Maintain Blood Glucose Concentrations Research Articles

Optimizing blood glucose regulation in type 1 diabetes: A fractional order controller approach

This study presents the design and implementation of a Fractional Order Proportional, Integral, and Derivative (FOPID) controller intended for the regulation of blood glucose levels in individuals with type 1 diabetes mellitus (T1DM). The efficacy of this controller is evaluated through its application to a nonlinear Stolwijk–Hardy model simulating T1DM patients, accounting for a range of physiological conditions. Utilizing a genetic algorithm, the parameters of the FOPID controller are fine-tuned. By conducting a comparative analysis with previously established control algorithms, the performance of the proposed controller is validated, demonstrating its superior performance. The results underscore the significant improvements achieved by the proposed controller in maintaining blood glucose concentrations within safe thresholds, particularly in scenarios involving disruptions due to meals.

The Role of Fueling Nutrition in Athletic Performance

Abstract Physical activity, athletic performance and recovery from exercise are enhanced by optimal nutrition. This paper couples a rigorous, systematic, evidence-based analysis of nutrition and performance-specific literature with current scientific data related to energy needs, assessment of body composition, strategies for weight change, nutrient and fluid needs, special nutrient needs during training and competition, the use of supplements , nutrition recommendations for vegetarian athletes and the roles and responsibilities of sports dietitians. Energy and macronutrients need especially carbohydrate and protein, must be met during times of high physical activity to maintain body weight, replenish glycogen stores, and provide adequate protein to build and repair tissue. Fat intake should be sufficient to provide the essential fatty acids and fat-soluble vitamins, as well as contribute energy for weight maintenance. Adequate food and fluid should be consumed before, during, and after exercise to help maintain blood glucose concentration during exercise, maximize exercise performance and improve recovery time. Athletes should be well hydrated before exercise and drink enough fluid during and after exercise to balance fluid losses. Sports beverages containing carbohydrates and electrolytes may be consumed before, during, and after exercise to help maintain blood glucose concentration, provide fuel for muscles, and decrease the risk of dehydration and hyponatremia. Vitamin and mineral supplements are not needed if adequate energy to maintain body weight is consumed from a variety of foods. However, athletes who restrict energy intake, use severe weight-loss practices, eliminate one or more food groups from their diet, or consume unbalanced diets with low micronutrient density, may require supplements. Because regulations specific to nutritional ergogenic aids are poorly enforced, they should be used with caution, and only after careful product evaluation for safety, efficacy, potency, and legality.

Analysis of the performances of various controllers adopted in the biomedical field for blood glucose regulation: a case study of the type-1 diabetes

Diabetes remains a critical global health concern that necessitates urgent attention. The contemporary clinical approach to closed-loop care, specifically tailored for insulin-dependent patients, aims to precisely monitor blood glucose levels while mitigating the risks of hyperglycaemia and hypoglycaemia due to erroneous insulin dosing. This study seeks to address this life-threatening issue by assessing and comparing the performance of different controllers to achieve quicker settling and convergence rates with reduced steady-state errors, particularly in scenarios involving meal interruptions. The methodology involves the detection of plasma blood glucose levels, delivery of precise insulin doses to the actuator through a control architecture, and subsequent administration of the calculated insulin dosage to patients based on the control signal. Glucose-insulin dynamics were modelled using kinetics and mass balance equations from the Bergman minimal model. The simulation results revealed that the PID controller exhibited superior performance, maintaining blood glucose concentration around the preferred threshold ∼98.8% of the time, with a standard deviation of 2.50. This was followed by RST with a success rate of 98.5% and standard deviation of 5.00, SPC with a success rate of 58% and standard deviation of 2.99, SFC with a success rate of 55% and standard deviation of 10.08, and finally LCFB with a rate of 10% and significantly higher standard deviation of 64.55.

PID and LQG controllers for diabetes system with internal delay: a comparison study

Closed-loop treatment for insulin dependent type 1 diabetes patients is a recent medical practice in insulin delivery (bionic pancreas) which aims to achieve tight control of glucose level in plasma and ensure minimizing risk of hypoglicemia. Among those most popular closed-loop controller strategies, proportional integral derivative (PID) and linear quadratic Gaussian (LQG) controllers are designed and compared for insulin delivery in diabetic patients. The controllers are designed based on individual and nominal model which is to study the ability of each controller in order to maintain blood glucose concentration for similar patient’s dynamic. The comparison is conducted numerically not only for for patients suffering type 1 diabetes mellitus (T1DM), but also type 2 diabetes mellitus (T2DM), and double diabetes mellitus (DDM) in the present of internal delay systems, which causes instability. The responses show that the proposed PID controller is better at maintaining the blood glucose level in the normal range for a longer delay of delay in hepatic glucose production. The patient with longer performing physical exercise has lower oscillation peaks in blood glucose concentration.

Nanofibrous Scaffolds for Diabetic Wound Healing

Chronic wounds are one of the secondary health complications that develop in individuals who have poorly managed diabetes mellitus. This is often associated with delays in the wound healing process, resulting from long-term uncontrolled blood glucose levels. As such, an appropriate therapeutic approach would be maintaining blood glucose concentration within normal ranges, but this can be quite challenging to achieve. Consequently, diabetic ulcers usually require special medical care to prevent complications such as sepsis, amputation, and deformities, which often develop in these patients. Although several conventional wound dressings, such as hydrogels, gauze, films, and foams, are employed in the treatment of such chronic wounds, nanofibrous scaffolds have gained the attention of researchers because of their flexibility, ability to load a variety of bioactive compounds as single entities or combinations, and large surface area to volume ratio, which provides a biomimetic environment for cell proliferation relative to conventional dressings. Here, we present the current trends on the versatility of nanofibrous scaffolds as novel platforms for the incorporation of bioactive agents suitable for the enhancement of diabetic wound healing.

The Contribution of Intestinal Gluconeogenesis to Glucose Homeostasis Is Low in 2-Day-Old Pigs

Background: Active gluconeogenesis is essential to maintain blood glucose concentrations in neonatal piglets because of the high glucose requirements after birth. In several adult mammals, the liver, kidney, and possibly the gut may exhibit gluconeogenesis during fasting and insulinopenic conditions. During the postnatal period, the intestine expresses all of the gluconeogenic enzymes, suggesting the potential for gluconeogenesis. Galactose in milk is a potential gluconeogenic precursor for newborns.Objective: Our aim was to quantify the rate of intestinal glucose production from galactose in piglets compared with the overall rate of glucose production.Methods: A single bolus of [U-14C]-galactose was injected into 2-d-old piglets (females and males; mean ± SEM weight: 1.64 ± 0.07 kg) through a gastric catheter. Galactosemia, glycemia, and glucose turnover rate (assessed by monitoring d-[6-3H]-glucose) were monitored. Intestinal glucose production from [U-14C]-galactose was calculated from [U-14C]-glucose appearance in the blood and isotopic dilution. Galactose metabolism was also investigated in vitro in enterocytes isolated from 2-d-old piglets that were incubated with increasing concentrations of galactose.Results: In piglet enterocytes, galactose metabolism was active (mean ± SEM maximum rate of reaction: 2.26 ± 0.45 nmol · min-1 · 106 cells-1) and predominantly oriented toward lactate and pyruvate production (74.0% ± 14.5%) rather than glucose production (26.0% ± 14.5%). In conscious piglets, gastric galactose administration led to an increase in arterial galactosemia (from 0 to 1.0 ± 0.8 mmol/L) and glycemia (35% ± 12%). The initial increase in arterial glycemia after galactose administration was linked to an increase in glucose production rate (33% ± 15%) rather than to a decrease in glucose utilization rate (3% ± 6%). The contribution of intestinal glucose production from galactose was <10% of total glucose production in 2-d-old piglets.Conclusion: Our results indicate that there is a low contribution to glucose homeostasis from intestinal gluconeogenesis in 2-d-old piglets.

Care of the brain dead organ donor

Organ donation is becoming more common but there is still a large gap between the number of people requiring transplants and the organs donated. There are set criteria for organ donation. When organ donation is considered after brain death, the physician must ensure that the prerequisites for testing are met and proceed to establish brain death using standard guidelines. The pathophysiological changes that occur after brain death must be borne in mind and utmost care should be given to counter those changes that would result in dysfunction of the donated organs. The brain dead patient must be maintained as stable as possible in the ICU. General nursing and medical care must continue. Core temperature must be maintained and infections must be treated. Blood pressure is best maintained with fluids and minimal vasopressors. Low tidal volume ventilation, optimal levels of positive end-expiratory pressures to maintain minimal FIO2, will maintain airways open and reduce extravascular lung water. Maintain euvolaemia. Maintain urine output at 0.5–3 ml/kg/h. Electrolyte abnormalities must be corrected. Maintain blood glucose concentrations between 120-180 mg %. Triple hormonal therapy improves organ function. Organ retrieval is performed in an operation theatre and a well conducted anaesthetic care is essential for the viability of these organs. One brain-dead organ donor can potentially donate ‘lives’ to eight individuals. To enhance or preserve the maximum potential of the donated organs, the anaesthesiologist and intensivist play a vital role in preserving the organs as best as possible.

Neurocognitive Outcomes at Age 2 Years After Neonatal Hypoglycemia in a Cohort of Participants From the hPOD Randomized Trial

Neonatal hypoglycemia is common, but its association with later neurodevelopment is uncertain. To examine associations between neonatal hypoglycemia and neurocognitive outcomes at corrected age 2 years. Exploratory cohort analysis of the Hypoglycaemia Prevention With Oral Dextrose (hPOD) randomized clinical trial was conducted. The trial recruited participants from January 9, 2015, to May 5, 2019, with follow-up between January 26, 2017, and July 31, 2021. Infants were recruited from 9 maternity hospitals in New Zealand and assessed at home or in a research clinic. Children born late preterm and at term at risk of neonatal hypoglycemia but without evidence of acute or imminent illness in the first hour after birth were screened and treated to maintain blood glucose concentrations greater than or equal to 47 mg/dL. Hypoglycemia was defined as any blood glucose concentration less than 47 mg/dL, recurrent as 3 or more episodes, and severe as less than 36 mg/dL. Neurologic examination and tests of development (Bayley III) and executive function. The primary outcome was neurosensory impairment (any of the following: blindness, deafness, cerebral palsy, developmental delay, or executive function total score worse than 1.5 SD below the mean). A total of 1197 of 1321 (91%) eligible children were assessed at a mean of corrected age 24 months; 616 (52%) were male. Compared with the normoglycemia group, children who experienced hypoglycemia were more likely to have neurosensory impairment (111 [23%] vs 125 [18%]; adjusted risk ratio [aRR], 1.28; 95% CI, 1.01-1.60), particularly if they experienced severe episodes (30 [28%] vs 125 [18%]; aRR, 1.68; 95% CI, 1.20-2.36), but not recurrent episodes (12 [19%] vs 125 [18%]; aRR, 1.06; 95% CI, 0.63-1.80). The risk of cognitive, language, or motor delay was similar between groups, but children who experienced hypoglycemia had lower Bayley-III composite cognitive (adjusted mean difference [aMD], -1.48; 95% CI, -2.79 to -0.18) and motor scores (aMD, -2.05; 95% CI, -3.30 to -0.79). In children born at risk of hypoglycemia but otherwise well, those who experienced neonatal hypoglycemia were more likely to have neurosensory impairment at corrected age 2 years, with higher risks after severe episodes. Further research is required to determine causality.

Glycemic Control for Type 2 Diabetes Mellitus Patients: A Systematic Review

Diabetes mellitus is a chronic metabolic disorder resulting in hyperglycemia and microvascular and macrovascular complications in individuals globally. Type 2 diabetes mellitus (T2DM) is highly prevalent and accounts for 90% of patients. Maintaining blood glucose concentration is essential to avoid severe complications.Glycemic control is the optimal serum glucose concentration in diabetic patients. It is necessary to identify factors affecting the glycemic control of patients to prevent control and complications. We conducted this systematic review to assess the factors affecting glycemic control among type 2 diabetes mellitus patients.Published literature between the years 2020 to 2022 was retrieved from PubMed, Science Direct, and Google Scholar using different combinations of keywords: T2DM, Glycemic control, Poor, Good, Adequate, Inadequate, Factors, Association, and Determinants. All original articles written in the English language with full-text available and the value of glycemic control defined were included. A total of 1866 studies were retrieved. After the title, abstract, screening, and full-text screening, 12 studies were eligible.The prevalence of poor glycemic control was high, and it ranged between 45.2% and 93% among the studies. The factors associated with glycemic control were stratified into four categories: personal or body-related, clinical, medication-related, and behavioral factors. There was a high prevalence of poor glycemic control in all included studies. The glycemic control was associated with various factors; some were related to the patient or medical conditions while others were related to the behavior of the patients or the medication administrated.

Mechanisms of Diabetic Neuropathies and Antioxidant Therapy

Background: Diabetic neuropathy is very common and affects half of patients with either type 1 or type 2 diabetes mellitus. It is the leading cause of diabetes-related hospital admissions and nontraumatic amputations. Currently, the keys to management are maintaining blood glucose concentration within the normal range and treatment of symptoms. Despite many studies of chronic pain associated with diabetic neuropathy, few improvements have been made.&#x0D; Main Finding: This is a review of the classification of diabetic neuropathy, molecular mechanisms, and treatment options focusing on antioxidants.&#x0D; Conclusion: As oxidative stress may play a significant role in the pathophysiology of diabetic neuropathy, the study of molecular mechanisms by which hyperglycemia induces oxidative stress is important. New targets for disease-modifying drugs could be elucidated.

In Silico Testing of a Closed-Loop Artificial Pancreas Based on Generalized Predictive Control

The artificial pancreas (AP) system is a promising approach to maintain blood glucose concentration (BGC) of patients with type 1 diabetes (T1D) in a euglycemic range (70–180 mg/dl). A controller based on generalized predictive control (GPC) with an adaptive reference glucose trajectory and an adaptive softening factor (GPC+AA) was proposed for AP system in our previous research. It was built and tested with the University of Virginia (UVA)/Padova type 1 diabetes mellitus simulator (T1DMS), which embodies the biophysiological parameters of in-silico population accepted by the US Food and Drug Administration. It was showed that the GPC+AA controller realized effective control of the BGC of in-silico patients with T1D. Here, the effectiveness of the GPC+AA controller was further tested with strict conditions, including a pump with noise and error, a continuous glucose monitoring sensor and a high carbohydrate intake. Test results showed that the BGC of adolescent group was not effectively controlled with the GPC+AA controller. Then, the adaptive softening factor strategy was further optimized and a GPC controller with an adaptive reference glucose trajectory and an optimized adaptive softening factor (GPC+AO) was proposed here. It was demonstrated that the optimized adaptive softening factor strategy significantly improved the performance of the GPC controller, and the average BGC percentage within the euglycemic range of 9 adults and 10 adolescents increased to 80% and 70%, respectively. Thus, our GPC+AO controller is effective for patients with T1D and can be potentially applied in the AP systems.

MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States.

Diabetes results from the inability of pancreatic islets to maintain blood glucose concentrations within a normal physiological range. Clinical features are usually not observed until islets begin to fail and irreversible damage has occurred. Diabetes is generally diagnosed based on elevated glucose, which does not distinguish between type 1 and 2 diabetes. Thus, new diagnostic approaches are needed to detect different modes of diabetes before manifestation of disease. During prediabetes (pre-DM), islets undergo stress and release micro (mi) RNAs. Here, we review studies that have measured and tracked miRNAs in the blood for those with recent-onset or longstanding type 1 diabetes, obesity, pre-diabetes, type 2 diabetes, and gestational diabetes. We summarize the findings on miRNA signatures with the potential to stage progression of different modes of diabetes. Advances in identifying selective biomarker signatures may aid in early detection and classification of diabetic conditions and treatments to prevent and reverse diabetes.

Dietary sugars, exercise and hepatic carbohydrate metabolism.

The present paper reviews the physiological responses of human liver carbohydrate metabolism to physical activity and ingestion of dietary sugars. The liver represents a central link in human carbohydrate metabolism and a mechanistic crux point for the effects of dietary sugars on athletic performance and metabolic health. As a corollary, knowledge regarding physiological responses to sugar ingestion has potential application to either improve endurance performance in athletes, or target metabolic diseases in people who are overweight, obese and/or sedentary. For example, exercise increases whole-body glycogen utilisation, and the breakdown of liver glycogen to maintain blood glucose concentrations becomes increasingly important as exercise intensity increases. Accordingly, prolonged exercise at moderate-to-high exercise intensity results in depletion of liver glycogen stores unless carbohydrate is ingested during exercise. The exercise-induced glycogen deficit can increase insulin sensitivity and blood glucose control, and may result in less hepatic lipid synthesis. Therefore, the induction and maintenance of a glycogen deficit with exercise could be a specific target to improve metabolic health and could be achieved by carbohydrate (sugar) restriction before, during and/or after exercise. Conversely, for athletes, maintaining and restoring these glycogen stores is a priority when competing in events requiring repeated exertion with limited recovery. With this in mind, evidence consistently demonstrates that fructose-containing sugars accelerate post-exercise liver glycogen repletion and could reduce recovery time by as much as half that seen with ingestion of glucose (polymers)-only. Therefore, athletes aiming for rapid recovery in multi-stage events should consider ingesting fructose-containing sugars to accelerate recovery.

In Silico Modeling of Minimal Effective Insulin Doses Using the UVA/PADOVA Type 1 Diabetes Simulator.

Background:The objective of this study was to identify the minimum basal insulin infusion rates and bolus insulin doses that would result in clinically relevant changes in blood glucose levels in the most insulin sensitive subjects with type 1 diabetes.Methods:The UVA/PADOVA Type 1 Diabetes Simulator in silico population of children, adolescents, and adults was administered a basal insulin infusion rate to maintain blood glucose concentrations at 120 mg/dL (6.7 mmol/L). Two scenarios were modeled independently after 1 hour of simulated time: (1) basal insulin infusion rates in increments of 0.01 U/h were administered and (2) bolus doses in increments of 0.01 U were injected. Subjects were observed for 4 hours to determine insulin delivery required to change blood glucose by 12.5 mg/dL (0.7 mmol/L) and 25 mg/dL (1.4 mmol/L) in only 5% of the in silico population.Results:The basal insulin infusion rates required to change blood glucose by 12.5 mg/dL and 25 mg/dL in 5% of children, adolescents, and adults were 0.03, 0.11, and 0.10 U/h and 0.06, 0.21, and 0.19 U/h, respectively. The bolus insulin doses required to change blood glucose by the target amounts in the respective populations were 0.10, 0.28, and 0.30 U and 0.19, 0.55, and 0.60 U.Conclusions:In silico modeling suggests that only a very small percentage of individuals with type 1 diabetes, corresponding to children with high insulin sensitivity and low body weight, will exhibit a clinically relevant change in blood glucose with very low basal insulin rate changes or bolus doses.

Software-guided versus nurse-directed blood glucose control in critically ill patients: the LOGIC-2 multicenter randomized controlled clinical trial

BackgroundBlood glucose control in the intensive care unit (ICU) has the potential to save lives. However, maintaining blood glucose concentrations within a chosen target range is difficult in clinical practice and holds risk of potentially harmful hypoglycemia. Clinically validated computer algorithms to guide insulin dosing by nurses have been advocated for better and safer blood glucose control.MethodsWe conducted an international, multicenter, randomized controlled trial involving 1550 adult, medical and surgical critically ill patients, requiring blood glucose control. Patients were randomly assigned to algorithm-guided blood glucose control (LOGIC-C, n = 777) or blood glucose control by trained nurses (Nurse-C, n = 773) during ICU stay, according to the local target range (80–110 mg/dL or 90–145 mg/dL). The primary outcome measure was the quality of blood glucose control, assessed by the glycemic penalty index (GPI), a measure that penalizes hypoglycemic and hyperglycemic deviations from the chosen target range. Incidence of severe hypoglycemia (<40 mg/dL) was the main safety outcome measure. New infections in ICU, duration of hospital stay, landmark 90-day mortality and quality of life were clinical safety outcome measures.ResultsThe median GPI was lower in the LOGIC-C (10.8 IQR 6.2–16.1) than in the Nurse-C group (17.1 IQR 10.6–26.2) (P < 0.001). Mean blood glucose was 111 mg/dL (SD 15) in LOCIC-C versus 119 mg/dL (SD 21) in Nurse-C, whereas the median time-in-target range was 67.0% (IQR 52.1–80.1) in LOGIC-C versus 47.1% (IQR 28.1–65.0) in the Nurse-C group (both P < 0.001). The fraction of patients with severe hypoglycemia did not differ between LOGIC-C (0.9%) and Nurse-C (1.2%) (P = 0.6). The clinical safety outcomes did not differ between groups. The sampling interval was 2.3 h (SD 0.5) in the LOGIC-C group versus 3.0 h (SD 0.8) in the Nurse-C group (P < 0.001).ConclusionsIn a randomized controlled trial of a mixed critically ill patient population, the use of the LOGIC-Insulin blood glucose control algorithm, compared with blood glucose control by expert nurses, improved the quality of blood glucose control without increasing hypoglycemia.Trial registrationClinicalTrials.gov, NCT02056353. Registered on 4 February 2014.

Association of Neonatal Glycemia With Neurodevelopmental Outcomes at 4.5 Years

Hypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown. To test the hypothesis that neurodevelopment at 4.5 years is related to the severity and frequency of neonatal hypoglycemia. The Children With Hypoglycemia and Their Later Development (CHYLD) Study is a prospective cohort investigation of moderate to late preterm and term infants born at risk of hypoglycemia. Clinicians were masked to neonatal interstitial glucose concentrations; outcome assessors were masked to neonatal glycemic status. The setting was a regional perinatal center in Hamilton, New Zealand. The study was conducted from December 2006 to November 2010. The dates of the follow-up were September 2011 to June 2015. Participants were 614 neonates born from 32 weeks' gestation with at least 1 risk factor for hypoglycemia, including diabetic mother, preterm, small, large, or acute illness. Blood and masked interstitial glucose concentrations were measured for up to 7 days after birth. Infants with hypoglycemia (whole-blood glucose concentration <47 mg/dL) were treated to maintain blood glucose concentration of at least 47 mg/dL. Neonatal hypoglycemic episode, defined as at least 1 consecutive blood glucose concentration less than 47 mg/dL, a severe episode (<36 mg/dL), or recurrent (≥3 episodes). An interstitial episode was defined as an interstitial glucose concentration less than 47 mg/dL for at least 10 minutes. Cognitive function, executive function, visual function, and motor function were assessed at 4.5 years. The primary outcome was neurosensory impairment, defined as poor performance in one or more domains. In total, 477 of 604 eligible children (79.0%) were assessed. Their mean (SD) age at the time of assessment was 4.5 (0.1) years, and 228 (47.8%) were female. Those exposed to neonatal hypoglycemia (280 [58.7%]) did not have increased risk of neurosensory impairment (risk difference [RD], 0.01; 95% CI, -0.07 to 0.10 and risk ratio [RR], 0.96; 95% CI, 0.77 to 1.21). However, hypoglycemia was associated with increased risk of low executive function (RD, 0.05; 95% CI, 0.01 to 0.10 and RR, 2.32; 95% CI, 1.17 to 4.59) and visual motor function (RD, 0.03; 95% CI, 0.01 to 0.06 and RR, 3.67; 95% CI, 1.15 to 11.69), with highest risk in children exposed to severe, recurrent, or clinically undetected (interstitial episodes only) hypoglycemia. Neonatal hypoglycemia was not associated with increased risk of combined neurosensory impairment at 4.5 years but was associated with a dose-dependent increased risk of poor executive function and visual motor function, even if not detected clinically, and may thus influence later learning. Randomized trials are needed to determine optimal screening and intervention thresholds based on assessment of neurodevelopment at least to school age.

The Lower Infusion Rate of Glucose to Maintain Ketogenesis within Normal Level during Surgery

Background: Intraoperative low-dose glucose infusions suppress ketogenesis and attenuate postoperative insulin resistance (IR). However, the appropriate rate for intraoperative glucose infusion remains unclear, although a postoperative infusion of 0.08 g/kg/h effectively suppressed ketogenesis at the next morning. Therefore, we investigated the effects of an intraoperative rate of 0.08 g/kg/h on ketogenesis and postoperative IR. Methods: The present study included 15 patients who were undergoing maxillofacial surgery. The patients received glucose-free Ringer’s solution and a continuous glucose infusion (0.08 g/kg/h) during the surgery. Blood samples were collected to evaluate the concentrations of noradrenaline, cortisol, glucose, insulin, ketone bodies, and free fatty acid before anesthesia induction (T1), at 1 h after induction (T2), at 3 h after induction (T3), and at the end of surgery (T4). The glucose clamp test was performed on the days before and after surgery using the STG-55TM device. IR was quantified using the mean glucose infusion rate (M-value). Results: All 15 patients exhibited intraoperative blood glucose concentrations of 90 - 130 mg/dL. There was a non-significant trend towards higher plasma concentrations of total ketone bodies at T3 (p = 0.058). The plasma concentrations of acetoacetic acid at T3 and T4 were significantly higher than that at T1 (p = 0.0217 and p = 0.0306, respectively). All patients exhibited lower M-values after surgery (mean reduction: 48.0% ± 17.9%). Conclusion: Continuous intraoperative glucose at 0.08 g/kg/h helped maintain blood glucose concentrations, although it may suppress the ketogenesis to increase during surgery.

Infusion of fluoxetine, a serotonin reuptake inhibitor, in the shell region of the nucleus accumbens increases blood glucose concentrations in rats

The brain is well known to regulate blood glucose, and the hypothalamus and hindbrain, in particular, have been studied extensively to understand the underlying mechanisms. Nuclei in these regions respond to alterations in blood glucose concentrations and can alter glucose liver output or glucose tissue uptake to maintain blood glucose concentrations within strict boundaries. Interestingly, several cortico-limbic regions also respond to alterations in glucose concentrations and have been shown to project to hypothalamic nuclei and glucoregulatory organs. For instance, electrical stimulation of the shell of the nucleus accumbens (sNAc) results in increased circulating concentrations of glucose and glucagon and activation of the lateral hypothalamus (LH). Whether this is caused by the simultaneous increase in serotonin release in the sNAc remains to be determined. To study the effect of sNAc serotonin on systemic glucose metabolism, we implanted bilateral microdialysis probes in the sNAc of male Wistar rats and infused fluoxetine, a serotonin reuptake inhibitor, or vehicle after which blood glucose, endogenous glucose production (EGP) and glucoregulatory hormones were measured. Fluoxetine in the sNAc for 1h significantly increased blood glucose concentrations without an effect on glucoregulatory hormones. This increase was accompanied by a higher EGP in the fluoxetine infused rats compared to the controls. These data provide further evidence for a role of sNAc-serotonin in the regulation of glucose metabolism.

Glucokinase expression is regulated by glucose through O-GlcNAc glycosylation

Blood glucose fluctuates with the fasting-feeding cycle. One of the liver's functions is to maintain blood glucose concentrations within a physiological range. Glucokinase (GCK) or hexokinase IV, is the main enzyme that regulates the flux and the use of glucose in the liver leading to a compensation of hyperglycemia. In hepatocytes, GCK catalyzes the phosphorylation of glucose into glucose-6-phosphate. This critical enzymatic reaction is determinant for the metabolism of glucose in the liver which includes glycogen synthesis, glycolysis, lipogenesis and gluconeogenesis. In liver, simultaneous increase of glucose and insulin enhances GCK activity and gene expression, changes its subcellular location and interaction with regulatory proteins. The post-translational O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) acts as a glucose-sensitive modification and is believed to take part in hepatic glucose sensing by modifying key regulatory proteins. Therefore, we aimed to determine whether GCK is modified by O-GlcNAcylation in the liver of mice and investigated the role that this modification plays in regulating GCK protein expression. We demonstrated that endogenous GCK expression correlated with O-GlcNAc levels in the pathophysiological model ob/ob mice. More specifically, in response to the pharmacological inhibition of O-GlcNAcase (OGA) contents of GCK increased. Using the GlcNAc specific lectin succinylated-WGA and click chemistry labeling approaches, we demonstrated that GCK is modified by O-GlcNAcylation. Further, we demonstrated that siRNA-mediated Ogt knock-down not only decreases O-GlcNAc content but also GCK protein level. Altogether, our in vivo and in vitro results demonstrate that GCK expression is regulated by nutrient-sensing O-GlcNAc cycling in liver.

A Kinetic Model of Whole-Body Glucose Metabolism with Reference to the Domestic Dog (Canis lupus familiaris).

A new two-pool model to describe glucose kinetics in the steady state is presented. The pools are plasma glucose, Q 1, and tissue glucose, Q 2 (both µmol). The flows (all µmol/min) into the plasma pool (Pool 1) are absorbed glucose entry from dietary sources, labelled glucose infusion, and hepatic glucose production. There is one flow out of Pool 1, glucose uptake by the tissues. Inflows to the tissues pool (Pool 2) are from plasma and glycogenolysis. Outflows from Pool 2 are to plasma, glucose oxidation, and glycogenesis and other metabolism. Application of the model was illustrated using experimental data derived from healthy adult Labrador Retrievers in the fasted and fed (repeated meal feeding) states. In general, model derived estimates of glucose kinetics were representative of normal glucose metabolism, where rates of glucose production and uptake are similar and act to maintain blood glucose concentrations. Furthermore, estimates of within tissue glucose cycling indicated glycogenolysis in fasting and glycogenesis when fed. In the fasted state, model outputs were consistent with those reported in the canine literature derived using a single pool model.