Long-Standing Graves Disease Associated With Risk of Diabetes

Diabetes and thyroid disease often coexist in patients with the disorders, but the connection between new onset diabetes with thyroid dysfunction is unclear. Investigators looked for the link.

People with long-standing Graves disease who received radioactive iodine ablation (RIA) and long-term treatment with antithyroid drugs (ATDs) have an increased risk of diabetes compared with the general population, according to a study in Endocrinology and Metabolism.

The retrospective cohort study was based on data from the Korean National Health Insurance Service (NHIS) database. Patients were diagnosed with hyperthyroidism between 2005 and 2012 and began antithyroid drug (ATD) treatment within 90 days of diagnosis.

All participants had at least 1 National Health Screening Examination between 2010 and 2012 and were receiving active treatment for Graves disease (ATD or  RIA).

The participants were categorized into 2 groups based on subsequent treatment after an initial 24-month ATD course—those who continued ATD for at least 12 more months without RIA treatment (ATD group) and those who received RIA after the initial ATD course (RIA group). The primary outcome was new-onset diabetes.

A total of 4593 patients with long-standing Graves disease and 45,930 control participants were included in the study. Both groups had a median age of 48 years and 65% were women. For the patients with Graves disease, 4491 (97.8%) were in the ATD group and 102 (2.2%) were in the RIA group.

Diabetes was diagnosed in 751 (16.3%) patients with long-standing Graves disease and 6424 (14.0%) individuals in the control group after a mean follow-up of 7.3 years, with a significant difference occurring between the 2 groups (log-rank P < .001). The hazard ratio (HR) for diabetes was 1.18 (95% CI, 1.1 to 1.28; P < .001) in patients with hyperthyroidism after complete adjustment.

In the ATD group, the HR for diabetes was 1.17 (95% CI, 1.08 to 1.27; P < .001) vs 1.88 (95% CI, 1.22 to 2.88; P = .004) in the RIA group after complete adjustment. The RIA group had an increased risk of diabetes (HR 1.56; 95% CI, 1.01 to 2.42; P = .045), with the ATD group as a reference.

The risk of diabetes increased with an increase in treatment duration (P for trend = .019) when stratified according to ATD treatment duration (2-3, 3-4, and ≥4 years).

Study limitations include the retrospective design, lack of information on thyroid function tests, and diagnosis based on International Classification of Diseases Tenth Revision codes.

“A systematic approach to glucose monitoring in patients with Graves disease during follow-up, along with effective control of hyperthyroidism, may be reasonable to reduce the risk of developing [diabetes mellitus] in these patients,” the researchers concluded.


Song E, Koo MJ, Noh E, et al. Risk of diabetes in patients with long-standing Graves’ disease: a longitudinal study. Endocrinol Metab (Seoul). Published December 16, 2021. doi:10.3803/EnM.2021.1251