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

Graves病的胰岛素敏感性和 β 细胞功能及其与卡比唑诱导的甲状腺功能正常的关系

Graves’ disease (GD) is one of the most commonly encountered disorders in clinical practice with an annual incidence of 20–50 cases per 100,000 persons. Thyroid hormones (THs) play a key role in intermediate metabolism, and abnormal glucose tolerance and diabetes mellitus have been reported to occur in a significant proportion of patients with hyperthyroidism. Several factors like changes in insulin resistance, beta-cell function, abnormal gastric emptying, and intestinal absorption of glucose have been proposed as potential mechanisms that result in abnormal glucose homeostasis. THs contribute to a state of insulin resistance in the liver and peripheral tissues through several mechanisms. They induce the expression of enzymes such as phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase catalytic subunit (G6PC), the key mediators of gluconeogenesis and glycogenolysis, and glucose transporter 2 (GLUT2) in the liver, which contributes to increased hepatic glucose output. In adipose tissue, TH increases lipid oxidation and augments the sensitivity of adipocyte lipolysis to catecholamines and indirectly increases fatty acid efflux. In skeletal muscles, the rate of glycogen synthesis is reduced, and glucose, through conversion into lactate, is shunted to the Cori cycle in the liver. This results in increased glucose output. The rate of glycogenolysis has shown to be increased in animal models. However, changes in insulin sensitivity/resistance in patients with GD have not been consistently demonstrated in the literature. The other potential mechanism that can contribute to abnormal glucose tolerance is suboptimal beta-cell function. Studies measuring insulin secretion rates in response to stimulation by secretagogues like L-arginine and β2-receptor agonists and oral glucose load have also yielded conflicting results.

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