Inhibitors of dipeptidyl-peptidase-4: obvious and probable (literature review)

The purpose of the presented literature review was an attempt to sum up current estimates of the effect of the use of dipeptidyl peptidase-4 inhibitors (iDPP-4) in the algorithms of both traditional (diabetes mellitus) and a number of alternative nosologies, in particular, oncological and neurological pathology, as well as a new coronavirus infection (COVID-19). To do this, the most large-scale (as a rule) publications of 2018–2021 devoted to the problems under consideration were analyzed. The search was carried out by keywords in the Pubmed information base (ncbi.nlm.nih.gov). Factors contributing to the widespread use of IDP-4 in clinical practice are both pharmacologically clear mechanism of action and efficacy, as well as the possibility of oral use, a successful pharmacokinetic profile, low toxicity, in particular, a low risk of hypoglycemia. Newly obtained data on the mechanisms of mechanisms are discussed. Renoprotective action, the presence of cardioprotection is debated. The biochemical prerequisites for the possible effectiveness of iDPP-4 as blockers of the development of a hyperimmune reaction that causes, in particular, the severe course of the new coronavirus infection are discussed. At the same time, the results of studies of various designs are categorically compared, indicating both in favor of the use of iDPP-4 in patients with COVID-19, and not noticing its expediency. It is concluded that, given the large-scale biochemical role of DPP-4, it is important both to continue the active use of its inhibitors in diabetes mellitus, and to expand attempts to use them in a number of other nosologies, including COVID-19

Antenatal glucocorticosteroids treatment: mechanisms of child healths programming

Synthetic glucocorticoids are widely used in pregnancies at risk of preterm delivery and in pregnant women at risk of having a child with severe 21-hydroxylase deficiency. The positive effects of reducing mortality in preterm and virilisation in girls with congenital adrenal hyperplasia are now unquestionable. The adrenogenital syndrome responding to 21-hydroxylase deficiency is a common, potential fatal disease. Its incidence calculated on the basis of neonatal screening data makes 1 case for 14000 live newborns among the worldwide population, 1 for 9638 – In Russia. DEX passes through the placenta and decreases fetal ACTH production thereby suppressing the fetal production of androgens. The prenatal treatment does not preclude from a life-long treatment in future and it is not prevention of a salt-losing syndrome at the postnatal period, and dexamethasone safety in relation to cognitive development of children prenatally treated with dexamethasone is still up for debate. Adding to the concern is the fact that the doses of DEX that the fetus is exposed to are estimated to be 60 times the normal fetal cortisol level. The glucocorticoid and the mineralocorticoid receptors are highly expressed in the hippocampus, amygdala, and prefrontal cortex. These areas, important for executive functioning, emotional regulation, and memory, are vulnerable to high doses of GCs. Most experimental data from animal have shown that prenatal exposure to synthetic glucocorticoids programs the foetal HPA and may lead to altered susceptibility to metabolic and cardiovascular disease i.e. metabolic syndrome, high blood pressure. Prenatal glucocorticoid exposure also leads to modification of HPAassociated behaviours and cognition

To the question of the pathogenetic mechanisms of the influence of obesity on the level of vitamin D

The influence of obesity on human health, as a multifactorial and multigenic disorder, is a rather complex, interdisciplinary and at the same time extremely urgent problem of modern society. Vitamin D deficiency is one of the consequences of obesity that negatively affects a person’s life expectancy. Vitamin D deficiency is rightfully considered a silent, non-infectious metabolic pandemic of the 21st century. Its significant role in the functioning of the human body is deep and multifaceted, since vitamin D is an integral regulator of the transcriptional activity of genes that control 3–5% of the human genome. There are ongoing discussions among experts in the medical community about the negative impact of obesity on 25 (OH) D levels, and the opposite hypothesis is also being discussed, where vitamin D deficiency is considered an independent risk factor for obesity. Both external causes of the formation of vitamin D deficiency against the background of excessive deposition of adipose tissue and internal metabolic processes underlying the pathogenetic association are analyzed two pathological conditions

Effects of bariatric surgery on bone metabolism: focusing on vitamin D

The main goal of bariatric surgery is weight loss due to fundamental differential changes in the anatomical and physiological characteristics of the gastrointestinal tract. At the same time, one of the most frequent complications of obesity surgery, especially operations associated with malabsorption, is vitamin D deficiency. Patients with obesity initially have a wide range of predisposing factors for metabolic diseases of the skeleton due to lifestyle problems. Nutrient deficiencies with high-calorie diets and a sedentary lifestyle with a tendency to wear clothing that covers most of the skin — reduces serum 25 (OH) D levels. In addition, the situation is aggravated by a decrease in the bioavailability of 25 (OH) D due to its sequestration in adipose tissue and its complete inaccessibility to the central blood flow. The consequences of bariatric surgery — a decrease in the amount of skin and malabsorption can aggravate the existing deficiency. As a result of a decrease in the level of 25 (OH) D and subsequent hypocalcemia and secondary hyperparathyroidism, negatively affect the state of bone health. The presented literature review is devoted to the problems of obesity surgery and vitamin D deficiency. The main focus is on bone metabolism associated with bariatric surgery, the causes of pre and postoperative vitamin D deficiency are discussed, and recommendations for its treatment after obesity surgery are given

Obesity in the elderly: peculiarities of treatment in outpatient practice

Today there is a worldwide trend of population aging, in addition, the proportion of older people with obesity is increasing. In order to adequately manage these patients in the outpatient setting, it is critical to understand the dynamic relationship between body weight, chronic disease prevalence, development of functional disability, life expectancy, and health care costs. While the obesity epidemic has affected people of all age groups, empirical knowledge about the management of obese older people remains largely scarce. Currently, there is no single therapeutic approach to this problem. Weight loss should be treated with caution in people over 60 years of age. The risk of sarcopenia, malnutrition, bone loss, increased risk of falls and injury must be considered, which can lead to an increase in the number of people with disabilities and the associated costs of medical and social care. The analytical review focuses on the relationship between two of the greatest epidemiological trends: aging and obesity. This paper highlights the features of the pathophysiology of obesity in the elderly, the phenomenon of the «obesity paradox». Also from the perspective of evidence-based medicine approaches to the treatment of obesity in the elderly, including surgical interventions aimed at reducing body weight, are analyzed

Time in range is a tool for assessing the quality of glycemic control in diabetes

The presence of continuous glucose monitoring (CGM) systems has expanded diagnostic capabilities. The implementation of this technology into clinical practice allowed to determine the patterns and tendencies of excursions in glucose levels, to obtain reliable data concerning short-term glycemic control. Taking into consideration the large amount of obtained information using CGM systems, more than 30 different indicators characterizing glycemic variability were proposed. However, it is very difficult for a practitioner to interpret the data obtained due to the variety of indicators and the lack of their target values. The first step in the standardization of indices was the creation of the International Guidelines for CGM in 2017, where the Time in Range (TIR) (3,9–10,0 mmol/l, less often 3,9–7,8 mmol/l) was significant. To complement the agreed parameters and simplify the interpretation of obtained data using CGM, in 2019 the recommendations were prepared for the International Consensus on Time in Range, where TIR was validated as an additional component of the assessment of glycemic control along with HbA1c. In the literature review the issues of the association of TIR with the development of micro- and macrovascular complications in type 1 and 2 diabetes are considered. The relationship with other indicators of the glycemic control assessment was also analyzed and the dependence of insulin therapy on TIR was shown. TIR is a simple and convenient indicator, it has a proven link with micro- and macrovascular complications of diabetes and can be recommended as a new tool for assessing the glycemic control. The main disadvantage of TIR usage is the insufficient apply of CGM technology by the majority of patients with diabetes

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Oral semaglutide: the innovation in type 2 diabetes management

Oral semaglutide is the first-in-class glucagon-like peptide-1 receptor agonist available in the form of pills administered per os. PIONEER — the clinical trial program assessing the efficacy and safety of oral semaglutide — demonstrated the dose-­dependent efficacy of the drug: the reduction of up to -1,4% in terms of glucose-lowering effects and the decrease of up to 5 kg in terms of weight loss. Moreover, oral semaglutide is superior in this regard compared to empagliflozin 25 mg, liraglutide 1,8 mg and sitagliptin 100 mg according to the dedicated trials of clinical program. From the cardiovascular perspective oral semaglutide has been proven to be safe. Therapeutic concentration of semaglutide in oral form is reached under ­several conditions: taking tablets on a daily basis in a fasting state with up to half a glass of water and waiting 30 minutes before drinking, eating, or taking other drugs. Most frequent adverse events were GLP-1 associated gastrointestinal reactions (­nausea, vomiting and diarrhea), most of the events were transient and occurred generally during dose escalation

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background Liraglutide 3\ub70 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3\ub70 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2\ub77 times longer with liraglutide than with placebo (95% CI 1\ub79 to 3\ub79, p<0\ub70001), corresponding with a hazard ratio of 0\ub721 (95% CI 0\ub713\u20130\ub734). Liraglutide induced greater weight loss than placebo at week 160 (\u20136\ub71 [SD 7\ub73] vs 121\ub79% [6\ub73]; estimated treatment difference 124\ub73%, 95% CI 124\ub79 to 123\ub77, p<0\ub70001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3\ub70 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding Novo Nordisk, Denmark