Immunoreactive Insulin Concentrations Research Articles

Cardiometabolic profile in women after pregnancy hypertension: propency score matching

Оbjective: to assess the cardiometabolic profile and cardiovascular risk factors in women with a history of hypertension during pregnancy. Materials and methods: a case-control observational study based on a prospective cohort study included 66 women, divided into two groups: group 1 — with a history of hypertension during pregnancy (n=33), and group 2 (control) — with a history of normotensive pregnancy (n=33). We applied the propensity score -matching method. Results: women in group 1 women were more often had hypertension and obesity compared with the control group. The most significant changes in the cardiometabolic profile were found in group 1: the highest concentrations of glucose and immunoreactive insulin, glycated hemoglobin, uric acid, alanine aminotransferase, aspartate aminotransferase, C-reactive protein in serum, and HOMA-IR insulin resistance index. An increased left ventricular (LV) mass index and the urine albumin/ creatinine ratio were higher among women in group 1 compared with group 2. Conclusion: after applying the propensity score matching, the most significant differences were obtained in the frequency of hypertension, serum concentrations of alanine aminotransferase, C-reactive protein, and the frequency of elevated albumin/creatinine ratio.

The relationship between vitamin D deficiency and insulin resistance during pregnancy

Background. Vitamin D insufficiency is associated with metabolic complications during pregnancy, including insulin resistance. Physiological processes during pregnancy contribute to increased insulin resistance, which, in turn, is the main symptom of gestational diabetes. There is evidence that excessive weight gain during pregnancy negatively affects the concentration of 25-hydroxyvitamin D (25(OH)D). The aim of the study was to determine the effect of vitamin D insufficiency and deficiency during pregnancy on the occurrence of insulin resistance in the third trimester against the background of excessive weight gain. Materials and methods. The prospective study included 65 pregnant women with a gestation period of up to 20 weeks (on average 17 weeks). At the initial stage, a survey (body weight before pregnancy), and a clinical examination were conducted. Subsequent examinations were carried out in the second (20 weeks) and third (28 weeks) trimesters. Weight gain during pregnancy was calculated as the difference in body weight (between the third and second trimester) divided by the number of gestational weeks in that interval, following the Institute of Medicine guidelines. Gestational weight gain was classified as excessive, taking into account pre-pregnancy body mass index. Predicting the probability of insulin resistance (according to the HOMA-IR) was assessed by the dynamics of body weight gain. Results. Median 25(OH)D in the second and third trimesters of pregnancy was 23 and 24 ng/ml, respectively. Vitamin D insufficiency (25(OH)D < 30 ng/ml) was observed in at least one of the trimesters in 47 (72.3%) pregnant women, while the permanent nature of vitamin D insufficiency was noted in 36 (55.4%) cases. Vitamin D deficiency was established in 8 (12.3%) pregnant women in the second trimester. Excessive weight gain during pregnancy was observed in 34 (52.3%) women. Insulin resistance was determined in 31 (47.7%) pregnant women in the third trimester. The median of immunoreactive insulin concentration and HOMA-IR was higher among women with vitamin D deficiency. Conclusion. Vitamin D insufficiency is associated with insulin resistance in the third trimester of pregnancy, which depends on excessive gestational weight gain.

Indicators of carbohydrate metabolism and vitamin D levels in pregnant women with metabolic syndrome

The objective: to assess the level of vitamin D and its relationship with carbohydrate metabolism in women with metabolic syndrome in the I trimester of pregnancy. Materials and methods. 120 pregnant women were examined, of which 60 patients were diagnosed with metabolic syndrome before pregnancy (main group) and 60 patients without this pathology (control group). All women were measured for fasting blood glucose, glycated hemoglobin, immunoreactive insulin, HOMA-IR index, and serum vitamin D levels. Results. In women in the main group, the average level of vitamin D was 15.76±3.77 ng/ml, in the control group – 17.20±3.76 ng/ml. The concentration of vitamin D less than 20 ng/ml in the main group was found in 70.0% of patients, in the control group – in 51.7%, 20–30 ng/ml – in 30.0% and 48.3%, respectively (p<0.05). The mean body mass index was significantly higher in women of the main group relative to the control group (p=0.041) and in patients with metabolic syndrome did not differ from the values in women with vitamin D deficiency and insufficiency. However, body mass index was significantly higher in the presence of vitamin D deficiency between patients with and without metabolic syndrome (p=0.001). There was a significant difference in the concentration of immunoreactive insulin and the value of the HOMA-IR index between pregnant women with vitamin D deficiency and metabolic syndrome (p=0.040) and without it (p=0.023). Serum 25(OH)D levels in early pregnancy in persons with metabolic syndrome positively correlated with glucose (r=0.361; p>0.05), HbA1c (r=0.355; p>0.05) and HOMA-IR (r=0.239; p>0.05) in vitamin D deficiency and negative in 25(OH)D insufficiency: r=-0.795 (p<0.05), r=-0.464 (p>0.05) and r=-0.500 (p>0.05), respectively.Conclusions. Pregnant women with metabolic syndrome and vitamin D deficiency, compared with pregnant women without this syndrome, may have higher levels of immunoreactive insulin and HOMA-IR index. Between the women with the deficiency and insufficiency of vitamin D and the parameters of carbohydrate metabolism in the metabolic syndrome a multidirectional correlation was revealed.

Diabetic Cardiovascular Autonomic Neuropathy: Effects of Simvastatin and Omega-3 Polyunsaturated Fatty Acids on Insulin Resistance and Lipid Profile Parameters

Introduction. Currently, there is no unified treatment algorithm of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). The aim of the study was to investigate the effects of simvastatin (SIM) and -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) in patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Materials and methods. The study involved 72 patients with T2DM and definite CAN. Patients were divided into four groups: 1st - received standard hypoglycemic therapy - control (n = 15); 2nd (n = 22) – in addition simvastatin (SIM) 20.0 mg/q.d.; 3rd (n = 18) - in addition 1 capsule/q.d. of the ω-3 PUFAs; 4th (n = 17) - in addition SIM 10.0 mg/q.d and 1 capsule/q.d of the ω-3 PUFAs for three months. The concentration of glucose, glycated hemoglobin A1c, immunoreactive insulin (IRI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) in the blood were determined. Homeostasis model assessment IR (HOMA-IR), atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG and glucose index (TyG) were calculated. Results. Prescription of SIM was accompanied by a statistically significant decrease in TC, LDL-C, TG concentrations. In parallel, SIM induced a decrease of AC, TG/HDL-C, increase in HDL-C, and does not affect the IRI, HOMA-IR, TG/LDL-C, TG/TC, TC/LDL-C/HDL-C, TyG. The use of ω-3 PUFAs has contributed to a significant reduction in TG, AC, TG/LDL-C, TG/TC, TG/HDL-C, TyG index, increase in HDL-C, and was not accompanied by changes in IRI content, HOMA-IR, TC, LDL-C, and TC/LDL-C/HDL-C. The combined prescription of SIM and -3 PUFAs was accompanied by more pronounced, statistically significant changes in the blood lipid spectrum, as well as a decrease in the IRI and HOMA-IR. Conclusions. Obtained results justify the appropriateness of combined simvastatin and -3 polyunsaturated fatty acids prescription to patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Keywords: diabetes mellitus, cardiac autonomic neuropathy, treatment.

Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy.

Objective. Significantly underdiagnosed, diabetes-associated cardiac autonomic neuropathy (CAN) causes a wide range of cardiac disorders that may cause life-threatening outcomes. This study investigated the effects of alpha-lipoic acid (ALA) on arterial stiffness and insulin resistance (IR) parameters in type 2 diabetes mellitus (T2D) patients and definite CAN. Methods. A total of 36 patients with T2D and a definite stage of CAN were recruited. This investigation was carried out on two separate arms: traditional hypoglycemic therapy (n=18, control) and ALA (n=18) 600 mg in film-coated tablets/q.d. in addition to traditional hypoglycemic therapy. The duration of the study was three months. Results. In subjects with T2D and definite stage of СAN, treatment with ALA resulted in a significant decrease of glucose, immunoreactive insulin concentration, and Homeostasis Model Assessment (HOMA)-IR (HOMA-IR) parameters; pulse wave velocity (PWV), aorta augmentation index (AIxao) during the active period of the day and decrease of PWV, AIxao, and brachial augmentation index during the passive period of the day compared with the results, obtained in the control group. Therefore, the administration of ALA to patients with T2D for three months promotes the improvement of glucose metabolism and arterial stiffness parameters. Conclusions. In patients with T2D and definite stage of СAN treatment with ALA improved HOMA-IR and arterial stiffness parameters. These findings can be of clinical significance for the complex treatment of diabetes-associated CAN.

Віддалені результати корекції метаболічних порушень при синдромі полікістозних яєчників після лікування метформіном

Актуальність. Синдром полікістозних яєчників (СПКЯ) — поліморфне захворювання з надзвичайно варіабельною клінічною картиною та різними фенотипами, що відзначається у 5–10 % жінок репродуктивного віку. Протягом життя у жінок із СПКЯ в 10 разів підвищується ризик розвитку цукрового діабету (ЦД) 2-го типу, в 7 разів — артеріальної гіпертензії та ішемічної хвороби серця, в тому числі інфаркту міокарда, більш ніж удвічі — онкологічних захворювань яєчників, ендометрію, молочної залози. Мета дослідження — проведення аналізу динаміки показників інсулінорезистентності, дисліпідемії, порушеної толерантності до глюкози після лікування метформіном у пацієнток із СПКЯ з використанням показників індексів Caro та НОМА-IR. Матеріали та методи. Проаналізовані 26 історій хвороби пацієнток із СПКЯ, яким за період з 2012 по 2018 р. проводили терапію метформіном протягом шести місяців з моменту постановки діагнозу. Всім пацієнткам в 2018 р. було проведене дослідження ліпідного спектра крові, стандартний глюкозотолерантний тест і дослідження вмісту імунореактивного інсуліну в плазмі венозної крові. Оцінку стану вуглеводного обміну проводили за допомогою розрахункових показників індексів Caro та НОМА-IR. Результати. Результатом застосування метформіну у 26 жінок із СПКЯ й інсулінорезистентністю стало вірогідне зниження рівня імунореактивного інсуліну натще (з 21,4 ± 2,3 до 6,9 ± 0,8 мкОД/мл; р = 0,005) через 6 місяців, в той час як значущих змін рівня глікемії натще не спостерігалося. Відповідно, показник НОМА-IR знизився з 4,38 ± 1,26 до 1,17 ± 0,18 (р = 0,01), а індекс Caro підвищився з 0,24 ± 0,05 до 0,58 ± 0,14 (р = 0,02). Оцінка показників ліпідного обміну через 6 місяців після початку лікування метформіном підтвердила вірогідне зниження рівня холестерину з 5,4 ± 0,3 до 3,6 ± 0,5 ммоль/л (р = 0,01) і рівня тригліцеридів з 1,7 ± 0,2 до 0,8 ± 0,2 ммоль/л (р = 0,03). Обстеження, проведене у 2018 р. в цих же пацієнток, засвідчило збільшення маси тіла не тільки порівняно з показниками через 6 місяців після лікування метформіном, але і з початковими. Спостерігалося вірогідне підвищення рівня холестерину при обстеженні в 2018 р. до 6,7 ± 0,4 ммоль/л (р = 0,01 порівняно з показником після лікування метформіном). Висновки. Жінки із СПКЯ та інсулінорезистентністю, дисліпідемією мають найбільший ризик розвитку ЦД і серцево-судинної патології. Застосування метформіну розглядається як потенційно ефективний метод для подолання інсулінорезистентності, поліпшення гормональних, біохімічних параметрів і можливого зниження кардіоваскулярного ризику при СПКЯ.

Investigation of the utility of the 1.1B4 cell as a model human beta cell line for study of persistent enteroviral infection

The generation of a human pancreatic beta cell line which reproduces the responses seen in primary beta cells, but is amenable to propagation in culture, has long been an important goal in diabetes research. This is particularly true for studies focussing on the role of enteroviral infection as a potential cause of beta-cell autoimmunity in type 1 diabetes. In the present work we made use of a clonal beta cell line (1.1B4) available from the European Collection of Authenticated Cell Cultures, which had been generated by the fusion of primary human beta-cells with a pancreatic ductal carcinoma cell, PANC-1. Our goal was to study the factors allowing the development and persistence of a chronic enteroviral infection in human beta-cells. Since PANC-1 cells have been reported to support persistent enteroviral infection, the hybrid 1.1B4 cells appeared to offer an ideal vehicle for our studies. In support of this, infection of the cells with a Coxsackie virus isolated originally from the pancreas of a child with type 1 diabetes, CVB4.E2, at a low multiplicity of infection, resulted in the development of a state of persistent infection. Investigation of the molecular mechanisms suggested that this response was facilitated by a number of unexpected outcomes including an apparent failure of the cells to up-regulate certain anti-viral response gene products in response to interferons. However, more detailed exploration revealed that this lack of response was restricted to molecular targets that were either activated by, or detected with, human-selective reagents. By contrast, and to our surprise, the cells were much more responsive to rodent-selective reagents. Using multiple approaches, we then established that populations of 1.1B4 cells are not homogeneous but that they contain a mixture of rodent and human cells. This was true both of our own cell stocks and those held by the European Collection of Authenticated Cell Cultures. In view of this unexpected finding, we developed a strategy to harvest, isolate and expand single cell clones from the heterogeneous population, which allowed us to establish colonies of 1.1B4 cells that were uniquely human (h1.1.B4). However, extensive analysis of the gene expression profiles, immunoreactive insulin content, regulated secretory pathways and the electrophysiological properties of these cells demonstrated that they did not retain the principal characteristics expected of human beta cells. Our data suggest that stocks of 1.1B4 cells should be evaluated carefully prior to their use as a model human beta-cell since they may not retain the phenotype expected of human beta-cells.

The effect of diet therapy on the anthropometric and metabolic parameters in women with infertility and obesity

Aim: to monitor the anthropometric, hormonal and metabolic parameters in women of reproductive age with infertility and grade I gluteofemoral obesity during treatment with a balanced hypocaloric diet. Materials and methods . The study included 23 infertile women of reproductive age. All patients were prescribed a balanced, low-calorie diet (1200 kcal/day), exercise, and behavioral therapy. The anthropometric, metabolic and hormonal parameters were determined before and 12 months after the treatment. We measured the levels of leptin, total cholesterol, triglycerides, triglycerides, high-density and low-density lipoprotein cholesterol (HDL cholesterol and LDL cholesterol), fasting glycose. Following the measurements, the atherogenic and insulin resistance indices were calculated. In addition, the plasma concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, estrone, estradiol, testosterone, progesterone, and immunoreactive insulin were measured. Results. Twenty patients completed the study. A decrease in body weight (by average of 10.58 ± 5.70 kg) was found in 87 % of patients; in parallel, the body mass index decreased from 32.53 ± 1.40 to 28.55 ± 2.50 kg/m2 (p < 0.001). The decrease in body weight was accompanied by a statistically significant decrease in the levels of leptin (p < 0.001), estrone (p = 0.049), estradiol (p = 0.032), total cholesterol (p < 0.001), triglycerides (p = 0.004), LDL cholesterol (p = 0.001), fasting glycose (p < 0.001), insulin resistance index (p = 0.002), atherogenic index (p < 0.001) and an increase in the level of progesterone (p = 0.030). The ovulatory menstrual cycle was restored in all women (p = 0.007); within one year, wanted pregnancy occurred in 1 woman. Conclusion. The use of a low-calorie diet for 12 months in infertile women with grade I gluteofemoral obesity leads to normalization of metabolic parameters, weight loss and, the restoration of the ovulatory menstrual cycle in 100 % of cases.

Effect of the body weight index on the intensity of metabolic disorders in essential hypertension patients associated with ischemic heart disease and type 2 diabetes mellitus

Objective of the work is to study peculiarities of metabolic disorders in patients with essential hypertension stage I (EH stage I) associated with ischemic heart disease (IHD) and type 2 diabetes mellitus (DM 2) depending on the body mass index (BMI).Material and methods. 45 patients with EH stage II associated with IHD, 52 patients with EH stage II associated with IHD and DM 2, 26 practically healthy individuals representative by the age and sex were included into the investigation. The indices of carbohydrate and lipid metabolism, oxidative homeostasis, the content of nitrogen monoxide (NO) final metabolites in the blood depending on BMI were investigated.Results. In patients with EH stage II associated with IHD and excessive body weight compared with the control a reliable increase of immunoreactive insulin (IRI) concentration and HOMA-IR index were determined. In case of obesity I a reliable increase of glucose concentration in plasma, IRI, HOMA-IR index, decreased concentration of high density lipoprotein (HDL) cholesterol and increased content of low density lipoprotein (LDL) cholesterol, increased concentration of Malone aldehyde (MA) in erythrocytes were determined compared with the control and patients with normal body weight. A direct interrelation of a moderate density between IRI content and body weight, reverse direct correlation of a moderate density between HDL cholesterol and body weight were determined. In patients with EH stage II associated with IHD and DB 2 and obesity I a reliable increase of total cholesterol concentration (42,54%), triacylglyceroles (42,5%), LDL cholesterol (14,5%), MA of erythrocytes (16,14%), decreased content of HDL cholesterol (18,0%), reduced glutathione (17,75%), normalization of catalase activity in comparison with the patients with normal body weight were found. A direct correlation was found between moderate density and IRI level and body weight, total cholesterol, HDL cholesterol, MA, catalase; between body weight and total cholesterol.Conclusions. In patients with EH stage II associated with IHD dependence of certain indices of metabolism and body mass index was determined. In the blood of patients with obesity I compared with those having excessive body weight, a reliable (p&lt;0,05) increase of IRI concentration and HOMA-IR index, LDL cholesterol, decreased concentration of HDL cholesterol, increased content of MA in erythrocytes were found. More pronounced effect of increased body weight on metabolism was found in patients with EH stage II associated with IHD and DM 2.

Effects of benfotiamine on the insulin resistance state, some pro- and anti-inflammatory factors content in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy

Aim. The aim of the study was to analyze the effect of benfotiamine (BFT) on the insulin resistance state, the content of some pro- and anti-inflammatory factors in patients with type 2 diabetes mellitus (T2DM) and advanced stage of cardiac autonomic neuropathy (CAN). Material and methods. 40 patients with T2DM and advanced stage of CAN, aged between 50-59 yrs with disease term 1-6 yrs and average glycated hemoglobin A1c (HbA1c) 7,16%±0,19% were examined. Patients were divided into 2 groups. The patients from first group received standard hypoglycemic treatment (n=19, control) for three mo. To patients from the second (n=21, treatment group) was prescribed 300 mg/q.d. of the BFT in addition for three mo. The levels of blood glucose, HbA1c, immunoreactive insulin (IRI), high sensitivity C-reactive protein (hs-CRP), leptin, tumor necrosis factor-alpha (TNF-alpha), interleukins (IL)-6, IL-8 and IL-10 were determined. The Homeostasis Model Assessment (HOMA) insulin resistance (IR) index (HOMA-IR) parameters, TNF-alpha/IL-10 ratio were calculated. Results. Treatment with BFT led to significant decrease in the concentration of IRI [Δ=-12,74%±1,42% (p 0,05). Conclusion. Obtained data may indicate a decrease in the activity of the proinflammatory link of the immune response and allow us to consider BFT as a promising pharmacological agent in the complex treatment of the advanced stage of CAN.

Visceral Fat Accumulation Is Associated with Asthma in Patients with Type 2 Diabetes.

Objective The number of patients with type 2 diabetes has increased in Japan, and type 2 diabetes has attracted attention as a risk factor for asthma. However, the risk factors for the development of asthma in patients with type 2 diabetes have not been determined. This study was performed to clarify whether visceral fat accumulation (VFA) and insulin resistance are risk factors for the development of asthma in patients with type 2 diabetes. Materials and Methods A cross-sectional study was conducted. The study group comprised 15 patients with type 2 diabetes with asthma, and the control group comprised 145 patients with type 2 diabetes without asthma. Their fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. Their glucose status was assessed by measuring the fasting plasma glucose (FPG) concentration, fasting immunoreactive insulin concentration, homeostasis model assessment (HOMA) index, and hemoglobin A1c concentration. Results Among patients with type 2 diabetes, VFA was significantly greater in patients with asthma than those without asthma (P < 0.0001). The FPG concentration, fasting immunoreactive insulin concentration, and HOMA index were higher in patients with asthma than those without asthma (P < 0.05, P < 0.0001, and P < 0.0001, respectively). Multiple logistic regression analysis showed that VFA and the HOMA index were significantly associated with asthma in patients with type 2 diabetes (odds ratio, 1.78; 95% confidence interval, 1.31–3.89; P = 0.0115 and odds ratio, 3.65; 95% confidence interval, 1.37–7.85; P = 0.0078, respectively). Conclusions Our data suggest that VFA and insulin resistance are associated with the development of asthma in patients with type 2 diabetes.

Carbohydrate and lipid metabolism disorders in women with primary hyperparathyroidism: results of cross-sectional study

Background: Patients with primary hyperparathyroidism (PHPT) have increased mortality risk predominantly attributed to cardiovascular disease. Taking the risk factors for cardiovascular disease into account, such as overweight, atherogenic dyslipidaemia, carbohydrate metabolism disorders and insulin resistance (IR), investigation on the the study of the state of carbohydrate and lipid metabolism in patients with PHPT will help to shed light on the pathogenic mechanisms of the disease and, perhaps, to complement the algorithm for selecting treatment strategies for patients with PHPT.&#x0D; Aims: To study the prevalence of carbohydrate and lipid metabolism disorders among patients with PHPT and to identify the relationship between these two disorders with the indicators of mineral metabolism.&#x0D; Materials and methods: A case-control study of a total of age-matched 256 female patients, 220 patients with PHPT and 36 healthy individuals. The group patients with PHPT were sub-divided into two groups, symptomatic and mild form of PHPT. To verify the form of PHPT, ultrasound examinations of the parathyroid glands and kidneys, two-energy x-ray absorptiometry, biochemical studies (concentration of total and ionised calcium, serum phosphorus and the activity of alkaline phosphatase) and assessment of parathyroid hormone concentration were performed. The relationship between form of PHPT and body weight were evaluated retrospectively according to the survey. Among the 109 participants with PHPT (symptomatic PHPT: 82 patients; mild PHPT: 27 patients) and healthy individuals, the biochemical and hormonal parameters of fat (lipid spectrum of blood) and carbohydrate metabolism (content of immunoreactive insulin, HOMA index, presence of fasting glycemia disorder, glucose tolerance disorders and type 2 diabetes mellitus) were evaluated.&#x0D; Results: The symptomatic PHPT was associated with low body mass index (BMI) while the mild PHPT with high BMI. During an oral glucose tolerance test, the postprandial glycemia in symptomatic PHPT was significantly higher than that in mild PHPT (p = 0.036). The content of immunoreactive insulin in the symptomatic PHPT was not correlated with the concentration of parathyroid hormone, but positively correlated with the concentration of ionised calcium in the blood (r = 0.31; p = 0.006). Patients with PHPT showed a direct positive correlation between BMI and IR index (r = 0.67; p 0.001). It is shown that patients with PHPT have increased LDL content in the blood, and the actual blood lipid concentration is associated with the state of kidney function.&#x0D; Conclusions: The obtained data confirm the relationship between phosphoruscalcium metabolism disorders in PHPT and carbohydrate and lipid metabolism disorders. Prospective, controlled studies are warranted to better elucidate the causal relationships of mineral, carbohydrate and fat metabolism disorders in PHPT.

Metabolic disorders in patients suffering from stage III essential hypertension with comorbid ischemic heart disease and their correction by means of Quercetin and Arginine hydrochloride

Objective: to study peculiarities of metabolic disorders in patients suffering from stage III essential hypertension (III EH) with comorbid ischemic heart disease (IHD) and investigate the efficacy of their correction influencing on lipid peroxide oxidation (LPO) intensity and endothelial dysfunction by 5‑lipoxygenase inhibitor Quercetin (Corvitin) and NO donator — Arginine hydrochloride (Tivortin) against the underlying basic therapy (BT).Material and methods. 55 patients suffering from III EH and comorbid IHD were involved into the study and randomized into two groups. The first group included 25 patients receiving the common BT. The patients from the second group (30 individuals) during the first 6 days in addition to BT were subjected to infusion therapy with Quercetin (0,5 g), and the following 6 days — Arginine hydrochloride in the dose of 100 ml of the solution intravenously.Results. In the blood of patients suffering from III EH with comorbid IHD the following was found: reliable (р 0,05) was determined.Conclusions. The combined basic and metabolitotropic therapy with Quercetin and Arginine hydrochloride resulted in a positive effect on the indices of carbohydrate and lipid metabolism, lipid peroxide oxidation and antioxidant protection in the blood of patients suffering from III essential hypertension with comorbid ischemic heart disease. A reliable decrease of immunoreactive insulin concentration, HOMA-IR index, total cholesterol, triacylglycerols, low density lipoprotein cholesterol, increased content of high density lipoprotein cholesterol, reduced concentration of Malone aldehyde in plasma and erythrocytes. Decreased intensity of lipid peroxide oxidation processes was associated with activation of the antioxidant protection system: a reliable increase of reduced glutathione content, increased activity of glutathione peroxidase and catalase. A reliable increase of the content of final NO metabolites, concentration of vascular endothelial human growth factor (VEGF-A) was determined. In the control group of patients the dynamics of the indices indicated against the ground of the basic therapy only was found to be inconsiderable (р>0,05).

The Effect of Two Isocaloric and Energy-Matched Plant-Based and Processed-Meat Meals on Glucose Metabolism, Gastrointestinal Hormones, and Satiety in Subjects with T2D, Obese Subjects, and Healthy Controls—A Randomized Crossover Study

Objective: Gastrointestinal hormones play a key role in glucose metabolism and energy homeostasis. Methods: A randomized cross-over study was used to test the effects of two energy- (600 kcal) and macronutrient-matched plant-based and processed-meat meals (41% carbohydrates, 19% protein, and 40% lipids) on glucose metabolism, plasma concentrations of gastrointestinal hormones, and satiety in subjects with T2D (n=20), obese subjects (n=20) and healthy controls (n=20). Plasma concentrations of glucose, immunoreactive insulin, C-peptide, GLP-1, GIP, amylin and PYY, along with satiety, were determined at 0, 30, 60, 120 and 180 min. Repeated-measures ANOVA was used for statistical analysis. Results: An increase in stimulated secretion of immunoreactive insulin was observed in T2D and obese subjects (p=0.005, and p=0.045, respectively) after the plant-based meal. We observed an increase in stimulated secretion of C-peptide in all groups after the plant-based meal (p&amp;lt;0.001 for T2D, p=0.014 for obese subjects, and p=0.001 for healthy controls). An increase in postprandial concentrations of amylin was observed in T2D and healthy controls after the plant-based meal (p&amp;lt;0.001 for both groups). An increase in stimulated secretion of GLP-1 was observed in T2D obese subjects and healthy controls (p&amp;lt;0.001, and p=0.01, respectively) after the plant-based meal. A decrease in peak concentrations of GIP (at 60 min.), and an increase in peak concentrations of PYY, were observed in all groups after the plant-based meal. The participants in all groups reported greater satiety after the plant-based meal (p=0.004 for T2D, p&amp;lt;0.001 for obese subjects, and p&amp;lt;0.001 for healthy controls). Conclusions: Our study suggests that plant-based meals may be effective in increasing stimulated secretion of GLP-1, insulin, amylin and PYY, as well as in promoting satiety. Disclosure M. Klementova: None. L. Belinova: None. M. Haluzik: None. R. Pavlovicova: None. M. Hill: None. T. Pelikanova: None. H. Kahleova: None.

PP.14.07] LONG-TERM CHANGES IN LEFT VENTRICULAR GEOMETRY IN TREATED HYPERTENSIVE PATIENTS

Objective: to identify risk factors related to changes on left ventricular (LV) geometry in treated hypertensive patients after a mean period of 10 years. Design and method: 114 patients were examined initially and after 10 years. All patients underwent echocardiography, 24-h ambulatory blood pressure (BP) monitoring and measurement of fasting and postprandial immunoreactive insulin concentration on 60 and 120 min of standard oral glucose-tolerance test (OGTT). During 10 years patients have been treated by their primary care doctor with different antihypertensive drugs. Results: Initially the number of patients in 1st group with normal LV mass index (LVMI) and in 2nd group with LV hypertrophy (LVH) were 52 (46%) and 62 (54%), respectively (Table). Among patients without LVH the prevalence of normal geometry was 29% and concentric LV remodeling was 17%. In 2nd group 26 (23%) patients had concentric LVH and 36 (31%) patients had eccentric LVH. At the end of study the amount of patients with LVH increased to 95 patients (83%), predominantly it was patients (62%) with concentric LVH. After 10 years in 26 (50%) patients from 1st group was formed concentric LVH. In both groups average 24-h BP has been reduced, but BP goal rates haven’t been achieved. Multiple regression analysis demonstrated that baseline 24-h SBP index was predictor of LVMI (ß = −0.461, ρ = 0.001) and IVS (ß = −0.543, ρ = 0.0001), baseline night-time SBP was predictor of PWT (ß = 0.441, ρ = 0.0001) and baseline night-time DBP was predictor of RWT (ß = 0.273, ρ = 0.03) and δ plasma insulin concentration at 120 min of OGTT (ß = 0.364, p = 0.03) had prognostic value of LVMI.Conclusions: After 10 years of poorly controlled treatment the prevalence of concentric LVH increased to 83%. The development and progression of concentric LVH were associated with baseline night-time BP, systolic night-day BP ratio and postprandial hyperinsulinemia.

Incretin secretion and glucose metabolism in morbidly obese patients in the early and late periods after biliopancreatic diversion

To estimate the parameters of glucose metabolism and to assess the secretion of incretins in patients after biliopancreatic diversion (BPD) for morbid obesity (MO) in the early and late postoperative periods. The prospective part of the investigation included 22 patients with a body mass index of 35.8 to 68.4 kg/m2 and type 2 diabetes mellitus (T2DM). All the patients were examined before, 3 weeks and 3 months after BPD. The retrospective part covered 23 patients who were examined after BPD for MO; the postoperative period was 4.7 [2.3; 7.2] years. A control group consisted of 22 healthy, normal weight volunteers. A 75-g oral glucose tolerance test was carried out in all the groups to study the levels of glucose, immunoreactive insulin (IRI), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon at 0, 30, 60, and 120 min. T2DM patients showed improvement in glucose metabolism just 3 weeks after BPD; following 3 months, they had normalized fasting blood glucose levels (5.6 [5.0; 6.0] mmol/l). During 3 months, glycated hemoglobin decreased from 7.5 [6.6; 8.5] to 5.7 [5.3; 5.9]%. In the early period following BPD, there was an increase in basal and postprandial GLP-1 levels associated with the peak IRI concentration. In the late period after BPD, the enhanced secretion of IRI and GLP-1 persisted, which was followed by a reduction in postprandial glucose levels in 4 of the 23 patients. T2DM remission does not depend on weight loss in the early period after BPD. In this period, the significant improvement of glucose metabolic parameters in patients with obesity and T2DM is associated with elevated GLP-1 levels. The altered incretin response is a stable effect of BPD and remains in its late period.

Circadian Rhythms of Carbohydrate Metabolism in Women with Different Types of Obesity.

Blood levels of glucose and immunoreactive insulin were assessed in women with android and gynoid types of obesity or normal body weight (control group) in the dynamics of oral glucose tolerance test in the morning and in the evening. In the control group, the mean concentrations of glucose and immunoreactive insulin were significantly higher in the evening at all test terms (0, 60 and 120 min), which is indicative of physiological insulin resistance in the evening. In the group of women with gynoid obesity, no difference in the levels of glucose and immunoreactive insulin was revealed in the morning and evening tests, but in the evening tests, glucose (60 and 120 min) and immunoreactive insulin (120 min) levels were lower than in the control group. In the group of women with android obesity, the evening glucose level on minutes 60 and 120 of the test was higher than in the morning, but immunoreactive insulin did not vary throughout the day and on minutes 60 and 120 it surpassed the corresponding parameter in the control group by 2-4 times. In case of gynoid obesity, glucose load was followed by hyperinsulinemia and hypoglycemia; in android obesity, it was followed by hyperinsulinemia, hyperglycemia, and insulin resistance irrespective of the time of the day.

The distribution of the islets of Langerhans in pancreas of euglycemic spontaneously hypertensive rats

Учитывая то, что панкреатические бета-клетки ответственны за производство всего инсулина, необходимого организму для поддержания глюкозного гомеостаза, проблема контроля пула бета-эндокриноцитов у пациентов с гипертонической болезнью является актуальной, так как не исключено, что генетические дефекты формирования наследственной артериальной гипертензии развития могут затрагивать механизмы поддержания клеточной массы эндокриноцитов в поджелудочной железе и приводить к нарушению метаболизма глюкозы и диабету. Кроме того, к нарушению адекватной секреции инсулина поджелудочной железой может приводить нарушение цитоархитектоники панкреатических островков, что может быть спровоцировано региональными нарушениями кровообращения у пациентов с артериальной гипертензией. Цель работы – изучить параметры распределения панкреатических островков в поджелудочной железе у гипертензивных крыс линии SHR. Материалы и методы. Измерили уровень глюкозы в крови и концентрацию инсулина, а также анализ иммунофлюоресцентной реакции. Полученные данные обрабатывали пакетом статистических программ, для оценки достоверности различий в группах применяли t-критерий Стьюдента. Результаты. Морфометрический анализ показал, что у гипертензивных крыс линии SHR 78,8% панкреатических островков поджелудочной железы представлены маленькими островками, тогда как у нормотензивных крыс линии Wistar их доля составляет 44,3%. Обращает внимание большое количество единичных бета-эндокриноцитов в поджелудочной железе крыс линии SHR и полное отсутствие крупных островков. Вместе с тем уменьшение численности бета-клеток в железе у крыс линии SHR в значительной мере компенсировалось более высокой концентрацией иммунореактивного инсулина в эндокриноцитах, что, вероятно, обеспечивало сохранение достаточного уровня иммунореактивного инсулина в периферической крови и поддержание эугликемических показателей натощак. Выводы . Цитоархитектоника поджелудочной железы у гипертензивных крыс линии SHR характеризуется нарушением распределения панкреатических островков и доминированием малых островков. Бета-клетки у нормогликемических гипертензивных крыс линии SHR характеризуются в 2 раза более высокой, чем у номотензивных крыс линии Wistar, концентрацией иммунореактивного инсулина.

Primary insulin autoimmune syndrome in an Italian woman: a case report

Insulin autoimmune syndrome (IAS) is a rare syndrome characterized by fasting or postprandial hypoglycemia, high levels of anti-insulin antibodies and high concentration of total serum immunoreactive insulin. It is relatively known in Japan, rare in remaining Asia and it is extremely uncommon in Western countries, being characterized by a different race-related incidence and associated with HLADR4 alleles. Usually IAS is related to particular drugs, or to autoimmune, rheumatologic or hematological diseases, while it is very rare as a primary form. Here we described a case of an Italian woman affected by a primary form of Hirata syndrome.

Development of an ultrasensitive immunoassay using affinity maturated antibodies for the measurement of rodent insulin

The measurement of plasma insulin is important for clinical diagnosis of diabetes and for preclinical research of metabolic diseases, especially in rodent models used in drug discovery research for type 2 diabetes. Fasting immunoreactive insulin (F-IRI) concentrations are used to calculate the homeostasis model assessment ratio (HOMA-R), an index of insulin sensitivity. However, even the most sensitive commercially available enzyme-linked immunosorbent assay (ELISA) kits cannot measure the very low F-IRI concentrations in normal rats and mice. Therefore, we sought to develop a new rodent insulin ELISA with greater sensitivity for low F-IRI concentrations. Despite repeated efforts, high-affinity antibodies could not be generated by immunizing mice with mouse insulin (self-antigen). Therefore, we generated two weak monoclonal antibodies (13G4 and 26B2) that were affinity maturated and used to develop a highly sensitive ELISA. The measurement range of the sandwich ELISA with the affinity maturated antibodies (13G4m1 and 26B2m1) was 1.5 to 30,000pg/ml, and its detection limit was at least 10 times lower than those of commercially available kits. In conclusion, we describe the development of a new ultrasensitive ELISA suitable for measuring very low plasma insulin concentrations in rodents. This ELISA might be very useful in drug discovery research in diabetes.