Thesis for the Candidate’s of Medical Sciences degree by specialty 03.00.01 - Radiobiology (Medical Sciences). State Institution “National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine”, Kyiv, 2019.
The thesis is addressed to the study of particularities of clinical, hormonal, and metabolic alterations associated with a behavior pattern of the total adiponectin and proinflammatory cytokines concentration and possibility of their use as diagnostic and prognostic markers of cardiorenal syndrome development in the Chornobyl NPP (ChNPP) accident clean-up workers irradiated at a young age in the 5.0–560.0 mGy dose range and having got type 2 diabetes mellitus (T2DM).
Statistical analysis of the T2DM incidence and associated carbohydrate metabolic disorders, namely prediabetes and overweight / obesity, was conducted in the clean-up workers of the April – July 29, 1986 period (men aged 18–59 years at the time of accident, n = 28,240). Data for the 1992–2017 period were retrieved from the Clinical and Epidemiological Registry (CER) of the NRCRM. Average dose of external exposure in the younger age subgroup was (18.56 ± 6.01) mGy and in the middle age subgroup was (25.76 ± 4.68) mGy. High incidence of T2DM exceeding the nation-wide level was established in the late post-accident period among the clean-up workers irradiated at a young age. Incidence increase of T2DM 10 years after the accident was demonstrated irrespective of the age of irradiated persons. At the same time, the increase of T2DM incidence was observed 10 years earlier and at a higher rates in the clean-up workers irradiated at a young age, than in the middle-aged subgroup subjects.
Comprehensive clinical and laboratory examination of the clean-up workers (n = 200) of the April – July 29, 1986 period irradiated at a young age (18–35 years at the time of accident) demonstrated the T2DM development against a background of grade I-II obesity with prevalent visceral distribution of adipose tissue and its association with a complex of carbohydrate metabolic disorders, insulin resistance, and decreased insulin sensitivity of peripheral tissues. The latter deteriorated along with the increased disease duration up to 20 years, weight gain, and inadequate glycemic control. Key pathogenetic role of adiponectin and proinflammatory cytokines was found in the development of cardiorenal syndrome in the late post-accident period among individuals exposed to ionizing radiation at a young age at a dose range of 5.0-560.0 mGy. High frequency of cardiorenal syndrome among the clean-up workers of the Chernobyl NPP accident was revealed among irradiated at a young age in the range of doses of 5.0–560.0 mGy, being patients with type 2 DM – 36.36%. Components of the cardiorenal syndrome (diabetic nephropathy and changes in the structural and geometric remodeling of the left ventricle) developed with the participation of hypoadiponectinemia and with the increase in the concentration of proinflammatory cytokines (TNF-α and IL-6), systemic hormonal and metabolic changes with the possible involvement of fibroplastic processes.
Role of ionizing radiation at the external radiation doses exceeding 500 mGy was proven in the onset and development of T2DM complications, namely the significant left ventricular hypertrophy and dramatic development of myocardial fibrosis emerged as the basis of cardiorenal syndrome in the late period upon exposure. Concentration of the total adiponectin less than 4.0 μg / ml, TNF-α more than 4.0 pg / ml, and IL-6 above 7.0 pg / ml were recognized as markers of unfavorable disease course and probable development of cardiorenal syndrome.
Keywords: ionizing radiation, ChNPP accident clean-up workers, type 2 diabetes mellitus, adiponectin, TNF-α, IL-6, cardiorenal syndrome.
