Hypoglycemic Effects of Polyphenol Complexes from Bilberry Leaves and Fruits Sorbed on Brown Buckwheat Flour -- Experimental Evaluation and Prospects of Use

The effects of plant polyphenols on carbohydrate and/or lipid metabolism disorders have wide experimental and clinical justification; however, their effects are limited due to low bioavailability. Thus, the development of technological approaches enhancing their effectiveness and stability is relevant.The aim of this work was to evaluatein vivothe effects of polyphenols from bilberry leaves and fruits, sorbed on the brown buckwheat flour, on C57Bl/6c mice with carbohydrate and lipid metabolism disorders. We assessed in vivothe effect of a food matrix (FM1: bilberry leaf polyphenols sorbed on brown buckwheat flour) on C57Bl/6c mice with induced carbohydrate and lipid metabolism disorders. The aim of the second experiment was to evaluate the effectiveness of prolonged prophylactic consumption of another food matrix (FM2: billberry fruit polyphenols, sorbed on brown buckwheat flour) by C57Bl/6c micewith induced carbohydrate and lipid metabolism disorders. Technological approaches were developed and pilot batches of the food matrices FM1 and FM2were obtained. According to the in vivo testing, a significant decrease in the glucose levels and normalization of glucose tolerance and insulin sensitivity were found in animals treated with FM1. When assessing the in vivo effects of FM2, the hypoglycemic effect of bilberry fruit polyphenols in the composition of the matrix was established. The results of these studies can be used to justify the testing of the developed matrices in a clinical setting and using them as functional food ingredients for preventative nutrition in cases of carbohydrate metabolism disorders. Keywords: polyphenols, food matrix, functional food ingredient, carbohydrate metabolism, lipid metabolism

Results of Malnutrition Correction in Children with Cystic Fibrosis with Hypercaloric Formulas for Enteral Nutrition for One Month: Cohort Study

Background. The use of hypercaloric formulas in cystic fibrosis patients has the risks of negative effects on carbohydrate and lipid metabolism. Thus, it is interesting to analyze the efficacy of malnutrition correction and the safety of hypercaloric enteral products with a low glycemic index and with medium-chain triglycerides content of 50%.Objective. The aim of the study is analyze the efficacy of malnutrition correction with therapeutic hypercaloric product for enteral nutrition in children with cystic fibrosis.Methods. The study included patients aged from 3 to 18 years with malnutrition (BMI < 50 percentile) who were prescribed therapeutic hypercaloric formula to correct the malnutrition. Anthropometric indicators (height, body weight), actual nutritional status, pancreatin doses, lung function, carbohydrate metabolism rates, and cholestasis marker (bile acid concentration) were measured initially and after 1 month of using formula nutrition.Results. The children’ body weight (Me) has increased from 24.5 (21.2; 38.7) to 25.3 kg (21.6; 39.7) (p = 0.001), growth (Me) — from 133.5 (120.2; 146.5) to 136.5 cm (123.0; 148.5) (p < 0.001) after 1 month of using hypercaloric formula. The growth percentile increased from 33 to 40, the z-criterion values — from –0.5 to –0.3 SD (p < 0.001). There was no increase in BMI in dynamics due to the fact that the growth of children was ahead of body weight increase. The daily energy intake increased by an average of 450 kcal that was 21.8% regarding physiological need.Conclusion. The inclusion of hypercaloric formula in the diet of children with cystic fibrosis for 1 month significantly increases the indicators of linear growth and positively affects the overall physical development. There were no negative effect of formula on carbohydrate and lipid metabolism.

Specifics of functional activity of the immune system, carbohydrate and lipid metabolism in overweight and obese children with biliary dysfunction

Objective — to evaluate functional activity of the immune system, carbohydrate and lipid metabolism in children with biliary dysfunction against the background of overweight and obesity. Materials and methods. At the SI «Institute Gastroenterology of the National Academy of Medical Sciences of Ukraine» observations were performed on 108 children with the mean age 12.5 ± 2.51 years. Based on the results of investigation of motor and evacuator gallbladder (GB) function and body mass index, the pediatric patients were divided into three groups: group I included 52 overweight children with gallbladder hypofunction and obesity; group II consisted of 42 overweight children with normal gallbladder function and obesity; group III (comparison group) included 14 children with normal weight and biliary normokinesia. Investigations included anthropometric measurements and ultrasound imaging of the abdomen. ELISA was used to determine blood serum levels of insulin, interleukin‑6 (IL), IL‑10, tumour necrosis factor‑a (TNF‑a). Results. The following augmentation of the median levels was established when compared with group III: IL‑6 in 2.2 times (p < 0.05) and TNF‑a in 4.5 times (p < 0.05) in patients of group I, levels of IL‑6 in 2.3 times (p < 0.05) and TNF‑a in 4.3 times (p < 0.05) in patients of group II. The IL‑10 level in group I patients was lower in 2.5 times than in group II patients (p < 0.05), and in 4.4 times vs group III patients (p < 0.05). The serum insulin levels in children of groups I and II were in 2.2 times (p < 0.05) and 1.5 times (p < 0.05) lower, and HOMA‑IR index in 2.3 times (p < 0.05) and in 1.8 times (p < 0.05), respectively, in comparison with group III patients. The following blood serum levels vs group III were established: triglycerides (TG) increased in group I in 1.4 times (p < 0.001) and in group II in 1.5 times (p < 0.001); low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were increased both in I and II groups in 1.2 times, (p < 0.01) and 1.5 times, (p < 0.001), respectively. The atherogenic index (AI) raised in 1.6 times (p < 0.001) in group I patients and in 1.5 times (p < 0.05) in group II patients compared to group III, whereas high density lipoprotein (HDL) levels were decreased in the I and II groups in 1.2 times (p < 0.01) in comparison with group III patients. Conclusions. Regardless of the gallbladder functional state in overweight and obese pediatric patients, the abnormalities of the immune system indices have been established and, consequently, carbohydrate metabolism disorders (increased levels of insulin and index HOMA‑IR). The lipid metabolism disturbances have been established in the overweight and obese children with gallbladder hypofunction (significant increase in the levels of TG, LDL, VLDL, AI and decreased HDL levels). Correlation analysis in the groups of overweight and obese children with gallbladder hypofunction showed the presence of significant relationships between biliary sludge and IL‑6, TNF‑a levels, gallbladder volume and insulin and glucose levels, gallbladder hypofunction and levels of total cholesterol, HDL, LDL and as well as between the gallbladder dimensions and atherogenic index.

Aflatoxin and Disruption of Energy Metabolism

Aflatoxins constitute a cluster of mycotoxins that are derived from fungal metabolites and are produced from diverse fungi species, especially Aspergillus. They are a collection of closely linked heterocyclic compounds produced predominantly by two filamentous fungi, Aspergillus flavus and Aspergillus parasiticus. They are also known to cause severe health threats to humans and animals, thereby resulting to several complications like immunotoxicity, teratogenicity hepatotoxicity. Aflatoxins interfere with normal metabolic processes. This interference encompasses the regulatory processes that occur throughout the progression of energy metabolism. Thus, the effects of aflatoxins are seen in the inhibition of ATP generation, carbohydrate and lipid metabolism, mitochondrial structure and proteins synthesis. This chapter will focus on the mechanisms of aflatoxin-induced disruption of lipids, carbohydrates, and proteins metabolism, and how they affect the bioenergetic systems.

Association of angiotensinogen and angiotensin II receptor type I polymorphisms with biomarkers of carbohydrate and lipid metabolism in Dagestan residents with type 2 diabetes and hypertension

Aim. To study the associations of angiotensinogen (AGT) (s4762(С521Т), rs699(Т704C)) and angiotensin II receptor type I (AGTR1) (rs5186(A1166C)) genetic polymorphisms with serum levels of insulin, glucagon, C-peptide, leptin, as well as with dyslipidemia and glycemic levels in Dagestan residents with combination of type 2 diabetes (T2D) and hypertension (HTN), as well as with isolated T2D/HTN.Material and methods. We examined 16 patients with isolated T2D, 59 patients with T2D+HTN and 51 patients with isolated HTN from Dagestan. Genetic polymorphisms of the AGT and AGTR1 genes were studied. The levels of insulin, glucagon, C-peptide, and leptin were studied by enzyme-linked immunosorbent assay (ELISA), while lipid and carbohydrate metabolism — by biochemical methods.Results. In patients with T2D, the association of CC genotype of AGT gene rs4762(С521Т) polymorphism with a leptin decrease was determined, while its CT genotype was associated with an increase in serum level of triglycerides. The TC genotype of AGT gene rs699(Т704C) polymorphism was associated with an increase in leptin, triglyceride and glucose levels. The AA genotype of AGTR1 gene rs5186(A1166C) polymorphism was associated with an increase in insulin and glucose levels, as well as a decrease in leptin level. In patients with a combination of T2D and HTN, CC and CT genotypes of AGT gene rs4762(С521Т) polymorphism was associated with a decrease in glucagon level. The TT genotype of AGT gene rs699(Т704C) polymorphism was associated with an increase in insulin, triglyceride, glucose and body mass index (BMI) levels. In isolated HTN, the CC and CT genotypes of AGT gene rs4762(С521Т) polymorphism were associated ith a decrease in glucagon level. The TT genotype of AGT gene rs699(Т704C) polymorphism was associated with increased levels of insulin, low density lipoproteins, and BMI.Conclusion. Associations of AGT (s4762(С521Т), rs699(Т704C)) and AGTR1 (rs5186(A1166C)) genetic polymorphisms with carbohydrate and lipid metabolism changes are an important pathogenetic link of T2D and HTN, which allows developing an individual prognosis of these diseases in Dagestan residents.

Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes

Maternal diabetes is a prevalent pathology that increases the risk of cardiovascular diseases in the offspring, the heart being one of the main target organs affected from the fetal stage until the adult life. Metabolic, pro-oxidant, and proinflammatory alterations in the fetal heart constitute the first steps in the adverse fetal programming of cardiovascular disease in the context of maternal diabetes. This review discusses both human and experimental studies addressing putative mechanisms involved in this fetal programming of heart damage in maternal diabetes. These include cardiac epigenetic changes, alterations in cardiac carbohydrate and lipid metabolism, damaging effects caused by a pro-oxidant and proinflammatory environment, alterations in the cardiac extracellular matrix remodeling, and specific signaling pathways. Putative actions to prevent cardiovascular impairments in the offspring of mothers with diabetes are also discussed.

Peculiarities of carbohydrate and lipid metabolism in infertile patients with clomifen-resistant form of polycystic ovarian syndrome and obesity

Medical ovulation induction with clomiphene citrate is currently the first line treatment for anovulatory women with PCOS. Clomiphene resistance (failure to ovulate after taking clomiphene) is common, occurring in approximately 15% to 40% of women with PCOS. Resistance is associated with an increased body mass index. The aim of the study was to elucidate the characteristics of carbohydrate and lipid metabolism in patients with clomiphene-resistant PCOS and obesity. Material and methods. A comprehensive examination of 97 infertile patients with PCOS with obesity and clomiphene-resistant PCOS and 46 conditionally healthy normoovulatory women of control group K with 18.5 ≤ body mass index (BMI) < 25 kg/m2, without clinical or biochemical signs of hyperandrogenism, with ovarian volume less than 9 cm3 and without previously known endocrine disease. Clinical-anamnestic, anthropometric, sonographic, immunochemical, enzyme-linked immunosorbent assay, colorimetric, statistical research methods are used. Results and discussion. It was found that the most characteristic features of carbohydrate metabolism disorders in clomiphene-resistant women with PCOS and obesity are increased levels of hypoglycemic index, C-peptide, glucose levels after 2 h in oral glucose tolerance test, HOMA index; and of lipid metabolism - an increase in atherogenic factor, triglycerides, total cholesterol on the background of increased production of leptin and vaspin and decreased secretion of adiponectin, omentin and visfatin.. Conclusions. Visceral obesity plays an important role in the development of insulin resistance and hyperinsulinemia in infertile patients with clomiphene-resistant PCOS and obesity. This category of women in preconception training, before carrying out ovarian drilling or controlled ovarian stimulation, it is necessary to correct disorders of carbohydrate and lipid metabolism.

Concerning effective and safe dosages of vitamin D3: mega-analysis of clinically effective studies as a basis for actual evidence

The negative effects of hypovitaminosis D3 and vitamin D3 deficiency in 80% of Russians make eliminating vitamin D deficiency an issue of state concern. Hundreds of effective clinical studies showed realistic opportunities of vitamin D3 to help patients with disorders of carbohydrate and lipid metabolism, high levels of nonspecific inflammation, tuberculosis, and women with a higher risk of complications and pregnancy losses. Vitamin D3 supplements are essential for the prevention and treatment of a wide range of “bone” and “extraosseous” diseases. One of the most important aspects of the clinical uses of vitamin D3 is the dosage and dosage regimen of the vitamin. This paper presents the results of a “mega-analysis” of 3965 clinical studies of vitamin D3 in terms of the effectiveness of different dosages in achieving different clinical outcomes. It was shown that dosages of 2000 IU/day and 4000 IU/day correspond to the peak values of the effectiveness index, regardless of the diagnoses studied (mega-analysis of 420 randomized trials). Some effectiveness in the treatment of rickets, gestational diabetes, calcium metabolism disorders, disorders of bone density and structure, diseases of the musculoskeletal system and connective tissue can be achieved using weekly dosages of 50,000 IU/week (mega-analysis of 196 studies). It has been shown that dosages of 100,000-1,000,000 IU, intended for a single dose once a month, are almost always found only among studies with a negative result (mega-analysis of 368 studies).

The Role of Insulin-like Growth Factor-1 (IGF-1) in the Control of Neuroendocrine Regulation of Growth

In mammals, the neuroendocrine system, which includes the communication between the hypothalamus and the pituitary, plays a major role in controlling body growth and cellular metabolism. GH produced from the pituitary somatotroph is considered the master regulator of somatic development and involved, directly and indirectly, in carbohydrate and lipid metabolism via complex, yet well-defined, signaling pathways. GH production from the pituitary gland is primarily regulated by the counter-regulatory effects of the hypothalamic GHRH and SST hormones. The role of IGF-1 feedback regulation in GH production has been demonstrated by pharmacologic interventions and in genetically modified mouse models. In the present review, we discuss the role of IGF-1 in the regulation of the GH-axis as it controls somatic growth and metabolic homeostasis. We present genetically modified mouse models that maintain the integrity of the GH/GHRH-axis with the single exception of IGF-1 receptor (IGF-1R) deficiency in the hypothalamic GHRH neurons and somatotroph that reveals a novel mechanism controlling adipose tissues physiology and energy expenditure.