Efficiency of Shidnitsa mineral waters in complex rehabilitation of patients with chronic pancreatitis with concomitant diabetes mellitus

Relevance. Rehabilitation of patients with chronic pancreatitis (CP) combined with diabetes mellitus (DM) requires a complex systemic and personified approach, since such comorbidity is characterized by complicated interactions of these nosology items, with more lesions of pancreas as the main organ involved in the formation and depth pathological manifestations of each patient, as well as the involvement of adjacent organs of the gastrointestinal tract, other organs and systems. Process of integrated rehabilitation, which purpose is to maximally restore the lost functions of the above organs, especially the pancreas, should include, in addition to standard protocol approaches, the adjuvant effective techniques that showed their practical effectiveness but require research and scientific substantiation. Such techniques include the use of therapeutic mineral water (MW) both in resorts and in outpatient practice according to the place of residence of patients. 
The aim of the study is to investigate the effectiveness of rehabilitation of patients with CP and concomitant DM with the use of the drug ademetionin in the sublingual form (Agepta) and the course of treatment with drinking MW of the Shidnitsa deposit. 
Material and methods of research. 77 patients with CP and concomitant DM were examined. According to treatment programs, patients were divided into 3 groups: Group 1 (protocol treatment (PT) — 26 patients) — received enzyme preparation of pure pancreatin, proton pump inhibitor (pantoprazole 40 mg), anesthetics (mebeverin) and/or prokinetic (motilium), metformin 1000 mg twice a day); Group 2 (PT + ademetionin — 26 patients) — in addition to PT received a drug ademetionin (sublingual tablets Agepta 400 mg) 1 tablet 2 times per day 30–60 min before eating, holding under tongue at least 15–20 min — until complete dissolution, 1 month course; Group 3 — in addition to PT and Agepta in the above-mentioned scheme, they took the course of treatment by drinking MW of the Shidnitsa deposit according to the proposed scheme. 
Results. Positive dynamics in all groups of comparison was revealed, but its intensity differed in those groups. Improvement of exocrine and endocrine pancreatic function was found: level of fecal α-elastase increased by 58.5% in Group 1, by 82.6% in Group 2, by 93.4% in Group 3; level of blood glucose decreased by 9.2% in Group 1, by 13.3% in Group 2, by 19.5% in Group 3; level of HbA1c — by 4.9% in Group 1, by 9.2% in Group 2, by 12.2% in Group 3; changes in the coprogram — by 24.5% in Group 1, by 38.6% in Group 2, by 55.2% in Group 3. 
Discussion. There was a statistically significant improvement in the results of Group 2 as compared to Group 1 (p<0.05), which indicates the effectiveness of use of ademetionin (Agepta sublingual tablets) in a comprehensive correction program for patients with CP and DM. However, the most evident dynamics of indicators of exocrine and endocrine pancreatic function was found in Group 3 as compared to Groups 2 and 1, respectively, indicating the expediency of the additional appointment of the therapeutic course of drinking MW of the Shidnitsa deposit according to the proposed scheme. 
Conclusion. The effectiveness of inclusion of ademetionin in complex standard protocol program of treatment of patients with CP with concomitant DM in sublingual tablets (Agepta) with 400 mg twice a day during 1 month and 14-day course of treatment with drinking MW of the Shidnitsa deposit according to the proposed scheme was proved by statistically significant improvement of the indices of exocrine and endocrine pancreatic function (p<0.05).

Modern protocol treatment (PT) of CP is carried out in accordance with the protocols of the Ministry of Health of Ukraine and aims at: eliminating, if possible, aggressive provoking factors (alcohol and tobacco); adherence to a diet taking into account the accompanying pathologies, in particular NAFLD, reduction of pain syndrome; correction of secretory and incretory pancreas failure; treatment of comorbidities; vocational and social rehabilitation; antispasmodics and prokinetics; if necessaryneuroleptics, analgesics, including narcotic; adequate replacement therapy [3,5].
Oral enzyme therapy has been shown in patients with existing exocrine pancreatic insufficiency (EPI) or other clinical and laboratory evidence of nutrient deficiency. Preference should be given to mini-microspheres or microspheres with enteric-coated coatings, which have shown higher efficacy in the treatment of patients with exocrine malnutrition [2,5]. Standard basic therapy of CP comorbidity with diabetes is not effective enough for the correction of exocrine and endocrine malnutrition, as well as the correction of dyslipid disorders, insufficient antioxidant defense systems, as well as the condition of the liver as an organ of metabolic detoxification and other vital and vital functions. [5].
Therefore, in such a situation, it is recommended to increase the use of adetionin for the restoration of liver function in case of malnutrition, alcohol consumption or due to the harmful effects of endogenous and exogenous factors. Moreover, it was proposed to receive ademetionine in the most bioavailable non-invasive formoral sublingual, which is advantageous for the continuation of treatment in the primary care setting. Sublingual form, in which the tablet dissolves under the tongue, provides the main substance easier to get into the bloodstream, bypassing the esophagus and stomach [2,3].
Rehabilitation of patients with chronic pancreatitis (CP) combined with diabetes mellitus (DM) requires a complex systemic and personified approach, since such comorbidity is characterized by complicated interactions of these nosologies, with more lesions of pancreas as the main organ involved in the formation and depth pathological manifestations of each patient, as well as the involvement of adjacent organs of the gastrointestinal tract (GIT), other organs and systems. Process of integrated rehabilitation, which purpose is to maximally restore the lost functions of the above organs, especially the pancreas, should include, in addition to standard protocol approaches, the adjuvant effective techniques that showed their practical effectiveness but require research and scientific substantiation. Such techniques include the use of therapeutic mineral water (MW) both in resorts and in outpatient practice according to the place of residence of patients [4]. The low-mineralized MW of Naftusya type (Skhiderny source No 18) enhances the release of pancreatic juice with the activation of pancreatic enzymes in it. MW type "Naftusya" of the Skhidnytskyi field, which has a similar therapeutic effect, differs from Truskavets slightly higher content of hydrocarbons, which positively affects the alkaline-acid balance of patients with diabetes mellitus [4]. Therefore, with CP in the phase of mild exacerbation or unstable remission, especially when combined with diabetes, "Naftusia" was prescribed in a limited dosage of 100-150 ml per intake, heated to 37-40°C, 3 times a day for 60 min before meals. With concomitant hypertension, "Naftusya" was administered with caution, better MW source No 10 (it is slightly weaker, acts more gently) in a similar mode.  Table 1.   changes in the coprogramby 24.5% in Group 1, by 38.6% in Group 2, by 55.2% in Group 3.

Discussion.
There was a statistically significant improvement in the results of