Diabetes and Hyperthyroidism: Is There a Causal Link?

Diabetes mellitus (DM) and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. It is well known that Hashimoto’s thyroiditis and Graves’ disease are autoimmune disorders that constitute the most prevalent forms of TD [1]. It is also known that type 1 DM occurs due to autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiency [2]. The combination of these types of TD and type 1 DM, as autoimmune-induced endocrine disorders, is termed polyglandular autoimmune syndrome [3]. Beyond these relationships between autoimmune-induced endocrine disorders, several studies have demonstrated that TD is closely related to DM. TD is more common in patients with type 2 DM than in the general population and can adversely influence their metabolic control. The overall prevalence of TD in patients with type 2 DM in several countries has been reported to range from 4% to 20% [4,5]. It is well known that both hyperthyroidism and hypothyroidism can change glucose and lipid metabolism. Metabolic changes in patients with hyperthyroidism mainly result from increased insulin resistance, because excess thyroid hormone increases endogenous glucose production and insulin requirements and reduces hepatic insulin sensitivity [6]. Therefore, when hyperthyroidism occurs in patients with DM, they are at an elevated risk of severe hyperglycemia and poor glycemic control. However, although the association between hyperthyroidism and glucose metabolism is well documented, few studies have prospectively investigated the relationship between TD and new-onset DM. Moreover, the studies that have addressed this issue have predominantly investigated the relationship between hypothyroidism and the incidence of DM [7,8]. In this respect, it is necessary to investigate the risk of DM in patients with hyperthyroidism and to establish a screening program accordingly. In this issue of Endocrinology and Metabolism, Song et al. [9] published a study investigating the risk of DM in patients with long-standing Graves’ disease using retrospective data from the Korean National Health Insurance Service database. Long-standing Graves’ disease was defined as anti-thyroid drug (ATD) treatment for more than 24 months after the diagnosis of hyperthyroidism. The patients were also subclassified into a group that maintained ATD for more than 12 months after initial treatment for 24 months and a group that received radioactive iodine ablation (RIA) therapy after initial treatment. The authors reported that the hazard ratio for DM occurrence was 1.18 in patients with hyperthyroidism after adjustment compared to the control group. The risk of DM increased with an increased duration of ATD treatment, as well as in the RIA therapy group. From these results, we can infer that hyperthyroidism increases the incidence of DM by causing changes in blood glucose metabolism, especially in patients receiving long-term ATD therapy or RAI therapy. Notably, the risk of DM was particularly prominent in patients with a relatively low body mass index (BMI) and those without dyslipidemia. Because high BMI and dyslipidemia are regarded as conventional risk factors for DM, it is noteworthy that the risk of DM increased in patients with a low BMI and a normal lipid profile in this analysis. Therefore, this result means that hyperthyroidism and hypothyroidism may