Pathogenetic Mechanisms of Relationship of Metabolic and Morphofunctional Disorders of Thyroid and Adrenal Glands in Diabetes Mellitus and Obesity

Abstract

BACKGROUND: The issues of the pathogenetic relationship of thyroid-adrenal disorders in diabetes mellitus (DM) remain relevant, despite certain advances in the study of the pathogenesis and the clinic of DM. These issues are especially actual in the case of a combination of DM with ischemic heart disease (IHD) and obesity.

AIM: The aim was to reveal the pathogenetic mechanisms of the relationship between metabolic and morphofunctional thyroid-adrenal disorders in DM and obesity.

METHODS: The study included 395 patients with type 1 and 2 diabetes. The diagnosis of DM was verified in accordance with International Programs and was based on WHO criteria. The glycemic level of patients was determined using a One Touch® basic glucometer (Johnson&Johnson, USA). The degree of carbohydrate metabolism compensation was assessed by the level of glycated hemoglobin (HbA1c), determined using a laboratory analyzer DCA-2000 MT (BAYER, Germany). The concentration of C-peptide in the blood serum was determined by the method of immunoluminometric analysis “Immunotech” (Czech Republic). Caro and HOMA-IR indices were calculated to identify and assess the insulin resistance (IR). The indices of hormone metabolism were determined by ELISA using DSL kits (USA) with subsequent measurement of optical density on a Spectra Classic reader from Tecan (Austria): Corticotropic hormone, adrenaline, noradrenaline, cortisol, free hydrocortisone; 17-ketosteroids, 17-oxycorticosteroids, glucogone, insulin, somatotropic hormone (STH); thyroid-stimulating hormone (TSH); thyroxine (T4); and thyroxine (T3). Instrumental-functional and radiation research methods. Ultrasound examination of the adrenal glands, thyroid gland, lungs, liver, and kidneys was performed in all patients. Morphological changes were assessed using histological and morphometric methods.

RESULTS: Disorders of carbohydrate metabolism in diabetic patients were revealed by increased glycemic parameters – in 2.14 times, immunoreactive insulin (IRI) – in 2.8 times, HbA1c – in 1.85 times, and HOMA – in 5.3 times compared with the control group. The following indicators were significantly higher in patients with combination of DM, IHD, and obesity: Glycemia – in 2.29 times (p < 0.05), IRI – in 3.81 times, HbA1c – in 2.01 times, and HOMA – in 7.76 times compared with Co and CIHD groups. An increase in the content of pyruvate and lactate and the ratio in the DM2o and DM2IHDo groups indicate an acceleration of glycolysis and the degree of pyridine nucleotides reduction, as well as excessive lipolysis and progression of tissue hypoxia. Thus, the rate of glucose oxidation in patients of DM2o subgroup is reduced in 3.02 times, in patients of DM2IHDo subgroup (p < 0.05) – in 3.18 times compared with Co group. Computed tomography (CT) revealed an increase in the volume of adipose tissue in relation to muscle and bone tissue in patients of DM2o and DM2IHDo subgroups. Abdominal obesity type is expressed in these patients. An increase of glucose promotes its conversion into triglycerides (TG) of adipose tissue under the condition of hyperinsulinemia. Lipogenesis in the body of patients with DM and coronary heart disease increases, and obesity develops. The increase of cortisol and TSH (p < 0.01) levels was observed in patients of DM2o, DM2IHDo groups compared with the control groups. In patients of DM1 group, the parameters of norepinephrine were increased in 2.23 times, TSH (p < 0.01) – in 3.15 times, and the content of STH was reduced in 3.76 times and the content of cortisol – in 1.5 times significantly (p < 0.01) compared to C1 group. Ultrasound and CT with contrast revealed diffuse adrenal hyperplasia, signs of a decrease in the size of the thyroid gland with a medium-grained structure, areas of its cystic degeneration in the form of hypoechoic zones with a medium-grained echo structure. Thus, the expressed atrophic processes in the lobes of the thyroid gland were observed in 27 (15.4%) patients of DM2 group and in 13 (13%) patients of DM2CHDo group. Analysis of spectral characteristics during Doppler ultrasonography of the thyroid gland vessels made it possible to determine low peak systolic blood flow velocities in CIHD group. Pathomorphological examination of the adrenal glands on electronograms recorded that the porosity of the walls of the sinusoidal capillaries increased primarily within the bundle zone of the cortex. Corticocytes of the fascicular and reticular zones underwent degenerative and necrotic changes. Along with this, some of the epithelial cells contained the usual number of light and an increased number of dark fat droplets. The study of the sectional material revealed signs of suppression of the function of the thyroid gland, dystrophic changes in the cells increased, which contributed to a decrease in the functional capabilities of the follicular epithelium, destruction of individual thyrocytes, and substitutional sclerosis with an increase in the exchange surface area in the blood-tissue barriers.

CONCLUSION: The main pathogenetic mechanism of suppression of the structural and functional state of the adrenal and thyroid glands is due to dystrophic changes in the microvasculature. With the addition of ischemic heart disease, the oppression of their functions of the glands develops, which leads to destruction, an increase in vascularization, porosity of the capillary walls, and tissue hardening. There is a further aggravation of hormonal and metabolic disorders in patients with DM with coronary heart disease. It is confirmed by a significant increase in the lactate/pyruvate index and the index of IR. The volume of adipose tissue in relation to muscle and bone tissue on CT was significantly higher (p < 0.05) compared to the control groups. The predominance of the abdominal type of fat deposition is expressed.