Maximum Glucose Research Articles

The Association Between Glycemic Variability and Mortality in Critically Ill Patients: A Multicenter Prospective Observational Study.

Background: Glycemic variability (GV) is a prevalent and significant condition observed in critically ill patients. This study aimed to investigate the relationship between early glycemic variability parameters and 28-day mortality in critically ill patients. Methods: A multicenter, prospective, and observational study was performed at five tertiary intensive care units (ICUs) in Turkey. All patients who had more than six blood glucose level (BGL) measures per 24 h were included. The parameters of GV including the SD, MGL, MGD (the difference between the maximal and minimal glucose level), and the CV (the percentage of SD to the MGL) in the first 24 h were recorded. Results: A total of 578 eligible patients were enrolled in the study, of whom 43.6% were women. The mean age of the patients was 68.09 ± 16.62 years. Overall mortality was 31.5% (n = 182). The glycemic parameters of the CV, SD, and MGD were significantly higher in the non-survivor group than in the survivor group (p = 0.040, 0.006, and 0.002, respectively). The multivariate logistic regression analysis revealed that the CV (OR 1.023; 95% CI 1.004-1.042; p = 0.017) was an independent factor that increased mortality. Spearman's rho correlation analysis revealed a strong (r:0.871) and statistically significant correlation (p < 0.001) between the CV and MGD. Conclusions: The CV calculated within the first 24 h of ICU admission is independently associated with 28-day mortality. The MGD is correlated with the CV and is maybe a practical tool to predict increased risk of mortality at the bedside. However, further studies are needed to establish the independent association of the MGD with mortality.

DESIGN, SYNTHESIS, AND BIO PROFILING OF 2, 3-DIHYDROQUINAZOLIN-4(1H)-ONE DERIVATIVE AS TYPE II DIABETES AGENTS: A COMPREHENSIVE IN SILICO, IN VITRO, AND IN VIVO STUDY

Objective: Diabetes mellitus is a significant global health challenge, with Type 2 Diabetes Mellitus (T2DM) being a leading cause of mortality worldwide, demanding the need for effective interventions by developing innovative therapeutic strategies or novel antidiabetic agents. This study explores in silico, in vitro, and in vivo approaches to identify the most potent 2,3-Dihydroquinazolin-4(1H)-One derivative molecule with antidiabetic activity. Methods: Eleven new derivatives were designed, studied in silico to identify the most promising compounds, synthesized, studied spectrally to describe them, and evaluated for both in vitro and in vivo investigations. Alpha amylase and alpha-glucosidase inhibitory activities were investigated in vitro. The endogenous suppression of glucose synthesis in Hepatoblastoma cell line 2(HepG2) cells and the in vitro glucose absorption assay on cultivated L6 cell lines were conducted. To assess the ability of the newly synthesized compounds to prevent diabetes, in vivo investigations were conducted on Streptozotocin (STZ)-induced diabetic rats and the effects on various biochemical parameters were identified.Results: Leveraging computational methods, the QZ9 molecule was identified with stable interactions with key biomolecules associated with T2DM. Subsequent in vitro assays confirmed the inhibitory effects of QZ2, QZ8, and QZ9 on alpha-amylase and alpha-glucosidase activities, suggesting their potential as enzyme inhibitors. Additionally, QZ8 and QZ9 demonstrated enhanced glucose uptake and production inhibition in HepG2 cells, indicating their role in improving glucose homeostasis. In vitro, the top-ranked molecules QZ2, QZ8, and QZ9 were analyzed to validate the in silico findings and assess their potential as therapeutic agents for T2DM. The inhibition of α-amylase activity by QZ2, QZ8, and QZ9 was dose-dependent, with maximum inhibition observed at 1000 µg/ml: 57.33% for QZ2, 52.21% for QZ8, and 87.16% for QZ9. Similarly, α-glucosidase inhibition at 1000 µg/ml was 59.96% for QZ2, 53.50% for QZ8, and 81.51% for QZ9. Both QZ8 and QZ9 significantly increased glucose uptake and inhibited glucose production in HepG2 cells, with maximum glucose production inhibition at 100 µg/ml: 62.22% for QZ8 and 62.35% for QZ9. These findings suggest that QZ8 and QZ9 contribute to glucose homeostasis. QZ9 demonstrated superior enzyme inhibition compared to QZ2 and QZ8, with α-amylase and α-glucosidase inhibition up to 87.16% and 81.51%, respectively, at 1000 µg/ml. In vivo investigations in Diabetic rat models further confirmed the efficacy of these compounds by showing significant reductions in blood glucose levels. These results suggests the potentiality of QZ9 as a promising novel Antidiabetic agent.Conclusion: Combining computational predictions with experimental validations, this integrated approach highlights the promise of 2,3-Dihydroquinazolin-4(1H)-One derivative QZ9 as a novel antidiabetic agent, warranting further investigation for clinical translation.

Comparison of a customized glycemic pellets challenge with the oral sugar test to measure glycemic and insulinemic responses in horses.

Testing for insulin dysregulation (ID) in horses is commonly performed to guide management and therapeutic strategies. To evaluate a newly developed glycemic pellets challenge (GPC) and compare results to those obtained using the low-dose oral sugar test (OST). Twenty-four adult horses with unknown insulin status. A randomized crossover trial was performed. Horses underwent GPC (0.5 g glycemic carbohydrates/kg body weight) and OST (0.15 mL corn syrup/kg body weight) 7 days apart. Feed was withheld before testing and blood samples were collected at T0, T60, T120, and T180 minutes for GPC and at T0, T60, and T90 minutes for OST. Blood glucose concentration was measured using a point-of-care glucometer and insulin by radioimmunoassay. Comparisons were made using nonparametric tests, linear regression, and Bland-Altman agreement analysis. Eighteen horses consumed >85% of the GPC pellets within 10 minutes and had acceptable OST results. Maximum glucose (P = .02) and insulin (P = .007) concentrations were significantly higher for GPC compared with OST. Time to maximum insulin concentration (Tmax[ins]) varied within and between tests and neither Tmax[ins] (P = .28) nor maximum insulin concentration (P = .46) was correlated with the time horses took to consume pellets. The GPC is well tolerated and may offer another diagnostic testing modality for ID. Blood glucose and insulin concentrations increase during GPC and reach higher concentrations than observed with low-dose OST. The Tmax[ins] varied for GPC and OST, emphasizing the importance of identifying the optimal time range for the collection of samples to capture diagnostically relevant changes in insulin concentration.

Enhanced bioethanol production from cassava waste: optimization of thermochemical pretreatment for maximum sugar recovery and characterisation of potential fractions

ABSTRACT Thermochemical pretreatment is an interesting approach for the effective separation of lignocellulosic biomass before fermentation for bioethanol production. This research focused on optimising the thermochemical pretreatment conditions of cassava waste using response surface methodology to predict the glucose yields under the optimal condition. The optimised conditions of 0.045 M of NaOH concentration at 153.59 °C for 48.03 min resulted in the maximum glucose yield of 93.87%. In addition, fermentation process can generate ethanol within a range of solid loading from 10% to 20%. The highest concentration of ethanol was 34.53 ± 0.56 g/L after 72 h, equivalent to ethanol yield of 0.46 g/g. The co-products were also characterised for further utilisation in biorefinery concept. The results of this study confirmed that the thermochemical pretreatment process using the NaOH catalyst could provide high glucose yields, which can be easily converted into bio-based fuels and further valorised of co-products to value-added chemicals.

12596 Characterizing Glycemic Variability In Novel Subphenotypes Of Individuals At Elevated Risk For Type 2 Diabetes Using Continuous Glucose Monitoring

Abstract Disclosure: A.J. Kretowski: None. P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. M. Klak: None. A. Golonko: None. A. Szklaruk: None. L. Szczerbinski: None. Background: The heterogeneity among individuals at elevated risk for Type 2 Diabetes (T2D) recently has led to the identification of six subphenotypes, each with distinct risks for developing T2D, its complications, and mortality. Our study leveraged Continuous Glucose Monitoring (CGM) to offer a detailed characterization of these subphenotypes, aiming to uncover differences in glycemic variability and control. Methods: CGM data from 616 individuals without diabetes, from the Polish Registry of Diabetes (PolReD) study, classified into six clusters, were analyzed. The PolReD used Freestyle Libre 2 (Abbott) as the CGM device. CGM-derived measures of glucose control and glucose variability were calculated using the iglu R package. We utilized Analysis of Variance (ANOVA) and Analysis of Covariance (ANCOVA), adjusting for age and sex, to identify significant differences in CGM parameters across the clusters. Results: Our analysis identified significant differences in several CGM-derived parameters among the clusters, notably in the Glycemic Risk Assessment Diabetes Equation (GRADE), Standard Deviation of weekly glucose values (SDw), Mean Amplitude of Glycemic Excursions (MAGE), Maximum glucose value, Glucose range, and Mean Absolute Glucose (MAG). Clusters 3 and 5, characterized by beta-cell dysfunction and high insulin resistance respectively, and associated with the highest risk of T2D, exhibited the greatest glucose variability, with elevated risk for glycemic excursions. In contrast, Cluster 4, indicative of a metabolically healthy obesity profile with a low risk of T2D, demonstrated the most stable glycemic control and the lowest variability among the clusters. Conclusions: This study shows that subtypes of patients at elevated risk for T2D exhibit distinct patterns in CGM-derived parameters, indicating variations in glucose control and stability that extend beyond traditional fasting and post-challenge glucose assessments. Notably, we found that subtypes facing the highest T2D risk display increased glycemic variability, despite their differing underlying mechanisms of dysglycemia. These findings highlight the utility of CGM as a tool for identifying individuals at an increased risk of T2D, reducing the need for extensive phenotyping typically required for cluster assignment. Presentation: 6/1/2024

Effect of Single Low-Dose Dexamethasone on Peri-operative Blood Glucose Levels

Background: Post-operative nausea and vomiting (PONV) is the second most common complaint reported after surgery with an incidence of 30%-80%. PONV is associated with numerous morbidities, hence prevention is beneficial. Dexamethasone is used as a prophylactic anti-emetic agent, however, being a corticosteroid, it could cause hyperglycaemia which is associated with a number of other adverse effects. Objectives: To study the effect of a single low-dose intravenous dexamethasone given as a prophylactic anti-emetic agent on perioperative blood glucose levels. Methods: Eighty-eight women who had elective myomectomy or hysterectomy under combined spinal-epidural (CSE) anaesthesia were randomised into two groups of 44 each. Following baseline blood glucose estimation, one group had 4 mg (1 ml) of intravenous dexamethasone 1-2 seconds after blood glucose check while the control group had 1 ml of normal saline. Blood glucose was measured every hour intra-operatively and two-hourly post-operatively till 12 hours after drug administration. Nausea, vomiting, dyspepsia, pain, motor block duration and urinary output were assessed hourly. Results: The mean maximum change in blood glucose from baseline in the dexamethasone group was statistically significantly higher than in the control group, 51.00±26.57 mg/dl vs. 35.80±25.71 mg/dl (p = 0.007) so also was the mean maximum blood glucose, 153.93±31.63 mg/dl vs. 139.52±28.95 mg/dl (p = 0.028) respectively. Conclusion: Intravenous dexamethasone at a single, low-dose (4 mg) used as a prophylaxis for nausea and vomiting is associated with significant increase in blood glucose concentration.

Yeast based biorefinery for xylitol and ethanol production from sugarcane bagasse

Lignocellulosic biomass is one of the biggest renewable reservoirs for organic carbon that can be exploited as feed for various value-added products like fuel, nutraceuticals enzymes, and proteins. Biofuel is not only valuable but also a top priority target to address the energy crisis. Hence the current work was planned to valorize the cellulose-rich residual biomass (CRB), left after xylitol production for ethanol fermentation by yeast. Xylose-rich hydrolysate was prepared with dilute acid pretreatment (0.1 M H2SO4, 145 ℃, and 90 min) for xylitol production and CRB was further processed for enzymatic hydrolysis (crude cellulase). Acid hydrolysis offered maximum reducing sugars of 0.33±0.01 g⋅g−1biomass comprised of xylose 0.31±0.01 g⋅g−1biomass. Besides sugar, biomass hydrolysis also produced 0.21 ±0.01 g.L−1 furans and 0.34±0.11 g.L−1 acetic acid. Pichia guilliermondii RLV-04 (MH588234.1) have shown 0.90±0.02 gxylitol.g−1xylose conversion of xylose to xylitol. The primary process has left more than 50–55 % biomass that was rich in cellulose. Enzymatic hydrolysis of the CRB using crude cellulase showed maximum glucose recovery of 0.56±0.02 g⋅g−1available cellulose at 15 FPU at 50 ℃, after 12 h. In addition, yeast biomass recovered from xylitol production was hydrolysed and used as a nitrogen source. Under an anaerobic environment, a maximum ethanol yield of 0.36±0.01 g.g−1glucose was achieved with commercial baker’s yeast while the addition of yeast biomass hydrolysate improved the alcohol yield to 0.48±0.02 g.g−1glucose. Reutilization of biocatalysts as nitrogen source not only upgraded fermentation processes but also lowered process waste and improved process economics.

Impact of Intraoperative Dexamethasone on Perioperative Blood Glucose Levels: Systematic Review and Meta-Analysis of Randomized Trials.

Dexamethasone is associated with increased blood glucose levels that could impact patient outcomes or management. This study aimed to synthesize the available evidence regarding the impact of an intraoperative single dose of dexamethasone on blood glucose levels. We searched CENTRAL, MEDLINE, and clinicaltrials.gov for randomized controlled trials (RCTs) comparing a single intraoperative dose of dexamethasone to control in adult patients who underwent noncardiac surgery. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the review was registered in PROSPERO (CRD42023420562). Data were pooled using a random-effects model. We reported pooled dichotomous data using odds ratios (OR) and continuous data using the mean difference (MD), reporting 95% confidence intervals (95% CIs), and corresponding P-values for both. Confidence in the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. As primary outcomes we assessed maximum blood glucose levels measurement and variation from baseline within 24 hours of surgery; blood glucose levels measurement and variation from baseline at 2, 4, 8, 12, and 24 hours after dexamethasone administration. As secondary outcomes, we evaluated insulin requirements and hyperglycemic events. We included 23 RCTs, enrolling 11,154 participants overall. Dexamethasone was associated with a significant increment in blood glucose levels compared to control at all timepoints. The results showed an increase compared to control of 0.37 mmol L-1 (6.7 mg dL-1) at 2 hours (95% CI, 0.16-0.58 mmol L-1 or 2.9-10.5 mg dL-1), 0.97 mmol L-1 (17.5 mg dL-1) at 4 hours (95% CI, 0.67-1.25 mmol L-1 or 12.1-22.5 mg dL-1), 0.96 mmol L-1 (17.3 mg dL-1) at 8 hours (95% CI, 0.55-1.36 mmol L-1 or 9.9-24.5 mg dL-1), 0.90 mmol L-1 (16.2 mg dL-1) at 12 hours (95% CI, 0.62-1.19 mmol L-1 or 11.2-21.4 mg dL-1) and 0.59 mmol L-1 (10.6 mg dL-1) at 24 hours (95% CI, 0.22-0.96 mmol L-1 or 4.0-17.3 mg dL-1). No difference was found between subgroups regarding diabetic status (patients with diabetes versus patients without diabetes) in all the outcomes except 2 (maximum blood glucose levels variation within 24 hours and variation at 4 hours) and dexamethasone dose (4-5 mg vs 8-10 mg) in all the outcomes except 2 (blood glucose levels at 24 hours and hyperglycemic events). Mean blood glucose levels rise between 0.37 and 1.63 mmol L-1 (6.7 and 29.4 mg dL-1) within 24 hours after a single dose of dexamethasone administered at induction of anesthesia compared to control, but in most patients this difference will not be clinically relevant.

Twenty-Four Hour Glucose Profiles and Glycemic Variability during Intermittent Religious Dry Fasting and Time-Restricted Eating in Subjects without Diabetes: A Preliminary Study.

Intermittent religious fasting increases the risk of hypo- and hyperglycemia in individuals with diabetes, but its impact on those without diabetes has been poorly investigated. The aim of this preliminary study was to examine the effects of religious Bahá'í fasting (BF) on glycemic control and variability and compare these effects with time-restricted eating (TRE). In a three-arm randomized controlled trial, 16 subjects without diabetes were assigned to a BF, TRE, or control group. Continuous glucose monitoring and food intake documentation were conducted before and during the 19 days of the intervention, and the 24 h mean glucose and glycemic variability indices were assessed. The BF and TRE groups, but not the control group, markedly reduced the daily eating window while maintaining macronutrient composition. Only the BF group decreased caloric intake (-677.8 ± 357.6 kcal, p = 0.013), body weight (-1.92 ± 0.95 kg, p = 0.011), and BMI (-0.65 ± 0.28 kg, p = 0.006). Higher maximum glucose values were observed during BF in the within-group (+1.41 ± 1.04, p = 0.039) and between-group comparisons (BF vs. control: p = 0.010; TRE vs. BF: p = 0.022). However, there were no alterations of the 24 h mean glucose, intra- and inter-day glycemic variability indices in any group. The proportions of time above and below the range (70-180 mg/dL) remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes.

Cascading Recovery of Added-Value Cocoa Bean Shell Fractions Through Autohydrolysis Treatments

AbstractIn this work, an autohydrolysis treatment was applied to cocoa bean shells (CBS) to obtain different potentially added-value fractions rich in phenolic compounds with antioxidant potential and oligosaccharides with potential prebiotic properties. The final residue was enzymatically treated to deliver sugars that can undergo fermentation-based biotransformation. This hydrothermal pretreatment was assessed for maximum temperatures (Tmax) between 120 to 200 °C and severities (S0) between 1.1 and 3.4. The highest oligosaccharide concentration (5.5 g/L) was achieved at S0 of 3.4. The increase of S0 during the process allowed to increase the recovery of interesting bioactive compounds, achieving a maximum TPC and antioxidant activity of 2.8 g/L and 17178.5 µmol Fe2+/L, respectively, when the Tmax reached 200 °C. However, at this temperature, a significant amount of degradation products such as organic acids and HMF was already formed, and a compromise temperature of 160 °C was chosen for further tests. It was possible to obtain a maximum glucose yield of 71% when the pretreated solids were enzymatically hydrolysed. Hence, the use of autohydrolysis, avoiding the use of toxic chemicals, has proved to be a sustainable alternative to obtain different CBS fractions with interesting composition to be potentially employed in multiple sectors.

Co-production of high-concentration fermentable sugar and lignin-based bio-adhesive from corncob residue via an enhanced enzymatic hydrolysis

Xylose plants (produce xylose from corncob through dilute acid treatment) generate a large amount of corncob residue (CCR), most of which are burned and lacked of valorization. Herein, to address this issue, CCR was directly used as starting material for high-solid loading enzymatic hydrolysis via a simple strategy by combining PFI homogenization (for sufficient mixing) with batch-feeding. A maximum glucose concentration of 187.1 g/L was achieved after the saccharification with a solid loading of 25 wt% and enzyme dosage of 10 FPU/g-CCR. Furthermore, the residue of enzymatic hydrolysis (REH) was directly used as a bio-adhesive for plywood production with both high dry (1.7 MPa) and wet (1.1 MPa) surface bonding strength (higher than the standard (0.7 MPa)), and the excellent adhesion was due to the interfacial crosslinking between the REH adhesive (containing lignin, free glucose, and nanosized fibers) and cell wall of woods. Compared with traditional reported adhesives, the REH bio-adhesive has advantages of formaldehyde-free, good moisture resistance, green process, relatively low cost and easy realization. This study presents a simple and effective strategy for better utilization of CCR, which also provides beneficial reference for the valorization of other kinds of lignocellulosic biomass.

High-sensitive glucose sensor based on tilted fiber Bragg gratings

In this paper, we proposed a high-sensitive glucose sensor using the tilted fiber Bragg gratings (TFBGs). The TFBGs with different tilt angle has been fabricated by phase mask scanning method with an argon ion double-frequency 244 nm laser. As tilt angle increases, the bandwidth of the cladding mode excited by TFBGs gradually expands and cladding mode region shifts towards shorter wavelengths. The higher-order cladding modes appeared at the shorter wavelength side demonstrate a larger separation in the spectrum. TFBGs with different tilt angles for glucose concentration measurement have been investigated experimentally. When the concentration of glucose solution increases, the surrounding refractive index changing make the cut-off mode resonance shift to a longer wavelength. In addition, the tilt angle of TFBGs does affect the glucose sensitivity, that the larger tilt angle is, the higher sensitivity could achieve. In this work, a maximum glucose sensitivity of 80.91 pm/(mg/ml) could be obtained for TFBGs with tilt angle of 10°. The proposed TFBGs with superiorities of high glucose sensitivity and wider detection range, makes it potential for glucose detection in the field of chemical and biomedical sensing.

Nutritional Prescription in ICU Patients: Does it Matter?

The nutritional status of the patients before critical illness and nutrition support given during the critical illness play an important role in the recovery. We aimed to evaluate the nutritional prescription and its effect on ICU mortality. This was a prospective observational study conducted after institutional ethical committee approval (IEC 94/2018, CTRI/2018/06/014625) in a case-mixed (medical and surgical) ICU. Patients admitted to the ICU were enrolled within 24 hours of admission. The amount of calories and proteins prescribed and received by the patients was collected for 7 days. The primary outcome was ICU mortality. A total of 100 patients were included. The mean age was 48.63 (16.25) years, and 62% were males. The acute physiology and chronic health evaluation (APACHE II), sequential organ failure assessment (SOFA), and modified Nutric (mNUTRIC) scores were comparable between the two groups. The ICU mortality was 30%. The calorie and protein deficits were comparable between survivors and non-survivors. Among the secondary outcomes, a significant time effect (p = 0.013) and interaction effect (p = 0.004) were noted for maximum glucose levels. The glucose variability calculated by coefficient of variation (CV) was significantly higher in non-survivors than survivors (p = 0.031). The calorie and protein deficits did not affect ICU mortality. The maximum glucose variability and CV were significant parameters associated with ICU mortality. Havaldar AA, Selvam S. Nutritional Prescription in ICU Patients: Does it Matter? Indian J Crit Care Med 2024;28(7):657-661.

Co-production of fermentable sugars and highly active lignin from eucalyptus via a mild preprocessing with diethylene glycol and chromic chloride

Eucalyptus was pretreated with diethylene glycol catalyzed by 0.02 mol/L CrCl3 for 10 min, resulting in 91 % delignification and 98 % cellulose recovery, with trace fermentation inhibitors generated. After the mild pretreatment, the accessibility and affinity of cellulase to eucalyptus was enhanced, especially since enzyme adsorption rate increased by 1.6-fold. Therefore, glucose yield of pretreated eucalyptus was 7.9-fold higher than that of untreated eucalyptus after hydrolyzed 48 h, in which the maximum glucose concentration reached 62 g/L from eucalyptus by adding Tween 80. According to the characterization analysis, the structure of the eucalyptus lignin-carbohydrate complexes structure was destroyed during the pretreatment, while lignin fragments was likely reacted with diethylene glycol to form the stabilized aromatic ethers. Moreover, the extracted Deg-lignin exhibited better performances than commercial alkali lignin such as higher fluorescence intensity, less negative surface charge, and lower particle size. The mild pretreatment method with diethylene glycol and CrCl3 provided a promising approach for co-production of fermentable sugars and high activity lignin from lignocellulosic biomass.

Personalized glycemic management for patients with diabetic ketoacidosis based on machine learning

To explore the optimal blood glucose-lowering strategies for patients with diabetic ketoacidosis (DKA) to enhance personalized treatment effects using machine learning techniques based on the United States Critical Care Medical Information Mart for Intensive Care- IV (MIMIC- IV). Utilizing the MIMIC- IV database, the case data of 2 096 patients with DKA admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center from 2008 to 2019 were analyzed. Machine learning models were developed, and receiver operator characteristic curve (ROC curve) and precision-recall curve (PR curve) were plotted to evaluate the model's effectiveness in predicting four common adverse outcomes: hypoglycemia, hypokalemia, reductions in Glasgow coma scale (GCS), and extended hospital stays. The risk of adverse outcomes was analyzed in relation to the rate of blood glucose decrease. Univariate and multivariate Logistic regression analyses were conducted to examine the relationship between relevant factors and the risk of hypokalemia. Personalized risk interpretation methods and predictive technologies were applied to individualize the analysis of optimal glucose control ranges for patients. The machine learning models demonstrated excellent performance in predicting adverse outcomes in patients with DKA, with areas under the ROC curve (AUROC) and 95% confidence interval (95%CI) for predicting hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stays being 0.826 (0.803-0.849), 0.850 (0.828-0.870), 0.925 (0.903-0.946), and 0.901 (0.883-0.920), respectively. Analysis of the relationship between the rate of blood glucose reduction and the risk of four adverse outcomes showed that a maximum glucose reduction rate > 6.26 mmol×L-1×h-1 significantly increased the risk of hypoglycemia (P < 0.001); a rate > 2.72 mmol×L-1×h-1 significantly elevated the risk of hypokalemia (P < 0.001); a rate > 5.53 mmol×L-1×h-1 significantly reduced the risk of GCS score reduction (P < 0.001); and a rate > 8.03 mmol×L-1×h-1 significantly shortened the length of hospital stay (P < 0.001). Multivariate Logistic regression analysis indicated significant correlations between maximum bicarbonate levels, blood urea nitrogen levels, and total insulin doses with the risk of hypokalemia (all P < 0.01). In terms of establishing personalized optimal treatment thresholds, assuming optimal glucose reduction thresholds for hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stay were x1, x2, x3, x4, respectively, the recommended glucose reduction rates to minimize the risks of hypokalemia and hypoglycemia should be ≤min{x1, x2}, while those to reduce GCS score decline and extended hospital stay should be ≥ max{x3, x4}. When these ranges overlap, i.e., max{x3, x4} ≤ min{x1, x2}, this interval was the recommended optimal glucose reduction range. If there was no overlap between these ranges, i.e., max{x3, x4} > min{x1, x2}, the treatment strategy should be dynamically adjusted considering individual differences in the risk of various adverse outcomes. The machine learning models shows good performance in predicting adverse outcomes in patients with DKA, assisting in personalized blood glucose management and holding important clinical application prospects.

Extended-Release Versus Immediate-Release Triamcinolone Acetonide in Patients Who Have Knee Osteoarthritis and Type 2 Diabetes Mellitus

BackgroundIntra-articular corticosteroid injections may cause hyperglycemia (glucose level >180 mg/dL). In a phase 2 study of 33 patients who had osteoarthritis of the knee and type 2 diabetes mellitus, triamcinolone acetonide extended-release (TA-ER) was associated with minimal glycemic control disruption compared with triamcinolone acetonide immediate-release (TA-IR). This post hoc analysis characterizes the clinical relevance of these results. MethodsPatients who had symptomatic osteoarthritis of the knee for ≥6 months, type 2 diabetes mellitus for ≥1 year, and hemoglobin A1c ≥6.5 and ≤9.0% were randomized to receive an intra-articular injection of either TA-ER or TA-IR. Changes in continuous glucose monitor daily glucose level, percentage of time in or above the target glucose range (>70 to 180 mg/dL), time to glucose level 250 mg/dL and maximum glucose level >250 mg/dL, and glycemic variability were evaluated. ResultsAcross postinjection days 1 to 3, the TA-ER group (n = 18) had a lower median change from baseline in maximum glucose level (92.3 versus 169.1 mg/dL), a reduced percentage of time with a glucose level >250 mg/dL (12 versus 26%), a smaller proportion of patients who had a maximum glucose level >250 mg/dL (50 versus 93%), and a greater percentage of time in the target glucose range (62 versus 48%) versus the TA-IR group (n = 15). There was less glycemic variability and lower glucose spikes in the TA-ER versus TA-IR group. Median times to glucose level 250 mg/dL (44 versus 6 hours) and maximum glucose level (34 versus 13 hours) were significantly longer in the TA-ER versus TA-IR group. ConclusionsUse of TA-ER was associated with a clinically meaningful reduction in hyperglycemia versus TA-IR.

Epoxygenase Cyp2c44 Regulates Hepatic Lipid Metabolism and Insulin Signaling by Controlling FATP2 Localization and Activation of the DAG/PKCδ Axis.

Cytochrome P450 epoxygenase Cyp2c44, a murine epoxyeicosatrienoic acid (EET) producing enzyme, promotes insulin sensitivity and Cyp2c44(-/-) mice show hepatic insulin resistance. Because insulin resistance leads to hepatic lipid accumulation and hyperlipidemia, we hypothesized that Cyp2c44 regulates hepatic lipid metabolism. Standard chow diet (SD) fed male Cyp2c44(-/-) mice had significantly decreased EET levels and increased hepatic and plasma lipid levels compared to wild-type mice. We showed increased hepatic plasma membrane localization of the FA transporter 2 (FATP2) and total unsaturated fatty acids and diacylglycerol levels. Cyp2c44(-/-) mice had impaired glucose tolerance and increased hepatic plasma membraneassociated PKCδ and phosphorylated IRS-1, two negative regulators of insulin signaling. Surprisingly, SD and high fat diet fed (HFD) Cyp2c44(-/-) mice had similar glucose tolerance and hepatic plasma membrane PKCδ levels, suggesting that SD-fed Cyp2c44(-/-) mice have reached their maximal glucose intolerance. Inhibition of PKCδ resulted in decreased IRS-1 serine phosphorylation and improved insulin-mediated signaling in Cyp2c44(-/-) hepatocytes. Finally, Cyp2c44(-/-) HFD-fed mice treated with the analog EET-A showed decreased hepatic plasma membrane FATP2 and PCKDδ levels with improved glucose tolerance and insulin signaling. In conclusion, loss of Cyp2c44 with concomitant decreased EET levels leads to increased hepatic FATP2 plasma membrane localization, diacylglycerol accumulation, and PKCδ-mediated attenuation of insulin signaling. Thus, Cyp2c44 acts as a regulator of lipid metabolism by linking it to insulin signaling.

Chronic UCN2 Administration Alters Muscle Mass, Exercise Metabolism, and Exercise Capacity in Lean Mice

Urocortin 2 (UCN2) is a member of the corticotropin-releasing hormone (CRH) family and an agonist of the G protein-coupled receptor CRH receptor type 2 (CRHR2), which is highly expressed in skeletal muscle but absent from liver in both rodents and humans. UCN2 overexpression or chronic administration increases muscle mass in both lean and diet-induced obese (DIO) mice and is also believed to increase peripheral insulin sensitivity, reminiscent of the effect of acute exercise. However, how these effects of UCN2 may impact muscle function and exercise capacity remain incompletely understood. We hypothesized that treatment with a long term UCN2 treatment would increase lean and muscle mass and improve aerobic exercise capacity in lean, healthy mice. Lean 10-week-old male C57Bl/6J mice completed treadmill acclimatization and an incremental running test to exhaustion to determine maximal running distance and peak oxygen consumption (VO2). Mice were assigned to sedentary or maximal running groups and were treated with UCN2 for 18 days. After the final dose, body composition was assessed by qNMR. Vehicle- and UCN2-treated mice assigned to the maximal running group completed a second maximal test, and immediately upon completion of exercise, blood glucose was measured, and tissues were collected. Blood glucose and tissues were collected from sedentary vehicle- and UCN2-treated mice in the fed state. UCN2 treatment increased food intake, qNMR lean mass, and individual muscle weights. UCN2-treated mice had reduced maximal running distance, peak VO2, and blood glucose in response to exercise compared to vehicle mice. In addition, UCN2-treated mice had reduced hepatic glycogen in both the sedentary and post maximal exercise states. Gastrocnemius muscle from sedentary UCN2-treated mice had increased glycogen content and reduced phosphorylation of glycogen synthase. Following maximal exercise, UCN2-treated mice had higher gastrocnemius glycogen compared to vehicle mice. This indicated similar total glycogen utilization between treatment groups in response to maximal exercise, despite UCN2-treated mice performing less work. Follow-up studies in sedentary mice demonstrated UCN2 dosing increased phosphorylation of proteins involved in insulin-dependent and -independent glucose uptake in gastrocnemius muscle. These findings indicate that UCN2 affects whole-body and muscle substrate utilization and glucose regulation and signaling which results in increased muscle mass and altered exercise capacity. However, the unpredictability of the effects of UCN2 agonism on these parameters requires much further study. This research was funded by Eli Lilly and Company. This is the full abstract presented at the American Physiology Summit 2024 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.

Vietnam National Survey on Parenteral Nutrition Practice in Preterm Neonates: Practice Status, Barriers, and Implications.

Due to high risks of feeding intolerance, preterm infants often receive parenteral nutrition (PN) to ensure sufficient nutrition and energy intake. However, there is a lack of data on the status of clinical PN practice and barriers among neonatal care units in low- to middle-income countries like Vietnam. This extensive survey explores the status and barriers of PN practice for preterm infants in neonatal units across Vietnam and identifies the practical implications of enhancing nutritional outcomes in preterm infants. A multicenter nationwide web-based survey on PN practice in preterm infants was conducted across 114 neonatal units from 61 provinces in Vietnam. Among 114 neonatal units receiving a request for surveys, 104 units (91.2%) from 55 provinces participated. Neonatal units were categorized as level I (2/104, 1.9%), II (39/104, 37.5%), III (56/104, 53.8%), and IV (7/104, 6.8%). We found that the initiations of PN within the first hour and the first two hours of life occurred in 80.8% (84/104) and 95.2% (99/104) of the units, respectively. The early provision of amino acids, or AA (within the first day of life) and lipids (within two days of life) were documented by 85% (89/104) and 82% (84/104) of the respondents, respectively. The initial dose of AA ranged from 0.5 to 3 g/kg/day; the dose of AA less than 1 g/kg/day was reported by 7.7% (8/104) of the respondents; the maximum dose of AA ranged from 2 to over 4.5 g/kg/day, with 4 g/kg/day reported by 47.1% (49/104) of the respondents. The initial dose of lipids was between 0.5 and 2 g/kg/day, frequently 1 g/kg/day, reported by 51.9% (54/104) of the respondents; the target lipid dose ranged from 3 to 4 g/kg/day in 93.3% (97/104) respondents; the maximum target dose for lipid was 4 g/kg/day in 36.5% (38/104) of the respondents. The initial glucose dose was distributed as follows: 46.2% of respondents (48/104) administered 4 mg/kg/minute, 21.2% (22/104) used 5 mg/kg/minute, 28.8% (30/104) used 6 mg/kg/minute, and 3.8% (4/104) used 3 mg/kg/minute. Additionally, 48.1% of respondents (50/104) reported a maximum glucose infusion rate above 13 mg/kg/min and 19.2% (20/104) above 15 mg/kg/min. Nineteen percent (20/104) of the respondents reported a lack of micronutrients. Barriers to PN initiation included difficulty in establishing intravenous lines, the absence of standardized protocols, the lack of lipids and micronutrients, infections, and unavailable software supporting neonatologists in calculating nutrition paradigms. This study's findings highlight the highly variable PN practice across neonatal units in Vietnam. Deviations from current practical guidelines can be explained by various barriers, most of which are modifiable. A monitoring network for nutritional practice status and a database to track the nutritional outcomes of preterm infants in Vietnam are needed.

Association of Relative Dysglycemia With Hospital Mortality in Critically Ill Patients: A Retrospective Study.

Relative dysglycemia has been proposed as a clinical entity among critically ill patients in the ICU, but is not well studied. This study aimed to clarify associations of relative hyperglycemia and hypoglycemia during the first 24 hours after ICU admission with in-hospital mortality and the respective thresholds. A single-center retrospective study. An urban tertiary hospital ICU. Adult critically ill patients admitted urgently between January 2016 and March 2022. None. Maximum and minimum glycemic ratio (GR) was defined as maximum and minimum blood glucose values during the first 24 hours after ICU admission divided by hemoglobin A1c-derived average glucose, respectively. Of 1700 patients included, in-hospital mortality was 16.9%. Nonsurvivors had a higher maximum GR, with no significant difference in minimum GR. Maximum GR during the first 24 hours after ICU admission showed a J-shaped association with in-hospital mortality, and a mortality trough at a maximum GR of approximately 1.12; threshold for increased adjusted odds ratio for mortality was 1.25. Minimum GR during the first 24 hours after ICU admission showed a U-shaped relationship with in-hospital mortality and a mortality trough at a minimum GR of approximately 0.81 with a lower threshold for increased adjusted odds ratio for mortality at 0.69. Mortality significantly increased when GR during the first 24 hours after ICU admission deviated from between 0.69 and 1.25. Further evaluation will necessarily validate the superiority of personalized glycemic management over conventional management.