Glucose Delivery Research Articles

Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males

BackgroundThe appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients. ObjectivesThe purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed. MethodsPlasma LEAP2 concentration was measured in blood samples from 5 clinical cross-over trials, following 1) 36 h of fasting (n = 8), 2) 10 h of fasting (n = 37, baseline data pooled from 4 of the clinical trials), 3) Oral and intravenous glucose administration (n = 11), 4) Oral and intravenous Na-lactate administration (n = 10), and 5) Oral and intravenous Na-β-hydroxybutyrate (BHB) administration (n = 8). All 5 trials included healthy males. ResultsCompared with a 10-h fasting period, the median LEAP2 concentration was 38% lower following 36 h of fasting (P < 0.001). Oral administration of glucose elevated, whereas intravenous glucose administration lowered LEAP2 concentration (intervention x time, P = 0.001), resulting in a mean difference of 9 ng/mL (95% confidence interval [CI]: 1, 17) after 120 min. Oral lactate increased, and intravenous lactate decreased LEAP2 (intervention x time, P = 0.007), with a mean difference between interventions of 10 ng/mL (95% CI: 6, 15) after 120 min. In contrast, oral and intravenous administration of BHB reduced the LEAP2 concentration (main effect of time, P < 0.001). ConclusionsOur investigations show that LEAP2 concentration was lower after a 36-h fast than an overnight fast and that oral delivery of glucose and lactate elevated LEAP2 concentration compared with intravenous administration, whereas LEAP2 concentrations decreased with both oral and intravenous BHB. This indicates that the LEAP2 concentration is sensitive to intestinal exposure to specific substrates, highlighting the need for future studies exploring the relationship between nutrients and LEAP2.This trial was registered at clinicaltrials.gov as NCT01840098, NCT03204877, NCT04299815, NCT03935841, and NCT01705782.

Conceptualizing ‘food parcel for colon microbes' designed for delivering to human colon which assists the growth of the probiotics there: An exploratory in vitro study with Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12

Long-term colonization of desired probiotic bacteria in human colon environment is still tough to achieve for now. In this exploratory in vitro study, we demonstrated the difficulties in proliferation of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis BB-12 (BB-12) in the substrate of post intestinal digestion products (PIPD) made from skimmed milk. Results of poor growth in the digesta (1.54 log N/N0 for LGG, while −0.54 log N/N0 for BB-12) provided evidence on mechanisms of low survival of the two strains in simulated colon environment. Adscititious glucose significantly promoted viable counts of LGG and BB-12 in PIPD, thus is promising to serve as possible tailor made ‘food’ for colon fermentation of probiotics. Based on the results, we propose a new concept that may be called as ‘food parcel for colon microbes’, which can be delivered to simulated human colon environment and assist the growth of the probiotics already existing there. In the current study, we selected the ‘glucose parcel’ as an initial example. The ‘glucose parcel’ can be released into colon based on its pH-dependent dissolvability. With the direct delivery of glucose, the log (N/N0) values of LGG in single-species and mixed-species cultivations reached 2.10 and 2.24, respectively. The log (N/N0) value of BB-12 was 1.04 in single-species, and 1.30 in mixed-species cultivation. ‘Food parcel for colon microbes’ will be hopeful in promoting colonic probiotic fermentation and providing an innovative strategy for achieving long-term colonization of the probiotics and regulating the gut microbiota in human colon.

Carbohydrate ingestion attenuates the reduction in complex cognitive function and cerebral blood flow during prolonged passive heat stress in humans

PurposeTo determine whether carbohydrate ingestion would reduce cognitive dysfunction in humans following long duration passive heat stress (PHS) versus consuming electrolytes alone. MethodsFifteen young (27 ± 4 y) healthy adults were exposed to 120 min of PHS through the use of a liquid perfused suit (50 °C) on two randomized visits. Subjects consumed fluids supplemented with electrolytes (E) or electrolytes + carbohydrates (E + C). Pre- and post-heat stress, body mass (BM) and plasma osmolality (pOsm) were measured. Heart rate (HR), blood pressure (BP), Physiological Strain Index (PSI), core temperature (Tc), plasma glucose, respiration rate (RR), end-tidal CO2 (PetCO2) and internal carotid artery (ICA) blood flow were recorded at baseline and every 15 min of heat stress. Cognitive function was assessed via the Automated Neuropsychological Assessment Metric at baseline and at 30- and 120 min during heat stress. ResultsThere were no significant differences between fluid conditions for BM, pOsm, PSI, Tc, RR or PetCO2. Plasma glucose was ∼75% greater in the E + C condition compared to the E condition after 90 min of PHS (P < 0.05). Cognitive function (120 min) was impaired following PHS only in E condition (P < 0.05) and performance on complex cognitive tasks were better by ∼22–340% in the E + C vs. E (P < 0.05). Compared to the E condition, HR and BP were lower and ICA blood flow, vascular conductance, and glucose delivery was ∼90% greater in the E + C after 90 min of PHS (P < 0.05). ConclusionsThese data are the first to demonstrate that carbohydrate ingestion may have a protective effect on cognitive function during long duration PHS. Furthermore, this protection was associated with preserved ICA blood flow and glucose delivery to the brain.

A Self‐Sustaining Hydrogels with Autonomous Supply of Nutrients and Bioactive Domains for 3D Cell Culture

AbstractPhoto‐crosslinkable platelet lysate (PL)‐based hydrogels have been proven to support human‐derived cell cultures owing to their high content of bioactive molecules, such as cytokines and growth factors. As a unique self‐maintained and biocompatible 3D scaffold, the recently reported self‐feeding hydrogels with enzyme‐empowered degradation capacity have shown high biological performance in vitro and in vivo. To take advantage of all features of both PL and self‐feeding hydrogels, here UV responsive laminaran‐methacrylate (LamMA) and PL‐methacrylate (PLMA) derivatives plus glucoamylase (GA), which significantly improve the overall features of a 3D system, is coupled. This self‐sustaining hybrid hydrogel emerges as a unique scaffold due to the sustained delivery of glucose produced via enzymatic degradation of laminaran while granting the release of growth factors through the presence of PL. This biomaterial is applied to fabricate high‐throughput freestanding microgels with controlled geometric shapes. Furthermore, this multicomponent hybrid hydrogel is successfully implemented as the first reported glucose supplier bioink to manufacture intricate and precisely defined cell‐laden structures using a support matrix. Finally, such hydrogels are utilized as a proof of concept to serve as 3D in vitro cancer models, with the aim of recapitulating the tumor microenvironment.

Continuous Glucose Monitoring in Endurance Athletes: Interpretation and Relevance of Measurements for Improving Performance and Health

Blood glucose regulation has been studied for well over a century as it is intimately related to metabolic health. Research in glucose transport and uptake has also been substantial within the field of exercise physiology as glucose delivery to the working muscles affects exercise capacity and athletic achievements. However, although exceptions exist, less focus has been on blood glucose as a parameter to optimize training and competition outcomes in athletes with normal glucose control. During the last years, measuring glucose has gained popularity within the sports community and successful endurance athletes have been seen with skin-mounted sensors for continuous glucose monitoring (CGM). The technique offers real-time recording of glucose concentrations in the interstitium, which is assumed to be equivalent to concentrations in the blood. Although continuous measurements of a parameter that is intimately connected to metabolism and health can seem appealing, there is no current consensus on how to interpret measurements within this context. Well-defined approaches to use glucose monitoring to improve endurance athletes’ performance and health are lacking. In several studies, blood glucose regulation in endurance athletes has been shown to differ from that in healthy controls. Furthermore, endurance athletes regularly perform demanding training sessions and can be exposed to high or low energy and/or carbohydrate availability, which can affect blood glucose levels and regulation. In this current opinion, we aim to discuss blood glucose regulation in endurance athletes and highlight the existing research on glucose monitoring for performance and health in this population.

Hypoglycaemia management with a hypercaloric supplementation in neonatal puppies delivered by caesarean section.

There is a high perinatal mortality rate in dogs, estimated at 20%, and one of the leading causes of this rate is hypoglycaemia. Therefore, we aimed to evaluate the efficacy of a hypercaloric supplement containing vitamins and amino acids in newborn puppies presenting hypoglycaemia at birth. Ninety-nine pups were divided into four groups: normoglycaemic caesarean section (NORMOCS), hypoglycaemic caesarean section supplemented with the hypercaloric (SUPLCS), hypoglycaemic caesarean section supplemented with glucose (GLICCS) and eutocic delivery (EUT). We evaluated the following parameters glycaemia, Apgar score, neurological reflexes and rectal temperature of neonates at the following moments 5 min (M5), 30 min (M30) and 60 min (M60) after birth. Brachycephalic dogs were 73.3% (22/30) of caesarean sections (c-sections). The puppy's average glycaemia represented about 90% of the maternal glycaemia, while 15.1% (14/99) of the neonates had hypoglycaemia (<90 mg/dL) at M0 and 46.5% (44/99) at M60. Only four neonates had glycaemia below 40 mg/dL at M30 but without showing any clinical signs. The puppy's fasting while waiting for the intraoperative period and the dam's anaesthetic recovery was considered risk factors for hypoglycaemia. There was no difference in mean blood glucose levels or vitality parameters among puppies from the SUPLCS and GLICCS. In conclusion, the hypercaloric supplement can be used as a replacement for glucose in hypoglycaemic puppies and it can also bring nutritional benefits for the puppy. The prepartum glycaemia of the dam is an important parameter to be measured, and the appropriate management of it reduces the chances of the puppies being born with hypoglycaemia.

Total-Body Multiparametric PET Quantification of 18F-FDG Delivery and Metabolism in the Study of Coronavirus Disease 2019 Recovery.

Conventional whole-body static 18F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic 18F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue 18F-FDG delivery rate [Formula: see text] and the phosphorylation rate k 3, as well as the macroparametric 18F-FDG net influx rate ([Formula: see text]). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and [Formula: see text] in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k 3 but not with [Formula: see text], which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow 18F-FDG metabolism measured with SUV, SUVR, and [Formula: see text] but a significantly higher bone marrow [Formula: see text] in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung [Formula: see text] and a higher spleen [Formula: see text] than unvaccinated COVID-19 subjects. Conclusion: Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric 18F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of 18F-FDG can provide a more sensitive tool and more insights than conventional whole-body static 18F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.

Abstract P1135: Gene Expression Analysis Of Glycemic Memory In Heart Failure

Diabetes is a growing epidemic, with 37.3 million affected in the US. Diabetic patients are twice as likely to develop cardiovascular disease (CVD). Risk of CVD persists for years even following restoration of glycemic control in type-2-diabetic patients. These findings led to the hypothesis of glycemic memory, i.e., prior changes in glucose levels and delivery may lead to long-term molecular changes predisposing patients to CVD. We proposed that prior enhanced cellular glucose uptake leads to transcriptional changes that contribute to glycemic memory and enhances susceptibility to heart failure. We used a mouse model of doxycycline (DOX)-inducible cardiomyocyte-restricted glucose transporter 4 (GLUT4; mG4H), where mG4H is overexpressed for 2 wk (ON) and then returned to basal levels (OFF). Harvested left ventricular tissues from 4 groups of male mice (n=3) - ON and matched control (Con), OFF and DOX-matched Con (DCon) - were subjected to RNA sequencing analysis (Adjusted P &lt;0.1, Fold-Change&gt;

Endocrine and metabolic profiles in pregnant and non-pregnant Criollo mares

Gestation leads to metabolic changes, prioritizing nutrients’ delivery to the developing fetus (Fowden et al. Equine Veterinary Journal. 1984; 16(4), 239-246). Insulin, adiponectin, and leptin are key metabolic hormones that have been associated with pregnancy success in several species (Coverdale et al. J Anim Sci. 2015; 93(7), 3261-3267.; Meikle et al. Anim. Reprod., v.15, (Suppl.1), p.899-911. 2018). Information on these hormones and their metabolites during gestation of horses is lacking, specifically in native breeds. Therefore, the objective of this study was to establish the endocrine-metabolic profile in pregnant and non-pregnant Criollo mares, a native breed that is popular in South America. Mares (n=56) were categorized as pregnant (n=41) or non-pregnant (n=15). Animals were bled between days 200 and 250 of gestation and the Body Condition Score (BCS) was determined (scale 1-9, Henneke et al. Equine Veterinary Journal. 1983; 15(4), 371-372). The controls were assayed at the same time samples were taken, during the winter, between June and August. Insulin was determined by immunoradiometric analysis, leptin and adiponectin by Radioimmunoassay and other biochemistry variables by spectrophotometer. Hematology variables were determined by hematologic counter. Variables were analyzed by ANOVA using a mixed procedure. The reproductive status did not affect theleptin (9.4±1.6 vs 9.0±1.0 ng/mL, P=0.804 in pregnant and non-pregnant mares respectively), adiponectin concentrations (18.9±2.7 vs 15.5±1.6 ng/mL, P=0.304 in pregnant and non-pregnant mares respectively), nor the BCS (7.3±0.2 vs 7.6±0.1, P=0.356 in pregnant and non-pregnant mares respectively). Insulin (18.2±2.9 vs 17.7±1.7 UI/mL, P=0.644 in pregnant and non-pregnant mares respectively) and glucose (87.0±2.6 vs 83.0±1.6 mg/dL, P=0.180 in pregnant and non-pregnant mares respectively) concentrations were not affected either. Cholesterol concentrations were not affected by the reproductive status, while triglyceride concentrations were higher in pregnant when compared to non-pregnant mares (31.0±1.9 vs 21.6±3.1 mg/dL, P=0.012). Urea and creatinine concentrations were also higher in pregnant than in non-pregnant mares (52.8±1.0 vs 46.7±1.6 mg/dL, P=0.002 and 1.25±0.03 vs 1.01±0.05 mg/dL, P=0.0002 respectively). Hepatic enzymes and white blood cell count were not affected by the reproductive status. This study shows higher concentrations of triglycerides, urea and creatinine in pregnant mares. These changes could be associated with the metabolic prioritization of glucose delivery to the developing fetus, which leads to a differential nutrient partitioning, as reflected in different concentrations of specific metabolites of the protein and lipid pathways.

Investigating the Role of Neurovascular Coupling on Brain Function and Health

The brain consumes a disproportionate amount of energy, receiving 20% of the total cardiac output despite accounting for only 2% of the body’s weight. While total cerebral perfusion is homeostatically held constant, the neurovascular network dynamically modulates regional blood flow to deliver more nutrient-rich blood to highly active brain areas. Activity-dependent focal increases in cerebral blood flow, or neurovascular coupling (NVC), ensure that energy delivery is commensurate with neuronal metabolic demands. It is widely thought that neurovascular coupling is critical for normal brain function, as neurons lack energy stores and may require increases in oxygen or glucose delivery from the blood supply to fuel signaling operations that consume high levels of ATP. However, it is unknown which features of neuronal signaling are supported by NVC, if any. We are investigating this important question by using a genetic mouse model with NVC specifically impaired. This study will reveal new insights on how NVC supports normal brain function and health. HHMI, NHLBI NIH This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Exercise and Insulin Signaling on Glucose Transporter Type 4 in Skeletal Muscles: A narrative review

Introduction: Glucose transporter type 4 (GLUT4) is a membrane glucose transporter that is influenced by insulin signaling and muscle contraction. The aim of the present study was to review the function of GLUT4 in normal conditions and insulin resistance, as well as the role of exercise training on the kinetics of GLUT4 in skeletal muscles. In the present study, by searching for sports keywords; exercise; sports adaptations; glucose transporter; absorption of glucose; glucose transporter type 4; type 2 diabetes; insulin signaling; and insulin resistance was searched from electronic databases of related articles until November 2022 and entered into the study.&#x0D; Conclusion: Due to the pathological factors of type 2 diabetes, skeletal muscles are disturbed in the delivery, absorption, and metabolism of glucose; pathological disorders of muscle tissue affect insulin signaling and the quantity and function of GLUT4. In the present review, it was found that an exercise training session initiated the GLUT4 gene expression and protein production and its transfer from intracellular stores to sarcolemma; this effect of local exercise was related to muscle contraction. GLUT4 gene and protein expression increased in response to regular exercise and led to an increase in the total level of GLUT4 protein in skeletal muscles; furthermore, regular exercise has improve insulin signaling and, as a result, improved muscle efficiency for blood glucose collection. Considering the role of physical activity on muscle function in blood glucose collection, one of the treatment goals in type 2 diabetes is maintaining muscle mass, increasing muscle mass and also increasing muscle function (muscle quality).

Dilemmas in parenteral glucose delivery and approach to glucose monitoring and interpretation in the neonate.

Glucose control continues to be challenging for intensivists, in particular in high-risk neonates. Many factors play a role in glucose regulation including intrinsic and extrinsic factors. Optimal targets for euglycemia are debatable with uncertain short and long-term effects. Glucose measurement technology has continued to advance over the past decade; unfortunately, the availability of these advanced devices outside of research continues to be problematic. Treatment approaches should be individualized depending on etiology, symptoms, and neonatal conditions. Glucose infusions should be titrated based upon variations in organ glucose uptake, co-morbidities and postnatal development. In this article we summarize the most common dilemmas encountered in the NICU: ranges for euglycemia, physiological differences, approach for glucose measurements, monitoring and best strategies to control parenteral glucose delivery.

Response to: Comment on: Pancreatectomy With Islet-Autotransplantation as Alternative for Pancreato-Duodenectomy in Patients With a High-Risk for Postoperative Pancreatic Fistula: The Jury Is Still Out.

We thank Dr Thomas Frederik Stoop and colleagues for their keen interest in our study1 and their words of appreciation for our work. The first issue raised by the authors relates to the risk–benefit balance of total pancreatectomy associated with islet-autotransplantation (TP-IAT) versus pancreatoduodenectomy (PD). As for whether postoperative morbidity is the ideal endpoint for our trial, we point out that the 90-day overall complication rate is the standard primary endpoint of many studies on this topic. Furthermore, as for our trial is concerned, it was an unavoidable choice to ensure study feasibility. In facts, considering the 90-day mortality rate as primary outcome, 464 patients would be needed to detect a statistical difference with adequate power, an unrealistic sample size for a prospective randomized trial on autologous islet transplantation in candidates for pancreatic surgery and at high risk for POPF. Consequently, overall, disease-specific and disease-free survival were included as secondary endpoints. However, the point raised by Stoop and colleagues actually implies a question that goes beyond the results of our trial, namely whether primary total pancreatectomy (TP) in patients at high risk of POPF is justified and preferable to pancreaticoduodenectomy. This question is still very open, and our results suggest that there may be room for an approach based on TP. In our study, as in other recent retrospective single-center series,2-3 a 2%–4% mortality rate after TP is reported and, even in daily clinical practice, the 90-day mortality rate was 4% in centers performing more than 60 PDs per year.4 We are aware of and appreciate the results of the Dutch PORSCH trial, but that study population was not selected for being at high risk of POPF, and therefore, the results of PORSCH cannot be extrapolated to the patients enrolled in our study. A major contribution to the discussion on this topic will be hopefully provided by the recently initiated TETRIS study (NCT05212350), a multicenter RCT in a cohort of patients with a very high risk of POPF, comparing TP and primary pancreatic anastomosis for postoperative outcomes and quality of life. The second issue raised is related to the patient-reported outcomes. We fully agree that quality of life overtime is a highly relevant endpoint when determining the impact of TP on the life of our patients and their families. However, our study was not an appropriate setting to provide meaningful data on this issue. In fact, the heterogeneity of the underlying pancreatic diseases in terms of disease severity and the various adjuvant treatments patients had faced for extended periods of time after surgery were likely to have had a significant impact on patients’ relevant outcomes. The third issue relates to the relevance of glucose control. Islet-autotransplantation resulted in at least partial endogenous insulin secretion in around 90% of patients undergoing TP and good metabolic control at the last follow-up [day 388 (235–1307)] in 62% of the patients without severe hypoglycemic episodes or diabetes-related mortality. We were impressed by the recent results of the Dutch Pancreatic Cancer Group using a bihormonal artificial pancreas in 12 patients after TP. The 7-day follow-up in 9 of the 12 patients who completed the study showed an increased time spent between 70 and 180 mg/dL (time in range) of glucose levels. We hope these data will be confirmed through larger and longer RCTs involving unselected patients who underwent TP. We envision islet transplantation not as an alternative to the use of exogenous insulin and glucose sensor or delivery technology in patients with TP, but as a complementary and synergistic treatment for diabetes following TP since the bihormonal artificial pancreas hopefully wish to perform even better in patients with autologous islet transplantation after TP. We completely agree with Stoop and colleagues that the jury is still out. However, our study confirmed that IAT is a feasible choice in patients with pancreas diseases other than chronic pancreatitis, and this should be viewed as an important advance in the field. The decision to perform TP-IAT requires assessing the risk–benefit ratio of this procedure in each individual case and should be discussed with the candidate patient in the context of multidisciplinary teams. High-volume referral centers for pancreatic surgery should be encouraged to collaborate with an islet isolation facility to provide access to IAT when appropriate. At last, in our conclusion, we used “may” to convey a degree of uncertainty. The results of our study are not a final ruling and we hope the jury is still out also for Stoop and colleagues in their appreciation for the potentials of TP-IAT.

Responses to Hypoxia: How Fructose Metabolism and Hypoxia-Inducible Factor-1a Pathways Converge in Health and Disease.

Oxygen is critical for the high output of energy (adenosine triphosphate) generated by oxidative phosphorylation in the mitochondria, and when oxygen delivery is impaired due to systemic hypoxia, impaired or reduced delivery of red blood cells, or from local ischemia, survival processes are activated. One major mechanism is the activation of hypoxia-inducible factors (HIFs) that act to reduce oxygen needs by blocking mitochondrial function and stimulating glucose uptake and glycolysis while also stimulating red blood cell production and local angiogenesis. Recently, endogenous fructose production with uric acid generation has also been shown to occur in hypoxic and ischemic tissues where it also appears to drive the same functions, and indeed, there is evidence that many of hypoxia-inducible factors effects may be mediated by the stimulation of fructose production and metabolism. Unfortunately, while being acutely protective, these same systems in overdrive lead to chronic inflammation and disease and may also be involved in the development of metabolic syndrome and related disease. The benefit of SGLT2 inhibitors may act in part by reducing the delivery of glucose with the stimulation of fructose formation, thereby allowing a conversion from the glycolytic metabolism to one involving mitochondrial metabolism. The use of hypoxia-inducible factor stabilizers is expected to aid the treatment of anemia but, in the long-term, could potentially lead to worsening cardiovascular and metabolic outcomes. We suggest more studies are needed on the use of these agents.

Effectiveness of multidisciplinary intervention for gestational diabetes mellitus.

To explore the effectiveness of multidisciplinary intervention for patients with gestational diabetes mellitus (GDM). A total of 126 patients diagnosed with GDM from January 2020 to December 2021 in our hospital were enrolled in this retrospective study. Patients were divided into the control group (conventional treatment) and the study group (adding multidisciplinary intervention). Glucose index, self-management ability, psychological status, and delivery outcomes were evaluated. Fasting plasma glucose (4.32 ± 0.81 mmol/L), glycosylated hemoglobin (5.47 ± 1.09%), and postprandial blood glucose (6.02 ± 1.47 mmol/L) after intervention in study group were significantly lower than those in control group (p < 0.05), as well as those before intervention (p < 0.05). The score of GDM knowledge (38.03 ± 2.76), self-management (38.93 ± 2.32), social support (17.84 ± 1.23), and belief (17.93 ± 1.09) were all significantly higher than those of control group (p < 0.05), as well as those before intervention (p < 0.05). Besides, anxiety (7.83 ± 1.59) and depression (10.29 ± 1.82) evaluation scores showed that emotional relief were significantly achieved after intervention in study group compared with control group (p < 0.05). Moreover, the incidence of postpartum hemorrhage, cesarean delivery, premature delivery, macrosomia, and neonatal hypoglycemia was also significantly improved after intervention in study group compared with control group (p < 0.05). Multidisciplinary intervention can effectively control blood glucose levels, adjust self-management behavior, relieve psychological disorder, reduce complications, and improve delivery outcomes of GDM patients.

Evaluation of the impact of high-volume online hemodiafiltration on glycemic status, hydration status, and body fat content in diabetic patients

Abstract Background: The increasing patients with diabetes undergoing hemodialysis (HD) have concerned about the issue of glucose delivery with substitution fluid. We evaluate the effects of online high-volume hemodiafiltration (OL-HDF) versus high flux HD (HF-HD) on the influence of glycemic status and body fat content in patients with type 2 diabetes mellitus (T2DM) receiving HD. Objectives: The influence glucose in substitution fluid on glycemic status and body fat content in patients with type 2 diabetes mellitus. Methods: This study evaluated 117 patients receiving HD for more than 3 months (17 patients with T2DM receiving high-volume OL-HDF and the other 100 patients receiving HF-HD). Initially, we performed a cross-sectional study and later examined two modalities of high-volume OL-HDF in a 9-month cross-over study. Overall glycemic control was estimated from the fasting blood glucose (FBG) and the hemoglobin A1c (HbA1c) levels. Body composition and nutritional status were assessed by bioimpedance spectroscopy. Results: FBG and HbA1c were not significantly different in both groups of patients after having followed for 12 weeks. No significant differences were found in overhydration status and body fat content between the two therapy modalities. The blood hemoglobin (Hb) level increased in the high-volume OL-HDF group compared with the HF-HD group. Additionally, no differences were observed in glycemic status, body mass index, or body fat mass between both high-volume pre- and post-dilutional OL-HDF. Conclusion: High-volume OL-HDF did not have an adverse impact on glycemic status, body mass index, and body fat content in patients with diabetes undergoing HD in our short-term study. A large-scale and long-term follow-up study is required to confirm these results.

Integration of enzyme-encapsulated mesoporous silica between nanohole array electrode and hydrogel film for flow-type electrochemical biosensor.

We herein propose a simple and sensitive electrochemical flow biosensor platform without an external flow device. The sensing unit comprises a platinum nanohole array electrode deposited on a nanoporous track-etched membrane (PtNH/NPM), a packed-layer of glucose oxidase-encapsulated mesoporous silica particles (GOD/MPS), and bovine serum albumin hydrogel film (BSA gel film). This sensing unit was fixed at the open window at the side of the plastic container with internal solution containing NaCl as osmotic reagent. When the sample glucose solution (0.10mL) was pipetted at the sensing unit, a portion of the sample solution (5 μL) was spontaneously transferred into the BSA gel film. The concentration gradient of NaCl between the internal solution and the BSA gel film induced osmotic flow of water toward the internal solution. This osmotic flow assisted delivery of glucose to the GOD/MPS and enzymatically generated H2O2 to the PtNH/NPM. The proposed sensor could be used repeatedly and produced a linear current response for glucose, with a limit of detection of 16μM. These sensor performances confirmed availability of the sensor design utilizing the osmotic flow.

Multifield Modeling and Simulation of Nutrient Transport in Mechanically Stressed Meniscus Tissue.

Insights into the transport mechanisms of nutrients are essential for understanding the pathophysiology of menisci. In the present work, we focus on the modeling and numerical simulation of the transport of glucose molecules in mechanically stressed meniscus tissue. Therefore, a multifield model based on the theory of porous media is created. Due to a biphasic approach, the major phases of the solid and the fluid are represented. The description of the transport processes of the uncharged nutrient molecules, such as convection and diffusion, is given by three coupled partial differential equations valid for large deformations. Numerical simulations are performed for everyday types of stress such as (I) lying, (II) two-legged stance, (III) one-legged stance, (IV) level walking, and (V) stair descending using the finite element method. The results show that diffusion is the dominant process. However, in parts of the meniscus, the delivery of glucose can be improved by convection due to mechanical loading. Based on these basic insights, the model can now be adapted to individual patient's meniscus geometries. The model can thus give insights into the suitability of loading scenarios for rehabilitation after meniscus damage.

Dynamic glucose uptake, storage, and release by human microvascular endothelial cells.

Endothelia determine blood-to-tissue solute delivery, yet glucose transit is poorly understood. To illuminate mechanisms, we tracked [3H]-2-deoxyglucose (2-DG) in human adipose-tissue microvascular endothelial cells. 2-DG uptake was largely facilitated by the glucose transporters GLUT1 and GLUT3. Once in the cytosol, >80% of 2-DG became phosphorylated and ∼20% incorporated into glycogen, suggesting that transported glucose is readily accessible to cytosolic enzymes. Interestingly, a fraction of intracellular 2-DG was released over time (15-20% over 30 min) with slower kinetics than for uptake, involving GLUT3. In contrast to intracellular 2-DG, the released 2-DG was largely unphosphorylated. Glucose release involved endoplasmic reticulum-resident translocases/phosphatases and was stimulated by adrenaline, consistent with participation of glycogenolysis and glucose dephosphorylation. Surprisingly, the fluorescent glucose derivative 2-NBD-glucose (2-NBDG) entered cells largely via fluid phase endocytosis and exited by recycling. 2-NBDG uptake was insensitive to GLUT1/GLUT3 inhibition, suggesting poor influx across membranes. 2-NBDG recycling, but not 2-DG efflux, was sensitive to N-ethyl maleimide. In sum, by utilizing radioactive and fluorescent glucose derivatives, we identified two parallel routes of entry: uptake into the cytosol through dedicated glucose transporters and endocytosis. This reveals the complex glucose handling by endothelial cells that may contribute to glucose delivery to tissues.

Carbohydrate Ingestion Attenuates Cognitive Dysfunction Following Long-Duration Passive Heat Stress In Humans

PURPOSE: To determine if electrolyte or carbohydrate supplementation would reduce cognitive dysfunction in humans following long-duration passive heat stress. METHODS: Fifteen subjects performed 2 visits of 120 minutes of passive heat stress wearing liquid perfused suits infused with 50 °C water. In random order, subjects consumed fluids supplemented with electrolytes (E) or electrolytes+carbohydrates (E + C). Pre- and post-heat stress, body mass (BM) and plasma osmolality (pOsm) were measured. Heat rate, blood pressure, Physiological Strain Index (PSI), core temperature (TC), plasma glucose, plasma lactate, respiration rate, end-tidal CO2, internal carotid artery (ICA) velocity, and ICA diameter were recorded every 15 minutes. Cognitive function was assessed via the Automated Neurophysiological Assessment Metric (simple vs. complex cognitive tasks) at 30 minutes and at 120 minutes. RESULTS: There were no significant differences between fluid conditions (E & E + C) for BM loss (0.33 ± 0.2 & 0.22 ± 0.2 kg), pOsm (Δ3.6 ± 8.0 & 5.9 ± 6.7 mmol/L), peak-PSI (6.2 ± 0.3 & 5.9 ± 0.3), peak TC (38.9 ± 0.1 & 38.9 ± 0.1 °C), and ICA diameter (0.42 ± 0.01 & 0.42 ± 0.01 cm). Plasma glucose was significantly higher in the E + C condition at 60, 75, 90, 105, & 120 minutes (P < 0.05). No significant differences were noted between the 2 fluid conditions for the simple cognitive tasks however, in both fluid conditions, cognitive function was impaired following the bout of passive heat stress. Interestingly, compared to the E condition, the E + C condition demonstrated improved performance on all complex cognitive tasks (P < 0.05). Furthermore, compared to the E condition, the E + C condition demonstrated a significant increase in ICA blood velocity, blood flow, and vascular conductance at 90, 105, and 120 minute time points (P < 0.05) and a significant decrease in mean arterial pressure and heart rate at 60, 75, 90, 105, and 120 minute time points (P < 0.05). CONCLUSIONS: These data are the first to suggest that exogenous glucose administration may have a protective effect on cognitive function during long-duration passive heat stress. Furthermore, this protection is associated with elevated global cerebral blood flow and glucose delivery to the brain.