Insulin Sensitivity and Beta-Cell Function in Graves’ Disease and Their Changes with the Carbimazole-Induced Euthyroid State

Abstract

Background and Objective: Thyroid hormones play an important role in intermediate metabolism, and abnormal glucose tolerance is often observed in patients with hyperthyroidism. Several pathogenic mechanisms have been proposed as contributors. However, there is no conclusive evidence in the existing literature regarding the predominant underlying pathophysiology. Our objective was to determine the changes in insulin resistance parameters and beta-cell function in patients with Graves’ disease following restoration of a euthyroid state. Methodology: This was an observational study with a before-after study design. Forty-five treatment-naïve adults with Graves’ diseases were included and 36 completed the study. An oral glucose tolerance test was performed at baseline and after 3 months of achieving a stable euthyroid state to assess glucose tolerance, insulin sensitivity, and beta-cell function. All patients were treated with antithyroid medication. The outcome measures studied were the Homeostasis Model Assessment-2 Insulin Resistance (HOMA2-IR), Matsuda index, and Insulin Secretion-Sensitivity Index (ISSI)-2. Results: Two-thirds of the patients had abnormal glucose tolerance at baseline. Among those with abnormal glucose tolerance at baseline, 34.7% had persistent abnormality during follow-up. During follow-up, no significant change was noted in the indices of insulin resistance. Patients with abnormal glucose tolerance had a significantly lower ISSI-2 index at baseline and it improved after achieving a euthyroid state. Conclusions: Abnormal glucose tolerance is a significant metabolic consequence in patients with Graves’ disease. Decreased beta-cell function was observed among those with abnormal glucose tolerance and it improved during follow-up. In a proportion of patients, abnormal glucose tolerance persisted after 3 months, emphasizing the need for continued follow-up.

Association Between Thyroid Dysfunction and Hyperglycemia is More Significant in Females Younger Than 65 years old

“…Some recognized mechanisms, i.e., the uctuation of thyroid hormones can worsen glucose metabolic homeostasis, might explain the above phenomenon [22]. For hyperthyroidism patients, the excess of thyroid hormones promotes the insulin requirement and glucose production and absorption, while the peripheral insulin sensitivity is reduced [23][24][25]. The mechanisms clearance rate of insulin was also suggested to be faster in hyperthyroidism patients [26,27].…”

HbA1c: an independent risk factor for dysthyroid optic neuropathy

“…HOMA gives an estimate of basal insulin resistance (HOMA-IR, used to evaluate individual insulin resistance levels; HOMA-ISI, used to evaluate individual insulin sensitivity; HOMA-β, used to evaluate individual islets β indicators of cell function) (52). Decreased islet β-cell function was observed, and 34.7% had persistent abnormalities during follow-up (53).…”

The causal relationship between Graves’ disease and type 2 diabetes: Evidence from Bidirectional Mendelian Randomization Study

“…It reduces the rate of glycogen synthesis and diverts glucose toward conversion into lactate, a process that contributes to the Cori cycle in the liver. Consequently, this redirection of glucose metabolism leads to an elevated output of glucose (36)…”

“…It reduces the rate of glycogen synthesis and diverts glucose toward conversion into lactate, a process that contributes to the Cori cycle in the liver. Consequently, this redirection of glucose metabolism leads to an elevated output of glucose (36) Despite the established evidence of insulin resistance in GD patients, the precise risk of developing new-onset DM in individuals with hyperthyroidism in real-world clinical practice remains uncertain There are only a few long-term studies examining the risk of DM in individuals with thyroid dysfunction with most of them primarily associating this risk with hypothyroidism rather than exploring its link to hyperthyroidism (37)(38)(39).…”