Risk of Diabetes in Patients with Long-Standing Graves' Disease: A Longitudinal Study

Abstract

Background: The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies.

Methods: The risk of diabetes in patients with Graves' disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group.

Results: A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019).

Conclusion: The risk of diabetes was significantly higher in patients with long-standing Graves' disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

Keywords: Antithyroid agents; Diabetes mellitus; Graves disease; Hyperthyroidism; Radioiodine ablation.

Fig. 1

Flowchart of the study. DM, diabetes mellitus; ATD, antithyroid drug; RIA, radioactive iodine ablation.

Fig. 2

Kaplan–Meier curves for cumulative incidence of new-onset diabetes (A) in total long-standing Graves’ patients and (B) among the treatment modality groups compared to the controls. ATD, antithyroid drug; RIA, radioactive iodine ablation.

Fig. 3

Subgroup analysis comparing the hazard ratios (HRs) for developing diabetes between long-lasting graves’ patients and matched control group. The HRs were determined by conducting a multivariate Cox proportional hazards regression analysis adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, hypertension (HTN), dyslipidemia, systolic blood pressure, low-density lipoprotein, and fasting glucose. BMI, body mass index; CI, confidence interval.