|Year : 2018 | Volume
| Issue : 1 | Page : 55-60
Adult balanoposthitis patients have a higher risk of Type 2 diabetes mellitus: A nationwide population-based cohort study
Chi-Ping Huang, Chi-Shun Lien, Sheng-Wei Lee, Chao-Hsiang Chang, Cheng-Li Lin
Department of Urology, China Medical University and Hospital, Taichung, Taiwan
|Date of Web Publication||23-Feb-2018|
China Medical University Hospital, Taichung
Source of Support: None, Conflict of Interest: None
Background: We investigated the association between balanoposthitis and the risk of type 2 diabetes mellitus (type 2 DM) from a retrospective cohort study. Methods: From the Longitudinal Health Insurance Database (LHID) 2000, we selected male patients aged over 20 years and first diagnosed with balanoposthitis during 2000–2010. Men without balanoposthitis were also included in our analysis through frequency matching for age and index year. All participants were followed up until the diagnosis of type 2 DM. Diseases were coded in accordance with the International Classification of Diseases, Ninth Revision, Clinical Modification. Baseline comorbidity history for each participant was determined from the LHID dataset. A multivariable Cox proportional hazard regression model was established, and a Kaplan–Meier survival curve was plotted. Results: The incidence of type 2 DM was higher in the balanoposthitis cohort than in the nonbalanoposthitis cohort (14.8 vs. 5.42/1000 person-years) with a hazard ratio of 2.55 (95% confidence interval = 2.22–2.92) after adjusting for age and other comorbidities. The incidence of type 2 DM increased with age in both cohorts. Balanitis patients with hypertension, hyperlipidemia, or obesity had higher risks for type 2 DM than those without these conditions (all P < 0.05). Conclusions: Men with balanoposthitis may have a higher risk of type 2 DM in the future. Therefore, clinical physicians should pay more attention to the early evaluation and management of type 2 DM in the patients with balanoposthitis.
Keywords: Balanoposthitis, retrospective cohort study, type 2 diabetes mellitus
|How to cite this article:|
Huang CP, Lien CS, Lee SW, Chang CH, Lin CL. Adult balanoposthitis patients have a higher risk of Type 2 diabetes mellitus: A nationwide population-based cohort study. Urol Sci 2018;29:55-60
|How to cite this URL:|
Huang CP, Lien CS, Lee SW, Chang CH, Lin CL. Adult balanoposthitis patients have a higher risk of Type 2 diabetes mellitus: A nationwide population-based cohort study. Urol Sci [serial online] 2018 [cited 2020 Dec 1];29:55-60. Available from: https://www.e-urol-sci.com/text.asp?2018/29/1/55/226031
| Introduction|| |
Type 2 diabetes mellitus (type 2 DM) is positively related to balanitis. A recent study has reported that balanitis is found in 12% of newly diagnosed diabetics. In addition to balanitis, type 2 DM is related to the high occurrence of other infections.,, Poorly controlled blood glucose is associated with the proliferation of Candida species beneath the prepuce, which may lead to balanitis. A few studies revealed that type 2 DM is a risk factor for balanitis or progressive to phimosis.,
Metabolic syndrome (MS)-related diseases such as hypertension, hyperlipidemia, and obesity are associated with an increased risk for cardiovascular heart disease and type 2 DM.,, Obesity induces chronic systemic inflammation and increases the risk for type 2 DM development. Therefore, the aforementioned MS-related diseases are also involved in the incidence of type 2 DM and directly or indirectly associated with balanoposthitis.
Males may be diagnosed of balanoposthitis at any age, and the prevalence of the disease is based on age. Approximately 11% of men in the United States present with balanoposthitis in urology clinics, and approximately 3% of uncircumcised men are diagnosed with balanoposthitis globally. Blood glucose disorders are associated with increased risk for balanoposthitis or progressive to phimosis., However, whether or not balanoposthitis patients have a higher risk of subsequently developing type 2 DM and balanoposthitis remains unclear. Therefore, we constructed a retrospective cohort study and investigated the risk of type 2 DM in men with balanoposthitis after adjusting for potential comorbidities.
| Methods|| |
Taiwan launched the National Health Insurance (NHI) program in 1995. NHI enrolled up to 99% of the Taiwanese population and contracted with 97% of the medical providers. In 1999, as part of the NHI Research Database project, the Bureau of NHI began to release patient data in electronic format for research purposes; this electronic database contains all medical claims from 1996 to 2011 and is maintained by the National Health Research Institutes. The present study was performed using Longitudinal Health Insurance Database 2000 (LHID 2000), which comprises detailed health-care usage data from 1996 to 2011 of 1 million NHI enrollees who were randomly selected and proven to be representative of the distribution of the Taiwanese population in 2000 (http://nhird.nhri.org.tw/en/Data_Subsets.html). Diseases were coded in accordance with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). This study was exempted from full ethical review by the Institutional Review Board of China Medical University (CMU-REC-101-012).
From LHID 2000, we selected male patients aged more than 20 years and were diagnosed with balanoposthitis (ICD-9-CM 607.1, 607.81) from January 1, 2000, to December 31, 2010, as the balanoposthitis cohort. The date of first diagnosis for balanoposthitis was defined as the index date. We excluded participants who were younger than 20 years, had previous type 2 DM (ICD-9-CM 250.x0 and 250.x2), and lacked information on age or sex. For each corresponding patient in the balanoposthitis cohort, four male participants from the nonbalanoposthitis cohort were selected through frequency matching for age (with a span of every 5 years) and index year under the same exclusion criteria to increase the comparability between the two cohorts.
Outcome and relevant variables
All subjects were followed-up until subjected diagnosed of type 2 DM, or the subjects were not available for follow-up, or the insurance system was terminated, or until the 31st of December, 2011. The baseline comorbidity at the beginning of the study for each participant was determined from LHID 2000; the identified comorbidities included hypertension (ICD-9-CM codes 401–405), hyperlipidemia (ICD-9-CM codes 272), stroke (ICD-9-CM 430–438), coronary artery disease (CAD) (410–414), chronic kidney disease (CKD) (ICD-9-CM codes 585), heart failure (ICD-9-CM codes 428), obesity (ICD-9-CM 278), and Charlson Comorbidity Index (CCI). CCI index was counted for each participant from claims' data for outpatient visits or hospitalizations. The CCI is a scoring system that includes weighting factors on important concomitant diseases; it has been validated for use with ICD-9-CM-coded administrative database.,
The baseline characteristics were first analyzed using descriptive statistics and then compared using Chi-square tests for categorical variables and independent two-sample t-test for continuous variables. Person-years were calculated as the interval from the index date to the date of type 2 DM diagnosis, loss to follow-up, or at the end of 2011. We calculated the incidence rates of type 2 DM in both cohorts.
The proportional hazard model assumption was also examined using a test of scaled Schoenfeld residuals. In the model evaluating the risk of type 2 DM throughout the follow-up period, a significant relationship was found between Schoenfeld residuals for balanoposthitis and follow-up time, suggesting that the proportionality assumption was violated (P < 0.001). Therefore, we used univariable and multivariable extend Cox proportional hazard regression models to assess the risk of developing type 2 DM comparing between balanoposthitis and nonbalanoposthitis cohorts. Hazard ratio (HR) and 95% confidence interval (CI) were estimated in the Cox model. The multivariable model was controlled for age and other comorbidities that showed significant differences with the univariable Cox proportion hazard regression model. We used multiplicative analysis to evaluate the interaction effect of balanoposthitis and comorbidities (hypertension, hyperlipidemia, and obesity) on type 2 DM risk. Data analysis was performed using SAS 9.3 software (SAS Institute, Cary, NC, USA). The significance level of 0.05 was considered for two-sided testing.
| Results|| |
We established a balanoposthitis cohort of 3765 male patients and a nonbalanoposthitis cohort of 15,060 men. Most participants of balanoposthitis and nonbalanoposthitis cohorts were 20–34 years old (57.8% vs. 56.8%, respectively) [Table 1]. The males from the balanoposthitis and nonbalanoposthitis cohorts had mean ages of 37.0 (standard deviation [SD] = 15.2) and 36.9 (SD = 15.5) years, respectively. Compared with the nonbalanoposthitis cohort, the balanoposthitis cohort exhibited higher prevalence rates of hypertension (14.3% vs. 10.9%), hyperlipidemia (11.3% vs. 6.95%), CAD (6.67% vs. 4.85%), CKD (4.04% vs. 2.80%), heart failure (1.54% vs. 1.10%), and obesity (1.41% vs. 0.60%) (all P < 0.05). CCI score between the two cohorts was not different (P = 0.11). The mean follow-up years were 6.29 ± 3.27 years for the balanoposthitis cohort and 6.42 ± 3.18 years for the nonbalanoposthitis cohort. The cumulative incidence of type 2 DM was 6.57% higher in the balanoposthitis cohort (11.96%) than in the nonbalanoposthitis cohort (5.39%) at the end of follow-up [Figure 1]. Overall, the incidence of type 2 DM was higher in the balanoposthitis cohort than in the nonbalanoposthitis cohort (14.8 vs. 5.42/1000 person-years, crude HR = 3.57, 95% CI = 23.05–4.19), with an HR of 3.36 (95% CI = 2.86–3.94) after adjusting for age, CCI score, and comorbidities including hypertension, hyperlipidemia, stroke, CAD, CKD, heart failure, and obesity [Table 2]. The incidence of type 2 DM increased with age in both cohorts. The age-adjusted HRs of type 2 DM were significant for all age groups (adjusted HR = 5.18, 95% CI = 3.48–7.72 for the group aged ≤34 years; adjusted HR = 3.70, 95% CI = 2.87–4.76 for the group aged 35–49 years; and adjusted HR = 2.46, 95% CI = 1.89–3.18 for the group aged ≥50 years). For CCI score, adjusted HRs of type 2 DM were increased risks of 3.55 (95% CI = 3.00–4.20) and 2.14 (95% CI = 1.13–4.04) for those with CCI score 0 and 1, respectively. The related adjusted HRs of type 2 DM were 4.40 (95% CI = 3.46–5.59) and 2.66 (95% CI = 2.14–3.30) with and without comorbidity, respectively. In the first 2 years of follow-up, the balanoposthitis cohort had a higher diagnosis with type 2 DM compared with the nonbalanoposthitis cohort (adjusted HR = 3.10, 95% CI = 2.40–3.99). Moreover, the risk of type 2 DM in the balanoposthitis cohort was still significantly higher than that in the nonbalanoposthitis cohort after 6 years of follow-up (adjusted HR = 1.64, 95% CI = 1.19–2.26). [Table 3] shows the results of univariable and multivariable regression analyses for risk factors of type 2 DM. The adjusted HR of type 2 DM increased by 4% for every year of increase in age. Participants with CCI score 0 had the highest risk of type 2 DM (adjusted HR = 4.02, 95% CI = 1.49–10.8). The hazard of developing type 2 DM was high in the balanoposthitis patients with the comorbidity of hypertension (adjusted HR = 1.62, 95% CI = 1.34–1.96), hyperlipidemia (adjusted HR = 2.11, 95% CI = 1.77–2.52), or obesity (adjusted HR = 2.30, 95% CI = 1.43–3.70).
|Table 1: Demographic characteristics and comorbidity in patients with and without balanitis|
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|Figure 1: Cumulative incidence of type 2 diabetes for patients with and without balanitis|
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|Table 2: Comparison of incidence and hazard ratio of Type 2 diabetes mellitus stratified by sex, age, and comorbidity between patients with and without balanitis|
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|Table 3: Extended cox regression model with hazard ratios and 95% confidence intervals of Type 2 diabetes mellitus associated with balanoposthitis and covariates|
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[Table 4] illustrates the synergistic effect of balanoposthitis and comorbidities on type 2 DM risk. Patients with balanoposthitis and obesity had a higher risk of type 2 DM than those without these conditions (adjusted HR = 10.6, 95% CI = 5.79–19.3). Patients with balanoposthitis and hyperlipidemia were 6.76 fold more likely to develop type 2 DM than those without these conditions (95% CI = 5.26–8.68). Patients with balanoposthitis and hypertension had a higher risk of type 2 DM than those without these conditions (adjusted HR = 5.96, 95% CI = 4.62–7.68). However, balanoposthitis and hypertension, balanoposthitis and hyperlipidemia, or balanoposthitis and obesity exerted no significantly multiplicative interaction on type 2 DM risk (all interaction P > 0.05).
|Table 4: Extended cox regression model for the risk of Type 2 diabetes mellitus-associated balanitis with joint effect of hypertension and hyperlipidemia|
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| Discussion|| |
To the best of our knowledge, this study is the first to investigate the risk of developing type 2 DM in a large cohort of Taiwanese patients diagnosed with or without balanitis during a 10-year follow-up period. Balanoposthitis in this cohort was associated with an independent risk factor for type 2 DM. Furthermore, balanoposthitis patients with hypertension, hyperlipidemia, or obesity had higher risks for type 2 DM than those without these conditions.
Symptoms of balanoposthitis include pruritus, pain, tenderness, or erythematous change of the prepuce and glans penis. Thick foul-smelling discharge from urethral meatus may be found. This disease usually occurs in uncircumcised males, but the cause is often undetermined. The diagnosis of balanoposthitis is mainly based on clinical history and physical examination. Ke et al. proposed that a volcano-like appearance may be a typical finding in diabetic balanoposthitis. Fornasa et al. speculated that the cause of balanoposthitis is intertrigo, irritant dermatitis, maceration injury, or bacterial or candidal infection.
Type 2 DM is a risk factor for balanoposthitis. Poor blood glucose control is associated with Candida species infection beneath the prepuce. The initial evaluation and management of candidal balanoposthitis include the treatment of underlying diseases such as type 2 DM or immune deficiency. Furthermore, previous research revealed that type 2 DM is a risk factor for urinary tract infection (UTI). Glycosuria increases the growth of pathogenic bacteria., Impairments of the immune system may lead to the pathogenesis of UTI in type 2 DM patients. In addition, the previous study showed that type 2 DM patients are accompanied by an increased risk of vulvovaginitis or balanitis related to the induction of glucosuria. These mechanisms may be involved in the comorbidity of balanoposthitis and type 2 DM. In the present study, comorbidities such as hyperlipidemia and obesity are risk factors for type 2 DM., Obesity develops through the pathologic expansion of adipose tissue or the enlargement of preexisting differentiated adipocytes. This phenomenon leads to insulin resistance, which is associated with endocrine and metabolic problems.,, Obesity results in insulin resistance through chronic low-grade inflammation in the expanding adipose tissue but systematically progresses after the release of pro-inflammatory mediators including cytokines into the serum.,, Besides, in the present study, balanoposthitis concomitant with obesity or other comorbidities was significantly associated with an increased risk for type 2 DM after adjusting for age in the multivariate analysis. We suspected inflammation-related insulin resistance promotes the development of type 2 DM. But it need further study and investigation.
Our research has some limitations. First, patients with MS were not accurately identified from LHID 2000; therefore, further prospective research is necessary to explore the modified effect of MS on balanoposthitis-related risk for type 2 DM. In addition, the influence of lifestyle risk factors, including diet, smoking, actual lipid level, body mass index (BMI), and clinical index, was not evaluated from LHID 2000. These variables might be important confounding factors for type 2 DM development. Although we adjusted the important risk factors including hyperlipidemia and obesity categorized by ICD-9-CM codes, it may partly reflect the actual values of lipid level and BMI. Second, we think patient came to urologist outpatient clinic usually because of prepuce infection or inflammation, and they might not mention about diabetes mellitus symptoms nor signs. Hence, the population of concurrent diagnosis of balanoposthitis might be underestimated.
| Conclusions|| |
Patients with an initial presentation of balanoposthitis have a higher risk for type 2 DM in the future. Furthermore, balanoposthitis patients with hypertension, hyperlipidemia, or obesity have higher risks for type 2 DM. Thus, early detection and management of type 2 DM are important in these patients with balanoposthitis.
This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW104-TDU-B-212-113002), China Medical University Hospital, Academia Sinica Taiwan Biobank, Stroke Biosignature Project (BM104010092), NRPB Stroke Clinical Trial Consortium (MOST 103-2325-B-039 -006), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]