Leptin and adiponectin in patients with chronic kidney disease and secondary hyperparathyroidism

Background. The results of studies evaluating the levels of adiponectin, leptin and their ratios in chronic kidney disease (CKD) are conflicting. It is assumed that hyperleptinemia and changes in adiponectin clearance are consequences of a decrease in the glomerular filtration rate, they exacerbate renal impairment and may affect the prognosis of survival due to cardiovascular events. It is known that secondary hyperaparathyroidism is the most frequent complication of CKD, which not only affects calcium-phosphorus metabolism and bone tissue, but also contributes to the development of pathological processes involving other hormonal and metabolic markers. Of greatest interest is the assessment of adipocytokine levels in the development of secondary hyperparathyroidism against the background of CKD as an independent factor of increasing cardiovascular risks. The purpose of the study was to assess adipocytokine levels (adiponectin, leptin) and their ratios in patients with different stages of chronic kidney disease and their relationship with manifestations of secondary hyperparathyroidism. Materials and methods. This cross-sectional study enrolled 160 people with CKD and 40 healthy individuals as a comparison group. Results. Leptin level reduction and an increase in the proportion of patients with hypoleptinemia with a decrease in the glomerular filtration rate were found, which may be an important factor determining nutritional status. Correlations were revealed between leptin level, body mass index (ρ = 0.411) and patients’ age (ρ = 0.189), as well as between leptin/adiponectin and adiponectin/leptin ratios (ρ = 0.395 and ρ = –0.395) and body mass index in patients with CKD persisting in subgroups by stage of renal failure. A relationship was found with sex for leptin and a decrease in its levels below normal values in both men and women. Conclusions. The proportion of patients with hyperadiponectinemia was significantly higher among those with end-stage CKD compared to patients with stages 1–2. There was no statistically significant relationship between adipocytokine and parathyroid hormone levels and the presence of secondary hyperparathyroidism in patients examined.

Effect of probiotics and incretine mimeticss on the levels of glucagon-like peptide-1 in blood serum of patients with type 2 diabetes mellitus

Background. Type 2 diabetes mellitus is characterized by a violation of the incretin effect, in particular a decrease in the secretion of glucagon-like peptide-1 (GLP-1) by intestinal endothelial cells. In recent decades, the intestinal microbiota has been shown to play a key role in the regulation of various metabolic pathways, immune system activity, and intestinal permeability. It has been shown that the composition of bacterial genera in the intestine can unfluence the effectiveness of antidiabetic drugs (eg metformin and GLP-1 receptor agonists), which may be reduced in dysbiosis. Therefore, it is of interest to study the mechanisms that mediate the effect of microbiota on the incretin secretion. The purpose was to establish the relationship between the effects of probiotic therapy, incretin therapy and the level of endogenous GLP-1 in the serum of patients with type 2 diabetes mellitus, taking into account anthropometry and body composition. Materials and methods. We examined 23 patients with type 2 diabetes mellitus (11 women and 12 men), their average age was 56.4 ± 10.5 years (M ± SD). At the beginning of the study, the mean HbA1c level was 7.7 ± 1.5 %; all patients took metformin at an average dose of 1,500 mg/day. Patients were randomized into 2 groups: group 1 (n = 11) received a probiotic, group 2 (n = 12) — a long-acting GLP-1 receptor agonist. The concentration of GLP-1 in the blood serum was determined by the enzyme-linked immunosorbent assay, anthropometry parameters and body composition were assessed using the Tanita analyzer. Results. In the group of patients who took the probiotic, a significant increase in GLP-1 was observed, but less pronounced compared to an increase in GLP-1 level in the group of patients who took GLP-1 receptor agonists. In group 2, on the background of taking GLP-1 receptor agonists, a significant decrease in body weight, total and abdominal fat content, and a decrease in dehydration were revealed. Conclusions. An increase in the concentration of endogenous GLP-1 against the background of probiotic therapy indicates a possible positive effect of normalization of the intestinal microbiota on the secretion of endogenous incretins. The results obtained suggest that the use of a combination of probiotic and GLP-1 receptor agonists may have an additive effect on the hormonal and metabolic profile in patients with type 2 diabetes mellitus.

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The effect of modern hypoglycemic therapy on the course of chronic kidney disease in patients with type 2 diabetes mellitus

The article presents the literature review of the possibilities of modern antidiabetic therapy in the prevention of chronic kidney disease in patients with type 2 diabetes mellitus. The mechanisms of development and features of kidney disease in type 2 diabetes mellitus are described. The results of most recent clinical trials for studying the possibility of nephroprotection with new groups of hypoglycemic agents are reviewed: dipeptidyl peptidase-4 inhi-bitors, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors. The advantages of usage and the nephroprotective effects of agonists of glucagon-like peptide-1 receptors and sodium-glucose loop cotransporter-2 inhibitors are determined. Particular attention is paid to the nephroprotective effect of sodium-glucose loop co-transporter inhibitors as the only class of drugs that have demonstrated a reduction in the rate of decrease in glomerular filtration rate in patients with diabetes. The expediency of further study of the efficacy of the combined use of sodium-glucose cotransporter-2 inhibitors and agonists of glucagon-like peptide-1 receptors in diabetic chronic kidney disease is indicated. For a long time, approaches to the treatment of diabetic kidney disease did not differ for patients with type 1 and type 2 diabetes. The stu­dies of recent years have shown that new hypoglycemic drugs can not only lower blood glucose levels but also have a beneficial effect on renal function. The mechanisms of nephroprotective effects have not been fully studied, but it is clear that they are beyond the scope of improved glycemic control. The possibility of the nephroprotective effect of these drugs on a glomerular filtration rate in the range of 30–15 ml/min/1.73 m2 and below remains unexplored. The effect of the combined use of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors is also unclear: will this combination predominate over monotherapy, and, if so, to what extent?

Decrease in the efficacy of glucagon-like peptide-1 receptor agonists: what is the reason?

The review deals with the drugs of a group of glucagon-like peptide-1 receptors agonists (GLP-1RA) the action of which is based on the incretin effect. In addition to insulinotropic and glucagonostatic action, GLP-1RA contributes to the improvement of glycemic control, a decrease in body weight, and also reduces cardiovascular effects in diabetic patients. The members of this group are divided into short- and long-acting preparations that is determined by their pharmacodynamic properties. Studies have shown that the long-acting GLP-1RA, which are administered once a week, demonstrate better glycemic control with a similar or less risk of the hypoglycemia and gastrointestinal side effects than their short-acting analogues. However, with long-term use of GLP-1RA, there is a reduction in the hypoglycemic action associated with a decrease in the inhibition of intestinal motility due to the phenomenon of tachyphylaxis (desensitization) of the GLP-1 receptors as a result of the vagus nerve activation. Promising means to overcome this shortcoming are considered, such as the development of modified and combined coagonists of dipeptidyl peptidase 1 receptors, as well as oral forms of GLP-1RA. In addition, we have described possible mechanisms influencing the effectiveness of GLP-1RA due to the production of antibodies to various drugs in this group, and the relationship between the effects of incretin mimetics with the state of the intestinal microbiota. In conclusion, the group of incretin-based drugs provides broad perspectives for use in type 2 diabetic patients, with the possibility of correction of both basal and prandial glycemia, and new efficient and safe forms of drugs of this group are actively creating.

Efficacy of the R(+)-enantiomer of alpha-lipoic acid in clinical practice

The article presents current data from the scientific medical literature on the effective use of the R(+)-enantiomer of α-lipoic acid in various pathological conditions. The authors analyze the literature data on the comparative assessment of the activity of racemic and dextrorotatory forms of thioctic (alpha-lipoic) acid in low back pain, the effect of the R(+)-enantiomer in combination with hyperbaric oxygen therapy on the production of interleukin-6, tumor necrosis factor α and vascular endothelial growth factor in the healing of chronic ulcers of the lower extremities, as well as the use of R-α-lipoic acid in patients with mild to moderate carpal tunnel syndrome. It should be noted that recently around the world there is a tendency to gradual transition from the course treatment of diabetic neuropathy towards long-term and continuous use of pathogenetic therapies in order to maintain their positive effects. Alpha-lipoic acid is widely used in neurological practice, as evidenced by our data. Also, α-lipoic acid is actively used in gastroenterology in the treatment of chronic liver diseases. Currently, the action of α-lipoic acid is being actively studied in terms of the prevention and treatment of atherosclerosis. Based on the analyzed data, the authors concluded that it is the R(+)-enantiomer of α-lipoic acid that has a positive biological effect, and treatment with it should be carried out almost constantly, taking breaks in its intake. The duration of R-α-lipoic acid use depends on the specific clinical situation, and given the current personalized approach to treatment, as shown by the analysis of modern medical sources, people with diabetes in a state of decompensation of carbohydrate metabolism should be prescribed it for 6 months continuously with a break of 2 months and repeated courses.

Correction of eating habits in patients with carbohydrate metabolism disorders

The International Diabetes Federation estimates that approximately 10 % of the adult population in Ukraine has prediabetes. According to many studies, prediabetes is observed in every second obese patient, and later prediabetes can progress to type 2 diabetes mellitus. Therefore, timely detection of early disorders of carbohydrate metabolism is very important, as well as implementation of recommendations for lifestyle changes, the use of modern drugs to prevent type 2 diabetes and cardiovascular diseases. In recent years, increasing attention is drawn to dietary fibers as an integral part of a healthy diet. They help prevent obesity, metabolic syndrome and adverse changes in the gut, and also help increase the population of beneficial bacteria in the gut. That is why nutritionists recommend that obese people include dietary fibers in their diet. One of the most famous dietary fibers is psyllium, which comes from the husk of plantain seeds (Plantago ovata). Numerous studies show that psyllium has a positive effect on the functioning of many organs and systems, including the pancreas, intestines and heart muscle. Psyllium also lowers glucose and cholesterol and is an effective way to lose weight for people who are overweight. Fibolex® plant complex contains dietary fibers (psyllium and natural wheat fibers) and green tea extract. Due to the combined herbal composition, Fibolex® can be used in obese people, patients with prediabetes, metabolic syndrome, type 2 diabetes and other metabolic disorders for the correction of eating habits in order to improve carbohydrate and lipid metabolism.

Prospects for the use of laser Doppler flowmetry to assess cutaneous blood microcirculation in diabetes mellitus

The аrticle considers the scientific and clinical aspects of laser Doppler flowmetry (LDF) in the diagnosis of the state of the microcirculatory bed in diabetes mellitus. LDF is a non-invasive quantitative method of microcirculation assessment; its capabilities include the analysis of microcirculatory rhythms and functional testing with different types of provocation tests, which provides a study of the state of regulatory mechanisms of microcirculation. The difficulties with studying the microcirculation are caused by the very small size of microvessels. The prevention and treatment of various microcirculatory disorders is one of the most important problems in medical practice. The findings of some studies suggest that microcirculatory disorders are not only a pathogenetic link in the development of complications, but are also observed in patients with early disorders of carbohydrate metabolism and may precede the manifestation of diabetes mellitus. The use of LDF in scientific researches will make it possible to reveal changes in microcirculatory bed functioning that are characteristic of diabetes mellitus. The possibility of non-invasive quantitative assessment of the state of microcirculatory blood flow in real time and the relative ease of use explains the high popularity of LDF in scientific researches and makes this method promising for use in clinical practice. This method can be of important diagnostic value for the study of the state of different levels of regulation of the microcirculatory tract and dynamic monitoring of the effectiveness of the prescribed treatment. Combined use of LDF to identify the risk of developing diabetic foot syndrome will allow to personify the treatment of diabetes. Among the most promising points of application should be noted the study of microcirculation in the early diagnosis of diabetes and its complications, clarifying the risk of complications, monitoring the effectiveness of treatment. The development of optimal evaluation methods of microcirculation is a prospect for further research.

Vitamin D effects on androgen levels in men

Background. Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system. Considering the potential link between vitamin D and human fertility, authors performed this review summarizing current literature on vitamin D and possible mechanisms explaining the link of vitamin D with androgen metabolism in men. The purpose of this review was to provide an overview on the effects of vitamin D on androgen metabolism in men. Methods. Author performed a systematic literature search in PubMed for relevant English language publications published from January 2011 until September 2021. Results. The vitamin D receptor and vitamin D-metabolizing enzymes are found in reproductive tissues. In men, vitamin D status has been associated with androgen levels and hypogonadism. Further, there is some evidence for a favorable effect of vitamin D supplementation on testosterone concentrations, although others failed to show a significant effect on testosterone levels. Vitamin D might play an important role in androgen metabolism. Existing evidence from available trials evaluating the effect of vitamin D supplementation on androgen levels in men is insufficient to recommend measurement of 25(OH)D levels or vitamin D supplementation in hypogonadal men. We cannot exclude vitamin D effects on androgen levels in men with low TT levels or in men with severe vitamin D deficiency. This question remains to be answered in future investigations. Conclusions. Vitamin D deficiency is associated with adverse fertility outcomes including hypogonadism, but the evidence is insufficient to establish causality. High-quality trials are needed to further evaluate the effects of vitamin D supplementation on androgen levels in men.

Necrobiosis lipoidica: a rare clinical and pathomorphological case

According to modern scientific researches, necrobiosis lipoidica (NL) is a disease characterized by focal disorganization and lipid collagen dystrophy. It is believed that the basis of skin changes in this dermatosis is diabetic microangiopathy that is accompanied by sclerosis and obliteration of blood vessels, which leads to necrobiosis with subsequent deposition of lipids in the dermis. This pathology is registered relatively rarely, in 1 % of patients with diabetes mellitus (DM) on average. The combination of NL with DM, according to the literature data, ranges from 25 to 70 %; more often (in 40–60 % of cases) DM is preceded by NL, and in 10–25 % of cases they occur simultaneously. In addition, in 10–50 % of cases NL is diagnosed in people without concomitant diabetes. The variability of clinical, epidemiological features and the relatively low prevalence of this pathology is often the cause for misdiagnosis or late diagnosis. The described clinical case is typical in terms of the epidemiological data: sex, age, presence of DM. At the same time, it is rare in terms of the clinical picture: it is not classically diabetic by localization (symmetrical areas of the legs are typical), by appearance of necrobiosis areas — granulomatous type of necrobiosis in the form of granuloma annulare, by histological structure — area of chronic perivascular lymphoplasmocytic inflammation with the involvement of single giant cells, which required additional clinical and anamnestic data for an objective report of the pathologist. Biopsy in this case was used as a differential diagnosis between granuloma annulare and necrobiotic necrogranuloma. In addition, this method of diagnosis has played an additional therapeutic role. This case may have demonstrated the activation of the cellular and humoral immune response in the area of chronic inflammation in response to a mechanical damage and the resolution of inflammation with complete tissue repair.