INFLUENCE OF INSULIN RESISTANCE ON THE THYROID HOMEOSTASIS OF RATS IN CONDITIONS OF CONGENITAL AND ACQUIRED IODINE DEFICIENCY

The relevance of the study is driven by a steady tendency to the increase of the prevalence of type 2 diabetes mellitus and prediabetes, especially in women. At the same time, about 11% of patients with diabetes mellitus have disorders of thyroid homeostasis. Uncorrected hyperglycemia under the conditions of insulin resistance is capable of triggering a number of metabolic disorders. Taking into account the high risk of iodine deficiency in Ukraine, especially in endemic regions, it is of high interest to find out the thyroid profile under thconditions of insulin resistance. Such data will allow us to extend the prevention measures and diagnostics of minimal thyroid insufficiency. The aim of the study is to investigate the influence of insulin resistance on the thyroid homeostasis of rats in the context of congenital and acquired iodine deficiency, taking into account sexual dimorphism. The studies were performed using non-linear mature rats (males and females) weighing 150-180 g, which were divided into six groups: group I – control (intact animals); group II – insulin-resistant animals; group III – animals with congenital iodine deficiency; group IV – animals with acquired iodine deficiency; group V – insulin-resistant animals, for which iodine-deficient diet was used in the second generation; group VI – insulin-resistant animals for which iodine-deficient diet was used after puberty. Insulin resistance in animals was simulated by adding 10% fructose solution to drinking water for 8 weeks (experimental groups II, V and VI). Animals in the study groups III-VI have received an iodine-deficient diet, in particular, in the groups III and V – diet in the second generation was used, in the groups IV and VI – diet was used for 45 days of the experiment. Rats from the control group were on a standard diet. Animal care, feeding and euthanasia (decapitation under ketamine anaesthetization, 100 mg/kg of body weight) met current international animal humane treatment requirements. As a result of the study in the blood serum of insulin-resistant animals, there was found a decrease of the content of thyroid-stimulating hormone in adenogipophysis – TSH (only changes in females – at 43%, p1-2 <0.05 were reliable), free triiodothyronine (fT3) – in males and females at 36 and 39% (p1-2 <0.05), respectively, whereas the level of free thyroxine (fT4) was not significantly different from control. Such dynamics caused a significant decrease of the TSH/fT4 index (more in females) relative to the initial data. It has been confirmed that insulin resistance violates the central mechanisms of hypothalamic-pituitary regulation, which is accompanied by changes in the compensatory reaction of the thyroid gland to the influence of strumogenic agents. Therefore, markers for the diagnostics of thyroid homeostasis disorders in conditions of insulin resistance are such indices decrease: TTH/fT4, fT3/fT4. Under these conditions, the iodine content of the urine was not significantly different from those of intact animals. Iodine deficiency is accompanied by a predominant secretion of T3 against the background of hyperthyroidism, which causes an increase of TSH/fT4, as well as the index of peripheral conversion of fT3/fT4. Thus, it has been established that insulin resistance is a risk factor for the development of hypothyroid dysfunction. More dangerous is the development of insulin resistance against the background of iodine deficiency (especially in the context of congenital iodine deprivation). The probability of thyroid dysfunction formation is higher in adult females.