Short-Term Effects of Supplemental L-Arginine, Diosmin, Troxerutin, and Hesperidin in Diabetic Patients: A Pilot Study

Background and Aims. Inflammatory, oxidative stress, and endothelial dysfunction play a key role in the pathogenesis of long-term cardiovascular complications in patients with diabetes. The present observational prospective study is aimed at evaluating the effects of micronutrients and phytochemicals contained in the dietary supplement Flebotrofine® (AMNOL Chimica Biologica) on biochemical markers of inflammation, endothelial dysfunction, and glycemic control in patients with diabetes. Methods. 105 type 1 or type 2 diabetes patients regularly took a daily dose of the dietary supplement Flebotrofine® for three consecutive months, and haematological and biochemical parameters were checked at baseline, after three months of treatment, and one month after its suspension. Statistical comparison of the laboratory parameters was performed using the two-tailed ANOVA test for repeated samples with a statistical significance level set at p < 0.05 . Results. The daily use of Flebotrofine® did not change the glycemic metabolic compensation of enrolled patients. After three months of regular Flebotrofine® intake, the plasma levels of the antioxidant β-carotene and of arginine were significantly higher compared with the baseline values, with a decrease in the ADMA/arginine ratio. In contrast, apolipoprotein B, ApoB/ApoA1 ratio, and platelet and leukocyte counts significantly dropped. Conclusion. The daily use of Flebotrofine® might be a valid supplement of arginine, the precursor of NO, and essential in the prevention of endothelial dysfunction. The regular intake of arginine and phytochemicals also improved the antioxidant and antithrombotic profile of enrolled patients. Therefore, Flebotrofine® could be a useful dietary supplement to prevent long-term complications in patients with diabetes.

The assessment of the relationship between the severity of gingivitis and the glycosylated hemoglobin levels in adolescent and adult patients with type 1 diabetes

Abstrakt Background Diabetes and periodontitis belong to the group of civilizational diseases, which are not associated with any specific bacterial or viral infection but with the rapid development of civilization and technological advances that affect comfort and quality of life. Civilizational diseases occur in highly developed and developing societies. Glycosylated hemoglobin A1c (HbA1c) is one of the standard indicators for the assessment of metabolic compensation in diabetes that reflects the risk of disease complications. One of the significant complications of diabetes that manifests in the oral cavity is gingival and periodontal inflammation, which is directly related to increased insulin resistance and worsened diabetes compensation. Factors influencing inflammation are the patient’s age, directly linked with fine motor skills when it comes to cleaning teeth, and patients’ awareness related to cause-and-effect relationship between dental hygiene, gingival and periodontal inflammation, and HbA1c testing during routine check-ups. Objectives To compare the relationship between gingival inflammation and metabolic compensation (HbA1c levels), depending on the patient’s age. Materials and methods The study involved 100 patients (50 adolescents and 50 adults, 42 M; 58 F) with type 1 diabetes. The study group was divided according to sex and age into 19 male adolescent patients (10–18 years old; mean age 15.5) and 23 male adult patients (19–45 years old; mean age 27.1). The mean duration of diabetes was 7 years in the group of adolescents and 11 years in the group of adults. The HbA1c levels and gingival index (GI) were measured in all patients. The obtained results were statistically analyzed. Results By comparing the study groups, higher HbA1c values were reported in the group of adolescents. HbA1c has been shown to correlate with the GI in adolescents and adults. Despite poorer compensation for diabetes (higher HbA1c), GI values were similar in adolescents and adults.

Breaking Free from Thermodynamic Constraints: Thermal Acclimation and Metabolic Compensation in a freshwater zooplankton species

Ectothermic organisms’ respiration rates are affected by environmental temperatures, and sustainable metabolism at high temperatures sometimes limits heat tolerance. Organisms are hypothesized to exhibit acclimatory metabolic compensation effects, decelerating their metabolic processes below Arrhenius expectations based on temperature alone. We tested the hypothesis that either heritable or plastic heat tolerance differences can be explained by metabolic compensation in the eurythermal freshwater zooplankton crustacean Daphnia magna. We measured respiration rates in a ramp-up experiment over a range of assay temperatures (5 °C - 37 °C) in 8 genotypes of Daphnia representing a range of previously reported acute heat tolerances and, in a narrower range of temperatures (10 °C - 35 °C), in Daphnia with different acclimation history (either 10°C or 25°C). We discovered no difference in temperature-specific respiration rates between heat tolerant and heat-sensitive genotypes. In contrast, we observed acclimation-specific compensatory differences in respiration rates at both extremes of the temperature range studied. Notably, there was a deceleration of oxygen consumption at higher temperature in the 25°C-acclimated Daphnia relative to their 10°C-acclimated counterparts, observed in active animals, a pattern corroborated by similar changes in filtering rate and, partly, by changes in mitochondrial membrane potential. A recovery experiment indicated that the reduction of respiration was not caused by irreversible damage during exposure to a sublethal temperature. Response time necessary to acquire the respiratory adjustment to high temperature was lower than to low temperature, indicating that metabolic compensation at the lower temperatures require slower, possibly structural changes.

Diabetic Retinopathy. Association with Metabolic Compensation, Duration of Diabetes and Other Micro and Macrovascular Complications in Patients with Type 1 Diabetes Mellitus

SummaryIntroductionDiabetic retinopathy (DR) is a severe complication that can lead to complete vision loss and still is one of the main blindness-causing reasons among patients with type 1 diabetes mellitus (T1DM). DR as a complication can cause vision loss to people at their working age. More than 90% of patients with type 1 diabetes will develop DR by 20 years post diagnosis (Leslie R. Dye, 2018). DR is more likely to develop in patients with T1DM (Kanski's Clinical Ophthalmology, 2016). This complication can be very serious speaking of the ability to see. Sometimes vitrectomy plays a vital role in the management of severe complications of DR at its end-stage (Myron Yanoff et al., 2020).Aim of the studyTo prove the development severity of DR that depends on the duration of diabetes and metabolic compensation. Additionally, to determine retinopathy's association with other micro and macrovascular diabetes mellitus complications for a better understanding of what are the contributory factors for these complications to develop and which of those may coexist.Materials and MethodsA retrospective study was held at the Pauls Stradins Clinical University Hospital (Riga, Latvia). From January 2016 to March 2018, 79 (158 eyes) patient histories were analyzed who have type 1 diabetes mellitus. To obtain more precise research results, almost all patients have done check-up visits to one certain ophthalmologist. The IBM SPSS Statistics version 25.0 was used to process data. Tables were made in SPSS and Microsoft Excel 2016 programs. Statistically significant value (p) was set at < 0,05.ResultsNo statistically significant difference is seen in the mean duration of the disease: in the group of proliferative diabetic retinopathy (PDR): 25.23 (median = 22.0) years and non-proliferative group: 24.68 (median = 23.50) years. Results show that the duration of diabetes mellitus is considerably smaller in a group without DR 11.24 (median = 8.50) years. Metabolic compensation (%) in diabetes mellitus is not statistically different between patients with diverse forms of DR; no association found either. No statistically significant difference in best corrected visual acuity (BCVA) was detected among patients with various forms of DR. Three groups were compared: both types of DR and no DR. It was detected that BCVA in patients without DR was higher in both eyes: 0.83 ± 0.27 dioptres. No statistically significant difference (pχ > 0.05) was detected between the groups of DR and therefore no association was made between the form/existence of DR and arterial hypertension. There is a strong association between DR and microvascular complications (V = 0.40) with the existence of DR and there is an even stronger association (V = 0.61) with the forms of DR. There is no statistically reliable difference (pχ > 0.05) between the groups of DR; therefore, no association with the existence of microvascular complications and also risk factors.ConclusionsMore than two-thirds of patients included in the research have some signs of DR. Because of the strong association of DR and other microvascular complications, patients with diabetes should be screened regularly for retinopathy, nephropathy, and neuropathy. And likewise, if a patient has at least one microvascular complication, he or she should be tested for the rest possible complications as well. According to data, most of the patients in this study have poor metabolic compensation; consequently, the metabolic compensation screening should be done certainly every three months.

Heart failure therapy in patients with diabetes

The great interest in the problem “Heart failure” (HF) by the diabetolo­gist has been born in recent years and is mainly linked to the availabil­ity of new antidiabetic drugs which have shown a significant benefit in reducing hospitalizations for heart failure and cardiovascular mortality. Diabetes patients have more than double the risk of developing HF compared to patients without diabetes. The Framingham study has shown that diabetes increases the risk of heart failure up to 2 times in men and 5 times in women compared to controls over age. In addition, 12% of patients with DMT2 have heart failure and 30% of patients with heart failure are diabetic. Hospitalization for HF is associated with very high rates of both post-dis­charge mortality and new hospitalizations. Readmission rates for clinically stable patients discharged after recent hospitalization for HF are approximately 25% at 6 months and all-cause mortality exceeds 30% at 1 year. In particular, a worse prognosis and a longer hospital stay are associated with hospitalized diabetes patients. There is a close correlation between metabolic compensation and HF. In fact, in patients with diabetes a 1% increase in HbA1c is associated with an 8% increase in the risk of HF and still the improvement of the glycometabolic control reduces the risk of HF (in the UKPDS the 1% re­duction in HbA1c was associated with a 16% reduction in the risk of HF occurring). KEY WORDS T2DM; heart failure; SGLT2-inhibitors; diabetic cardiomyopathy.

Systems of continuous subcutaneous insulin infusion to maintain metabolic compensation for type 1 diabetes mellitus among children and adolescents

BACKGROUND: Insulin pumps (IP) are a widespread treatment for type 1 diabetes mellitus (T1D) in children because of its several advantages over multiple insulin injection regimens (MII). However, the long-term effectiveness of continuous subcutaneous insulin infusion (CSII) in achieving and maintaining sustained metabolic compensation remains controversial. OBJECTIVE: To determine the factors affecting the long-team effectiveness of CSII in children and adolescents with T1DM in real clinical practice. METHODS: Data of 239 children and adolescents treated with CSII for 3 years were examined during the registration of patients receiving insulin pump therapy in Saint-Petersburg was formed. HbA1с level changes over time were analysed before switching to CSII and were assessed depending on sex and age, baseline HbA1с level and factors as the frequency of using continuous glucose monitoring (CGM), temporary transitions from CSII to MII with injection pens and use of bolus calculators (BC). RESULTS: The final HbA1с value showed no significant changes as compared with the HbA1с level before switching to CSII (baseline, 7.821.46%; final, 7.931.30%). Approximately 42% of patients had HbA1с level of 7.5%. Better results were observed in the 4.57-year age group, where 67% of patients had HbA1с level of 7.5%; in 1218-year age group, only 35% of patients reached the target HbA1с level. Majority of patients with baseline HbA1с level of 7.5% remained within the target level during the final examination, whereas only 23% of patients with HbA1с level of 7.5% before switching to CSII reached the target level. Better glycaemic control was also observed in patients treated with CSII regularly, as compared to patients who periodically switched to MII with the injection pen (p0.05). HbA1с appeared to be lower in the group of 1218-year-old adolescents who used CGM regularly, as compared to the group not treated with CGM (p0.05). CONCLUSION: Children and adolescents treated with CSII for 3 years did not experience a significant improvement in metabolic control. However, the influence of factors in maintaining the metabolic control, such factors as the patients age, initial HbA1с level, CGM use and frequency, and the presence or absence of changes in insulin therapy regimen is observed.

Bayesian Modeling Reveals Ultrasensitivity Underlying Metabolic Compensation in the Cyanobacterial Circadian Clock

Mathematical models can enable a predictive understanding of mechanism in cell biology by quantitatively describing complex networks of interactions, but such models are often poorly constrained by available data. Owing to its relative biochemical simplicity, the core circadian oscillator in Synechococcus elongatus has become a prototypical system for studying how collective dynamics emerge from molecular interactions. The oscillator consists of only three proteins, KaiA, KaiB, and KaiC, and near-24-h cycles of KaiC phosphorylation can be reconstituted in vitro. Here, we formulate a molecularly-detailed but mechanistically agnostic model of the KaiA-KaiC subsystem and fit it directly to experimental data within a Bayesian parameter estimation framework. Analysis of the fits consistently reveals an ultrasensitive response for KaiC phosphorylation as a function of KaiA concentration, which we confirm experimentally. This ultrasensitivity primarily results from the differential affinity of KaiA for competing nucleotide-bound states of KaiC. We argue that the ultrasensitive stimulus-response relation is critical to metabolic compensation by suppressing premature phosphorylation at nighttime.SynopsisThis study takes a data-driven kinetic modeling approach to characterizing the interaction between KaiA and KaiC in the cyanobacterial circadian oscillator and understanding how the oscillator responds to changes in cellular metabolic conditions. An extensive dataset of KaiC autophosphorylation measurements was gathered and fit to a detailed yet mechanistically agnostic kinetic model within a Bayesian parameter estimation framework.KaiA concentration tunes the sensitivity of KaiC autophosphorylation and the period of the full oscillator to %ATP.The model reveals an ultrasensitive dependence of KaiC phosphorylation on KaiA concentration as a result of differential KaiA binding affinity to ADP- vs. ATP-bound KaiC.Ultrasensitivity in KaiC phosphorylation contributes to metabolic compensation by suppressing premature phosphorylation at nighttime.