Diabetes mellitus, chronic pancreatitis and primary hyperparathyroidism: is there a connection?

Hyperparathyroidism is a relatively frequent condition characterized by hypersecretion of parathyroid hormone. There are several forms of primary hyperparathyroidism. Each form affects its target region. In the visceral form, nephrocalcinosis, nephrolithiasis and peptic and duodenal ulcers are common. The pancreas is also a target organ. This article describes a clinical case of a patient with diabetes mellitus and previously treated primary hyperparathyroidism. The patient was admitted to the hospital due to poor glycaemic control. During the hospitalization, diabetes mellitus developed as a consequence of frequent relapses of chronic pancreatitis (outcome of the visceral form of primary hyperparathyroidism and severe hypertriglyceridemia). Glycaemic control was achieved after treatment of acute pancreatitis and insulin administration. This clinical case is an example of the impact of previous primary hyperparathyroidism (even after radical treatment and remission) on the development of a multi-faceted comorbidity

Состояние нутритивного статуса, физического и психомоторного развития недоношенных детей: наблюдательное проспективное сравнительное исследование

Background. The development of premature infants is slower than that of term ones, often due to nutritional status disorders in preterm infants. Objective. Our aim was to study the nutritional status, physical, and psychomotor development of infants.Methods. Nutritional status — the composition (the ratio of fat and fat-free tissues) and the value of lean body mass (LBM) — was assessed by plethysmography and densitometry; physical development — by measuring the mass and length of the body, the circumference of the head and chest, calculating the body mass index (BMI); psychomotor development — assessing compliance with the schedule of neuropsychological development of infants (GNOM). The examination was carried out at 12–14 and 16–18 weeks of the corrected age for preterm and actual age for full-term infants. Initially, the diet of infants was assessed by determining the amount, content of macronutrients and energy in the breast milk and/or milk formula and complementary food consumed. The diet was considered to be balanced if the diet parameters diverged not more than 10% of the norm.Results. The study included 23 preterm infants with extremely low (ELBW), 20 — with very low (VLBW), 34 — with low body weight (LBW), and 33 full-term infants. At 12–14 weeks of the corrected age, the magnitude of LBM in infants with ELBW — 3,397 (3,096; 3,608) and with VLBW — 3,824 (3,797; 3,899) was lower than in infants with LBW — 4,497 (4,034; 4,651) and full-term infants — 4,511 (3,887; 4,647) (Kruskal–Wallis test, p = 0.048). Protein balanced diet was in 2 (9%) infants with ELBW, energy balanced diet — in 1 (4%) infant. Among infants with ELBW, 17/23 (74%) referred to the risk group, 6/23 (26%) — to the developmental disorder group. Compared with infants with ELBW and VLBW, infants with LBW and full-term infants had a higher LBM and, correspondingly, higher body weight and BMI. Improvement of the nutritional status after 4–6 weeks due to correction of protein and energy consumption in infants with ELBW was accompanied by some increase in lean body mass, while its proportion was much higher and the proportion of fat mass was lower, which was accompanied by an improvement in the psychomotor development in individual infants: 5/23 (22%) became age-appropriate, and in the risk group of developmental disorders, the proportion of infants decreased from 17 (74%) to 13/23 (57%). The obtained results testify to the influence of nutritional status on the physical and psychomotor development of infants.Conclusion. The importance of dynamic assessment of the nutritional status of premature infants with individualized correction of their diet for improving the physical and psychomotor development of the child during the first year of life is shown.Развитие недоношенных детей происходит медленнее, чем у детей, родившихся в срок, часто по причине отклонений в нутритивном статусе недоношенных.Цель исследования — изучить состояние нутритивного статуса, физического и психомоторного развития детей первого года жизни.Методы. Нутритивный статус — состав (соотношение жировых и безжировых тканей) и значение безжировой массы тела (БЖМТ) — оценивали методами плетизмографии и денситометрии; физическое развитие — путем измерения массы и длины тела, окружности головы и груди, расчета индекса массы тела (ИМТ); психомоторное развитие — оценивая соответствие графику нервно-психического развития младенцев (ГНОМ). Обследование проводилось в 12–14 и 16–18 нед корригированного возраста для недоношенных и фактического возраста для доношенных детей. Исходно оценивали рацион питания детей, определяя объем, содержание макронутриентов и энергии в потребляемом грудном молоке и/или молочной смеси и продуктах прикорма. Рацион считали сбалансированным при отклонении параметров рациона не более 10% от нормы.Результаты. В исследование были включены 23 недоношенных ребенка с экстремально низкой (ЭНМТ), 20 — с очень низкой (ОНМТ), 34 — с низкой массой тела (НМТ) и 33 доношенных ребенка. В 12–14 нед корригированного возраста величина БЖМТ у детей с ЭНМТ — 3397 (3096; 3608) и ОНМТ — 3824 (3797; 3899) была ниже, чем у детей с НМТ — 4497 (4034; 4651) и доношенных — 4511 (3887; 4647) (тест Краскела–Уоллиса, р=0,048). Сбалансированный по белку рацион был у 2 (9%) детей с ЭНМТ, по энергии — у 1 (4%). Среди детей с ЭНМТ 17/23 (74%) относились к группе риска, 6/23 (26%) — к группе нарушения развития. По сравнению с детьми с ЭНМТ и ОНМТ, дети с НМТ и доношенные имели большую БЖМТ и, соответственно, большие массу тела и ИМТ. Улучшение нутритивного статуса через 4–6 нед за счет коррекции потребления белка и энергии сопровождалось у детей с ЭНМТ некоторым увеличением безжировой массы тела, при этом ее доля была значительно выше, а доля жировой массы — ниже, что сопровождалось улучшением психомоторного развития у отдельных детей: 5/23 (22%) стали соответствовать возрасту, а в группе риска нарушения развития доля детей сократилась с 17 (74%) до 13/23 (57%) человек. Полученные результаты свидетельствуют о влиянии нутритивного статуса на физическое и психомоторное развитие детей.Заключение. Показана важность динамической оценки нутритивного статуса недоношенных детей с возможностью индивидуализированной коррекции их рациона для улучшения физического, психомоторного развития ребенка на протяжении первого года жизни.Конфликт интересовТ.В. Турти — получение исследовательского гранта от компании Nutricia Advance на проведение научно-исследовательской работы «Оценка влияния специализированного детского молочного продукта для энтерального питания «Инфатрини» на нутритивный статус детей раннего возраста с задержкой физического развития (производство N.V. Nutricia, Нидерланды)»

Cardiovascular and metabolic status in patients with primary hyperparathyroidism: a single-center experience

IntroductionCardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary hyperparathyroidism (PHPT) is also associated with a greater incidence of CVD and MD. The aim of the present study was to describe the prevalence and structure of CVD and MD in hospitalized patients with PHPT and to search for possible associations between these pathologies.Methods838 patients with a verified PHPT were included in the study. The studied cohort was divided into 2 groups according to their age at the time of admission: patients aged 18 to 49 years (group A, n = 150); patients aged 50 years and older (group B, n = 688).ResultsThere were no significant differences between two groups in parameters of calcium-phosphorus metabolism. Obesity was diagnosed in 24.2% of patients in group A and in 35.9% in group B. Type 2 diabetes mellitus was more common in older patients (14.4% in group B vs. 2.6% in group A). Arterial hypertension, ischemic heart disease, chronic heart failure and brachiocephalic arteries atherosclerosis were more frequent in older patients, occurring in 79.1%, 10.8%, 8.4%, and 84% of cases respectively. The cutoff points that increased the risk of CVD detection turned out to be age above 56 years, eGFR below 92 ml/min/1.73m2, BMI above 28.3 kg/m2.DiscussionThe present study demonstrated a high incidence of some CVD, as well as disorders of lipid, carbohydrate and purine metabolism in patients with PHPT

Keratinocytes differentiation and wound healing in rats with streptozotocin – induced diabetes and severe hyperglycemia

BACKGROUND: Diabetes mellitus leads to disruption of the skin repair processes, but the leading mechanisms of this pathology have not yet been identified. In this regard, in our work, we decided to check how hyperglycaemia affects the process of keratinocyte phenotype changes during wound healing. AIMS: To study the effect of hyperglycaemia on wound healing and differentiation of keratinocytes in a rat streptozotocin-induced diabetes model. MATERIALS AND METHODS: Diabetes mellitus was induced in rats by using streptozotocin, 65 mg / kg, intraperitoneally, once. The wound was applied in the supra-scapular region on the 42nd day, after which (after 8, 16, and 24 days) the repair process was evaluated using histological methods. Immunohistochemistry was used to evaluate the expression of cytokeratin-10 and cytokeratin-17. RESULTS: In rats with diabetes mellitus, wound healing slowed down in the later stages, compared with the control group. In general, wound healing was accompanied by an increase in the expression of cytokeratin-10 in its region compared with intact skin, and contractile keratinocytes activation was disrupted in diabetic rat wounds. CONCLUSIONS: Hyperglycaemia slightly slows wound healing in rats and impairs contractile keratinocytes activation

Dynamics of heart rate variability in rats with streptozotocin-induced diabetes

Background: Diabetes mellitus (DM) has a negative impact on all organs. This is due to insufficiency of blood supply and the disruption of the trophic function of the nervous system. One of the most serious complication of DM is diabetic foot caused be vascular and neurological reasons. Correction of vascular disorders is effectively treated by modern therapeutic approaches, but the damage of nervous system has been studied insufficiently. Aims: To investigate the dynamics of damage to the vegetative nervous system on the laboratory model of DM. Materials and methods: DM in rats was induced by injection of streptozotocin at a dose of 65 mg/kg in citrate buffer (DM group). The control group of rats received a citrate buffer equivalent (CB group). Rats with DM were given a maintenance therapy with insulin in a dose of 2 units/kg/day. On 42 days of experience, a round wound with a diameter of 2 cm on the back of the animals was observed. Before the DM simulation, then on the 42, 50, 58 and 66 days of its development, an electrocardiogram (ECG) was recorded in the rats at a frequency of 2 kHz digitising in a state of calm wakefulness and after cold exposure. For 5 minutes ECG fragments, heart rate and heart rate variability (HRV) in the temporal domain were calculated, characterising: 1) the total heart rate variability (tHRV) according to SDRR, SDHR, KVRR and KVHR; 2) the effect of the parasympathetic department of the autonomic nervous system (aANS) for RMSSD and pNN3; 3) the contribution of the sympathetic department of the ANS (sANS) by SDAvgRR, SDAvgHR. The spectral parameters were estimated in the frequency domain: the total power of the spectrum is TR (range: 0–2.5 Hz), the powers in the low and high frequency ranges are LF (range: 0.2–0.8 Hz) and HF (range: 0.8–2.5 Hz) LF/HF. Weekly, the tail withdrawal time was measured in a temperature pain test (55°C). Results: During the development of diabetes, the level of glucose in the blood increased 4–7 times compared with the normal level. The reaction time of the pain test in rats with DM increased by 20%–30% at the end of the experiment. At 42 days, the development of bradycardia (267 beats/min) was observed in rats with DM. The indicators of tHRV decreased by a factor of 2 due to a decrease in the contribution of sANS. The reaction to CP in the SD group differs from the norm by the severity of the individual components of the HRV structure, which indicates functional denervation of the heart and the development of diabetic neuropathy. Conclusions: As the diabetes progressed, signs of neuropathy were observed. The overall HRV parameters decreased, the ratio of the contributions of sANS and pANS to the regulation of heart rate changed, and the temperature sensitivity decreased

Nutritional Status, Physical and Psychomotor Development of Premature Infants: A Prospective Observational Comparative Study

Background. The development of premature infants is slower than that of term ones, often due to nutritional status disorders in preterm infants. Objective. Our aim was to study the nutritional status, physical, and psychomotor development of infants.Methods. Nutritional status — the composition (the ratio of fat and fat-free tissues) and the value of lean body mass (LBM) — was assessed by plethysmography and densitometry; physical development — by measuring the mass and length of the body, the circumference of the head and chest, calculating the body mass index (BMI); psychomotor development — assessing compliance with the schedule of neuropsychological development of infants (GNOM). The examination was carried out at 12–14 and 16–18 weeks of the corrected age for preterm and actual age for full-term infants. Initially, the diet of infants was assessed by determining the amount, content of macronutrients and energy in the breast milk and/or milk formula and complementary food consumed. The diet was considered to be balanced if the diet parameters diverged not more than 10% of the norm.Results. The study included 23 preterm infants with extremely low (ELBW), 20 — with very low (VLBW), 34 — with low body weight (LBW), and 33 full-term infants. At 12–14 weeks of the corrected age, the magnitude of LBM in infants with ELBW — 3,397 (3,096; 3,608) and with VLBW — 3,824 (3,797; 3,899) was lower than in infants with LBW — 4,497 (4,034; 4,651) and full-term infants — 4,511 (3,887; 4,647) (Kruskal–Wallis test, p = 0.048). Protein balanced diet was in 2 (9%) infants with ELBW, energy balanced diet — in 1 (4%) infant. Among infants with ELBW, 17/23 (74%) referred to the risk group, 6/23 (26%) — to the developmental disorder group. Compared with infants with ELBW and VLBW, infants with LBW and full-term infants had a higher LBM and, correspondingly, higher body weight and BMI. Improvement of the nutritional status after 4–6 weeks due to correction of protein and energy consumption in infants with ELBW was accompanied by some increase in lean body mass, while its proportion was much higher and the proportion of fat mass was lower, which was accompanied by an improvement in the psychomotor development in individual infants: 5/23 (22%) became age-appropriate, and in the risk group of developmental disorders, the proportion of infants decreased from 17 (74%) to 13/23 (57%). The obtained results testify to the influence of nutritional status on the physical and psychomotor development of infants.Conclusion. The importance of dynamic assessment of the nutritional status of premature infants with individualized correction of their diet for improving the physical and psychomotor development of the child during the first year of life is shown

Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock

Mice deficient in the circadian transcription factor BMAL1 (brain and muscle ARNT-like protein) have impaired circadian behavior and demonstrate loss of rhythmicity in the expression of target genes. Here we report that Bmal1(−/−) mice have reduced lifespans and display various symptoms of premature aging including sarcopenia, cataracts, less subcutaneous fat, organ shrinkage, and others. The early aging phenotype correlates with increased levels of reactive oxygen species in some tissues of the Bmal1(−/− )animals. These findings, together with data on CLOCK/BMAL1-dependent control of stress responses, may provide a mechanistic explanation for the early onset of age-related pathologies in the absence of BMAL1

BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system

Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop. In the form of a heterodimer, they drive transcription from E-box enhancer elements in the promoters of responsive genes. We have examined abundance, posttranslational modifications, cellular localization of endogenous and ectopically expressed CLOCK and BMAL1 proteins. Nuclear/cytoplasm distribution of CLOCK was found to be under circadian regulation. Analysis of subcellular localization of CLOCK in embryo fibroblasts of mice carrying different germ-line circadian mutations showed that circadian regulation of nuclear accumulation of CLOCK is BMAL1-dependent. Formation of CLOCK/BMAL1 complex following ectopic coexpression of both proteins is followed by their codependent phosphorylation, which is tightly coupled to CLOCK nuclear translocation and degradation. This binding-dependent coregulation is specific for CLOCK/BMAL1 interaction, as no other PAS domain protein that can form a complex with either CLOCK or BMAL1 was able to induce similar effects. Importantly, all posttranslational events described in our study are coupled with active transactivation complex formation, which argues for their significant functional role. Altogether, these results provide evidence for an additional level of circadian system control, which is based on regulation of transcriptional activity or/and availability of CLOCK/BMAL1 complex

The Relevance of Hypovitaminosis Prevention in Infants

Determining risk groups for the development of vitamin-deficient conditions in infants is important for the timely appointment of preventive doses of the necessary vitamins and vitamin complexes by a practicing pediatrician. The article contains information on the causes of vitamin deficiency and the biological value of vitamins D, C, A. The data of real clinical practice allowing the doctor to decide on the appointment of a complex of vitamins for hypovitaminosis prevention in infants is highlighted