Interstitial Fluid Glucose Levels Research Articles

Protocol of a Prospective Observational Study on the Relationship Between Glucose Fluctuation and Cardiovascular Events in Patients with Type 2 Diabetes.

IntroductionA recent study demonstrated that large glucose fluctuations were associated with an increased incidence of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction. However, it is unknown whether glucose fluctuations are related to the incidence of CVD or the progression of atherosclerosis in patients with T2DM with no apparent history of CVD. In this protocol, we will be investigating the relationships of glucose fluctuations evaluated by continuous glucose monitoring (CGM) to the incidence of composite cardiovascular events and the progression of atherosclerosis in patients with T2DM who had no apparent history of CVD.MethodsThis is a prospective, multicenter, 5-year follow-up observational study. Between April 2018 and October 2019, 1000 participants are expected to be recruited at 34 medical institutions. CGM using FreeStyle Libre Pro is useful for evaluating glucose fluctuations by continuously monitoring glucose levels in interstitial fluid for up to 14 days. The primary study outcome is the relationship between fluctuations in glucose levels evaluated by CGM and the incidence of composite cardiovascular events. Secondary outcomes include the relationships of fluctuations in glucose levels evaluated by CGM to changes in carotid intima media thickness evaluated by echography or grayscale median (an index of tissue characteristics of the carotid wall), brachial–ankle pulse wave velocity, development or progression of diabetic retinopathy or nephropathy, quality-of-life-related diabetes therapy, quality of sleep, development of dementia, and autonomic nerve function.Planned OutcomeThis protocol is designed to investigate the relationship between glucose fluctuations and the incidence of composite cardiovascular events. We completed the registration of 1000 participants in March 2019. Thus, results will be available in 2024. We expect that evaluating glucose fluctuations will aid the identification of patients with a high probability of developing CVD.Trial RegistrationClinicalTrials.gov identifier, UMIN000032325.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-0665-8) contains supplementary material, which is available to authorized users.

Glucose-responsive poly(vinyl alcohol)/β-cyclodextrin hydrogel with glucose oxidase immobilization

Glucose-responsive poly(vinyl alcohol)/β-cyclodextrin (PVA/β-CD) hydrogels cross-linked by citric acid were prepared through an environment-friendly synthesis procedure. The glucose oxidase (GOx) was physically immobilized within the β-CD cavity for accurate detection of interstitial fluid glucose levels reaching approximately 1 mM. We evaluated the viscoelastic behavior of the PVA/β-CD solutions through dynamic oscillatory shear testing, and the PVA/β-CD/GOx hydrogel 10 shows the optimal properties with excellent water absorption (312 ± 17%), low solubility, and long moisture retention time (approximately 4.5 h for complete drying at 37 °C). The PVA/β-CD/GOx hydrogel showed the high flexural and tensile strengths of ≥ 400 and ≥ 5 MPa, respectively. Furthermore, the fabricated PVA/β-CD/GOx hydrogel 10 displayed a linear amperometric response (R2 is 0.984) in the glucose concentration range from 1.0 to 5.0 mM with a relatively high sensitivity of 7.58 µA mM−1 and a low detection limit of 5.141 × 10−4 M at low applied potential (0.27 V vs. Ag/AgCl coated with Prussian blue), indicating its great potential as a patch sensor for noninvasive glucose monitoring.

A cellulose/β-cyclodextrin nanofiber patch as a wearable epidermal glucose sensor

In this study, we aimed to develop a cellulose/β-cyclodextrin (β-CD) electrospun immobilized GOx enzyme patch with reverse iontophoresis for noninvasive monitoring of interstitial fluid (ISF) glucose levels (0.1–0.6 mM dm−3). In vitro analysis, performed using a sensor attached to flexible substrates, revealed that the high diffusion coefficient (9.0 × 10−5 cm2 s−1), the linear correlation coefficient (R2 = 0.998), the detection limit (9.35 × 10−5 M), and the linear range sensitivity (0–1 mM) of the sensor (5.08 μA mM−1) remained unaffected by the presence of interfering substances (e.g., fructose, sucrose, uric acid, and acetaminophen) at physiological levels. The present results indicate that the new epidermal sensing strategy using nanofibers for continuous glucose monitoring has potential to be applied in diagnosis of diabetes.

Use of flash glucose-sensing technology (FreeStyle Libre) in youth with type 1 diabetes: AWeSoMe study group real-life observational experience.

Frequent glucose testing is required for optimal management of type 1 diabetes (T1D). Limited data are available regarding real-world experience of the novel technology for monitoring by continuous interstitial fluid glucose (IFG), using flash glucose-sensing technology (FSL-CGM). We aimed to assess the effect of FSL-CGM in a real-life clinical setting on glycemic control parameters, compliance, and adverse events among pediatric and young adult T1D patients. This observational multi-center study assessed FSL-CGM use (6-12months) in T1D patients (mean ± SD age 13.4 ± 4.9years) who purchased the device out-of-pocket. Outcome measures included HbA1c, mean IFG levels, CGM metrics [time in hypoglycemia (< 54mg/dL; < 3mmol/L), in target range (70-180mg/dL; 3.9-10mmol/L), and in hyperglycemia > 240mg/dL; > 13.3mmol/L)], frequency of self-monitoring of blood glucose, acute complications, skin reactions, and reasons for initiation/discontinuation. Among patients with regular use of the FSL-CGM (n = 59), mean HbA1c decreased from 8.86 ± 0.23 to 8.05 ± 0.2% (73.3-64.5mmol/mol) in 3 months (p = 0.0001) and plateaued thereafter. A clinically significant reduction in HbA1c (defined as a decrease of ≥ 0.5%) was associated with shorter diabetes duration. Of 71 patients who initiated use of the FSL-CGM, 12 (16.9%) discontinued during the study period. No statistically significant changes were found after FSL-CGM use, in mean and standard deviation IFG levels, and in time of glucose levels in target, hypoglycemia, and hyperglycemia ranges. One patient with hypoglycemia unawareness was found dead-in-bed while using FSL-CGM. Real-life observational data in a self-selected young T1D population demonstrated a significant and sustained reduction in HbA1c with FSL-CGM in one-third of the participants. Surveillance of glucose monitoring should be individualized, especially for patients with hypoglycemia unawareness.

Risk Factors of Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Study Based on Continuous Glucose Monitoring

The objective of this study was to determine the risk factors of hypoglycemia by evaluating the glycemic profile using continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM). The participants were 294 patients with T2DM who received inpatient diabetes education. The mean blood glucose (MBG), coefficient of variation (CV), mean postprandial glucose excursion, low blood glucose index (LBGI), and percentage of time with blood glucose (BG) at <70 mg/dL were measured on admission using CGM. We predicted the risk of hypoglycemia utilizing transform to Gaussian model. The primary end point was the relationship between CGM parameters and hypoglycemia. Multivariate logistic regression analysis showed that disease duration, MBG, CV, LBGI, and Predicted% of BG correlated significantly with hypoglycemia. Receiver operating characteristic curve analysis showed that the optimal cutoff points for MBG and CV in predicting hypoglycemia were 152 mg/dL and 22%, respectively. The proportion of patients with hypoglycemia was 0% for the group with no hypoglycemia risk factors, 4.2% for the group with one risk factor, and 36.6% for the group with two risk factors, showing a linear increase across the groups (P < 0.001). LBGI was the best predictor of hypoglycemia; and Predicted% BG <70 mg/dL was very useful as an index to predict hypoglycemia. Patients with low MBG levels and large fluctuations in BG were more likely to develop hypoglycemia, suggesting that assessment of these two variables is useful for the prediction of hypoglycemia. To achieve good glycemic control free of hypoglycemia, approaches are needed that do not only lower BG level but also minimize fluctuations in blood and interstitial fluid glucose level.

Self-measurement of Blood Glucose and Continuous Glucose Monitoring - Is There Only One Future?

Monitoring glycaemic control in patients with diabetes has evolved dramatically over the past decades. The introduction of easy-to-use systems for self-monitoring of blood glucose (SMBG) utilising capillary blood samples has resulted in the availability of a wide range of systems, providing different measurement quality. Systems for continuous glucose monitoring (CGM) – used mainly in patients with type 1 diabetes (T1D) – were made possible by the development of glucose sensors that measure glucose levels in the interstitial fluid (ISF) in the subcutaneous tissue of the skin. CGM readings might not correspond exactly to SMBG measurement results taken at the same time, especially during rapid changes in either blood glucose or ISF glucose levels. The mean absolute relative difference is the most popular method used for characterising the measurement performance of CGM systems. Unlike the International Organization for Standardization 15197:2013 criteria for SMBG systems, no accuracy standards for CGM systems exist. Measurement quality of CGM systems can vary based on several factors, limiting their safety and effective use in managing diabetes. Patients have to be trained adequately to make safe and efficient use of CGM systems (like with SMBG systems). Also, systems for CGM must be evaluated in terms of patient safety and the ability to provide accurate measurements regardless of the fluctuation of glucose levels. As new technological advancements in glucose monitoring are essential for improved management options of diabetes, such as automated insulin dosing systems, there is a need for a critical view of all such developments. It is likely that both, SMBG and CGM systems, will play important future roles in the treatment of diabetes.

Interstitial Glucose and Lactate Levels Are Inversely Correlated With the Body Mass Index: Need for In Vivo Calibration of Glucose Sensor Results With Blood Values in Obese Patients.

Continuously measured glucose and lactate levels in interstitial fluid (ISF) may markedly differ from their respective blood levels. Combining microdialysis with a bioanalytical microsystem, the interstitial glucose and lactate concentrations of eight male volunteers with different body mass index (BMI) were monitored during a 2-fold glucose tolerance test over the period of three hours. Significant correlations were found between abdominally measured sensor results and reference measurements ( R2 = .967 for glucose and R2 = .936 for lactate, P < .05). The physiological delay of the abdominally observed glucose appearance in the ISF correlated positively with the BMI ( R2 = .787, P < .05). The relative in vivo recovery of glucose and lactate was inversely proportional to the BMI of the volunteers ( R2 = .540 for glucose, R2 = .609 for lactate, P < .05). One subject with a BMI of > 34 kg/m2 showed abdominally as well as the antebrachially significantly reduced tissue glucose values compared to blood glucose values ( P < .001). A very good correlation between abdominally measured sensor results and the results of the reference method verified the reliability of the BioMEMS. The abdominally measured glucose level in ISF decreased significantly with increasing BMI. Therefore, an in vivo calibration of glucose levels in ISF with blood levels seems to be necessary especially in markedly obese subjects.

Using meta-differential evolution to enhance a calculation of a continuous blood glucose level

We developed a new model of glucose dynamics. The model calculates blood glucose level as a function of transcapillary glucose transport. In previous studies, we validated the model with animal experiments. We used analytical method to determine model parameters. In this study, we validate the model with subjects with type 1 diabetes. In addition, we combine the analytic method with meta-differential evolution. To validate the model with human patients, we obtained a data set of type 1 diabetes study that was coordinated by Jaeb Center for Health Research. We calculated a continuous blood glucose level from continuously measured interstitial fluid glucose level. We used 6 different scenarios to ensure robust validation of the calculation. Over 96% of calculated blood glucose levels fit A+B zones of the Clarke Error Grid. No data set required any correction of model parameters during the time course of measuring. We successfully verified the possibility of calculating a continuous blood glucose level of subjects with type 1 diabetes. This study signals a successful transition of our research from an animal experiment to a human patient. Researchers can test our model with their data on-line at https://diabetes.zcu.cz.

Metabolic control and depression in type 1 diabetes mellitus

The most common mental disorder in patients with diabetes mellitus (DM) is depression (DS). Despite the large number of papers about DS in DM, its prevalence in type 1 DM (T1DM) remains unclear. Aim. The aim of this study was to investigate the prevalence of DS in T1DM and its possible association with metabolic control disorders. Materials and Methods. The study included 163 patients with T1DM. The patients were aged 18?65 years, and the mean duration of T1DM was 11.18 years (range 4.28?22.33 years). The control group included 75 apparently healthy individuals. The subjects underwent physical examination, and the standard self-report Hospital Anxiety and Depression Scale questionnaire was administered to evaluate the level of anxiety and DS. Psychological counselling was conducted to diagnose DS and its severity. The continuous glucose monitoring system (CGMS) was used to monitor interstitial fluid glucose levels. Statistical analysis was conducted using SPSS Statistics 17.0 and StatSoft Statistica 6.0. Results. The prevalence of DS among the patients with T1DM was much higher (approximately two-fold) than the prevalence among the healthy individuals. Female sex and age over 40 years were associated with the presence of DS. Conclusion. The development of DS in patients with T1DM is accompanied by poor glycaemic control and increased risk of hypoglycaemic episodes.

Blood glucose level reconstruction as a function of transcapillary glucose transport

A diabetic patient occasionally undergoes a detailed monitoring of their glucose levels. Over the course of a few days, a monitoring system provides a detailed track of their interstitial fluid glucose levels measured in their subcutaneous tissue. A discrepancy in the blood and interstitial fluid glucose levels is unimportant because the blood glucose levels are not measured continuously. Approximately five blood glucose level samples are taken per day, and the interstitial fluid glucose level is usually measured every 5min. An increased frequency of blood glucose level sampling would cause discomfort for the patient; thus, there is a need for methods to estimate blood glucose levels from the glucose levels measured in subcutaneous tissue. The Steil–Rebrin model is widely used to describe the relationship between blood and interstitial fluid glucose dynamics. However, we measured glucose level patterns for which the Steil–Rebrin model does not hold. Therefore, we based our research on a different model that relates present blood and interstitial fluid glucose levels to future interstitial fluid glucose levels. Using this model, we derived an improved model for calculating blood glucose levels. In the experiments conducted, this model outperformed the Steil–Rebrin model while introducing no additional requirements for glucose sample collection. In subcutaneous tissue, 26.71% of the calculated blood glucose levels had absolute values of relative differences from smoothed measured blood glucose levels less than or equal to 5% using the Steil–Rebrin model. However, the same difference interval was encountered in 63.01% of the calculated blood glucose levels using the proposed model. In addition, 79.45% of the levels calculated with the Steil–Rebrin model compared with 95.21% of the levels calculated with the proposed model had 20% difference intervals.

Maternal glucose response to betamethasone administration.

This study aims to describe the pattern of maternal glucose response to betamethasone administration using a continuous glucose monitoring system. A prospective observational trial was conducted among women receiving clinically indicated betamethasone between 24 and 34 weeks gestation. At the time of initial betamethasone administration, a continuous glucose monitoring device was inserted which measured interstitial fluid glucose levels every 5 minutes. Glucose levels were monitored for 7 days, until delivery, or until hospital discharge, whichever came first. We recorded the percentage of time women spent above three glucose thresholds: 110, 144, and 180 mg/dL, respectively. A total of 17 women were enrolled at the time of betamethasone administration and data were available for 15 patients. There were 11 nondiabetic and 4 diabetic women. Both diabetic and nondiabetic women had the highest recorded blood glucose readings between 24 and 48 hours after the first injection of betamethasone. In that period, nondiabetic women spent 73, 40, and 17% of the time with blood glucose levels above the 110, 144, and 180 mg/dL thresholds, respectively. Nondiabetic women receiving betamethasone manifest significant hyperglycemia after betamethasone administration. If delivery is imminent, maternal glucose response to betamethasone may need to be monitored to prevent possible neonatal hypoglycemia.

Glucose predictability, blood capillary permeability, and glucose utilization rate in subcutaneous, skeletal muscle, and visceral fat tissues

This study suggests an approach for the comparison and evaluation of particular compartments with modest experimental setup costs. A glucose level prediction model was used to evaluate the compartment's glucose transport rate across the blood capillary membrane and the glucose utilization rate by the cells. The glucose levels of the blood, subcutaneous tissue, skeletal muscle tissue, and visceral fat were obtained in experiments conducted on hereditary hypertriglyceridemic rats. After the blood glucose level had undergone a rapid change, the experimenter attempted to reach a steady blood glucose level by manually correcting the glucose infusion rate and maintaining a constant insulin infusion rate. The interstitial fluid glucose levels of subcutaneous tissue, skeletal muscle tissue, and visceral fat were evaluated to determine the reaction delay compared with the change in the blood glucose level, the interstitial fluid glucose level predictability, the blood capillary permeability, the effect of the concentration gradient, and the glucose utilization rate. Based on these data, the glucose transport rate across the capillary membrane and the utilization rate in a particular tissue were determined. The rates obtained were successfully verified against positron emission tomography experiments. The subcutaneous tissue exhibits the lowest and the most predictable glucose utilization rate, whereas the skeletal muscle tissue has the greatest glucose utilization rate. In contrast, the visceral fat is the least predictable and has the shortest reaction delay compared with the change in the blood glucose level. The reaction delays obtained for the subcutaneous tissue and skeletal muscle tissue were found to be approximately equal using a metric based on the time required to reach half of the increase in the interstitial fluid glucose level.

Glycosylated Hemoglobin and Albumin-Corrected Fructosamine Are Good Indicators for Glycemic Control in Peritoneal Dialysis Patients

PurposeDiabetes mellitus (DM) is the most common cause of end-stage renal disease and is an important risk factor for morbidity and mortality after dialysis. However, glycemic control among such patients is difficult to assess. The present study examined glycemic control parameters and observed glucose variation after refilling different kinds of fresh dialysate in peritoneal dialysis (PD) patients.MethodsA total of 25 DM PD patients were recruited, and continuous glucose monitoring system (CGMS) was applied to measure interstitial fluid (ISF) glucose levels at 5-min intervals for 3 days. Patients filled out diet and PD fluid exchange diaries. The records measured with CGMS were analyzed and correlated with other glycemic control parameters such as fructosamine, albumin-corrected fructosamine (AlbF), glycosylated hemoglobin (HbA1c), and glycated albumin levels.ResultsThere were significant correlations between mean ISF glucose and fructosamine (r = 0.45, P<0.05), AlbF (r = 0.54, P<0.01), and HbA1c (r = 0.51, P<0.01). The ISF glucose levels in glucose-containing dialysate increased from approximately 7–8 mg/dL within 1 hour of exchange in contrast to icodextrin dialysate which kept ISF glucose levels unchanged.ConclusionHbA1c and AlbF significantly correlated with the mean ISF glucose levels, indicating that they are reliable indices of glycemic control in DM PD patients. Icodextrin dialysate seems to have a favorable glycemic control effect when compared to the other glucose-containing dialysates.

In Vivo Noninvasive Monitoring of Glucose Concentration in Human Epidermis by Mid-Infrared Pulsed Photoacoustic Spectroscopy

The noninvasive determination of glucose in the interstitial layer of the human skin by mid-infrared spectroscopy is reported. The sensitivity for this measurement was obtained by combining the high pulse energy from an external cavity quantum cascade laser (EC-QCL) tunable in the infrared glucose fingerprint region (1000-1220 cm(-1)) focused on the skin, with a detection of the absorbance process by photoacoustic spectroscopy in the ultrasound region performed by a gas cell coupled to the skin. This combination facilitates a quantitative measurement for concentrations of skin glucose in the range from <50 mg/dL to >300 mg/dL, which is the relevant range for the glucose monitoring in diabetes patients. Since the interstitial fluid glucose level is representative of the blood glucose level and follows it without significant delay (<10 min), this method could be applied to establish a noninvasive, painless glucose measurement procedure that is urgently awaited by diabetes patients. We report here the design of the photoacoustic experiments, the spectroscopy of glucose in vivo, and the calibration method for the quantitative determination of glucose in skin. Finally, a preliminary test with healthy volunteers and volunteers suffering from diabetes mellitus demonstrates the viability of a noninvasive glucose monitoring for patients based on the combination of infrared QCL and photoacoustic detection.

Prediction of Interstitial Glucose Level

Glucose is an important source of energy for cells. In clinical practice, we measure glucose level in blood and interstitial fluid. Each method has its pros and cons, and both levels correlate with each other. As the body tries to maintain the glucose level within a particular range to avoid adverse effects, it is desirable to predict future glucose levels in order to aid provided health care. We can see this desire in research, e.g., research on glucose transporters of cells. As yet another example, we can see it with diabetic patients, patients in a metabolic intensive care unit, particularly. In this paper, a glucose level prediction method is proposed.

Feasibility of Continuous Glucose Monitoring in Critically Ill Emergency Department Patients

BackgroundGlucose control is important in the management of critically ill patients. However, strict glucose control requires a large amount of nursing resources, especially in overcrowded emergency departments (EDs). ObjectivesA continuous glucose monitoring system (CGMS) may be beneficial for glucose control in the ED. The objective of this study was to determine the test characteristics of CGMS in critically ill ED patients. MethodsA prospective observational study of critically ill ED patients was conducted. During a patient’s visit to the ED, a CGMS sensor measured their interstitial fluid glucose levels continuously. Capillary glucose was measured every hour and used for glucose control and as a reference value. CGMS values were recorded in real time and compared with capillary glucose values. ResultsA total of 122 pairs of capillary and CGMS glucose values in 12 patients were analyzed. The correlation coefficient was 0.87, and Bland-Altman analysis showed that 117 pairs (95.9%) were within a 95% confidence interval. A Clarke Error Grid Analysis indicated an overall accuracy of 96.8% (Zones A and B). However, the mean absolute relative difference (MARD) was significantly higher in the hypoglycemic range than in a normo- or hyperglycemic range (p = 0.001). The sensitivity and positive predictive value of CGMS for detecting hypoglycemia were 33.3% and 16.7%, respectively. The CGMS specificity and negative predictive value were 95.8% and 98.3%, respectively. There was no linear correlation between MARD and body mass index, axillary temperature, inotrope score, and base deficit (all p-value >0.05). ConclusionCGMS demonstrated good clinical accuracy by Clarke Error Grid Analysis. There also was high agreement between CGMS and capillary glucose levels. However, CGMS demonstrated only limited real-time hypoglycemia detection ability in critically ill ED patients.

1082 Continuous Glucose Monitoring in Morbidly Obese Children with Normal Fasting Bg and Normal Ogtt

This study has been undertaken to assess the glucose metabolism disorder by CGMS in morbidly obese children (BMI > 28) who have normal fasting glucose level and normal oral glucose tolerance. Methods: Ten morbidly obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 72 hours as well as by self-monitored blood glucose (SMBG) (3-4 times per day). The circulating fasting glucose, insulin, c-peptide, free T4, TSH, and HbA1C concentrations were measured. Results: The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.742, P 7.6 mmol/L 2 h after food intake) and one had a diabetic curve (T2DM) (BG > 11.2 mmol/L 2 h after food intake). None of the children had elevated HbA1C level. Hyperinsulinemia and/or high C-peptide was recorded in 9 out of the 10 children. Conclusions: Our data suggest that glucose metabolism disorder including impaired postprandial glycemia and type 2 DM can be early diagnosed in morbidly obese children using CGMS when fasting BG and HbA1C levels are still normal. Further studies are required to improve the criteria of early diagnosis of glycemic abnormalities using CGMS.

Differences in complexity of glycemic profile in survivors and nonsurvivors in an intensive care unit: A pilot study*

To investigate glycemic dynamics and its relation with mortality in critically ill patients. We searched for differences in complexity of the glycemic profile between survivors and nonsurvivors in patients admitted to a multidisciplinary intensive care unit. Prospective, observational study, convenience sample. Multidisciplinary intensive care unit of a teaching hospital in Madrid, Spain. A convenience sample of 42 patients, aged 29 to 86 yrs, admitted to an intensive care unit with an Acute Physiology and Chronic Health Evaluation II score of >or=14 and with an anticipated intensive care unit stay of >72 hrs. A continuous glucose monitoring system was used to measure subcutaneous interstitial fluid glucose levels every 5 mins for 48 hrs during the first days of intensive care unit stay. A 24-hr period (n = 288 measurements) was used as time series for complexity analysis of the glycemic profile. Complexity of the glycemic profile was evaluated by means of detrended fluctuation analysis. Other conventional measurements of variability (range, sd, and Mean Amplitude of Glycemic Excursions) were also calculated. Ten patients died during their intensive care unit stay. Glycemic profile was significantly more complex (lower detrended fluctuation analysis) in survivors (mean detrended fluctuation analysis, 1.49; 95% confidence interval, 1.44-1.53) than in nonsurvivors (1.60; 95% confidence interval, 1.52-1.68). This difference persisted after accounting for the presence of diabetes. In a logistic regression model, the odds ratio for death was 2.18 for every 0.1 change in detrended fluctuation analysis.Age, gender, Simplified Acute Physiologic Score 3 or Acute Physiologic and Chronic Health Evaluation II scores failed to explain differences in survivorship. Conventional variability measurements did not differ between survivors and nonsurvivors. Complexity of the glycemic profile of critically ill patients varies significantly between survivors and nonsurvivors. Loss of complexity in glycemia time series, evaluated by detrended fluctuation analysis, is associated with higher mortality.

Brain interstitial fluid TNF-α after subarachnoid hemorrhage

Objective TNF-α is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-α may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH). Methods We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8 h and recorded at the same point that brain interstitial fluid TNF-α was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations. Results Each patient had a mean of 9 brain tissue TNF-α measurements obtained over an average of 72 h of monitoring. TNF-α levels rose progressively over time. Predictors of elevated brain interstitial TNF-α included higher brain interstitial fluid glucose levels ( β = 0.066, p < 0.02), intraventricular hemorrhage ( β = 0.085, p < 0.021), and aneurysm size > 6 mm ( β = 0.14, p < 0.001). There was no relationship between TNF-α levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate–pyruvate ratio. Interpretation Brain interstitial TNF-α levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels.

Correlations of Glucose Levels in Interstitial Fluid Estimated by Continuous Glucose Monitoring Systems and Venous Plasma

Continuous glucose monitoring systems (CGMS) are relatively new technology that measures interstitial glucose every 5 minute over a period of 72 hours [1]. Continuous glucose monitoring by CGMS provides accurate data to patients and physicians about blood glucose variability during the measurement period. Two types of CGMS devices, intended for professional and personal use, are available. Professional devices allow physicians to download and analyze data and for use in clinical decision making. Personal devices allow patients to monitor real time glucose data and use such data for self-monitoring and medication adjustments. For this reason, the American Association of Clinical Endocrinologists has recommended the use of personal devices for glucose control and prevention of hypoglycemia in patients with type 1 diabetes [2,3] and pregnancy with diabetes [4,5]. The article, correlation and accuracy of glucose levels between interstitial fluid and venous plasma by continuous glucose monitoring system [6] clearly showed a glucose time lag between blood levels and subcutaneous interstitial levels. Blood and interstitial fluid had different peak times and peak values after meal loading, but the trends of glucose excursion were very similar. In addition, CGMS data showed delayed peaks and lowered peak values compared to venous blood sugar levels after the ingestion of different kinds of food. These lags between the two compartments did not differ by food. The use of CGMS devices, which provide accurate control and monitoring of blood glucose levels, is suitable for use in uncontrolled diabetic patients and to help physicians make decisions regarding treatment modalities. In the treatment of diabetes, glucose variability, especially postprandial hyperglycemia, is a major risk factor for cardiovascular complications. By using CGMS devices, clinicians can easily access glucose variability in patients. Although patients more easily achieved target HbA1c levels when practicing self monitoring of glucose using the CGMS device than by other methods, systemic reviews comparing the results of CGMS use and intermittent fingertip glucose monitoring do not indicate significantly superior benefits of CGMS. However, they do support the improved detection of asymptomatic nocturnal hypoglycemia [7]. CGMS systems offer many advantages to patients and physicians. However, the sensitivity of glucose sensing decreases over time. After 3 to 5 days, the sensing amplitude of CGMS sensors becomes unreliable. The accuracy of sensors is affected by localized tissue reactions and fibrous encapsulation [8]. For these reasons, patients should calibrate sensing amplitudes through comparisons with fingertip glucose values regularly. Methods of blocking fibrous tissue aggregation and reducing tissue reactions, such as corticosteroid sprays or anticancer drug coatings, were used in attempts to address these problems [9,10]. Also, if we placed the sensor in subcutaneous space during continuous monitoring, small glucose diffusion gap from blood level to subcutaneous tissue fluid was another limitation. Recently, ubiquitous health systems have been introduced to help outpatients to control their blood sugar levels. If patients send their blood glucose profiles to physicians over the internet, their physicians can provide advice to meet their patients' needs. The use of CGMS systems connected to Internet networks has the potential to provide effective, evidence-based support to clinicians in their daily efforts to optimize glycemic control [11]. The closed loop pump is a state of the art technology [12,13]. But major pitfall of this closed loop pump is sensing problems of glucose sensor and limited space of insulin reservoir in transplanted pump. Closed loop pumps are expected to replace open loop pumps and decrease the pain associated with insulin injections. Permanent usable blood glucose sensors and interstitial glucose sensors are also expected to be developed [9,10]. Rapid development of information technology devices and techniques will solve the relevant technological problems, and closed loop systems will be available to patients in the future.