Lower Glucose Levels Research Articles

Deubiquitinating enzyme USP2 alleviates muscle atrophy by stabilizing PPARγ.

Insulin resistance, a hallmark of type 2 diabetes, accelerates muscle breakdown and impairs energy metabolism. However, the role of Ubiquitin Specific Peptidase 2 (USP2), a key regulator of insulin resistance, in sarcopenia remains unclear. Peroxisome proliferator activated receptor γ (PPARγ) plays a critical role in regulating muscle atrophy. This study investigates the role of deubiquitinase USP2 in mitigating muscle atrophy. Our findings revealed reduced USP2 expression in skeletal muscles of patients with type 2 diabetes. In mouse models of diabetes- and dexamethasone (DEX)-induced muscle atrophy, USP2 expression was downregulated in skeletal muscles. Usp2 knockout exacerbated muscle loss and functional impairment induced by diabetes or DEX. Moreover, skeletal muscle-specific Usp2 knockout further aggravated muscle loss and functional impairment induced by diabetes. Local injection of AAV-Usp2 into the gastrocnemius muscles of diabetic mice increased muscle mass, and improved skeletal muscle performance and endurance. It enhanced insulin sensitivity in diabetic mice, shown by lower fasting serum glucose and insulin levels and better glucose tolerance. Mechanistic analysis showed USP2 directly interacted with PPARγ by deubiquitinating it, stabilizing its protein levels, enhancing insulin signaling and sensitivity, and maintaining muscle mass. Loss of PPARγ abolishes the regulatory effects of USP2 on insulin sensitivity and muscle atrophy. MYOD1 activates USP2 transcription by binding to its promoter region. This study demonstrates the protective role of USP2 in mitigating muscle atrophy by stabilizing PPARγ through deubiquitination, particularly in models of diabetic and DEX-induced muscle atrophy. Targeting the USP2-PPARγ axis may offer promising therapeutic strategies for metabolic disorders and sarcopenia.

Towards a decision support system for post bariatric hypoglycaemia: development of forecasting algorithms in unrestricted daily-life conditions

BackgroundPost bariatric hypoglycaemic (PBH) is a late complication of weight loss surgery, characterised by critically low blood glucose levels following meal-induced glycaemic excursions. The disabling consequences of PBH underline the need for the development of a decision support system (DSS) that can warn individuals about upcoming PBH events, thus enabling preventive actions to avoid impending episodes. In view of this, we developed various algorithms based on linear and deep learning models to forecast PBH episodes in the short-term.MethodsWe leveraged a dataset obtained from 50 patients with PBH after Roux-en-Y gastric bypass, monitored for up to 50 days under unrestricted real-life conditions. Algorithms’ performance was assessed by measuring Precision, Recall, F1-score, False-alarms-per-day and Time Gain (TG).ResultsThe run-to-run forecasting algorithm based on recursive autoregressive model (rAR) outperformed the other techniques, achieving Precision of 64.38%, Recall of 84.43%, F1-score of 73.06%, a median TG of 10 min and 1 false alarm every 6 days. More complex deep learning models demonstrated similar median TG but inferior forecasting capabilities with F1-score ranging from 54.88% to 64.10%.ConclusionsReal-time forecasting of PBH events using CGM data as a single input imposes high demands on various types of prediction algorithms, with CGM data noise and rapid postprandial glucose dynamics representing the key challenges. In this study, the run-to-run rAR yielded most satisfactory results with accurate PBH event predictive capacity and few false alarms, thereby indicating potential for the development of DSS for people with PBH.

In Vitro and In Vivo Interventions Reveal the Health Benefits of Levan-Type Exopolysaccharide Produced by a Fish Gut Isolate Lactobacillus reuteri FW2.

Microorganisms synthesize diverse types of exopolysaccharides (EPSs). EPSs with varying structural and physical properties can demonstrate unique health benefits, which allow for their tailored applications as functional foods such as prebiotics. Levan, a fructose-based EPS, is gaining considerable attention as an effective prebiotic to support the growth of beneficial gut bacteria. Consequently, this enhances digestive health, boosts the immune system, and reduces the risk of chronic diseases. Unfortunately, limited studies are available on levan-type EPSs to demonstrate their role as prebiotics. Therefore, in this study, we conducted in vitro and in vivo experiments, concerning intestinal cell integrity and metabolic syndrome, to assess the therapeutic potential of levan derived from Lactobacillus reuteri FW2. The in vitro experimental results revealed that levan improved the survival of impaired HT-29 epithelial cells of the intestine and also exerted antioxidant effects. In the in vivo experiments, mice fed with levan-supplemented feed exhibited low body weight gain, blood glucose, and serum cholesterol levels compared to the control group. These findings highlight the biotherapeutic potential of L. reuteri FW2-derived levan for improving metabolic syndrome and its associated aspects. It also signifies the need for a further detailed investigation based on clinical trials to include levan in dietary supplements for improved health and well-being.

Growth performance, antioxidant, and immune responses of Nile tilapia (Oreochromis niloticus) fed on low-fishmeal diets enriched with sodium chloride and its adaptability to different salinity levels

The current investigation assessed the beneficial impacts of dietary sodium chloride (NaCl) on the growth performance, oxidant/antioxidant, and immune responses of Nile tilapia (Oreochromis niloticus) and its adaptability to different salinity levels. After acclimating the fish to the laboratory conditions for 2 weeks, the acclimated fish (10.5 ± 0.16 g) were randomly distributed into 25 110-L rectangular glass tanks (15 fish/tank) to represent five groups in five replicates. The fish were fed with experimental feeds fortified with 0.0 (control), 5, 10, 15, and 20 g NaCl/kg feed for 60 days. Following the nutritional experiment, fish of all groups were adapted to different salinity levels from 0 to 32 g /L for a further 3 weeks, during which fish mortality was recorded. Blood samples were taken after the feeding trial and at a salinity level of 24 g/L. Growth performance and hematological parameters (WBCs, RBCs, hemoglobin, and hematocrit), total protein, albumin, globulin, digestive enzymes, antioxidant activity, and immunity status were markedly improved with increased NaCl rates in the fish diets up to 10 g/kg feed, after which all previous parameters were declined. On the other hand, feeding fish on a diet containing 10 g NaCl/kg feed showed substantially lower levels of cortisol, glucose, cholesterol, triglycerides, aspartate transaminase (AST), alanine transaminase (ALT), and malondialdehyde (MDA). Exposing the control fish group to salinity stress (32 g/L) for 3 weeks markedly decreased their digestive enzyme activity, immunity status, and antioxidant response, along with significant increases in cortisol, glucose, cholesterol, triglycerides, AST, ALT, and MDA levels. Conversely, feeding fish on a diet containing 10 g NaCl/kg feed alleviated the negative impacts of salinity stress and helped fish to tolerate salinity stress up to 24 g/L.

Toll-like receptor adaptor protein TIRAP has specialized roles in signaling, metabolic control and leukocyte migration upon wounding in zebrafish larvae.

The TIRAP protein is an adaptor protein in TLR signaling which links TLR2 and TLR4 to the adaptor protein Myd88. The transcriptomic profiles of zebrafish larvae from a tirap, myd88 and tlr2 mutant and the corresponding wild type controls under unchallenged developmental conditions revealed a specific involvement of tirap in calcium homeostasis and myosin regulation. Metabolomic profiling showed that the tirap mutation results in lower glucose levels, whereas a tlr2 mutation leads to higher glucose levels. A tail-wounding zebrafish larval model was used to identify the role of tirap in leukocyte migration to tissue wounding. We found that more neutrophils were recruited to the wounded region in the tirap mutant larvae compared to the wild type controls, whereas there was no difference in macrophage recruitment. In contrast, published data show that tlr2 and myd88 mutants recruit fewer neutrophils and macrophages to the wounds. Based on cell tracking analysis, we demonstrate that the neutrophil migration speed is increased in the tirap mutant in contrast to neutrophil behavior in myd88 and tlr2 mutants. In conclusion, we show that tirap plays specialized roles distinct from tlr2 and myd88 in signaling, metabolic control, and in regulating neutrophil migration speed upon wounding.

Postbariatric Hypoglycaemia

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery which is characterized by low glucose levels in patients following bariatric procedures. The development of postbariatric hypoglycaemia can be dangerous and also significantly impact patients’ quality of life and mental health. Timely diagnosis of PBH and prompt treatment in patients suffering from it is crucial. This case report describes the management of postbariatric hypoglycaemia in a 56-year-old female who had undergone sleeve gastrectomy 16 years ago. She presented to our outpatient department with postprandial hypoglycaemic episodes. She was advised medical nutrition therapy (MNT) and pharmacological agents such as voglibose and diazoxide were added due to the recurrence of hypoglycemic episodes. Eventually, with education and medical management, she gained a better understanding of her condition and started adhering to the MNT prescribed and she chose to transition away from the continuous glucose monitoring. Instead, she opted for self-monitoring of glucose levels using a home glucometer, allowing for greater autonomy.

Effects of blenderized watermelon consumption on satiety and postprandial glucose in overweight and obese adolescents.

Watermelon and its rind are rich in fiber, vitamins, minerals, and L-citrulline. Despite these nutritional benefits, research on the effects of blenderized watermelon (WM), especially in adolescents, remains limited. This study aimed to address this gap by examining the impact of blenderized WM (Citrullus lanatus, including both flesh and rind) on satiety, postprandial glucose responses, and overall acceptability among overweight and obese adolescents. In a randomized crossover design, 20 participants consumed 240mL of either blenderized watermelon (WM) or an isocaloric sugar-sweetened beverage (SSB) on separate days. A triangle sensory test assessed participants' ability to distinguish between WM with and without rind, while acceptability assessments rated flavor, sweetness, and overall satisfaction using a seven-point hedonic scale. Blenderized WM consumption resulted in significantly lower postprandial glucose levels at 20 and 40min (P<0.01) compared to SSB. Satiety responses showed delayed increases in hunger and desire to eat with WM. Feelings of fullness increased at 20min for WM (P=0.033), while SSB resulted in lower fullness than baseline at 120min (P=0.006). Participants reported increased appetite after 120min with WM, compared to 60min with SSB (P<0.05). In the triangle sensory test, 70% of participants correctly identified WM with and without rind, with acceptability assessments favoring WM without rind. Blenderized WM shows potential for stabilizing postprandial glucose levels and enhancing satiety in overweight and obese adolescents. However, improving the sensory qualities of WM with rind is crucial to increase its appeal as a healthier alternative to sugary snacks. While these findings highlight its promise for managing glucose and promoting satiety, further efforts to enhance its palatability are needed.

Factors Associated with In-Hospital Mortality in Adult Patients with Bacterial Meningitis.

Background/Objectives: The aim of this study was to evaluate the association between various clinical and laboratory findings and in-hospital mortality in community-acquired bacterial meningitis (BM). Methods: We retrospectively analyzed 339 adult (≥18 years old) patients with bacterial meningitis who were admitted to the Hospital for Infectious Diseases in Warsaw between January 2010 and December 2017. Results: Altogether, 56 patients (16.5%) died during hospitalization. On admission, the non-survivors scored lower on the Glasgow Coma Scale (GCS) (median 7 vs. 13, p < 0.001) and higher on the Sequential Organ Failure Assessment (SOFA) score (median 6 vs. 2, p < 0.001) and were less likely to complain about headaches (18.75% vs. 54.21%, p < 0.001) and nausea and/or vomiting (1.89% vs. 36.2%, p < 0.001), but were more likely to manifest peripheral nerve palsies (21.43% vs. 9.61%, p = 0.02). The patients who died were also more likely to be immunocompromised (53.57% vs. 34.28%, p = 0.01), have Streptococcus pneumoniae etiology (35.71% vs. 16.25%, p = 0.001), higher concentrations of procalcitonin (median 5.035 ng/mL vs. 2.245 ng/mL, p = 0.003) and urea (median 10.7 mmol/L vs. 5.865 mmol/L, p < 0.001) in the blood and higher protein (median 4.57 g/L vs. 2.605 g/L, p = 0.014) and lower glucose levels (median 0.765 mmol/L vs. 1.89 mmol/L, p = 0.006) in the cerebrospinal fluid (CSF). In a multiple logistic regression analysis, which was conducted separately for the GCS and SOFA, both scoring systems (OR = 0.67, OR 95% CI 0.59-0.75, p < 0.001 for GCS and OR = 1.42, OR 95% CI 1.29-1.60, p < 0.001 for SOFA) as well as an age over 70 years (OR = 3.99, OR 95% CI 1.39-12.93, p = 0.014) and Streptococcus pneumoniae etiology (OR = 2.38, OR 95% CI 1.12-4.99, p = 0.022) were associated with in-hospital deaths. Conclusions: The survivors and non-survivors with BM differed with respect to a number of signs and symptoms, etiology, the results of blood and CSF laboratory tests, and the immune deficiency status, as well as the GCS and SOFA scores. In the multiple logistic regression analysis, both of the GCS and SOFA scoring systems, age and Streptococcus pneumoniae etiology showed high associations with the in-hospital deaths.

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Body Composition and Fluid Status in Cardiovascular Rehabilitation Patients with Coronary Artery Disease and Heart Failure.

Background and Objectives: Sodium glucose cotransporter-2 (SGLT-2) inhibitors have emerged as integral therapeutic tools in the management of patients with cardiovascular-kidney-metabolic (CKM) syndrome. In addition to their well-documented effects on lowering glucose levels and cardiovascular- and reno-protective actions, SGLT-2 inhibitors, through a reduction in body weight (BW), generate changes in the body composition and volume status that have not been clearly studied. Materials and Methods: This retrospective, observational longitudinal cohort, single-center study analyzed and compared body composition and fluid status measured by bioelectrical impedance analysis (BIA) from weeks 0 to 12 after the initiation of the cardiac rehabilitation (CR) program for coronary artery disease and heart failure in 59 patients who started treatment with SGLT-2 inhibitors (SGLT-2iG) and 112 patients without SGLT-2 inhibitors (non-SGLT-2iG). Results: Changes between the baseline and week 12 in the SGLT-2iG and non-SGLT-2iG were -0.3 L (p = 0.003) and -0.03 L (p = 0.82) in extracellular water (ECW) (p = 0.05), -0.39 L (p < 0.001) and -0.14 L (p = 0.33) in intracellular water (ICW) (p = 0.12), -0.69 (p < 0.001) and -0.16 (p = 0.52) in total body water (TBW) (p = 0.08), and -0.01 (p = 0.37) and -0.001 (p = 0.25) in the ECW/TBW ratio, respectively. After 3 months of exercise therapy in the CR program, patients in the SGLT-2iG showed a greater decrease than the non-SGLT-2iG in weight (-1.34 kg, p < 0.001 vs. -0.99, p = 0.02), body mass index (BMI) (-0.45 kg/m2, p < 0.001 vs. -0.38, p = 0.004), arm circumference (-0.57 cm, p = 0.008 vs. -0.12 cm, p = 0.21), waist circumference (-1.5 cm, p = 0.04 vs. -0.11 cm, p = 0.83), systolic blood pressure (SBP) (-8.9 mmHg, p = 0.049 vs. -4.19, p = 0.08), and diastolic blood pressure (DBP) (-5.15, p = 0.03 vs. -2.85, p = 0.01). The bioelectrical impedance analysis (BIA) revealed a significant decrease in body fat mass (BFM) and visceral fat area, without a loss of lean body mass (LBM) or skeletal muscle mass in the SGLT-2iG. Conclusions: SGLT-2 inhibitors exert beneficial effects on body compartments and volume status. Although they induce modest weight loss, this appears to be mainly directed at ECW, BFM, and visceral fat, without a loss of LBM nor skeletal muscle mass, which could contribute to the observed CKM benefits.

Metabolic profile evolution in relapsed/refractory B-cell non-Hodgkin lymphoma patients treated with CD19 chimeric antigen receptor T-cell therapy and implications in clinical outcome.

Plasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/B-NHL) infused with approved CD19.CAR-T cell products at the time of pre-lymphodepletion (PLD) and at day +1, +7, and +30 after CAR-T cell infusion. At the PLD time point, a metabolic profile characterized by high lipoproteins and lactate and low glucose contributed to poor outcome prediction in association with high lactate dehydrogenase levels. At day+1, higher plasma levels of lipid metabolism products and lower glucose and glycoproteins levels were observed in tisa-cel compared to axi-cel-treated patients. At day+30, discriminant analysis found two clusters in a subgroup of patients, one with CR lasting one year after therapy, and another who relapsed within one year (relapsed>D30). This latter showed a higher content of N-GlycA, a known biomarker of systemic inflammation that is also correlated with C-reactive protein in our case setting of relapsing patients. Our data show complex metabolomic changes that track the evolution of the disease and drug activity in the first 30 days of CAR-T cell therapy. Conceivably, a pro-inflammatory drift may be linked to a forthcoming disease relapse in CAR-T patients.

Diet, physical activity, and sleep in relation to postprandial glucose responses under free-living conditions: an intensive longitudinal observational study

BackgroundIt remains unclear what lifestyle behaviors are optimal for controlling postprandial glucose responses under real-world circumstances in persons without diabetes. We aimed to assess associations of diet, physical activity, and sleep with postprandial glucose responses in Asian adults without diabetes under free-living conditions.MethodsWe conducted an observational study collecting intensive longitudinal data using smartphone-based ecological momentary assessments, accelerometers, and continuous glucose monitors over nine free-living days in Singaporean men and women aged 21–69 years without diabetes. The outcome was the 2-h postprandial glucose incremental area under the curve (mmol/l*min). Associations were estimated using linear mixed-effect models.ResultsThe analyses included 11,333 meals in 789 participants. Greater variations in glucose and lifestyle measures were observed within individuals than between individuals. Higher consumption of carbohydrate-rich and deep-fried foods and lower consumption of protein-rich foods were significantly associated with higher postprandial glucose levels (incremental area under the curve). The strongest association was observed for including refined grains (46.2 [95% CI: 40.3, 52.1]) in meals. Longer postprandial light-intensity physical activity (-24.7 [(-39.5, -9.9] per h) and moderate-to-vigorous-intensity physical activity (-58.0 [-73.8, -42.3]) were associated with substantially lower postprandial glucose levels. Longer daily light-intensity physical activity (-7.5 [-10.7, -4.2]) and sleep duration (-2.7 [-4.4, -1.0]) were also associated with lower postprandial glucose levels. Furthermore, postprandial glucose levels were the lowest in the morning and the highest in the afternoon. The results were largely consistent for males and females and for participants with and without prediabetes.ConclusionsConsuming less refined grains and more protein-rich foods, getting more physical activity (particularly during the postprandial period), and having a longer sleep duration were associated with lower postprandial glucose levels in Asian adults without diabetes. Our findings support multi-component lifestyle modifications for postprandial glucose control and highlight the importance of the timing of eating and physical activity.

Characterization of Recombinant Barley D-Enzyme and Its Ability to Influence Wort Sugar Profiles

Recombinant barley disproportionating enzyme 1 (rDPE1) is a functional D-enzyme capable of disproportionating maltotriose (G3) into glucose (G1) and maltopentaose (G5) in the reaction, G3 + G3 ←→ G1 + G5. Maltotriose accumulates in wort during mashing and cannot be further broken down by diastatic power enzymes. This reaction mechanism could theoretically reduce maltotriose levels in wort replacing them with more easily fermentable sugars (glucose) or substrates (maltopentaose) to be broken down by diastatic power enzymes like β-amylase. Barley rDPE1 was most active between pH 6.5 and 6.8 but was functional between pH 4.5 and 8.0. Activity levels were relatively stable between 37 °C and 50 °C, peaking at 45 °C, with half the activity remaining after incubation at 55 °C. The thermostability and pH activity profiles of rDPE1 allow for at least partial survival under mashing conditions. rDPE1 released glucose from maltotriose, maltotetraose, and maltopentaose, but could not use maltose, maltohexaose, or maltoheptaose as substrates. Moreover, barley rDPE1 synthesized maltotetraose, maltohexaose, and maltoheptaose when given maltotriose as a substrate. An assortment of maltooligosaccharides were formed by rDPE1 when given the substrates maltotriose, maltotetraose, maltopentaose, maltohexaose, and maltoheptaose. The most novel reaction observed was the accumulation of maltose when rDPE1 used maltotetraose as a substrate. Barley rDPE1 (63 µg) was added to a 60-min 65 °C isothermal mash (1 mL) at 5, 30, and at 60 min (i.e., post-mash) and significantly lowered glucose, fructose, and maltotriose levels and increased maltotetraose, maltopentaose, and non-fermentable sugar levels.

Extraction Methods and Characterization of β-Glucans from Yeast Lees of Wines Produced Using Different Technologies.

Wine lees, the second most significant by-product of winemaking after grape pomace, have received relatively little attention regarding their potential for valorization. Despite their rich content in bioactive components such as β-glucans, industrial utilization faces challenges, particularly due to variability in their composition. This inconsistency impacts the reliability and standardization of final products, limiting broader adoption in industrial applications. β-Glucans are dietary fibers or polysaccharides renowned for their diverse bioactive properties, including immunomodulatory, antioxidant, anti-inflammatory, antitumor, and cholesterol- and glucose-lowering effects. They modulate the immune system by activating Dectin-1 and TLR receptors on immune cells, enhancing phagocytosis, cytokine production, and adaptive immune responses. Their antioxidant activity arises from neutralizing free radicals and reducing oxidative stress, thereby protecting cells and tissues. β-Glucans also exhibit antitumor effects by inhibiting cancer cell growth, inducing apoptosis, and preventing angiogenesis, the formation of new blood vessels essential for tumor development. Additionally, they lower cholesterol and glucose levels by forming a viscous gel in the intestine, which reduces lipid and carbohydrate absorption, improving metabolic health. The biological activity of β-glucans varies with their molecular weight and source, further highlighting their versatility and functional potential. This study investigates how grape variety, vinification technology and extraction methods affect the yield and properties of β-glucans extracted from wine lees. The physico-chemical and mineral composition of different wine lees were analyzed, and two extraction methods of β-glucans from wine lees were tested: acid-base extraction and autolysis. These two methods were also tested under ultrasound-assisted conditions at different frequencies, as well as without the use of ultrasound. The β-glucan yield and properties were evaluated under different conditions. FTIR spectroscopy was used to assess the functional groups and structural characteristics of the β-glucans extracted from the wine lees, helping to confirm their composition and quality. Rheological behavior of the extracted β-glucans was also assessed to understand the impact of extraction method and raw material origin. The findings highlight that vinification technology significantly affects the composition of wine lees, while both the extraction method and yeast origin influence the yield and type of β-glucans obtained. The autolysis method provided higher β-glucan yields (18.95 ± 0.49% to 39.36 ± 0.19%) compared to the acid-base method (3.47 ± 0.66% to 19.76 ± 0.58%). FTIR spectroscopy revealed that the β-glucan extracts contain a variety of glucan and polysaccharide types, with distinct β-glucans (β-1,4, β-1,3, and β-1,6) identified through specific absorption peaks. The rheological behavior of suspensions exhibited pseudoplastic or shear-thinning behavior, where viscosity decreased significantly as shear rate increased. This behavior, observed across all β-glucan extracts, is typical of polymer-containing suspensions. These insights are critical for optimizing β-glucan extraction processes, supporting sustainability efforts and waste valorization in the wine industry. Efficient extraction of β-glucans from natural sources like wine lees offers a promising path toward their industrial application as valuable functional compounds.

ИССЛЕДОВАНИЕ ВЛИЯНИЯ 20-ГИДРОКСИЭКДИЗОНА НА УГЛЕВОДНЫЙ ОБМЕН У ПОРОСЯТ

The effect of 20-hydroxyecdysone on carbohydrate metabolism indices was studied in crossbred piglets (♂ Danish Yorkshire ×♀ Danish Landrace) during the postnatal period of ontogenesis. At the age of 60 days, 2 groups of animals were formed: 1 (control, n=3) and 2 (experiment, n=4), which received compound feed con- taining (g/kg) crude protein 158.7; lysine 7.7; threonine 4.8; methionine 4.6 and metabolizable energy (MJ/kg) 12.7. 20-hydroxyecdysone was introduced into the diet of piglets in the experimental group at the rate of 30 mg/kg of feed. The parameters of carbohydrate metabolism (glucose, pyruvate, lactate concentrations, alpha-amylase and lactate dehydrogenase activity in the blood, glycogen content in the longissimus dorsi muscle and liver) were studied. Statistical processing of the obtained results was performed using the STATISTICA v.12.5 software package. The Mann-Whitney U-test was used to identify differences between animal samples. Differences be- tween groups were considered statistically significant at p≤0.05. The use of 20-hydroxyecdysone in animals dur- ing the postnatal period of ontogenesis for 2 months leads to a decrease in the lactate level in the blood serum (by 17.1%; p&lt;0.05). In animals of the experimental group, compared to the control, an increase in the pyruvate con- tent (by 15.8%; p&lt;0.05), the activity of lactate dehydrogenase and alpha-amylase enzymes in the blood serum was found against the background of a low glucose level in whole blood (by 22.8%; p&lt;0.05). At the same time, in an- imals receiving 20-hydroxyecdysone, compared to the control, an increase in the glycogen level in the liver and longissimus dorsi muscle was found (by 23.0% and 20.7%, respectively; p&lt;0.05). It was concluded that 20-hydroxyecdysone activates the intracellular signaling pathway of phosphatidylinositol-3-kinase and protein kinase B, which leads to an increase in the intensity and direction of carbohydrate metabolism, accompanied by complete oxidation of glucose to pyruvate with a large formation of adenosine triphosphoric acid (ATP) and ef- fective utilization of glucose for glycogen synthesis in the liver and longissimus dorsi muscle.

Glucose Metabolism Disorders and Parkinson's Disease: Coincidence or Indicator of Dysautonomia?

Background: Parkinson's disease (PD) and type 2 diabetes mellitus (T2DM) are both age-related diseases. Evidence from recent studies suggests a link between them. The existence of an interaction between autonomic nervous system dysfunction and the dysregulation of glucose metabolism is one of the proposed mechanisms to explain the complicated relationship between these diseases. The aims of this study are to assess the incidence of glycemic dysregulation in people with PD and to identify clinical factors that may predispose patients with PD to the occurrence of metabolic disturbances. Methods: In total, 35 individuals diagnosed with PD and 20 healthy control subjects matched in terms of age and gender participated in a study consisting of clinical and biometric assessments along with 14 days of continuous glucose monitoring (CGM) using the Freestyle Libre system. In the group of patients with PD, a comparative analysis was performed between patients with and without autonomic dysfunction. The severity of autonomic dysfunction was assessed using the SCOPA-AUT. Results: Participants diagnosed with PD demonstrated a trend toward lower morning glucose levels compared to the control group. PD patients with autonomic symptoms had greater glucose variability and a deeper trend toward lower glucose levels in the mornings. The presence of autonomic dysfunction, especially orthostatic hypotension and micturition disturbance, and the severity of autonomic symptoms were associated with greater glycemic variability. Conclusions: The occurrence of autonomic disorders in the course of Parkinson's disease predisposes patients to more profound glycemic dysregulation.

Monitoring individualized glucose levels predicts risk for bradycardia in type 2 diabetes patients with chronic kidney disease: a pilot study

Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) exhibit an elevated risk for cardiac arrhythmias, such as bradycardia, which may potentially lead to sudden cardiac death (SCD). While hypoglycemia, defined as a critical drop in glucose levels below the normal range, has long been associated with adverse cardiovascular events, recent studies have highlighted the need for a comprehensive reevaluation of its direct impact on cardiovascular outcomes, particularly in high-risk populations such as those with DM and CKD. In this study, we investigated the association between glucose levels and bradycardia by simultaneously monitoring interstitial glucose (IG) and ECG for 7 days in insulin-treated patients with DM and CKD. We identified bradycardia episodes in 19 of 85 patients (22%) and associated these episodes with personalized low, medium, and high relative glucose levels. Our analysis revealed a significant increase in bradycardia frequency during periods of lowest relative glucose, particularly between 06:00-09:00 and 12:00-15:00. Furthermore, leveraging a Random Forests classifier, we achieved a promising area under the curve (AUC) of 0.94 for predicting bradyarrhythmias using glucose levels and heart rate variability features. Contrary to previous findings, only 4% of bradycardia episodes in our study population occurred at glucose levels of 70 mg/dL or lower, with 28% observed at levels exceeding 180 mg/dL. Our findings not only highlight the strong correlation between relative glucose levels, heart rate parameters, and bradycardia onset but also emphasize the need for a more personalized definition of hypoglycemia to understand its relationship with bradyarrhythmias in high-risk DM and CKD patient populations.

Impact of eating duration on weight management, sleeping quality, and psychological stress: A pilot study.

The daily eating window significantly impacts weight and metabolic health, yet its ideal duration remains uncertain. Thirty-four healthy middle-aged women were randomly assigned to two intervention groups: 8-h time-restricted eating (TRE) and 14-h time-extended eating (EXE). Each intervention lasted 4 wk, with a 16-d washout period before switching to the other intervention. Clinical biomarkers were collected before and after each intervention, and sleep quality was assessed using the Korean Version of the Pittsburgh Sleep Quality Index (PSQI-K). Additionally, a daily visual analogue scale (VAS) was used to evaluate psychological changes. The TRE group experienced significant weight reduction, lower fasting plasma glucose and total serum cholesterol levels compared to the EXE group, but with an increase in systolic blood pressure. The EXE group showed improved blood pressure. The TRE group reported higher stress levels on the VAS, but the PSQI-K indicated improved sleep quality during the second intervention. An 8-h TRE, without calorie restriction or diet composition changes, proves more beneficial for weight management and plasma glucose control compared to the 14-h EXE among Korean women. Implementation of this approach is recommended to be gradual to mitigate psychological fluctuations and adverse blood pressure changes. The trial was registered with ClinicalTrials.gov (ID: NCT05964179) and Clinical Research Information Service (CRIS, Korea) (ID: KCT0008640).

Adequate sleep duration accentuates the effect of glucagon-like peptide-1 receptor variant on HbA1c: A gene-environment interaction study

BackgroundBoth glucagon-like peptide-1 receptor (GLP1R) agonists and lifestyle modifications are widely adopted in managing glycemia. However, the joint effects of GLP1R agonists with lifestyle on glycemic traits have not been evaluated. MethodsThis gene-environment study tested the interaction between GLP1R-rs10305492 variant, consistent with the effect of GLP1R agonist therapies, and four lifestyle factors (diet, physical activity, sleep duration, and chronotype) for glucose and glycated hemoglobin (HbA1c) levels among 263,846 UK Biobank participants. Linear regression models were conducted to evaluate the effects of the rs10305492 and lifestyle factors on glucose and HbA1c levels. ResultsGLP1R-rs10305492-AA/AG genotype combined a healthy diet, regular physical activity, adequate sleep duration, or morning chronotype were associated with lower glucose and HbA1c levels (all P for trend < 0.001). A synergistic effect was found between rs10305492 and sleep duration on HbA1c, suggesting a recommended adequate sleep duration (7–8 h/day) may amplify the HbA1c lowering effect of GLP1R agonists. Joint effects of the rs10305492 and adequate sleep were associated with a 26 % reduced risk of hyperglycemia (>7.8 mmol/L) risk and a 22 % lower of high HbA1c (>39 mmol/mol or 5.7 %). ConclusionsCombining GLP1R agonists with adequate sleep may provide additional benefits for glycemic control in clinical practice.

Enhancing therapeutic efficacy: In vivo mechanisms and biochemical effects of lycopene encapsulated in nanomicelles for acute inflammation and lipid metabolism

This study focuses on developing, characterizing, and evaluating lycopene nanomicelles formulations for their therapeutic potential in treating acute inflammation and obesity. Lycopene, a hydrophobic carotenoid with potent antioxidant, anti-inflammatory, and anticancer properties, faces challenges in bioavailability due to its poor solubility. To address this, the study utilized nanocarrier systems like liposomes, nanoparticles, and nanoemulsions to enhance the solubility, stability, and bioavailability of lycopene. The lycopene nanomicelles demonstrated significant anti-inflammatory and anticancer activities through multiple mechanisms. It inhibited the NF-κB pathway, reducing the expression of pro-inflammatory mediators, and modulated apoptotic pathways, leading to increased apoptosis and reduced cell proliferation in cancer cells. Furthermore, lycopene enhanced phase II detoxifying enzymes activity, interfered with gap junction communication, and potentially improved DNA repair mechanisms, contributing to its anticancer efficacy. In vivo studies revealed that lycopene nanomicelles effectively reduced leukocyte and neutrophil counts in an acute inflammation model, especially at higher doses, highlighting its potential as a nanodrug for inflammation management. However, the study found no significant alteration in triglyceride levels, indicating a need for further investigation into the effects of lycopene and its nanostructured forms on lipid metabolism. Biochemical analyses showed variations in liver enzyme levels, suggesting protective effects on the liver but also indicating potential pancreatic activity or stress and low glucose levels. These findings underscore the necessity for comprehensive safety evaluations. Overall, this research underscores the promising therapeutic applications of lycopene nanomicelles in inflammation and cancer while emphasizing the importance of addressing safety and metabolic effects for effective clinical translation.

Evaluating Continuous Glucose Monitoring after Total Pancreatectomy with or without islet autotransplatation: A Scoping Systematic Review.

The review was conducted adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. 15 studies including 147 patients (adult n = 71/paediatric n = 76) reported on CGM use post-TP (n = 42) and TPIAT (n = 105). 4 were randomized controlled trials and 10 observational studies. 6 studies evaluated CGM use in the peri-operative and 6 in the immediate post-operative period (n = 8) with variable follow-up (14 hours -20 months). CGM was used as a stand-alone device (8 studies) which allowed assessment of dynamic islet function and detection of hypoglycemia (n = 1) resulting in lower glucose levels (n = 1). 6 studies evaluated insulin pump with CGM with reduction in post-operative mean glucose (n = 4), and hypoglycaemic episodes (n = 2). There were no patient reported outcome measures (PROMs) or quality of life (QoL) measures reported. CGM can be used following TP for glucose monitoring and/or linked with insulin pump device in the peri-operative period with improved glycaemic control. However, the data are limited by short follow-up and lack of PROMs and QoL measures.