Hurkalo Y. Lesion of intestinal in patients with type 2 diabetes mellitus:specifics of development, course and treatment

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0823U101484

Applicant for

Specialization

  • 222 - Медицина

Specialized Academic Board

ДФ 26.613.148

Shupyk National Healthcare University of Ukraine

Essay

Diabetes mellitus (DM) is one of the most rapidly progressing issues of the 21st century. Analyzing all editions of the International Diabetes Federation's "Diabetes Atlas" from 2000 to the 9th edition in 2019, the number of affected individuals is steadily increasing. As of today, there are 463 million people diagnosed with DM worldwide. With the persistence of modern lifestyle trends and urbanization, an increase in the incidence is expected. Despite the undeniable success of modern medicine, diabetes remains a prominent concern and ranks high among the reasons for seeking medical care across various specialties. In recent years, Ukraine, like the rest of the world, has witnessed an increase in the number of patients with type 2 diabetes. This pathology is characterized by the development of a range of complications and concomitant diseases, including those involving the gastrointestinal tract. Although intestinal lesions are typically not a direct cause of death or disability in patients with type 2 diabetes mellitus, the quality of life of such patients is significantly reduced, elevating the issue to a position of high relevance. Type 2 diabetes mellitus is associated with a higher frequency of gastrointestinal symptoms, including abdominal pain, diarrhea, and constipation, collectively known as diabetic enterocolopathy (DECP). Under our observation, there were 138 patients with type 2 diabetes mellitus (T2D), aged between 39 and 67 years (average age 53 ± 5.1 years). Subsequently, the study included 117 patients with type 2 diabetes (56 men, 61 women) aged between 39 and 67 8 years. During the initial examination, 21 T2D patients were found to have organic intestinal pathology and were excluded from the study sample. The main group consisted of patients with diabetic enterocolopathy associated with T2D (72 patients, 61.5%), while 45 patients (38.5%) with T2D without intestinal involvement formed the first comparison group. There were no significant differences between the main group and the first comparison group in terms of the type and form of T2D (p < 0.5). Additionally, the second comparison group comprised 60 patients with irritable bowel syndrome (IBS) aged 35 to 54 years. The control group consisted of 30 practically healthy volunteers who had no gastrointestinal complaints during comprehensive examination for T2D and were excluded from the study. Analysis of patient complaints and clinical presentation revealed that clinical manifestations of diabetic enterocolopathy were characterized by changes in bowel movements with abdominal pain in 43 out of 72 (59.7%) patients. There were also patients with changes in bowel movements without abdominal pain - 29 (40.27%), with 19 (26.4%) experiencing constipation, and 10 (13.9%) having diarrhea. Diabetic enterocolopathy was more common in patients with T2D of longer duration (over 5 years) and was associated with microangiopathies, manifestations of autonomic neuropathy, and could be related to the decompensation of the underlying disease. Risk factors for DECP could include excess body weight, metabolic syndrome, a history of foodborne toxic infections, gastrointestinal infections, changes in dietary habits, and stress. The dominant complaints of DECP patients were abdominal pain, diarrhea, constipation, abdominal distention, and abdominal discomfort. Microvascular complications and signs of diabetic autonomic neuropathy were more frequently found in patients with DECP and T2D compared to the comparison group. Microvascular changes in DECP were observed in 28 (38.9%) patients, while 12 (26.7%) of those in the comparison group were diagnosed with microvascular changes (p < 0.05). Clinical manifestations of diabetic neuropathy were detected in 25 (34.7%) patients with DECP and T2D, while only 11 (24.4%) of patients with T2D without intestinal involvement had these signs (p < 0.05). The clinical association between 9 diarrhea and signs of diabetic neuropathy is clear evidence of the significant role of the autonomic nervous system in its pathogenesis. Using the polymerase chain reaction (PCR) method, the TGF-β1 gene polymorphism was examined. According to our data, the single nucleotide polymorphism TGF-β1*915 G/C, which reduces the synthesis of TGF-β1, played a minor role in the development of type 2 diabetes and DEP. Plasma concentrations of TGF-β1 and VEGF were also evaluated. The levels of TGF-β1 and VEGF in T2D patients significantly exceeded the indicators of healthy volunteers. In T2D patients with DECP, the levels of growth factors were also significantly higher than normal (p < 0.05). It was found that the level of TGF-β1 was highest in patients with DECP and T2D with constipation (26.02 ± 2.31 ng/ml), while VEGF levels were most significantly elevated in patients with DECP and diarrhea, surpassing the levels of DEP patients with constipation (p < 0.05).

Research papers

Dorofeyev AE, Popandopulo AG, Dorofeyeva AA, Dynia YuZ, Snisarevsky PP. Mesenhymal stem cells in treatment of pyoderma gangrenosum in patient with ulcerative colitis: clinical case. Gastroenterol Hepatol Open Access. 2019;10(1):56‒59. DOI: 10.15406/ghoa.2019.10.00356.

Дорофєєв АЕ, Швець НІ, Пархоменко ТА, Диня ЮЗ, Чичула ЮВ. Діабетична ентероколопатія у пацієнтів з цукровим діабетом 2-го типу. Міжнародний ендокринологічний журнал. 2019;15(1):61-65.

Дорофєєв АЕ, Голуб СВ, Ананьїн ОЕ, Диня ЮЗ. Моделювання взаємозв’язків біологічних маркерів при оцінці активності неспецифічного виразкового коліту. Східноєвропейський журнал внутрішньої та сімейної медицини. 2019;1:129-133. DOI: 10.15407/internalmed2019.01.129

Tkach SM, Kuzenko YH, Dorofeyev AE, Dynia YZ, Dorofeyeva AA. Fecal microbiota transplantation: the european consensus and first ukrainian experience. Gastroenterol Hepatol Open Access. 2019;10(3):138‒143. DOI: 10.15406/ghoa.2019.10.00372.

Dorofeyev AE, Dorofeyeva AA, Kiriyan EA, Rassokhina OA, Dynia YZ. Genetic polymorphism in patients with early and late onset of ulcerative colitis. Wiadomości Lekarskie. 2020;LXXIII(01):87‒90. DOI: 10.36740/WLek202001116.

Дорофєєв АЕ, Ткач СМ, Гдаль ВА, Диня ЮЗ. Вибір пробіотика у пацієнтів з діабетичною ентероколопатією. Клінічна ендокринологія та ендокринна хірургія. 2020;1(69):28-35. DOI: http://doi.org/10.30978/CEES-2020-1-28

Дорофєєв АЕ, Ткач СМ, Деркач ІА, Гдаль ВА, Диня ЮЗ, Беніах ОЧ. Дивертикулярна хвороба кишечника у пацієнтів із цукровим діабетом 2 типу. Український терапевтичний журнал. 2021;1:63-69. DOI: http://doi.org/10.30978/UTJ2021-1-63

Диня ЮЗ. Клініко-патогенетичні особливості ураження кишечника у пацієнтів з цукровим діабетом 2 типу. Сучасна гастроентерологія. 2021;5- 6:30-36. DOI: http://doi.org/10.30978/MG-2021-5-30

Дорофєєв АЕ, Ткач СМ, Гуркало ЮЗ, Куглер ТЄ, Жигаль ЮВ, Чичула ЮВ. Можливості лікування хворих з перехрестом функціональної диспепсії та синдрому подразненого кишечника. Сучасна гастроентерологія. 2023;1:32- 38. DOI:http://doi.org/10.30978/MG-2023-1-32

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