THE IMPACT OF ACID-BASE DISORDERS IN PATIENTS WITH CHRONIC PANCREATITIS COMORBID WITH TYPE 2 DIABETES ON LONG-TERM QUALITY OF LIFE AND POSSIBLE IMPROVEMENT WITH SMALL VOLUME INFUSION THERAPY

The article presents the results of the study of metabolic endogenous intoxication indexes (MEI) reflecting intoxication by organic compounds influencing the change of physiological pH balance and their correlation with the presence and severity of chronic pain syndrome and quality of life criteria. The dynamics of these indexes and improvement of QOL on the background of the suggested scheme of small volume infusion detoxification therapy (SWIDT) by hyperosmolar balanced crystalloid (HSC) containing components with reserve alkalinity in the section of 30-day period were researched. The aim of the study – to evaluate the therapeutic effect of SWIT on the severity of pH abnormalities as well as the effect of SWIT on the severity of chronic pain syndrome and related aspects of quality of life in patients with CP in comorbidity with T2DM. Materials and Methods. 115 patients divided into 5 groups were examined: Group 1 – 20 patients without complaints on the gastrointestinal tract, Group 2 – 30 patients with CP, Group 3 – 20 CP patients with concomitant T2DM received protocol treatment (PT), Group 4 and 5 – CP patients with concomitant T2DM, including 21 patients received PT with a course of SWIT for 3 days, and 24 patients – SWIT course for 5 days. The concentration of lactate and pyruvate in blood plasma was determined, the lactate/pyruvate ratio was calculated, the concentration of bicarbonates in blood plasma was determined, pain was determined by the QLQ-C30 and PAN28 questionnaires, pain syndrome severity was determined by the visual analogue scale (VAS). Statistical processing of the obtained data was performed using Microsoft Excel 2016 and Statistica 13.0. Results. A positive therapeutic effect on the dynamics of the level of mEI markers and COPD disorders in patients with CP with concomitant T2DM has been proved, which


INTRODUCTION
The causes of persistent metabolic acidosis in CP are: chronic inflammation of pancreatic tissue with the development of edema and impaired microcirculation and perfusion and, as a consequence, hypoxia [1]; oxidative stress of CP tissue with the predominance of acidic metabolites production; intestinal microflora activity with dysbacteriosis, reduced capacity of blood buffer systems [2].
An important pathogenetic factor of pH abnormality in patients with CP is concomitant diabetes mellitus [3]. Patients with both types of diabetes have high level of lactate in plasma on an empty stomach [4]. Diabetic patients with obesity have higher lactate levels compared with obese individuals without diabetes. The mechanisms underlying diabetes-associated hyperlactatemia include significant changes in intracellular glucose metabolism in insulin-sensitive tissues (decreased glycogen synthesis, impaired glucose oxidation metabolism and increased nonoxidative glycolysis rate) [5]. Thus, patients with insulin resistance/diabetes have increased glycolysis activity, which leads to the formation of NAD, pyruvate, and a decrease in NAD+ levels. There is a conversion of pyruvate to lactate by LDH by generating NAD+ from NAD in a redox reaction exacerbated by insulin resistance, as hyperinsulinemia causes increased glycolysis [6]. The main buffer system of the body is the bicarbonate-haemoglobin buffer (CO2-/HCO3-), which occupies more than 70 % of the total buffer capacity of the body [7]. For metabolic regulation of pH [8], the pancreas attracts circulating systemic bicarbonate reserves in blood. In the development of metabolic acidosis there is redistribution of bicarbonate buffer, which is reflected in the decrease of bicarbonate levels in blood [9].
Subclinical disorders of acid-base balance, according to the latest scientific data, have the following consequences for the patient [10]: directly affect the development of chronic pain syndrome, which is difficult to stop [11], worsen the effectiveness of the therapy involved, lead to chronicity of pathological processes [12], affect quality of life in the long-term period, provoke more frequent development of CP complications in comorbidity with T2DM [13].
The aim of the study -to evaluate the therapeutic effect of SWIT on the severity of chronic pain syndrome and related aspects of life quality patients with CP in comorbidity with T2DM.

RESULTS AND DISCUSSION
Defined statistically significant expression of pain syndrome, lactate and bicarbonate concentrations in blood plasma and lactate/pyruvate ratio.
We assessed the degree of severity of individual parameters of acid-base ratio in dynamics (at admission and one month after treatment), as well as the severity of CPS and related aspects of QOL of patients with CP comorbid with T2DM (Table 1).
After treatment, the main studied parameters in the groups changed as follows: lactate level decreased in the protocol treatment group by 9.52 %, in SWIT 3 group (CP+T2DM Protocol treatment+ SWIT 3) by 19.21 %, in SWIT 5 group (CP+T2DM Protocol treatment+ SWIT 5) by 33.14 %, the lactate/pyruvate ratio normalized in the groups by 1.63 %, 15.89 % and 21.51 % appropriately. Pain level on VAS decreased in the protocol treatment group by 13.73 %, in the SWIT 3 group by 25.48 % and in the SWIT 5 group by 45.38 %. (Diagram 1).
On the RA Pain scale, the scores of the treatment protocol group normalized by 31.92 %, the SWIT3 group by 38.9 %, and the SWIT5 group by 40.74 % (Diagram 2).
On the basis of the correlation-regression analysis between the parameters of lactate, pyruvate and bicarbonate deficiency and severity of chronic pain syndrome we found a significant level of close correlation relations, indicating that the levels of lactate, pyruvate and plasma bicarbonates are absolutely informative reliable in the long-term period ( Table 2).
On the background of small-volume infusion therapy we observe statistically significant decrease in markers of endogenous intoxication [9], and as a consequence -more rapid normalization of the main indices, indicating a direct impact of the duration of small-volume infusion therapy on the normalization of disorders.
This indicates the effectiveness of the proposed scheme of therapy, allowing more effectively and in a shorter time to stop the undesirable phenomena of endogenous intoxication, and as evidenced by the data obtained by correlation analysis, affect the course of the pathological process itself, reducing its severity and duration of manifestation.

CONCLUSIONS
1. Statistically significant increase of objective markers of ABR impairment due to mEI (lactate, lactate/pyruvate ratio) in CP patients with concomitant T2DM in comparison with the same in isolated CP was revealed (p<0.05).
2. Strong correlations between markers of mEI and pH disturbance towards metabolic acidosis mediated by lactate/pyruvate ratio and bicarbonate content were found.
3. It was found that under the influence of SWIT, the dynamics of normalization of the studied indices demonstrated better normalization trends compared to the protocol therapy group. Lactate level decreased in the protocol treatment group by 9.52 %, in SWIT 3 group (CP+T2DM Protocol treatment+SWIT 3) by 19.21 %, in SWIT 3 group (CP+T2DM Protocol treat-ment+SWIT 5) by 33.14 %, the lactate/pyruvate ratio normalized in the groups by 1.63 %, 15.89 % and 21.51 % appropriately. Pain level decreased in the protocol treatment group by 13.73 %, in the SWIT 3 group by 25.48 %, in the SWIT 5 group by 45.38 % 4. A higher level of efficiency of SWIT-5 application in complex therapy in comparison with SWIT-3 program has been found. 5. It is proved that normalization of the specified indexes directly correlates with duration of the SWIT course.