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Journal of Diabetes 6 (2014) 448–450

RESEARCH LETTER

Pioglitazone and thyroid cancer risk in Taiwanese patients with type 2 diabetes Chin-Hsiao TSENG1,2,3 1 Department of Internal Medicine, National Taiwan University College of Medicine, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, and 3Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Taipei, Taiwan

Keywords: diabetes, epidemiology, pioglitazone, Taiwan, thyroid cancer. Introduction The incidence of thyroid cancer is increasing around the world, including Taiwan.1,2 This has been speculated to be related to the increasing prevalence of insulin resistance status, one of the pathophysiological etiologies of thyroid cancer.3 However, it is interesting that the risk of thyroid cancer is not significantly increased in patients with diabetes.4 One of the possible explanations is the protective effect of some anti-diabetic drugs targeting insulin resistance. In a previous population-based study, rosiglitazone use can be associated with a 30–50% lower risk of thyroid cancer.5 The purpose of the present study was to further evaluate whether pioglitazone might affect thyroid cancer risk, by using the National Health Insurance (NHI) reimbursement databases of Taiwan.

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Materials and methods An ethic review board of the National Health Research Institutes approved this study (approval number 99274). A detailed description of the methods can be seen elsewhere.5 In brief, an entry date was set on 1 January 2006. The databases of all patients who had been diagnosed as having diabetes, remained in the NHI after the entry date, and under treatment with either oral antidiabetic agents or insulin during the period of 1996–2009 from the whole nation were first retrieved (n = 1 554 030). After excluding patients whose diabetes was diagnosed after 2006 (n = 342 351), patients having type 1 diabetes (n = 7120), patients having thyroid cancer before 2006 Correspondence Chin-Hsiao Tseng, Department of Internal Medicine, National Taiwan University Hospital, no. 7 Chung-Shan South Road, Taipei (100), Taiwan. Tel: +886 2 2388 3578 Fax: +886 2 2388 3578 Email: [email protected] Received: 28 January 2014; revised 6 March 2014; accepted 16 March 2014. doi: 10.1111/1753-0407.12149

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(n = 3640), those who died (n = 96 320) or withdrew from the NHI (n = 12 502) before entry date, duplicated identification number (n = 106), and unclear information on date of birth or sex (n = 5122), a total of 1 097 215 patients were recruited. Diabetes was coded 250.1–250.9 and thyroid cancer 193, based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). An ever-user of pioglitazone was defined as a patient who had ever been prescribed with the drug before the entry date. A never-user was defined as a patient who had never been prescribed with the drug before the entry date. The tertile cutoffs of three parameters were calculated and used in the analyses of a dose-response relationship: (i) time since starting pioglitazone (months); (ii) duration of therapy (months); and (iii) cumulative dose (mg). Comorbidities and covariates were determined as a status/diagnosis before the entry date by using the ICD9-CM codes as described in detail elsewhere5 and compared by χ2 test between never-users and ever-users of pioglitazone. “Potential detection examinations” included thyroid sonography, thyroid aspiration, and/or thyroid function test (T3, T4 and thyroid stimulating hormone). The calculation of the incidence density of thyroid cancer and the estimation of hazard ratios for thyroid cancer for ever-users versus never-users, and for the various subgroups of dose-response parameters had been described previously.5 The hazard ratios were estimated by Cox regression in models adjusted for age and sex, and for all baseline characteristics. Analyses were conducted using SAS statistical software, version 9.3 (SAS Institute, Cary, NC, USA). P < 0.05 was considered statistically significant. Results The baseline characteristics between ever-users (n = 58 378) and never-users (n = 1 038 837) of pioglitazone were all significantly different (Table 1). Ever-users were younger in age distribution, female predominant, and had higher proportions of diabetes duration ≥5 years,

© 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd

Research Letter Table 1

Baseline characteristics between never-users and ever-users of pioglitazone Never-users

Variables

n

n Age (years)

Pioglitazone and thyroid cancer risk in Taiwanese patients with type 2 diabetes 2.

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