Continuous Blood Glucose Measurement Research Articles

Hydrogel Capacitors Based on MoS2 Nanosheets and Applications in Glucose Monitoring.

Non-invasive/minimally invasive continuous monitoring of blood glucose and blood glucose administration have a high impact on chronic disease management in diabetic patients, but the existing technology is yet to achieve the above two purposes at the same time. Therefore, this study proposes a microfluidic microneedle patch based on 3D printing technology and an integrated control system design for blood glucose measurement, and a drug delivery control circuit based on a 555 chip. The proposed method provides an improved preparation of a PVA-PEG-MoS2 nanosheet hydrogel, making use of its dielectric properties to fabricate a microcapacitor and then embedding it in a microfluidic chip. When MoS2 nanosheets react with interstitial liquid glucose (and during the calibration process), the permittivity of the hydrogel is changed, resulting in changes in the capacitance of the capacitor. By converting the capacitance change into the square-wave period change in the output of the 555 chip with the control circuit design accordingly, the minimally invasive continuous measurement of blood glucose and the controlled release of hypoglycemic drugs are realized. In this study, the cross-linking structure of MoS2 nanosheets in hydrogel was examined using infrared spectroscopy and scanning electron microscopy (SEM) methods. Moreover, the critical doping mass fraction of MoS2 nanosheets was determined to be 2% via the measurement of the dielectric constant. Meanwhile, the circuit design and the relationship between the pulse cycle and glucose concentration is validated. The results show that, compared with capacitors in series, the microcapacitors embedded in microfluidic channels can be connected in parallel to obtain better linearized blood glucose measurement results.

The role of continuous glucose monitoring in physical activity and nutrition management: perspectives on present and possible uses

[Purpose] Continuous glucose monitoring (CGM) is on the rise as the prevalence of obesity and diabetes increases. This review aimed to explore the use of CGM and its potential novel applications in physical activity and nutrition management.[Methods] We searched PubMed, Web of Science, and Wiley Online Library databases using the keywords ‘continuous glucose monitor,’ ‘nutrition,’ ‘physical activity,’ and ‘numerical modeling.’[Results] Continuous blood glucose measurement is useful for individuals with obesity and diabetes. Long-term blood glucose data allow for personalized planning of nutritional composition, meal timing, and physical activity type and intensity, as well as help prevent hypoglycemia and hyperglycemia. Thus, understanding the limitations of CGM is important for its effective use.[Conclusion] CGM systems are being increasingly used to monitor and identify appropriate blood glucose controlling interventions. Blood glucose level is influenced by various factors such as nutrient composition, meal timing, physical activity, circadian rhythm, and cortisol levels. Numerical modeling can be used to analyze the complex relationship between stress, sleep, nutrition, and physical activity, which affect blood glucose levels. In future, blood glucose, sleep, and stress data will be integrated to predict appropriate lifestyle levels for blood glucose management. This integrated approach improves glucose control and overall wellbeing, potentially reducing societal costs.

Improving the Accuracy of Continuous Blood Glucose Measurement Using Personalized Calibration and Machine Learning.

Despite tremendous developments in continuous blood glucose measurement (CBGM) sensors, they are still not accurate for all patients with diabetes. As glucose concentration in the blood is <1% of the total blood volume, it is challenging to accurately measure glucose levels in the interstitial fluid using CBGM sensors due to within-patient and between-patient variations. To address this issue, we developed a novel data-driven approach to accurately predict CBGM values using personalized calibration and machine learning. First, we scientifically divided measured blood glucose into smaller groups, namely, hypoglycemia (<80 mg/dL), nondiabetic (81-115 mg/dL), prediabetes (116-150 mg/dL), diabetes (151-181 mg/dL), severe diabetes (181-250 mg/dL), and critical diabetes (>250 mg/dL). Second, we separately trained each group using different machine learning models based on patients' personalized parameters, such as physical activity, posture, heart rate, breath rate, skin temperature, and food intake. Lastly, we used multilayer perceptron (MLP) for the D1NAMO dataset (training to test ratio: 70:30) and grid search for hyperparameter optimization to predict accurate blood glucose concentrations. We successfully applied our proposed approach in nine patients with type 1 diabetes and observed that the mean absolute relative difference (MARD) decreased from 17.8% to 8.3%.

High dietary nucleotide consumption for one week increases circulating uric acid concentrations but does not compromise metabolic health: A randomised controlled trial.

Elevated circulating uric acid concentrations have been linked to various cardio-metabolic diseases. Bolus consumption of a nucleotide-rich dietary protein source increases postprandial serum uric acid concentrations. We assessed the impact of twice-daily nucleotide-rich mixed-meal consumption for one week on postabsorptive serum uric acid concentrations, insulin sensitivity (IS), glycaemic control and the plasma lipidome. Twenty healthy adults participated in a randomised, controlled, parallel-group trial in which they consumed a 7d fully-controlled eucaloric diet where lunch and dinner contained either nucleotide-depleted (LOW) or high-nucleotide (HIGH) mycoprotein. Postabsorptive blood samples were obtained pre, throughout and post-intervention, and oral glucose tolerance tests were performed pre- and post-intervention. Daily waking urine samples and 24h continuous blood glucose measurements were collected throughout. Postabsorptive serum uric acid concentrations remained unchanged in LOW but increased throughout the intervention week in HIGH (from 295±17 to 472±29μmolL-1by day 6; P<0.05). Urinary uric acid did not change throughout the intervention in either group. The intervention did not affect indices of IS, 24h glycaemic control, nor had a meaningful impact on the plasma lipidome. One week of twice-daily consumption of nucleotide-rich mixed-meals increases postabsorptive serum uric acid concentrations above clinically acceptable thresholds but these changes are not associated with deleterious effects on IS, daily glycaemic control or plasma lipid composition. NCT02984358 (https://clinicaltrials.gov/ct2/show/NCT02984358).

Postprandial Asymptomatic Glycemic Fluctuations after Gastrectomy for Gastric Cancer Using Continuous Glucose Monitoring Device.

PurposeAlthough dumping symptoms are thought to involve postprandial glycemic changes, postprandial glycemic variability without dumping symptoms remains poorly understood due to the lack of a method that allows the easy and continuous measurement of blood glucose levels.Materials and MethodsPatients having undergone distal gastrectomy with Billroth-I (DG-BI) or Roux-en-Y reconstruction (DG-RY), total gastrectomy with RY (TG-RY) and pylorus preserving gastrectomy (PPG) for gastric cancer 3 months to 3 years prior, diagnosed as pathological stage I or II, were prospectively enrolled from March 2018 to January 2020. The interstitial tissue glycemic levels were measured every 15 min, up to 14 days by continuous glucose monitoring. Moreover, using a diary recording the diet and symptoms, asymptomatic glucose profiles without sugar supplementation within 3 h postprandially were compared among the four procedures.ResultsA total of 40 patients were enrolled, 10 patients for each of the four procedures. There were 47 glucose profiles with DG-BI, 46 profiles with DG-RY, 38 profiles with TG-RY, and 46 profiles with PPG. PPG showed the slowest increase with a subsequent gradual decrease in glucose fluctuations, without hyperglycemia or hypoglycemia, among the four procedures. In contrast, TG-RY and DG-RY showed spike-like glycemic variability, sharp rises during meals, and rapid drops. The glucose profiles of DG-BI were milder than those of RY.ConclusionsThe asymptomatic glycemic changes after meals differ among the types of surgical procedures for gastric cancer. Given the mild glycemic fluctuations in PPG and the glucose spikes in TG-RY and DG-RY, pylorus preservation and physiological reconstruction without changes in food pathways may optimize postprandial glucose profiles after gastrectomy.

Errors-in-Variables Modeling of Personalized Treatment-Response Trajectories.

Estimating the impact of a treatment on a given response is needed in many biomedical applications. However, methodology is lacking for the case when the response is a continuous temporal curve, treatment covariates suffer extensively from measurement error, and even the exact timing of the treatments is unknown. We introduce a novel method for this challenging scenario. We model personalized treatment-response curves as a combination of parametric response functions, hierarchically sharing information across individuals, and a sparse Gaussian process for the baseline trend. Importantly, our model accounts for errors not only in treatment covariates, but also in treatment timings, a problem arising in practice for example when data on treatments are based on user self-reporting. We validate our model with simulated and real patient data, and show that in a challenging application of estimating the impact of diet on continuous blood glucose measurements, accounting for measurement error significantly improves estimation and prediction accuracy.

Automated Insulin Delivery - Continuous Blood Glucose Control During Ex Situ Liver Perfusion.

With the growing demand for livers in the field of transplantation, interest in normothermic ex situ machine perfusion (NMP) has increased in recent years. This may open the door for novel therapeutic interventions such as repair of suboptimal grafts. For successful long-term NMP of livers, blood glucose (BG) levels need to be maintained in a close to physiological range. We present an "automated insulin delivery" (AID) system integrated into an NMP system, which automatically adjusts insulin infusion rates based on continuous BG measurements in a closed loop manner during ex situ pig and human liver perfusion. An online glucose sensor for continuous glucose monitoring was integrated and evaluated in blood. A model based and a proportional controller were implemented and compared in their ability to maintain BG within the physiological range. The continuous glucose sensor is capable of measuring BG directly in human and pig blood for multiple days with an average error of 0.6mmol/L. There was no significant difference in the performance of the two controllers in terms of their ability to keep BG in the physiological range. With the integrated AID, BG was controlled within the physiological range on average in 80% and 76% of the perfusion time for human and pig livers, respectively. The presented work offers a method and shows the feasibility to maintain BG in the physiological range for multiple (up to ten) days during ex situ liver perfusion with the help of an automated AID. Maintaining BG within the physiological range is required to enable long-term ex situ liver perfusion.

Continuous Blood Glucose Monitoring Reveals Enormous Circadian Variations in Pregnant Diabetic Rats.

Diabetes in pregnancy is a major burden with acute and long-term consequences. Its treatment requires adequate diagnosis and monitoring of therapy. Many experimental research on diabetes during pregnancy has been performed in rats. Recently, continuous blood glucose monitoring of non-pregnant diabetic rats revealed an increased circadian variability of blood glucose that made a single blood glucose measurement per day inappropriate to reflect glycemic status. Continuous blood glucose measurement has never been performed in pregnant rats. We wanted to perform continuous blood glucose monitoring in pregnant rats to decipher the influence of pregnancy on blood glucose in diabetic and normoglycemic status. We used the transgenic Tet29 diabetes rat model with an inducible knock down of the insulin receptor via RNA interference upon application of doxycycline (DOX) leading to insulin resistant type II diabetes. All Tet29 rats received a HD-XG telemetry implant (Data Sciences International, USA) that measured blood glucose and activity continuously. Rats were divided into four groups and blood glucose was monitored until end of pregnancy or the corresponding period: Tet29 + DOX (diabetic) non-pregnant, Tet29 + DOX (diabetic) pregnant, Tet29 (normoglycemic) non-pregnant, Tet29 (normoglycemic) pregnant. All analyzed rats displayed a circadian variation in blood glucose concentration. Circadian variability was much more pronounced in pregnant diabetic rats than in normoglycemic pregnant rats. Pregnancy ameliorated variation in blood glucose in diabetic situation. Pregnancy continuously decreased blood glucose during normoglycemic pregnancy. Diabetic rats were less active than normoglycemic rats. We performed a calculation showing that application of continuous blood glucose measurement reduces animal numbers needed to detect a given effect in experimental setting by decreasing variability and SD. Continuous blood glucose monitoring via a telemetry device in pregnant rats provides a more informative picture of the glycemic situation in comparison to single measurements. This could improve diagnosis and therapy of diabetes, decrease animal numbers within experimental settings, and add another physiological parameter (activity) to the analysis that could be helpful in testing therapeutic concepts targeting blood glucose levels and peripheral muscle function. We propose continuous glucose monitoring as a new tool for the evaluation of pregnant diabetic rats.

Review: Non-Invasive Continuous Blood Glucose Measurement Techniques

Review: Non-Invasive Continuous Blood Glucose Measurement Techniques

Intravascular Microdialysis as a Method for Measuring Glucose and Lactate during and after Cardiac Surgery

The aim was to evaluate intravascular microdialysis as a method for measuring blood glucose and lactate in a clinical setting during and after cardiac surgery. Ten patients undergoing cardiac surgery were included. A microdialysis catheter was percutaneously placed in the superior vena cava or right atrium. Glucose and lactate values measured by the microdialysis technique were analyzed and compared with reference methods, i.e., arterial and venous blood gas values, once every hour up to 24 hours postoperatively. Laboratory plasma glucose was additionally analyzed every 4 hours for reference value. Mean absolute differences were low between microdialysis and reference methods for both glucose and lactate values. All microdialysis glucose values were in the clinically acceptable zone of error grid analysis when compared with plasma glucose values. Accuracy of glucose values was 92% according to International Organization for Standardization criteria. Intravascular microdialysis is a novel and promising technique for real-time and accurate measurement of glucose and lactate during and after open heart surgery. Development of sensor technology may allow for continuous measurement of blood glucose and lactate using intravascular microdialysis.

Optimal blood glucose regulation of diabetic patients using single network adaptive critics

AbstractDiabetes is a long‐term disease during which the body's production and use of insulin are impaired, causing glucose concentration level to increase in the bloodstream. Regulating blood glucose levels as close to normal as possible leads to a substantial decrease in long‐term complications of diabetes. In this paper, an intelligent online feedback‐treatment strategy is presented for the control of blood glucose levels in diabetic patients using single network adaptive critic (SNAC) neural networks (which is based on nonlinear optimal control theory). A recently developed mathematical model of the nonlinear dynamics of glucose and insulin interaction in the blood system has been revised and considered for synthesizing the neural network for feedback control. The idea is to replicate the function of pancreatic insulin, i.e. to have a fairly continuous measurement of blood glucose and a situation‐dependent insulin injection to the body using an external device. Detailed studies are carried out to analyze the effectiveness of this adaptive critic‐based feedback medication strategy. A comparison study with linear quadratic regulator (LQR) theory shows that the proposed nonlinear approach offers some important advantages such as quicker response, avoidance of hypoglycemia problems, etc. Robustness of the proposed approach is also demonstrated from a large number of simulations considering random initial conditions and parametric uncertainties. Copyright © 2009 John Wiley &amp; Sons, Ltd.

Continuous Measurement of Blood Glucose

Tight blood glucose control is used extensively in perioperative and critically ill patients. Several studies, however, have shown contradictory effects on patient outcomes. A major problem of these studies has been inadequate control of the prime variable, blood glucose. This paper describes the validation of a new intravascular continuous blood glucose sensor. The glucose sensor was placed in the superior caval vein of seven anesthetized pigs. Sensor readings were compared with arterial blood gas readings. Fluctuations in blood glucose were created using intravenous glucose and insulin. A total of 807 paired sensor and blood gas readings were obtained. The sensor was tested with a range of blood glucose values (0.63-15.75 mM [mean bias, 0.0131 mM]). Analysis using Bland-Altman plots yielded 95% limits of agreement at -0.908 and 0.934 mM. There were 121 paired measurements with a mean value below 2.2 mM, yielding 95% limits of agreement at -0.553 and 0.466 mM. The performance of the sensor was in agreement with blood gas measurements in a wide range of glucose values. For the clinician, it is noteworthy that performance was equally good in the hypoglycemic area.

Measurement of Glucose in Blood with a Phenylboronic Acid Optical Sensor

Current methods of glucose monitoring rely predominantly on enzymes such as glucose oxidase for detection. Phenylboronic acid receptors have been proposed as alternative glucose binders. A unique property of these molecules is their ability to bind glucose in a fully reversible covalent manner that facilitates direct continuous measurements. We examined (1) the ability of a phenylboronic-based sensor to measure glucose in blood and blood plasma and (2) the effect on measurement accuracy of a range of potential interferents. We also showed that the sensor is able to track glucose fluctuations occurring at rates mimicking those experienced in vivo. In vitro static measurements of glucose in blood and blood plasma were conducted using holographic sensors containing acrylamide, N,N'-methylenebisacrylamide, 3-acrylamidophenylboronic acid, and (3-acrylamidopropyl) trimethylammonium chloride. The same sensors were also used for in vitro measurements performed under flow conditions. The opacity of the liquid had no affect on the ability of the optical sensor to measure glucose in blood or blood plasma. The presence of common antibiotics, diabetic drugs, pain killers, and endogenous substances did not affect the measurement accuracy, as shown by error grid analysis. Ex vivo flow experiments showed that the sensor is able to track changes accurately in concentration occurring in real time without lag or evidence of hysteresis. The ability of phenylboronic acid sensors to measure glucose in whole blood was demonstrated for the first time. Holographic sensors are ideally suited to continuous blood glucose measurements, being physically and chemically robust and potentially calibration free.

Comparison of Continuous Blood Glucose Measurement with Conventional Documentation of Hypoglycemia in Patients with Type 2 Diabetes on Multiple Daily Insulin Injection Therapy

The primary objective of this study was to investigate the difference in the proportion of patients with conventionally detected hypoglycemia compared with continuous glucose monitoring system (CGMS, Medtronic MiniMed, Sylmar, CA)-detected glucose values < or = 60 mg/dL (< or = 3.3 mmol/L), during the 72-h CGMS measurement period after 8 weeks' treatment with insulin glargine. This was a multicenter (n = 125), open-label, single-arm study in patients with Type 2 diabetes mellitus (T2DM) on multiple daily injections. Patients received NPH insulin (2-week run-in) followed by glargine (8-week treatment phase). Glucose levels were measured by CGMS and self-monitored blood glucose (SMBG) profiles over the 72-h pre- and post-treatment phase. The full analysis set contained 367 patients [male 59%; mean age 59.2 years; mean body mass index 31.7 kg/m(2); mean hemoglobin A1c (HbA1c) 6.9%]. At end point, 209 patients (56.9%) experienced hypoglycemia according to CGMS; 97 (26.4%) recorded hypoglycemia by conventional methods. CGMS- and SMBG-determined mean daytime glucose levels were similar at baseline and end point; however, nocturnal glucose levels were significantly lower with CGMS versus SMBG at baseline [130.2 vs. 145.0 mg/dL (7.2 vs. 8.1 mmol/L)] and at end point [123.3 vs. 137.3 mg/dL (6.8 vs. 7.6 mmol/L)]. Glucose levels measured by CGMS and SMBG decreased, and HbA1c levels decreased from 6.90% at screening to 6.67% at end point (P < 0.001). This study demonstrates that CGMS can be successfully employed in large clinical trial settings in patients with T2DM. This easy-to-implement method may provide additional insights into glucose levels and valuable information regarding the time patients spend within the preferred glucose range.

HIS modelling and simulation based cost–benefit analysis of a telemedical system for closed-loop diabetes therapy

Objectives INCA (Intelligent Control Assistant for Diabetes) is an EU funded project aimed at improving diabetes therapy by creating a personal closed-loop system interacting with telemedical remote control. This study aims at identifying and applying suitable methods for a cost–benefit analysis from the perspective of the payor for health services. Methods For cost analysis MOSAIK-M was used, a method and tool for health information systems analysis and design. Two MOSAIK-M models were created describing conventional insulin pump based diabetes care (CSII), and INCA based diabetes care. Both models were parameterised with costs and simulated to determine yearly costs of diabetes management and treatment for a patient with no diabetes related complications. Probability of developing complications and their duration were determined based on the Archimedes model. It was parameterised with results of a clinical study concerning HbA1c-value changes using the INCA system compared with conventional CSII. The simulation results in form of years of disease within a 30-year time frame were multiplied with corresponding treatment costs. Results Yearly costs of conventional insulin CSII for a diabetes type 1 patient are €5908 (German health care system). Using INCA based on the clinical study setting would raise yearly costs by €2233. 24% of the INCA costs are generated by the continuous blood glucose measurement device, 5% by IT devices and services. Considering also diabetes related complications in a 30-year time frame and HbA1c value reductions from 7.9 and 7.6% (conventional CSII) to 7.5 and 7.3% (INCA) reduces the additional costs of INCA to €2102 and €2162. Conclusions The approach produces an estimation of a lower bound for cost savings concerning the treatment of diabetes related complications in a 30-year time frame. These savings alone do not prove cost efficiency of the INCA approach. Further work is needed to improve the approximation and to include indirect and intangible costs.

Diurnal glycemic profile in obese and normal weight nondiabetic pregnant women

A paucity of data exists concerning the normal glycemic profile in nondiabetic pregnancies. Using a novel approach that provides continuous measurement of blood glucose, we sought to evaluate the ambulatory daily glycemic profile in the second half of pregnancy in nondiabetic women. Fifty-seven obese and normal weight nondiabetic subjects were evaluated for 72 consecutive hours with continuous glucose monitoring by measurement interstitial glucose levels in subcutaneous tissue every 5 minutes. Subjects were instructed not to modify their lifestyle or to follow any dietary restriction. For each woman, mean and fasting blood glucose values were determined; for each meal during the study period, the first 180 minutes were analyzed. For the study group, the fasting blood glucose level was 75 +/- 12 mg/dL; the mean blood glucose level was 83.7 +/- 18 mg/dL; the postprandial peak glucose value level was 110 +/- 16 mg/dL, and the time interval that was needed to reach peak postprandial glucose level was 70 +/- 13 minutes. A similar postprandial glycemic profile was obtained for breakfast, lunch, and dinner. Obese women were characterized by a significantly higher postprandial glucose peak value, increased 1- and 2-hour postprandial glucose levels, increased time interval for glucose peak, and significantly lower mean blood glucose during the night. No difference was found in fasting and mean blood glucose between obese and nonobese subjects. Glycemic profile characterization in both obese and normal weight nondiabetic subjects provide a measure for the desired level of glycemic control in pregnancy that is complicated with diabetes mellitus.

The postprandial glucose profile in the diabetic pregnancy

ObjectiveA controversy exists regarding the time to monitor blood glucose in the diabetic pregnancy (60 or 120 minutes after meals). Using a novel approach that provides continuous measurement of blood glucose, we sought to determine postprandial glucose profile in the diabetic pregnancy. Study designSubjects were connected to a continuous glucose monitoring system for 72 consecutive hours. A continuous glucose monitoring system measures the interstitial glucose levels in subcutaneous tissue every 5 minutes. Women were instructed to record the time of each meal during the study period. For each meal, the first 240 minutes were analyzed. ResultsSixty-five women participated in the study: 26 women were treated by diet alone; 19 women received insulin therapy, and 20 women had type 1 diabetes mellitus. The time interval from meal to peak postprandial glucose levels was similar in all the evaluated types of diabetic pregnancies and in good and poor control insulin-treated patients with gestational diabetes mellitus (approximately 90 minutes). Failure to return to preprandial glucose values within a 3-hour observation period was identified in approximately 50% of the patients. A similar postprandial glucose peak time was obtained for breakfast, lunch, and dinner in all study groups. Postprandial hypoglycemia events were noted in approximately 10% of the meals and occurred about 160 minutes after mealtime. ConclusionThe time interval for postprandial glucose peak in diabetic pregnancies is approximately 90 minutes after meals throughout the day and is not affected by the level of glycemic control. This information should be considered in the treatment of diabetes mellitus in pregnancy.

Environmental stress and blood glucose change in insulin-dependent diabetes mellitus.

Blood glucose (BG) response to psychological stress in insulin-dependent diabetes mellitus (IDDM) patients has not been firmly established. We report a study designed to address the gaps and methodological difficulties reviewed. Subjects with IDDM were exposed to two sessions (12 weeks apart) of two 20-min standardized stressors (active and passive) and a control condition administered in counterbalanced order. To measure BG response, subjects were connected to a glucose/insulin infusion system providing continuous BG measurement. Mood checklist measures were obtained at prestressor, poststressor, and recovery periods. During the first session of testing, the active stressor was associated with significantly more absolute change in BG response than the passive stressor. Results also indicate that IDDM subjects' BG response to this active stressor was idiosyncratic but significantly reliable over time.

Glucose clamping and cardiovascular function in endotoxic dogs.

Fasted mongrel dogs were anesthetized with pentobarbital sodium and instrumented for the continuous measurement of blood glucose (BG), a lead II electrocardiogram, and pressures in the left ventricle (LV), pulmonary artery, and aorta. Cardiac output was measured every 15 min using thermodilution and LV stroke work, and pulmonary and systemic resistances were calculated. After a 30-min pretreatment period, glucose clamping was initiated. The desired glucose levels were reached within 45 min (hypoglycemic 20 +/- 1 mg/dl, n = 11; normoglycemic 85 +/- 1, n = 7; hyperglycemic 156 +/- 3, n = 7). At this point dogs were treated with either endotoxin (8 mg/kg to 6 hypoglycemic, 4 normoglycemic, and 4 hyperglycemic) or saline (5 hypoglycemic, 3 normoglycemic, and 3 hyperglycemic). All infusions were terminated after 2 h glucose clamping, and all dogs were monitored either until death or for a maximum of 10 h. Hypoglycemic clamping curtailed survival in endotoxic dogs. Hyperglycemic clamping markedly prolonged survival. Normoglycemic clamping left survival time unchanged compared with untreated dogs. The effects of glucose clamping on cardiovascular function during endotoxic shock paralleled the effects on survival. Cardiovascular function was also depressed in hypoglycemic-clamped saline dogs. It is concluded that glucose dyshomeostasis may be a crucial factor in the development of fatal cardiovascular dysfunction and shock after endotoxin administration.

On-line continuous measurement of blood glucose and meal pattern in free-feeding rats: The role of glucose in meal initiation

LouisSylvestre and LeMagnen have suggested that the premeal decline in blood glucose is or reflects a signal for meal initiation in rats. In order to extend and test this hypothesis, a computer controlled system for continuously and concurrently measuring blood glucose and food intake in free-feeding rats was developed. In 18 experiments (with and without intravenous saline infusions), blood glucose declined about 12 minutes prior to meal onset. During 2−1 2 hours of observation, no decline in blood glucose and no meal occurred in 19 other experiments. In 7 experiments in which 10 percent glucose was infused IV to partially block the premeal decline (average blockade=46.5%), the subsequent meal was significantly delayed. These results suggest that the pre-meal decline in blood glucose is not only correlated with but is also causally related to meal onset. These studies suggest that the premeal decline in blood glucose is among the signals for meal initiation.