VITAMIN B1 BIOLOGICAL FUNCTION IMPLEMENTATION IN THE BLOOD OF PATIENTS WITH STOMACH CANCER UNDER SURGICAL INTERVENTION

Background. The probability of undergoing surgery always predetermines the state of stress in a person; therefore, it is advisable to search for ways to optimize and (or) reduce this unfavourable effect. Objective. To find out the mechanism of vitamin B1 antistress activity during surgery. Material and methods. Metabolism intensity was investigated on donors’ blood lysates (n = 19) and those of patients with stage III stomach cancer (n = 64), referred to an elective surgery, aged 51-70. The blood was taken from the cubital vein three days before the operation, after premedication, during the most traumatic moment of the operation, after extubation, as well as on the first and third days of the postoperative period. The surgery was performed under combined multicomponent anesthesia using nitric oxide, sodium hydroxybutyrate, and epidural block. Thiamine and thiamine diphosphate kinase activities were assessed by the concentration of the formed thiamine di- and triphosphates of the vitamin. The activities of thiamine mono-, di- and triphosphatases were determined by the release of inorganic phosphate. The concentration of inorganic phosphate was recorded colorimetrically. The content of B1 and its derivatives in the blood was determined by the method of ion-pair reversed-phase HPLC. Results. There has been observed an increased content of thiamine monophosphate and that of free thiamine in the blood of donors and patients with stomach cancer. The registered rate of the hydrolytic thiamine monophosphatase reaction is not high. At the stages of premedication and maximum trauma of surgical exposure, the concentration of monophosphoric ester rapidly decreases alongside with monophosphatase activation. Therefore, the thiamine monophosphate hydrolysis is the rate-limiting link of vitamin B1 metabolism. The level of free thiamine remains persistently increased at all stages of surgical treatment. Thiamine monophosphatase activity is manifested at two pH optima – of 6.0 and 9.0. Thiamine monophosphate hydrolysis at pH of 9.0 is catalyzed by alkaline phosphatase. At pH of 6.0, in addition to thiamine monophosphoric ester, the enzyme hydrolyzes only p-nitrophenyl phosphate, flavin mononucleotide and phosphotyrosine, that allows it to be classified as hepatic acid phosphatase. The noted changes in B1 metabolism under stress concern mainly non-coenzyme forms - thiamine mono-, triphosphate, and free thiamine, which are used at the stages of thiol reduction as important components of insulin synthesis. Conclusions. The use of vitamin B1 allows to optimize the development of the stress response at all stages of surgical treatment. Its protective effect is achieved through the activation of the insulin-synthetic function of the pancreas, which increases the level of immunoreactive insulin in the blood. The formation of the most favorable physiological conditions for insulin synthesis provides an increased background of free thiamine, which is created due to the hydrolysis of noncoenzyme forms of the vitamin. The relationship between thiamine metabolism and B2 exchange and regulation of intracellular signaling pathways has been traced.

Clinical significance of leptin in systemic lupus erythematosus

Objective: to study the frequency of hyperleptinemia in patients with systemic lupus erythematosus (SLE), its relationship with clinical and laboratory manifestations of the disease, drug therapy, and other metabolic disorders.Patients and methods. The cross-sectional study included 46 women with a definite diagnosis of SLE (median age 40 [31; 48] years) and disease duration 3.0 [0.9; 9.0] years. Glucocorticoids (GC) were received by 38 (83%) patients, hydroxychloroquine – by 35 (76%), immunosuppressants – by 10 (22%), biologic disease-modifying antirheumatic drugs – by 5 (11%). In all patients, fasting levels of glucose, leptin, apoliproprotein B (ApoB) and immunoreactive insulin were determined, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Concentration of leptin ≥11.1 ng/ml, ApoB – >1.6 mg/ml were considered an elevated level. HOMA-IR index ≥2.77 corresponded to the presence of insulin resistance (IR).Results and discussion. Hyperleptinemia was found in 34 (74%) patients with SLE, an increased level of ApoB – in 19 (41%), IR – in 10 (22%). In patients with hyperleptinemia, serositis, positivity for anti-double-stranded DNA (aDNA) and hypocomplementemia were less common, overweight and obesity were more frequent, the SLEDAI-2K index was lower, the aDNA level was lower, and the concentration of the C3 component of complement, insulin, HOMA-IR index, body mass index (BMI) and disease duration were higher (p<0.05 for all cases). BMI <25 kg / m2 had 26 (57%) women, 14 (54%) of whom had hyperleptinemia. In patients with BMI <25 kg / m2, we found a relationship between leptin concentration and disease duration (r=0.4, p=0.04), SLE activity according to SLEDAI-2K (r=-0.6, p=0.003), levels of aDNA (r=-0.6, p<0.001), C3 component of complement (r=0.5, p=0.01), maximum (r=0.7, p<0.001) and supporting (r=0,5, p=0.023) GC doses.In patients with BMI ≥25 kg/m2 (n=20), no such relationship was observed.Conclusion. Hyperleptinemia was found in the majority of women with SLE; elevated levels of ApoB and IR were much less common. Patients with hyperleptinemia are characterized by a longer duration and less activity of the disease, as well as the presence of overweight and obesity and an increase in the HOMA-IR index. In SLE patients with normal body weight, the concentration of leptin increased along with GC dose elevation.

Indicators of lipid peroxidation and the activity of antioxidant system enzymes as predictors of the development of metabolic disorders in primary obesity

Aim. To assess the effectiveness of indicators of lipid peroxidation and the activity of antioxidant system enzymes in the early diagnosis of metabolic disorders. Methods. The study included 269 women of fertile age with primary obesity. The control group consisted of 35 women. The clinical examination included identification of the type of obesity, whole-body fat percentage, the level of glycemia and the index of insulin resistance, biochemical markers of lipids, hormones (leptin and insulin), malondialdehyde and enzyme activity (peroxidase and catalase). The statistical significance of the differences was determined by using the inversion test. Spearman's rank correlation coefficient was used to assess the degree of relationship between quantitative characteristics, and scatter diagrams were used to compare two variables (Statistica software version 10.0). Results. A statistically significant increase in basal and stimulated immunoreactive insulin was found in obese patients compared with the controls (p 0.01). Stimulated immunoreactive insulin levels, insulin resistance score (HOMA-IR) and the level of leptin in the group of patients with android obesity was higher than in the group with gynoid obesity (p 0.01). The relationship between the concentration of serum malondialdehyde and whole-body fat percentage was found to be more significant (r=0.412; p 0.001) than the relationship with the type of obesity (r=0.257; p 0.01). Positive correlations were found between serum malondialdehyde and insulin (r=0.35; p 0.001) and leptin (r=0.32; p 0.001) levels. The relationship between the concentration of serum malondialdehyde and the activity of enzyme systems was also noted. The activity of lipid peroxidation was higher in the group of patients with android obesity (malondialdehyde 3.3 mol/L) compared with the group of patients with gynoid obesity. In the same group, a higher activity of enzyme systems was noted. Conclusion. An increase in the concentration of serum malondialdehyde and the activity of enzyme systems should be considered as indicators of a high risk of developing metabolic syndrome.

FEATURES OF INSULIN RESISTANCE ASSESSMENT IN PATIENTS WITH TYPE 2 DIABETES MELLITUS WITH HYPERURICEMIA

Topicality. The link between hyperuricemia (HUA) and insulin resistance (IR) has been established in many studies, but the traditional «insulin» indices used to assess the severity of IR, although there are the most informative, sensitive and specific, have not been widely used in clinical practice. The aim of the research is to evaluate the possibility to use calculated «non-insulin» indices in clinical practice to assess IR in patients with type 2 diabetes (T2DM) with HUA. Materials and methods. We examined 395 patients with type 2 diabetes (231 women and 164 men) aged 39 to 81 years, the average — (54.6 ± 12.9) years, who received oral hypoglycemic therapy. Anthropometric indicators were determined — waist circumference (WC) and body mass index (BMI). The author determined the level of fasting blood glucose in capillary blood by glucose oxidase method, the concentration of uric acid (SUA) in the serum, the level of high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) — by colorimetric method; immunoreactive insulin — by immunochemiluminescent method. The IR severity was assessed by indices HOMA-IR, QUICKI, Caro, visceral obesity index (AVI), triglyceride-glucose index (TyG-index), TyG-BMI index, TyG-WC index, metabolic index (MI) and the ratio of TG/cholesterol-HDL (TG/HDL-C-ratio). Statistical analysis of the obtained data was performed using the software package «Statgraphics Plus for Windows 10.0». Results. Between groups of patients with T2DM on the concentration of SUA in the blood the author found significant differences in WC, BMI and TG level, which affected the calculated «non-insulin» indices: AVI (P = 0.026), TyG-index (P = 0.04), TyG-BMI-index (P = 0.001), TyG-WC index (P = 0.037) and MI (P = 0.03). A positive correlation between HOMA-IR and MI (rs = 0.44, P = 0.0006) and AVI (rs = 0.28, P = 0.01) was established; QUICKI with MI (rs = 0.32, P = 0.012), TyG-index (rs = 0.29, P = 0.02), TyG-BMI index (rs = 0.25, P = 0.04), TyG-WC index (rs = 0.34, P = 0.004) and AVI (rs = 0.31, P = 0.01). It has been determined that the Caro index at the trend level positively correlates with the TyG-index (rs = 0.23, P = 0.065). Among the studied calculated «non-insulin» indices in patients with T2DM with the concentration of SUA in the blood are significantly associated with TyG-index (rs = 0.19; P = 0.0034), TyG-BMI index (rs = 0.43; P = 0.0001), TyG-WC index (rs = 0.44; P = 0.00001), MI (rs = -0.17; P = 0.012) and TG/HDL-C-ratio (rs = 0.15); P = 0.011). Conclusions. the author established a positive correlation between HOMA-IR and MI and AVI in patients with T2DM with SUA; QUICKI with MI, TyG-index, TyG-BMI-index, TyG-WC-index and AVI. Among the calculated «non-insulin» IR indices with the concentration of SUA in patients with T2DM are significantly associated with TyG-index, TyG-BMI-index, TyG-WC-index, MI and TyG/HS-HDL. To adequately assess the severity of IR in patients with T2DM with HUA, it is advisable to use TyG-index, TyG-BMI-index, TyG-WC-index, MI and TG/HS-HDL.

Postloading insulinemia is independently associated with arterial stiffness in young Japanese persons

Associations of arterial stiffness with glucose, insulin, and proinsulin dynamics during the oral glucose tolerance test (OGTT) remain under debate. The aim of this study was to investigate whether plasma glucose (PG), insulin, and proinsulin (Pro) contribute to arterial stiffness, measured by pulse wave velocity (PWV), in young Japanese persons. PG, immunoreactive insulin (IRI), and Pro levels were determined in 1193 young Japanese subjects (<40 years of age) with normal glucose tolerance or nondiabetic hyperglycemia before and at 30, 60, and 120 min during a 75-g OGTT. Participants were divided into two groups according to the median PWV. Background factors, PG, IRI, and Pro levels during the OGTT, and insulin sensitivity (SI) indices in each group were compared. Several multiple regression analysis models were used to evaluate factors contributing to PWV. All IRI and Pro levels before and after glucose loading and the area under the curve (AUC) values for IRI and Pro increased with higher PWV. 1/HOMA-IR and ISI-Matsuda as measures of SI decreased with higher PWV. The IRI AUC and Pro level before glucose loading (Pro0) were independently associated with PWV, in addition to male sex, heart rate, and mean blood pressure. The IRI AUC had a stronger relationship with PWV than Pro0. The IRI AUC had an independent relationship with PWV, whereas both SI indices did not. Postloading insulinemia, but not reduced SI, was independently associated with arterial stiffness in young Japanese persons.

Clinical Case of Surreptitious Hypoglycemia Due to Deliberate Insulin Analog Administration

Hypoglycemic syndrome is a life-threatening condition that can lead to hypoglycemic coma and death. Surreptitious hypoglycemic syndrome is the deliberate use of insulin preparations or oral hypoglycemic drugs aimed to reduce blood glucose level. If human insulin is injected, high level of immunoreactive insulin (IRI) and low level of C-peptide at the moment of hypoglycemia are always detected. However, the fact of deliberate administration of insulin analogs is difficult to prove. In these cases if insulin kit test with low cross-reactivity with insulin analogs is used, the low levels of IRI and C-peptide will be suspected. Some experts suggest the presence of cross reactivity with analogs of insulin in a number of commercial kits, which makes it possible to detect cases of surreptitious hypoglycemia. We present a clinical case of a patient with surreptitious hypoglycemia due to the administration of insulin analogs and discuss the problems of its laboratory diagnosis.

A Novel Type of Extreme Insulin Resistance: Nonhypoglycemic Insulin Autoimmune Syndrome

Context Extreme insulin resistance is caused by genetic defects intersecting with the insulin action pathway or by the insulin receptor antibodies. Insulin autoimmune syndrome (IAS) is not considered one of the causes of extreme insulin resistance. Objective This work aimed to expand the current knowledge of extreme insulin resistance and to propose the diagnostic criteria and management strategy of a novel type of extreme insulin resistance. Methods A patient with IAS never experienced hypoglycemia but had persistent hyperglycemia and extreme insulin resistance with treatment with 200 U of intravenous insulin per day. Immunoreactive insulin (IRI), free insulin, and total insulin were measured. The ratio of free insulin to total insulin (insulin-free ratio, IFR) was calculated. Results Extreme insulin resistance has not been reported to be caused by IAS. At admission, IRI and free insulin were undetectable in our patient; total insulin was more than 20 160 pmol/L; and the IFR was lower than 0.03% (control, 90.9%). After adding 500 U porcine insulin to the precipitate containing insulin antibodies, the IRI was still undetectable. Since the patient started glucocorticoid therapy, the free insulin has gradually increased to 11.16 pmol/L, his total insulin has decreased to 5040 pmol/L, and the IFR has increased to 18.26%. Intravenous insulin was stopped, with good glycemic control. Conclusion High-affinity insulin autoantibodies with a large capacity can induce a novel type of extreme insulin resistance characterized by extremely high total insulin and very low free insulin levels. The IFR can be used to evaluate therapeutic effects.

Morphofunctional characteristic of endocrine part of pancreas under affecting of γ-HCH

In the last decades of the twentieth century, in the national economy of many countries, organochlorine pesticides were most widely used, characterized by stability in the external environment, the ability to cumulate in various tissues of organisms. Lindane (the gamma isomer of hexachlorocyclohexane) is listed as a restricted persistent organic pollutant and is an ecotoxic substance with severe and chronic effects on the human body. The study of the effect of lindane on carbohydrate metabolism at the present stage is still insufficient. This fact led to the study of the effect of γ-HCH on the insulinogenic function of the pancreas in in vivo and in vitro experiments. In experiments in vivo, the animals of the experimental groups were once orally administered γ-HCH at a dose equal to 1/5 DL50. Isolated pancreatic islets, precipitated in vitro and fixed on mica plates, were exposed to γ-HCH in amounts equivalent to 1/5 to 1/4 DL50. Paraffin sections of pancreatic tissue from experimental and control animals were stained with aldehyde fuchsin according to Gomori, and tissue preparations were also examined by a highly specific method for detecting insulin in β-cells using diethylpseudoisocyanin staining, followed by examination of the preparations in the ultraviolet light of a luminescent microscope. The samemethods were used to study preparations of isolated pancreatic islet tissue on the 4th day of cultivation. The influence of orally administered γ-HCH on the level of immunoreactive insulin in the blood of experimental animals was also studied. The insulin level was determined by the enzymatic-immunological method. The concentration of IRI was established before the start of the experiment and 4-4.5 hours after acute inoculation. Results and their significance. In the study of stained preparations of the pancreas of experimental animals, numerous islets of ordinary sizes were revealed, the cytoplasm of which was filled with aldehyde-fuccin granularity in quantities indistinguishable from those observed by microscopy of preparations of control animals. The value of the fluorescence coefficient in the histofluorimetric study of the control and experimental preparations did not differ significantly. However, the content of IRI in the blood serum showed a distinct decrease in the first hours after priming. In experiments in vitro, when studying the effect of γ-HCH on cultured tissue, introduced into the nutrient medium on the second day, in the field of view of the microscope, single, small pancreatic islets were revealed. Their number on a constant area of the plates was significantly lower than the value of the same indicator in the study of control preparations. Thus it has been shown that γ-HCH does not affect the histostructure of the endocrine pancreas, but causes a significant decrease in IRI in the blood serum, as well as a change in the histochemical characteristics of cultured β-cells.

EXOCRINE AND ENDOCRINE PANCREATIC INSUFFICIENCY IN DEVELOPMENT OF ATHEROSCLEROSIS

Objective: To evaluate the effect of chronic pancreatitis (CP) and exocrine insufficiency of the pancreas on the carotid intima media thickness (cIMT) in patients with type 2 diabetes mellitus (DM-2). Materials and methods: 91 patients were examined, they were divided into groups: 1st group-patients with DM-2 (n = 31) group 2nd – DM-2 combined with CP (n = 60). Fasting plasma glucose (FPG), HbA1c, immunoreactive insulin (IRI), HOMA-IR index, C-reactive protein (CRP), serum α-amylase and fecal-1 elastase (FE-1) were assessed. In order to assess the thickness of the cIMT, ultrasound of the common carotid artery was performed. The control group of healthy volunteers was representative by age and sex. Results: In the 1st and 2nd groups, the average value of cIMT was (1.02 ± 0.1 vs 1.21 ± 0.15) mm. Parameters of DM-2 management in the 1st and 2nd groups were (FPG 8.18 ± 0.92vs8.57 ± 1.2) mmol / l; HbA1c (7.23 ± 0.21vs7.49 ± 0.36)%; IRI (20.31 ± 0.9vs22.53 ± 1.2) μIU / ml; HOMA-IR (6.55 ± 1.5vs8.38 ± 2.2) μIU / ml * mmol / l; PSA (1.3 ± 0.12vs6.77 ± 0.31). HOMA-IR correlated with: CRP (r = 0.43, p <0.05 in group 1; r = 0.61, p <0.05 in group 2); FE-1 (r = -0.55, p <0.05 of the 2nd group); and cIMT (r = 0.42, p <0.05 in the 1st group; r = 0.53, p <0.05 in the 2nd group). IRI have relationship with: FE-1 (r = 0.41, p <0.05 in group 1; r = -0.3, p <0.05 in group 2); CRP (r = 0.42, p <0.05 in group 1; r = -0.28, p <0.05 in group 2); HbA1c had close relationships with cIMT (r = 0.38, p <0.05 in group 1; r = 0.51, p <0.05 in group 2). The relationship between cIMT and CRP was related in the 2nd group (r = 0.39, p <0.05); with α-amylase (r = 0.2, p <0.01 2nd group). There was no significant relationship between cIMT and FE-1 in the study. Conclusions: Obtained data allows us to conclude that hyperinsulinemia and insulin resistance have a direct atherogenic effect on the walls of blood vessels. It is established that the accession of the inflammatory process leads to increasing development of atherosclerotic lesions of the vessel, at the same time, the presence of exocrine dysfunction of the pancreas does not have a significant direct effect on the cIMT.

The role of metformin hydrochloride in complex therapy of disorders of carbohydrate metabolism in patients with paranoid schizophrenia treated with atypical antipsychotics

Introduction. According to the literature, mortality among patients with schizophrenia is 1.5 -2 times higher than in the healthy population. One explanation for this is the complication of neuroleptic therapy, which, according to various authors, occurs in 2 to 100% of cases. Purpose. We aimed to study some indicators of carbohydrate metabolism disorders in patients with paranoid schizophrenia who have been taking neuroleptics for a long time, to correct the established changes by adding metformin hydrochloride to the standard regimen and to monitor its effectiveness. Methodology. The study was conducted based on Municipal non-commercial enterprise "Precarpathian regional clinical center of mental health of Ivano-Frankivsk regional council. This study included patients diagnosed with paranoid schizophrenia according to the criteria of ICD-10 (F20.0). As a result of our studies in 63 patients, we found a violation of carbohydrate metabolism, which accounted for 52% of all examined. Among them, 55 patients with prediabetes: 12 (19.04%) patients with impaired glucose tolerance (IGT), 43 (68%) with impaired fasting glycemia (IFG), and 8 patients (12.7%) with type 2 diabetes mellitus (T2D). Subsequently, all these 63 patients were prescribed corrective therapy with a drug from the group of biguanides - metformin hydrochloride at a dose from 500 to 1000 mg/day: in violation of IFG at a dose of 500 mg/day; in case of IGT - 850 mg/day; in the case of T2D- 1000 mg/day. All studies were performed before and after 3 months of metformin correction. These included fasting glucose, postprandial hyperglycemia (PPG) (two hours after a meal), glycosylated hemoglobin (HbAIc), immunoreactive insulin (IRI), and, if necessary, an oral glucose tolerance test (OGTT). Fasting plasma glucose (FPG) was measured by the glucose oxidase method. HbAIc values were determined by ion-exchange high-performance liquid chromatography (HPLC). The determination of the IRI level was performed by enzyme-linked immunosorbent assay (ELISA) Results and Discussion. The results of the research showed that 52% of all surveyed found disorders of carbohydrate metabolism. They were prescribed corrective therapy with a drug from the group of biguanides - metformin hydrochloride at a dose of 500 to 1000 mg/day. As a result of the research, we found that in all groups of examined patients revealed a positive dynamics of carbohydrate metabolism under the influence of this drug. A significantly higher therapeutic effect of the treatment of carbohydrate metabolism disorders with metformin was found in patients receiving the latter in combination with haloperidol. The combination of metformin with risperidone and quetiapine showed a slightly lower clinical effect. Conclusion. Our own clinical experience gives grounds to recommend metformin hydrochloride as a medium for the correction of carbohydrate metabolism disorders in patients with a paranoid form of schizophrenia in the treatment of this category of patients with neuroleptics