13, 95% CI 1.06–1.20). The high-frequency corticosteroid group demonstrated the highest risk (aHR 1.27, 95% CI 1.09–1.48), while the moderate-potency corticosteroid group also showed a significant increase in risk (aHR 1.15, 95% CI 1.04–1.27). Notably, the diabetes risk in the moderate-potency group was comparable to that observed in the systemic corticosteroid group (aHR 1.20, 95% CI 1.14–1.26). Conclusion : In this study, the use of topical corticosteroids was significantly associated with the incidence of type 2 diabetes. These findings highlight the importance of considering diabetes risk factors when prescribing topical corticosteroids. Topical Corticosteroid use and risk of Type 2 Diabetes: A Nationwide Population-Based Cohort Study in Korea Seungwoo Kim 1* , An ji hui 2* , In Sun Ryou 3 , Yongho Jee 4 , 1 FELZ Inc, Goyang-daero, Deogyang-gu, Goyang-si, Gyeonggi-do, Republic of Korea 2 Institute of Ewha Medical Research, College of Medicine, Ewha Womans University, Seoul, Republic of Korea 3 Department of Family Medicine, Ewha Womans University Seoul Hospital, Seoul, Republic of Korea 4 Advanced Biomedical Research Institute, Ewha Womans University Seoul Hospital, Seoul, Republic of Korea Running Title Topical Steroid Use and Type 2 Diabetes Risk in Korea *These authors contributed equally to this article. Corresponding author Yongho Jee, PhD, MPH Advanced Biomedical Research Institute, Ewha Womans University Seoul Hospital, Seoul, Republic of Korea E-mail: [email protected] Abstract Purpose : Steroid-induced diabetes mellitus (SIDM) is a well-known side effect of corticosteroid agents. While diabetes induced by systemic corticosteroids has been extensively studied for over 60 years, evidence regarding the association between topical corticosteroids and type 2 diabetes remains limited. This study aimed to investigate the relationship between topical corticosteroid use and the risk of type 2 diabetes. Methods : A nationwide, population-based cohort study was conducted using data from the Korea National Health Insurance Service National Sample Cohort Database (NHIS-NSC2). A total of 186,057 adults with new-onset type 2 diabetes were identified as case subjects. Among these, 171,113 adults who had been treated with topical corticosteroids and 14,944 adults with no history of topical corticosteroid use were included and followed prospectively for approximately 9 years. The primary outcome was the incidence of type 2 diabetes following topical corticosteroid use, with additional analyses by frequency and potency of corticosteroid use. Kaplan-Meier curves and Cox proportional hazard models were used to estimate hazard ratios (HR) for type 2 diabetes. Results : The use of topical corticosteroids was significantly associated with an increased risk of type 2 diabetes (adjusted hazard ratio [aHR] 1.13, 95% CI 1.06–1.20). The high-frequency corticosteroid group demonstrated the highest risk (aHR 1.27, 95% CI 1.09–1.48), while the moderate-potency corticosteroid group also showed a significant increase in risk (aHR 1.15, 95% CI 1.04–1.27). Notably, the diabetes risk in the moderate-potency group was comparable to that observed in the systemic corticosteroid group (aHR 1.20, 95% CI 1.14–1.26). Conclusion : In this study, the use of topical corticosteroids was significantly associated with the incidence of type 2 diabetes. These findings highlight the importance of considering diabetes risk factors when prescribing topical corticosteroids. Key Words : Diabetes Mellitus, Steroids, Survival Analysis, Proportional Hazards Models Summary This study is one of the first to analyze the association between topical corticosteroid use and the risk of type 2 diabetes using a large-scale, nationwide cohort (NHIS-NSC2 database). The use of topical corticosteroids was significantly associated with an increased risk of type 2 diabetes (adjusted HR 1.13, 95% CI 1.06–1.20), with a dose-response relationship observed based on frequency and potency of use. The high-frequency corticosteroid users (aHR 1.27, 95% CI 1.09–1.48) and moderate-potency corticosteroid users (aHR 1.15, 95% CI 1.04–1.27) showed the highest risk, comparable to that of systemic corticosteroid users (aHR 1.20, 95% CI 1.14–1.26). These findings emphasize the need to consider the potential risk of diabetes when prescribing topical corticosteroids. 1. Introduction In Korea, the prevalence of diabetes has shown an increasing trend, rising from 12.4% in 2011 to 13.0% in 2014 and 14.4% in 2016. According to the Korean Ministry of Health and Welfare, the medical expenses for diabetes in Korea have sharply increased from 1.4 trillion won in 2010 to 2.2 trillion won in 2017, which not only increases the medical burden on individuals and society but also hinders the stabilization of the public healthcare system [1]. Diabetes is a representative metabolic disorder characterized by hyperglycemia due to defects in insulin secretion or action, and it is more frequently associated with chronic diseases compared to the general population without diabetes. According to Kim et al., 88% of diabetic patients in Korea had at least one comorbid condition such as hypertension or hyperlipidemia, which are well-known risk factors for cardiovascular diseases [2]. In 2018, diabetes ranked as the sixth leading cause of death in Korea, following cancer, heart disease, pneumonia, cerebrovascular disease, and suicide [1]. Corticosteroids are widely used for their anti-inflammatory and immunosuppressive effects in treating numerous conditions, ranging from chronic diseases such as chronic pulmonary disease, rheumatoid disorders, and psoriasis to acute conditions like gout, various malignancies, and organ transplants [3]. However, due to their various side effects, caution is required in their use. Among these side effects, steroid-induced diabetes mellitus (SIDM) is one of the adverse effects reported 60 years ago, where steroids absorbed through medication interfere with insulin action or promote glucose synthesis in the liver, leading to increased blood glucose levels and elevating the risk of type 2 diabetes [4]. Topical corticosteroids, which are applied to the skin, are commonly used in dermatology for a wide range of indications, from chronic inflammatory skin diseases such as psoriasis and atopic dermatitis to itching skin conditions like eczema. They are developed in various strengths and forms to be easily used by infants to the elderly [5]. Topical corticosteroids may be perceived as safer than oral medications due to their application on the skin. However, recent studies have shown that because their particles are small, they can affect the entire body through the bloodstream even when applied to the skin, and they are dose-dependent just like oral medications [6]. However, there is significantly less evidence compared to oral medications, and the existing studies were conducted in Western countries, which may differ from the general characteristics of the Korean population, pointing to limitations in applying these findings to Korean clinical practice. Additionally, no cohort studies have used family history of diabetes and body mass index, which are risk factors for SIDM, as adjustment variables, leading to interpretative limitations. Therefore, this study aims to investigate the risk of type 2 diabetes onset associated with the use of topical corticosteroids in the Korean population, using variables such as family history of diabetes and body mass index, which were identified as limitations in previous studies. The study will differentiate the risk according to the use, frequency of use, and potency of topical corticosteroids. 2. Methods Data Collection and Selection of Study Participants This study utilized the National Sample Cohort 2.0 (NHIS-NSC2) provided by the National Health Insurance Service (NHIS). The National Sample Cohort 2.0 is a research database established in June 2017, containing information from individuals’ NHIS enrollment, including hospital and clinic utilization data, as well as health examination results. As of 2006, it includes a cohort of 1 million people (approximately 2% of the entire population) representative of the national population, encompassing 14 years of information from 2002 to 2015. Our study population consisted of subjects aged 19 years or older with claims history between January 1, 2006, and December 31, 2007, from the National Health Insurance Service-National Sample Cohort 2.0. The topical corticosteroid use group was defined as individuals who were prescribed topical corticosteroids two or more times between 2006 and 2007. The period from January 1, 2002, to December 31, 2005, was set as a wash-out period, during which participants who could influence the study were excluded. First, individuals with primary or secondary outpatient diagnoses corresponding to E.11.X, those who had been prescribed hypoglycemic agents, had fasting blood glucose levels of 126 mg/dL or higher, or who self-reported having diabetes during medical examinations were defined as type 2 diabetes patients and excluded from the study. Furthermore, to eliminate the effect of topical corticosteroid use, participants with a prescription for topical corticosteroids during the wash-out period were excluded, as were those without health examination data. Definition and Classification of Variables The variables used in the study were selected and defined as shown in Supplementary table 1, based on the factors influencing corticosteroid use identified in previous studies through a literature review. According to Suh et al age, body mass index (BMI), family history of diabetes, history of impaired glucose tolerance, dosage and duration of treatment are known risk factors for diabetes related to steroid use [7]. In addition, hypertension, smoking, alcohol consumption, and fasting blood glucose, which are known risk factors for type 2 diabetes, were also selected as variables. More recently, it has been confirmed that the incidence of diabetes is higher in patients with psoriasis compared to the general population, and this was used as a confounding variable [8]. The independent variable, topical corticosteroids, and the confounding variable, systemic corticosteroids, were classified using the active ingredient codes employed by the Sample Cohort 2.0, derived from the entire range of corticosteroid types developed as medications. As shown in Table 2, the active ingredient codes consist of a total of nine components, with the 7th indicating the route of administration, and the 8th and 9th representing the formulation. According to the operational definitions in Table 3, corticosteroids designed in formulations such as creams and lotions, intended to act directly on the body surface like the skin, were classified as topical corticosteroids, while eye ointments were excluded from this classification. Systemic corticosteroids were defined as formulations acting on the entire body, such as oral medications or injections. The active ingredient codes were based on the status as of March 2008, and the types of drugs used in the analysis are listed in supplementary table 2. Topical corticosteroids can be classified into seven potency levels based on the degree of vasoconstriction, with higher potency indicating a stronger drug effect [9]. Accordingly, to examine the effect of potency, this study reclassified the seven potency levels into high, medium, and low potency groups and conducted a stratified analysis. The classification criteria are shown in supplementary table 3. The occurrence of type 2 diabetes, the dependent variable, was determined based on either of the following criteria: (1) if the KCD code E11.X, classified as type 2 diabetes, appeared three or more times as a primary or secondary diagnosis during the follow-up period, the first occurrence was considered the onset, or (2) if the individual was prescribed a hypoglycemic agent. Statistical analysis The analysis was conducted using Kaplan-Meier curves to perform stratified analyses based on the use and non-use groups, drug potency, and usage frequency (0, 1, 2-4, 5 or more times/2 years). Statistical significance was confirmed using the log-rank test. The start of patient follow-up was defined as the point of the second prescription of topical corticosteroids, and patients who did not develop diabetes during the follow-up period or those who died were censored. The Cox proportional hazards model was applied after reviewing the Schoenfeld residual test assumptions, and all models satisfied the proportionality assumption. For each group, crude and adjusted hazard ratios were calculated to identify risk factors. Statistical analysis was performed using SAS version 9.4, and a significance level of 5% was set for all analyses. 3. Results Among the participants with claims records from 2006 to 2007 in the National Health Insurance Service-National Sample Cohort 2.0, 961,653 individuals were identified, of whom 778,544 were aged 19 years or older. During the wash-out period, 112,239 individuals were excluded as type 2 diabetes patients, and 60,359 individuals who had experience with topical corticosteroid prescriptions were also excluded. A final cohort of 186,057 participants with available health examination data was selected for the study and followed up until 2015 (Figure 1). During the study enrollment period from 2006 to 2007, 14,944 individuals (6,508 men and 8,436 women) who were prescribed topical corticosteroids two or more times were classified as the user group, while the remaining 171,113 individuals (94,898 men and 76,215 women) were classified as the non-user group. The user group comprised 8% of the total sample. The prevalence of psoriasis (non-user group: 0.3%, user group: 3.3%), systemic steroid use (13.0%, 30.5%), mean age (42.2 years, 44.6 years), alcohol consumption (72.3%, 76.6%), hypertension (9.7%, 12.2%), and hyperlipidemia (12.3%, 13.5%) were higher in the user group compared to the non-user group. In contrast, smoking (41.6%, 32.9%), family history of diabetes (16.9%, 15.8%), and the proportion of males (55.5%, 43.6%) were higher in the non-user group. Follow-up and observation continued until December 31, 2015, with the average observation period being 8.59 years for the non-user group and 8.47 years for the user group (Table 1). During the observation period, the incidence of type 2 diabetes was higher in the corticosteroid user group (9.1%) compared to the non-user group (7.2%). The incidence rate per 1,000 person-years was 10.74 in the user group and 8.38 in the non-user group. The characteristics according to the frequency of topical corticosteroid use and the potency of topical corticosteroids are presented in Supplementary Tables 4 and 5, respectively (Supplementary table 4, 5) According to the Kaplan-Meier survival curve, the difference in the incidence of type 2 diabetes between the groups began to appear approximately two years after the use of topical corticosteroids, and this difference continued to widen over time (Figure 2). The risk of developing diabetes according to the frequency of topical corticosteroid use is depicted in Figure 3. During the observation period, the incidence of type 2 diabetes was 7.1%, 7.8%, 8.7%, and 12.1% for each group, with incidence rates per 1,000 person-years of 8.26, 9.03, 10.22, and 14.61, respectively. A trend was observed where higher frequencies of topical corticosteroid use were associated with an increased risk of developing diabetes. The Kaplan-Meier survival curve shows that individuals in the ’≥5 uses’ group had a significantly higher cumulative incidence of diabetes over time compared to those in the lower-use groups (Log rank test between ‘0, 1, 2-4’ group and ‘≥5’ group, p<0.0001) (Figure 3). The risk of diabetes according to the potency of topical corticosteroid use is depicted in Figure 4. During the observation period, the incidence of type 2 diabetes was 7.2%, 8.1%, 9.7%, and 9.0% for each group, with incidence rates per 1,000 person-years of 8.38, 9.50, 11.47, and 10.68, respectively. The use of mid-potency corticosteroids was associated with a higher tendency for diabetes development. The Kaplan-Meier survival curves demonstrate that the mid- to high-potency groups had a significantly higher cumulative incidence of diabetes over time compared to the non-use and mild-potency groups (Log rank test between ’mid-high’ group and ’non-mild’ group, p<0.001) (Figure 4). The risk of developing diabetes according to the frequency and potency of topical corticosteroid use is depicted in Figure 5. Kaplan-Meier survival curves were used to assess the cumulative incidence over time based on groups classified by the frequency and potency of topical corticosteroid use. The results showed that the group with high frequency (≥5 uses) and mid-potency had the highest risk of developing type 2 diabetes, followed by the group with high frequency and high potency. In contrast, the group with low frequency (1 use) and mild potency had a risk similar to the non-use group (Figure 5). The results of the Cox proportional hazards model showed that the risk of developing type 2 diabetes was 1.29 times higher in the topical corticosteroid user group compared to the non-user group (HR 1.29, 1.22-1.36, p<0.001). After adjusting for age, sex, and body mass index, the risk was 1.13 times higher (aHR 1.13, 1.07-1.20, p<0.001). When further adjusting for smoking, alcohol consumption, psoriasis, systemic steroid use, family history of diabetes, hypertension, hyperlipidemia, fasting blood glucose, and income level, the risk remained 1.13 times higher (aHR 1.13, 1.06-1.20, p<0.001) for developing type 2 diabetes (Table 2). Cox multivariate regression analysis identified the increased risk of developing diabetes to be associated with ’older age, female sex, higher body mass index, smoking, family history of diabetes, hypertension, hyperlipidemia, fasting blood glucose of 100-125 mg/dL, and the use of systemic corticosteroids.’ On the other hand, ’current alcohol consumption and income levels in the 9th and 10th deciles (Highest)’ were associated with a lower risk of developing diabetes. According to the Cox proportional hazards model, the risk of developing type 2 diabetes was higher in groups that were prescribed topical corticosteroids compared to the group that did not receive a prescription. Specifically, the risk was 1.09 times higher for those prescribed corticosteroids once, 1.24 times higher for those prescribed 2-4 times, and 1.79 times higher for those prescribed five or more times (HR 1.09, 1.04-1.15, p<0.001; HR 1.24, 1.17-1.32, p<0.001; HR 1.79, 1.57-2.05, p<0.001). After adjusting for age, sex, and body mass index, the risks were 1.07, 1.11, and 1.35 times higher, respectively (aHR 1.07, 1.02-1.25, p<0.05; aHR 1.11, 1.05-1.18, p<0.001; aHR 1.35, 1.19-1.55, p<0.001). After further adjustment for smoking, alcohol consumption, psoriasis, systemic steroid use, family history of diabetes, hypertension, hyperlipidemia, fasting blood glucose, and income level, the risks of developing type 2 diabetes remained elevated at 1.07, 1.12, and 1.27 times, respectively (aHR 1.07, 1.02-1.13, p<0.05; aHR 1.12, 1.05-1.20, p<0.001; aHR 1.27, 1.09-1.48, p<0.05) (Table 3). 4. Discussion This study investigated the association between the use of topical corticosteroids and the risk of developing type 2 diabetes among Koreans, using data from the National Health Insurance Service-National Sample Cohort 2.0 (NHIS-NSC2). The findings revealed that individuals using topical corticosteroids exhibited a higher risk of developing type 2 diabetes compared to non-users (adjusted hazard ratio [aHR] 1.13, 95% CI 1.06-1.20). Furthermore, a dose-response relationship was observed, with the risk increasing as the frequency of corticosteroid use escalated (1 use, aHR 1.07, 95% CI 1.02–1.13; 2–4 uses, aHR 1.12, 95% CI 1.05–1.20; 5 or more uses, aHR 1.27, 95% CI 1.09–1.48), reaching a risk comparable to that of systemic corticosteroid use (aHR 1.20, 95% CI 1.14–1.26). Several studies have suggested an association between topical steroid use and the risk of new-onset diabetes mellitus (DM). An analysis of the PHARMO Record Linkage System in the Netherlands found a significant dose-dependent relationship between topical corticosteroid use and diabetes risk (OR 1.20, 95% CI 1.06–1.35), although no correlation with corticosteroid potency was observed [10]. Similarly, case-control studies in Denmark (OR 1.25, 95% CI 1.23–1.28) and the United Kingdom (OR 1.27, 95% CI 1.23–1.31) demonstrated an association between topical corticosteroid use and diabetes. However, only the Danish study revealed a dose-dependent effect. A Danish cohort study further supported these findings, reporting an increased risk of incident type 2 diabetes with a dose-dependent adjusted hazard ratio (HR 1.27, 95% CI 1.26–1.29) [6]. Additionally, a meta-analysis of four case-control studies, involving over 3,500 participants, confirmed a dose-dependent relationship between topical steroid use and diabetes risk, regardless of corticosteroid potency (OR 1.24, 95% CI 1.15–1.34) [11]. These findings underscore the association between topical corticosteroid use and the increased incidence of diabetes. Steroids contribute to hyperglycemia and increase the risk of diabetes through several well-established mechanisms. They influence genes involved in carbohydrate metabolism, such as phosphoenolpyruvate carboxykinase (PEPCK), by upregulating their transcription. This process enhances hepatic gluconeogenesis, leading to elevated endogenous glucose production [11-14]. Additionally, steroids impair insulin sensitivity by reducing GLUT-4 translocation in skeletal muscle and adipose tissue, thereby decreasing peripheral glucose uptake. Steroids are also known to promote muscle protein breakdown and lipolysis in adipose tissue, resulting in unfavorable changes in body composition and increased systemic insulin resistance [11, 13, 15,16]. Chronic glucocorticoid exposure further exerts direct cytotoxic effects on pancreatic β-cells, impairing insulin production and secretion in a dose- and duration-dependent manner [11, 17-19]. These effects may not be limited to systemic administration. Topical steroids, despite their localized application, can exert systemic effects due to percutaneous absorption. Percutaneous absorption involves the passage of the drug through the epidermis and dermis into systemic circulation [20]. Although less than 2% of a single topical steroid application (e.g., hydrocortisone) is absorbed after remaining on the skin for more than a day [21], several factors influence the degree of absorption. These factors include the amount of steroid applied, the frequency of application, the surface area treated, the potency of the steroid, the use of occlusion, among other factors [20]. Skin conditions that disrupt the barrier function, such as eczema, can further enhance absorption, increasing the likelihood of systemic effects [22]. The stratum corneum serves as the primary barrier to percutaneous absorption [23], but its thickness and integrity vary by body site and individual factors. Moreover, the stratum corneum acts as a reservoir, allowing sustained release and absorption of the steroid for up to five days after a single application [24]. These systemic exposures, although minimal, can mimic the metabolic consequences of systemic steroid use, such as glucose dysregulation and increased diabetes risk. In our study, the frequency and amount of topical steroid use were significantly associated with an increased risk of diabetes. This observation can be explained by the mechanisms of percutaneous absorption. However, we also found that the risk of diabetes did not increase significantly with the potency of topical steroids. High-potency groups exhibited a similar or even lower risk compared to medium-potency groups. According to Li et al., two studies confirmed that adherence to medication among patients with atopic dermatitis who had a phobia of topical corticosteroid use was significantly lower than in those without such fears (49.4% vs 14.1%, 29.3% vs 9.8%) [25]. This reduced adherence may be attributed to past experiences of side effects, such as skin thinning, concerns about systemic effects, or fears of reduced efficacy with long-term use [25-27]. Furthermore, patients are often cautioned against using high-potency corticosteroids for more than three weeks or applying them to sensitive areas like the face, which may reinforce these concerns through educational efforts. As a result, even when high-potency corticosteroids are prescribed at the same frequency as lower-potency medications, actual usage may be reduced due to concerns about duration of use and potential side effects [9]. Additionally, high-potency corticosteroids are more commonly prescribed for patients with mild psoriasis, whereas medium-potency corticosteroids are frequently used for patients with atopic dermatitis. Since the affected area is generally larger in patients with atopic dermatitis compared to those with mild psoriasis, differences in application area may have influenced the results [9]. This study has several strengths. It is the first study, to our knowledge, to investigate the association between topical corticosteroid use and the risk of diabetes in an Asian population. It also validates a consistent risk of diabetes development previously observed in studies conducted on Caucasian populations. Furthermore, as this research is based on a large-scale nationwide dataset from Korea, it holds significant clinical value and provides robust evidence applicable to broader populations. However, this study has certain limitations. There is potential for selection bias, as individuals without health examination records were excluded from the analysis. The definition of topical corticosteroid use relied on prescription counts, which may not accurately reflect the actual amount used or the area of application among participants. Furthermore, the study did not account for the timing of initiation or discontinuation of both topical and systemic corticosteroid use, which may have influenced the observed associations. 5. Conclusions This study confirmed that the risk of developing type 2 diabetes increases with the use of topical corticosteroids, depending on both usage and frequency. Therefore, before initiating topical corticosteroid treatment, it is important to screen for impaired glucose tolerance and identify high-risk groups, allowing for the consideration of alternative treatments. If no alternatives are available, regular monitoring during treatment, education on the symptoms of diabetes and steroid-induced diabetes, as well as efforts to mitigate other risk factors, are essential. To prevent type 2 diabetes and ensure the safe use of topical corticosteroids, it is necessary to establish guidelines based on more systematic research as soon as possible. 5.1 Plain Language Summary Corticosteroids are widely used to treat inflammation, and it is well known that long-term use of systemic corticosteroids (oral or injectable forms) can increase the risk of diabetes. However, the potential link between topical corticosteroid use and type 2 diabetes remains unclear. In this study, we examined the association between topical corticosteroid use and the risk of type 2 diabetes using data from the Korean National Health Insurance Service (NHIS-NSC2) database. A total of 186,057 adults were included, among whom 171,113 had used topical corticosteroids and 14,944 had never used them. These individuals were followed for approximately nine years to assess their diabetes risk. The results showed that topical corticosteroid use was significantly associated with an increased risk of type 2 diabetes, particularly among those who used corticosteroids frequently or at moderate potency levels. Notably, the diabetes risk in the moderate-potency corticosteroid group was comparable to that observed in systemic corticosteroid users. This study highlights that topical corticosteroids should not be assumed to be entirely risk-free, and their potential impact on diabetes risk should be carefully considered when prescribing. Further research is needed to clarify the relationship between topical corticosteroid use and metabolic diseases. Author Contributions Seungwoo Kim and An ji hui conceptualized and designed the study and analyzed the data. In Sun Ryou provided clinical expertise. The manuscript was initially prepared Yongho Jee. All authors have revised and approved the final version of the paper and agree to be accountable for all aspects of their work. Funding This research was conducted with support from the National Research Foundation of Korea with funding from the Ministry of Science and ICT (No. RS-2023-00210888). Ethics Statement Our study’s data usage and study design were approved by the Institutional Review Board of Yonsei University Health System, and informed consent was obtained from each subject (Y-2019-0058). Conflict of Interest The authors declare that they do not have any competing interests. References 1. Kim BY, Won JC, Lee JH, Kim HS, Park JH, Ha KH, Won KC, Kim DJ, Park KS. Diabetes Fact Sheets in Korea, 2018: An Appraisal of Current Status. Diabetes Metab J. (2019): 43(4):487-494. 2. Kim SY, Nah EH, Cho S. Prevalence of Comorbidities among Patients with Diabetes. J Health Info Stat (2018): 43(3):237-244. 3. Fathallah N, Slim R, Larif S, Hmouda H, Ben Salem C. Drug-induced hyperglycaemia and diabetes. Drug Saf. (2015): 38:1153-68. 4. Perez A, Jansen-Chaparro S, Saigi I, Bernal-Lopez MR, Miñambres I, Gomez-Huelgas R. Glucocorticoid-induced hyperglycemia. J Diabetes (2014): 6:9-20. 5. Lee JH, Park YM. Proper use of topical corticosteroids. J Korean Med Assoc. (2018): 61(10):632-6. 6. Andersen YMF, Egeberg A, Ban L, et al., Association Between Topical Corticosteroid Use and Type 2 Diabetes in Two European Population-Based Adult Cohorts. Diabetes Care. (2019) Jun;42(6):1095-1103. 7. Suh SH, Park MK. Management of Steroid-induced Hyperglycemia. J Korean Diabetes. (2016);17:174-184. 8. Wan MT, Shin DB, Hubbard RA, Noe MH, Mehta NN, Gelfand JM. Psoriasis and the risk of diabetes: A prospective population-based cohort study. J Am Acad Dermatol. (2018): 78(2):315-322. 9. Ference JD, Last AR. Choosing topical corticosteroids. Am Fam Physician. (2009): 15;79(2):135-40. 10. M. W. van der Linden, F. J. Penning-van Beest, T. Nijsten, and R. M. Herings, “Topical corticosteroids and the risk of diabetes mellitus: a nested case-control study in Te Netherlands,” Drug Safety, vol. 32, pp. 527–537, 2009. 11. K. Phan and S. D. Smith, “Topical corticosteroids and risk of diabetes mellitus: systematic review and meta-analysis,” Journal of Dermatological Treatment, vol. 32, pp. 1–5, 2019 12. Andrews RC, Walker BR. ”Glucocorticoids and insulin resistance: old hormones, new targets.” Clinical Science. 1999;96(5):513-523. 13. van Raalte DH, Ouwens DM, Diamant M. ”Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options?” European Journal of Clinical Investigation. 2009;39(2):81-93. 14. Krug AW, Vögele AK, Matysik S, et al. ”Glucocorticoids in insulin resistance and diabetes mellitus.” Current Pharmaceutical Design. 2011;17(37):3878-3884. 15. Weinstein SP, Paquin T, Pritsker A, Haber RS. ”Glucocorticoid-induced insulin resistance: dexamethasone inhibits the activation of glucose transport in rat skeletal muscle by both insulin- and non-insulin-related stimuli.” Diabetes. 1995;44(4):441-445. 16. Kraegen EW, Clark PW, Jenkins AB, Daley EA, Chisholm DJ, Storlien LH. ”Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats.” Diabetes. 1991;40(11):1397-1403. 17. Weinhaus AJ, Bhagroo NV, Brelje TC, Sorenson RL. ”Dexamethasone alters the expression of key β-cell genes and reduces insulin secretion in rat islets.” American Journal of Physiology-Endocrinology and Metabolism. 2002;282(4):E679-E686. 18. Liu H, Bravata DM, Cabaccan J, Raff H, Ryzen E. ”Elevated late-night salivary cortisol levels in elderly type 2 diabetic patients.” Diabetes Care. 2005;28(10):2548-2553. 19. Shen CN, Chiang PH, Yang CK, et al. ”Glucocorticoids mediate pancreatic β-cell dysfunction by inhibiting glucose sensing, insulin secretion, and cell survival.” Journal of Molecular Endocrinology. 2016;57(3):R75-R87. 20. Dhar S, Seth J, Parikh D. Systemic side-effects of topical corticosteroids. Indian J Dermatol. 2014 Sep;59(5):460-4. 21. De Souza A, Strober BE. Principles of topical therapy. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, et al., editors. Fitzpatrick’s Dermatology in General Medicine. 6th ed. New York: Mc Graw-Hill; 2008. pp. 2643–51. 22. Carruthers JA, August PJ, Staughton RC. Observations on the systemic effect of topical clobetasolpropionate(Dermovate).BMJ1975;4: 203–204 23. Wester RC, Bucks DA, Maibach HI. In vivo percutaneous absorption of hydrocortisone in psoriatic patients and normal volunteers. J Am Acad Dermatol. 1983;8:645–7. 24. Riegelman S. Pharmacokinetics. Pharmacokinetic factors affecting epidermal penetration and percutaneous absorption. Clin Pharmacol Ther. 1974;16:873–83. 25. Li AW, Yin ES, Antaya RJ. Topical Corticosteroid Phobia in Atopic Dermatitis: A Systematic Review. JAMA Dermatol. (2017) 1;153(10):1036-1042. 26. Charman CR, Morris AD, Williams HC. Topical corticosteroid phobia in patients with atopic eczema. Br J Dermatol. (2000):142(5):931-6. 27. Müller SM, Tomaschett D, Euler S, Vogt DR, Herzog L, Itin P. Topical Corticosteroid Concerns in Dermatological Outpatients: A Cross-Sectional and Interventional Study. Dermatology. 2016;232(4):444-52. Supplementary Material File (pds-25-0165-file002.pptx) Download 879.05 KB Information & Authors Information Version history V1 Version 1 16 March 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords diabetes mellitus proportional hazards models steroids survival analysis Authors Affiliations Seungwoo Kim FELZ Inc View all articles by this author Ji hui An Ewha Womans University College of Medicine View all articles by this author In Sun Ryou Ewha Womans University College of Medicine View all articles by this author Yongho Jee 0000-0003-0365-8302 [email protected] Ewha Womans University Seoul Hospital View all articles by this author Metrics & Citations Metrics Article Usage 631 views 140 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Seungwoo Kim, Ji hui An, In Sun Ryou, et al. Topical Corticosteroid use and risk of Type 2 Diabetes: A Nationwide Population-Based Cohort Study in Korea. Authorea . 16 March 2025. DOI: https://doi.org/10.22541/au.174215714.49752623/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. 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