Interstitial Fluid Glucose Research Articles

Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system

Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, P<0.001). However, the correlation between ISF and capillary glucose levels was lower during the first hour than that in the later time period (r=0.722 vs r=0.830), and the ISF glucose levels in 69.62% of children were higher than baseline levels in the initial 1-3 hours. In 79 obese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.

Tight glycemic control: comparison of a real-time continuous interstitial tissue glucose monitoring system with arterial plasma glucose measurement in critically ill patients

The purpose of the study was to compare the results of interstitial glucose measurements obtained by the Guardian Real-time system and arterial plasma glucose concentration in mechanically ventilated, critically ill patients. The Guardian Real-time continuous glucose monitoring system is an external device that uses a subcutaneous microsensor that measures the concentrations of glucose in interstitial fluid.

Continuous Glucose Monitoring in Dogs and Cats

Use of continuous glucose monitoring in veterinary medicine is gaining popularity. Through use of a commercially available continuous glucose monitor system, insights into daily glucose changes in dogs and cats are achievable. The continuous glucose monitoring system measures glucose concentrations in the interstitial fluid of the subcutaneous space by use of a small, flexible probe. When placed in the subcutaneous tissue, the probe is connected to a recording device that is attached to the animal and records the interstitial fluid glucose concentration every 5 minutes (288 readings per 24 hours). Once attached and properly calibrated, the instrument can remain in place for several days, hospitalization of the patient is not necessary, and the normal daily routine of the animal can be maintained. The data from the recording device are then downloaded and a very detailed picture of the interstitial fluid glucose concentration over that time period can be obtained. Subcutaneous interstitial fluid glucose concentrations have a good correlation to blood glucose concentrations within a defined range. The continuous glucose monitoring system has distinct advantages over traditional blood glucose curves and is a valuable tool for managing diabetic dogs and cats. In addition, other clinical uses for continuous glucose monitoring are being developed. This review is designed to outline the technology behind the continuous glucose monitoring system, describe the clinical use of the instrument, provide clinical examples in which it may be useful, and discuss future directions for continuous glucose monitoring in dogs and cats.

Continuous Subcutaneous Glucose Monitoring Shows a Close Correlation between Mean Glucose and Time Spent in Hyperglycemia and Hemoglobin A1c

The Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study highlighted hemoglobin A1c (HbA1c) as the main predictor of diabetic complications. Currently, diabetes is managed by frequent capillary spot glucose measurements, but continuous monitoring systems may have the capacity of improving diabetic control. The SCGM 1 system is microdialysis based and allows for monitoring of changes in interstitial fluid glucose levels every minute. The aim of this study was to evaluate the correlation between HbA1c and short-term glucose excursions in patients with type 1 diabetes. We investigated 91 patients with type 1 diabetes (mean +/- standard deviation (SD); age 34 +/- 10 years, body mass index 24.2 +/- 4.1 kg/m2) with a duration of diabetes of 17 +/- 11 years for 4.8 +/- 0.4 days. The average HbA1c was 7.9 +/- 1.4%. From the monitoring profiles we determined individual mean glucose, the SD of glucose, and the relative time spent in hyperglycemia and hypoglycemia calculated as the area under the curve (AUC) with arbitrary cutoffs of 180 and 70 mg/dl, respectively. Mean glucose, SD glucose, and hyperglycemic and hypoglycemic AUC all correlated with HbA1c, but with decreasing statistical power. In multiple linear regression analysis, mean glucose was the sole independent variable (r = 0.626, p < 0.0001). A close correlation between HbA1c and various measures of short-term hyperglycemic values was observed. There was a close correlation between mean glucose and SD glucose, pointing toward increased variability with increasing mean glucose. Mean glucose generated after short-term continuous monitoring is the main predictor of HbA1c and reveals increased lability of glucose with increasing mean glucose and HbA1c.

The Role of Continuous Glucose Monitoring in Clinical Decision-Making in Diabetes in Pregnancy

Numerous studies have shown that improved glucose control in pregnancy will lessen both maternal and fetal complications, but adverse outcomes remain more frequent in diabetic than in nondiabetic pregnancies. Complications increase with the degree of glucose intolerance. The continuous glucose monitoring system (CGMS) can provide a glucose profile over 72 hours. It consists of a disposable glucose-sensing device that is placed just beneath the skin and connects by cable to a pager-size glucose monitor. Interstitial-fluid glucose levels are estimated at 10-second intervals and averaged every 5 minutes. Pregnant women with diabetes were offered the CGMS in the setting of standard diabetes care. Its accuracy was determined by comparing the readings with patient's finger-prick glucose readings. Sixty-eight CGMS traces were obtained in 55 pregnant women: 37 with gestational diabetes, 10 with type 2 diabetes, and 8 with type 1 diabetes. Forty-two CGMS traces, 62% of the total, provided information beyond that available from the patients' home glucose monitoring diary. Examples include undetected postprandial hyperglycemia and overnight hypoglycemia. The CGMS was generally most helpful in women with type 1 diabetes, in whom all but 2 of 18 studies yielded additional information. More than three-fourths of women responding to a questionnaire expressed a belief that the benefits of the CGMS outweigh its inconvenience. All but 4 of 48 participants found the CGMS to be easy to use. In addition, 90% of respondents felt that they had a better understanding of how to control blood glucose since using the CGMS. In this community-based cohort study, these investigators found the CGMS to be of substantial help in managing preexisting and gestational diabetes in pregnant women. By adding information to that available from finger-prick monitoring, it may help clinicians to optimize glycemic control and prevent hypoglycemia.

Putative Delays in Interstitial Fluid (ISF) Glucose Kinetics Can Be Attributed to the Glucose Sensing Systems Used to Measure Them Rather than the Delay in ISF Glucose Itself

Since the advent of subcutaneous glucose sensors, there has been intense focus on characterizing the delay in the interstitial fluid (ISF) glucose response and the effect of insulin to alter the plasma-to-ISF glucose gradient. The Medtronic MiniMed continuous glucose monitoring system (CGMS) has often been used for this purpose; however, many of the studies have used experimental conditions that fall outside its intended use, for example, studies that have assessed the delay during rapid glucose excursions brought about by intravenous infusion of glucose or insulin. Under these conditions, it is possible that the rate of glucose change may exceed that allowed by CGMS filtering routines. If so, the estimated delay may be because of the filter rather than the ISF. Also, sensor characteristics, such as nonspecific offset current or stability, may have been inadvertently attributed to changes in the plasma-to-ISF gradient. The potential for these issues to have confounded the understanding of ISF glucose delay and gradient is investigated. An in vitro preparation in which no delay or gradient exists between sensor and measurement solution was used to recreate a rapidly changing glucose profile from a previously published in vivo study. The CGMS system (N = 6 sensors) was then used to estimate any artifactual delay and gradient introduced by the system per se. One-point calibration resulted in an apparent change in gradient as glucose was lowered from approximately 100 to 50 mg/dl. After a two-point calibration, sensor glucose followed the glucose profile as it was decreased slowly from approximately 100 to approximately 60 mg/dl; however, when the glucose level was subsequently increased rapidly to approximately 150 mg/dl, CGMS filtering routines limited the rate of change of sensor glucose and introduced a delay similar to that previously attributed to ISF glucose equilibration delay. Studies that have previously used the Medtronic MiniMed CGMS system to assess changes in the plasma-to-ISF glucose gradient may need to be reassessed to ensure that the offset current was estimated accurately. Studies that have used the system to assess ISF glucose delay during rapid, unphysiologic changes in glucose and did not remove the CGMS smoothing filters may have attributed CGMS filter delay to ISF glucose equilibration.

Reconstruction of Glucose in Plasma from Interstitial Fluid Continuous Glucose Monitoring Data: Role of Sensor Calibration

Continuous glucose monitoring (CGM) sensors measure glucose concentration in the interstitial fluid (ISF). Equilibration between plasma and ISF glucose is not instantaneous. Therefore, ISF and plasma glucose concentrations exhibit different dynamic patterns, particularly during rapid changes. The purpose of this work was to investigate how well plasma glucose can be reconstructed from ISF CGM data. Six diabetic volunteers were monitored for 2 days using the TheraSense FreeStyle Navigator (Abbott Diabetes Care, Alameda, CA), a minimally invasive device that, on the basis of an initial calibration procedure (hereafter referred to as standard calibration), returns ISF glucose concentration. Simultaneously, plasma glucose concentration was also measured every 15 minutes. First we identified, in each subject, the linear time-invariant (LTI) two-compartment model of plasma-interstitium kinetics. Then, a nonparametric regularization deconvolution method was used to reconstruct plasma from ISF glucose. Deconvoluted profiles were always closer to plasma glucose than ISF ones. However, the quality of the reconstruction is unsatisfactory. Some visible discrepancies between average plasma and ISF time series suggest problems either in the applicability of the LTI model of plasma-interstitium kinetics to normal life conditions or in the standard calibration with which ISF glucose is determined from the sensor internal readings. Assuming that the LTI model of plasma-interstitium kinetics is correct, we focused on the influence of calibration and we employed a recently proposed method to recalibrate ISF data. After the recalibration step, the relative error in reconstructing plasma glucose was reduced significantly. Results also demonstrate that further margins of improvement of plasma glucose reconstruction are possible by developing more sophisticated recalibration procedures.

Numerical simulation of the effect of rate of change of glucose on measurement error of continuous glucose monitors.

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg*dl(-1)*min(-1) (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg*dl(-1)*min(-1) (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone. Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy. The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose. The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.

Microdialysis Technique as a Monitoring System for Acute Complications of Diabetes

The objective of the study was to establish the quasi-continuous courses, using microdialysis technique, of glucose, lactate, and glycerol concentrations in interstitial fluid of abdominal adipose tissue during the standard treatment of acute diabetes complications. Clinical studies were carried out on 31 diabetic patients during the initial 48 h of the treatment. In all but two obese female patients with hyperglycemic hyperosmolar state (HHS) did glucose concentration in perfusion fluid (PF) reflect concentration in capillary blood. The recovery of glucose correlated with patients' body mass index (r = 0.55). It was significantly higher in lean and overweight patients (91 +/- 15%) than in obese patients (55 +/- 31%). The course of lactate concentration in PF coincided with the course in venous blood (2.1 +/- 0.3 mmol/L vs. 2.0 +/- 0.5 mmol/L, P = 0.35). Glycerol concentration was 267 +/- 41 micromol/L and 133 +/- 40 micromol/L in PF and venous blood, respectively (P = 0.004). The study indicated that microdialysis may be an effective tool to monitor concentration of different metabolites in interstitial fluid of the adipose tissue during treatment of the acute complications of diabetes. Applicability of the technique in the monitoring of HHS, especially in obese female patients, needs further investigation.

Tissue response to subcutaneous implantation of glucose-oxidase-based glucose sensors in rats

Considerable progress in improved control of disturbed glucose metabolism can be expected by continuous glucose monitoring. The aim of the study was to evaluate in male Sprague–Dawley rats tissue response to implantation of a new amperometric glucose-oxidase-based glucose sensor (NTS) compared to a commercially available sensor system CGMS of MiniMed. Both sensors were tested under working conditions over a period of 3 days. Using NTS, glucose in interstitial fluid reflected glucose in arterial blood even in rapidly changing hyper- and hypoglycaemia whereas the CGMS did not detect the experimentally induced glucose changes adequately. Gene expression profiling was performed using Affymetrix chips. Acute phase response to injury by sensor application for a short time is indicated by down regulation of the increase in mRNA of proteases e.g. metallothionein-1α and matrix metalloprotease-3 at day 3. Improvement of anabolic situation is suggested by decrease in mRNA of insulin-like growth factor binding protein whereas increase of heme oxygenase and hypoxia-inducible factor may be related to defense mechanisms. Changes of mRNA together with slight fibrous capsule formation suggest good histocompatibility. Comparability of the patterns of changed mRNA in tissue surrounding SCGM with and without operating voltage as shown in dendrogram indicates no contribution of hydrogen peroxide to worsening biocompatibility. Beside established histological investigations of foreign body reaction weeks or months after implantation, gene expression profiling provides additional information to biocompatibility already early after implantation.

Accuracy of the 5-Day FreeStyle Navigator Continuous Glucose Monitoring System

The purpose of this study was to compare the accuracy of measurements of glucose in interstitial fluid made with the FreeStyle Navigator Continuous Glucose Monitoring System with Yellow Springs Instrument laboratory reference measurements of venous blood glucose. Fifty-eight subjects with type 1 diabetes, aged 18-64 years, were enrolled in a multicenter, prospective, single-arm study. Each subject wore two sensors simultaneously, which were calibrated with capillary fingerstick measurements at 10, 12, 24, and 72 h after insertion. Measurements from the FreeStyle Navigator system were collected at 1-min intervals and compared with venous measurements taken once every 15 min for 50 h over the 5-day period of sensor wear in an in-patient clinical research center. Periods of high rates of change of glucose were induced by insulin and glucose challenges. Comparison of the FreeStyle Navigator measurements with the laboratory reference method (n = 20,362) gave mean and median absolute relative differences (ARDs) of 12.8 and 9.3%, respectively. The percentage in the clinically accurate Clarke error grid A zone was 81.7% and that in the in the benign error B zone was 16.7%. During low rates of change (< +/-1 mg x dl(-1) x min(-1)), the percentage in the A zone was higher (84.9%) and the mean and median ARDs were lower (11.7 and 8.5%, respectively). Measurements with the FreeStyle Navigator system were found to be consistent and accurate compared with venous measurements made using a laboratory reference method over 5 days of sensor wear (82.5% in the A zone on day 1 and 80.9% on day 5).

Monitoring Blood Glucose with Microdialysis of Interstitial Fluid in Critically Ill Children

Hyperglycemia, a common feature in critically ill patients, was traditionally perceived as an adequate stress response reflecting the severity of the disease state and was treated only if glycemia exceeded 11–13.5 mmol/L. In recent studies in intensive care patients, we showed that tight glycemic control (TGC) with intensive insulin therapy (IIT) reduced the risk of organ failure and death (1). In critically ill children, peak blood glucose (BG) and duration of hyperglycemia are associated with risk of mortality (2). Implementing TGC and avoiding hypoglycemia with intensive insulin therapy requires frequent BG sampling. Microdialysis of interstitial fluid (ISF) is a promising approach to reduce diagnostic blood loss. Continuously sampling dialyzed ISF and converting the ISF glucose concentration (IFG) to a BG value is a promising new method for glucose monitoring in diabetes patients. We conducted a prospective clinical trial in critically ill children to evaluate the feasibility of prolonged subcutaneous microdialysis and the correlation between BG and IFG. The study was approved by the Institutional Ethical Review Board. Twenty children were …

Technology to Treat Hyperglycemia in Trauma

Technology to Treat Hyperglycemia in Trauma

LOSS OF GLYCEMIC CONTROL OVER TIME AFTER INFUSION LINE CHANGE IN PATIENTS WITH TYPE 1 DIABETES TREATED WITH CONTINUOUS SUBCUTANEOUS INSULIN INFUSIONS.

Purpose of Study Continuous subcutaneous insulin infusion (CSII) is a well-established modality for treating patients with type 1 diabetes mellitus. The current recommendations, based on anecdotal data, are to change the pump infusion every 48 hours. We report here an analysis of a substudy from 12 patients in a randomized, controlled, crossover study comparing insulin aspart and insulin lispro among subjects with type 1 DM treated with CSII. The aim of this substudy was to determine the optimal duration of a pump infusion line, without loss of glycemic control. Methods Used Data from 12 patients (M = 2, F = 10; mean age 43 years, HbA1c 7.4 ± 0.4%) were analyzed. A continuous glucose monitoring system (CGMS) was inserted between 24 to 48 hours after a pump infusion line change and continued for 3 days. Site infection and/or blood sugar > 300 mg/dL were predetermined reasons for terminating the study. The time intervals reported were in relation to the time of line change. Summary of Results Data downloaded from the CGMS were pooled and then analyzed using the paired t-test. Interstitial fluid glucose between 70 and 180 mg/dL was defined as being within target range, whereas those above 180 mg/dL were defined as above range. From the point of line change, data were analyzed for difference between days 2 (from 24-48 hours after line change), 3 (from 48 to 72 hours after line change), 4 (from 72-96 hours after line change), and 5 (from 96-100 hours after the line change). There was a statistically significant increase in the percentage of time spent above range between days 2 and 3 (p = .027, CI 1.3-17.5), and days 3 and 4 (p = .027, CI 1.2-16.4). Statistically significant differences were also present for the average blood sugar between days 2 and 3 (p = .001, CI 12.4-29.0) and days 3 and 4 (p = .026, CI 2.1-26.9). Conclusions Glycemic control in patients with type 1 diabetes treated with CSII begins deteriorating 24 hours after a change in the infusion line. Since this may limit optimal control in pump-treated patients, strategies need to be developed to improve longevity of the infusion systems. Patient education on frequent line change is essential.

Regional changes in renal cortical glucose, lactate and urea during acute unilateral ureteral obstruction

Acute unilateral ureteral obstruction (UUO) leads to changes in kidney function and metabolism. Microdialysis offers the possibility of topical analysis of changes in kidney metabolism. We applied microdialysis to the porcine kidney and evaluated its impact on gross kidney function. Furthermore, we investigated regional variations in renal interstitial fluid (RIF) glucose, lactate and urea during acute UUO. Eight anesthetized pigs were used. Microdialysis probes were inserted in the upper, middle and lower thirds of the left renal cortex and perfused with Ringer's chloride at a rate of 0.3 microl/min. Dialysates were fractionated for 30-min periods. Bilateral intrapelvic pressure, urinary output, urinary osmolality, the excretion fractions of sodium and potassium, renal blood flow and the glomerular filtration rate were measured. Subsequently, left-sided graded ureteral obstruction was initiated, using the kidney's own urine production as a counter-pressure. The application of three microdialysis probes did not have any impact on kidney function. Ureteral obstruction decreased RIF glucose in the upper and lower thirds of the kidney, but not in the middle third. RIF lactate did not change. Interstitial urea increased in all regions of the kidney, but most markedly in the upper and lower poles. Microdialysis is of potential value for assessing the renal interstitial milieu under different pathophysiological conditions. Ureteral obstruction resulted in regional differences in cortical metabolites, predominantly affecting the upper and lower poles.

Continuous glucose monitoring: key challenges to replacing episodic SMBG

Lag between blood and interstitial fluid (ISF) glucose levels can contribute significantly to accuracy errors in current and anticipated continuous glucose monitoring systems. Mitigating this physiological lag can be an important and useful means for improving the accuracy, and hence the clinical utility of continuous glucose monitors. In a test of 22 subjects with diabetes, two ISF samples (control and mitigated) and a finger capillary blood glucose sample were taken and compared. The methodology presented here of using a pressure modulation technique to create an elevation in blood flow holds promise for significantly mitigating one of the most significant components of accuracy error for continuous monitoring systems.

Continuous glucose monitoring in interstitial fluid using glucose oxidase-based sensor compared to established blood glucose measurement in rats

Glucose monitoring is of importance for success of complex therapeutic interventions in diabetic patients. Its impact on treatment and glycemic control is demonstrated in large clinical trials. Up to eight blood glucose measurements per day are recommended. Notwithstanding, a substantial number of diabetic patients cannot or will not monitor their blood glucose appropriately. Considerable progress in control of disturbed metabolism in diabetic patients can be expected by continuous glucose monitoring. The aim of the study was to evaluate the performance of a new amperometric glucose oxidase-based glucose sensor in vitro and in vivo after subcutaneous implantation into rats. For in vitro testing current output of sensors was measured by exposure to increasing and decreasing glucose concentrations up to 472 mg dL −1 over a time period of 7 days. After subcutaneous implantation of sensors into interscapular region of male rats glucose in interstitial fluid was evaluated and compared to glucose in arterial blood up to 7 days. Hyper- and hypoglycaemia were induced by intravenous application of glucose and insulin, respectively. Current of each implanted sensor was converted into glucose concentration using the first blood glucose measurement only. A change of current with glucose of 0.35 nA mg −1 dL −1 indicates high sensitivity of the sensor in vitro. The response time (90% of steady state) was calculated by approximately 60 s. Test strips for blood glucose measurement as reference for sensor readings was found as an appropriate and rapidly available method in rats by comparison with established hexokinase method in an automated lab analyzer with limits of agreement of +32.8 and −25.7 mg dL −1 in Bland-Altman analysis. In normo- and hypoglycaemic range sensor readings in interstitial fluid correlated well with blood glucose measurements whereas hyperglycaemia was not reflected by the sensor completely when blood glucose was changing rapidly. The data given characterize a sensor with high sensitivity, long term stability and short response time. A single calibration of the sensor is required only in measurement periods up to 7 days. The findings demonstrate that the sensor is a highly promising candidate for assessment in humans.

Development of a highly responsive needle-type glucose sensor using polyimide for a wearable artificial endocrine pancreas

To produce a long-life, stable, miniature glucose sensor for a wearable artificial endocrine pancreas (WAEP), we developed a novel microneedle-type glucose sensor using polyimide, designated the PI sensor (outer diameter, 0.3 mm; length, 16 mm), and investigated its characteristics in vitro and in vivo. In the in vitro study, we tested the sensor in 0.9% NaCl solution with varying glucose concentrations and observed an excellent linear relationship between the sensor output and glucose concentration (range: 0-500 mg/100 ml). In in vivo experiments, the PI sensor was inserted into the abdominal subcutaneous tissue of beagle dogs (n = 5), and interstitial fluid glucose concentrations were monitored after sensor calibration. Simultaneously, blood glucose concentrations were also monitored continuously with another PI sensor placed intravenously. The correlation and time delay between subcutaneous tissue glucose (Y) and blood glucose concentrations (X: 30-350 mg/100 ml) were Y = 1.03X + 7.98 (r = 0.969) and 6.6 +/- 1.2 min, respectively. We applied the new WAEP system/PI sensor and an intravenous insulin infusion algorithm developed previously for glycemic control in diabetic dogs. The use of the WAEP system resulted in excellent glycemic control after an oral glucose challenge of 1.5 g/kg (post-challenge blood glucose levels: 176 +/- 18 mg/100 ml at 65 min and 93 +/- 23 mg/100 ml at 240 min), without any hypoglycemia. Thus, we confirmed that our new PI sensor has excellent sensor characteristics in vitro and in vivo. The new WAEP using this sensor is potentially suitable for clinical application.

Microdialysis in Clinical Practice

Clinical examination is still the gold standard of postoperative free flap monitoring, but with intraorally situated and/or buried flaps, it can be difficult or impossible. Microdialysis is a sampling technique which offers the possibility to monitor the metabolism of a flap continuously. Ischemia can be detected by monitoring the changes in glucose, lactate, and pyruvate levels in interstitial fluid of the specific tissue. Our aim was to use microdialysis to monitor the metabolism of free flaps used for reconstructions inside the oral cavity/oropharynx and to evaluate the reliability and usefulness of this new monitoring method.Twenty-five consecutive patients who underwent oral cavity/oropharynx cancer resection and immediate reconstruction with free flap were included in the study. A microdialysis catheter was placed into the subcutaneous adipose tissue of the flap in the end of the surgical procedure. Dialysate samples were taken on an hourly basis for 72 hours postoperatively. Routine clinical monitoring was carried out by experienced nursing staff. Clinical findings were recorded and later compared with microdialysis values. Two flaps out of 25 failed in spite of reoperations. In both problem cases, microdialysis indicated ischemia 1 to 2 hours before it became clinically evident. During flap ischemia, the lactate/pyruvate ratio increased, glucose concentrations reduced, whereas lactate level increased when compared with normal values. Our results indicate that microdialysis is safe for the patient and the flap. It can reliably detect flap ischemia at an early stage. This is especially useful in buried flaps when clinical monitoring is difficult. Microdialysis may also reduce the patient discomfort caused by repeated clinical examination of the flap.

Automated insulin delivery for type 1 diabetes

Purpose of review Automated insulin delivery using the subcutaneous site for both glucose sensing and insulin delivery, while not commercially available, is starting to be implemented in the research environment. Here, we review issues with glucose sensing and insulin delivery algorithms that need to be resolved in order to achieve a closed-loop system. Recent findings Glucose sensing technology is improving. New studies demonstrating minimal delay in the subcutaneous interstitial fluid glucose response are reviewed, together with early studies indicating longer delay. The pharmacokinetics/pharmacodynamics of subcutaneous insulin, which pose a significant obstacle to closing the delivery loop, are also reviewed, together with approaches being used to develop algorithms to overcome the delay in insulin absorption from this site. Closed-loop data using the Medtronic MiniMed external Physiologic Insulin Delivery system are presented. Summary Initial closed-loop data in both animals and humans suggest that a completely automated insulin delivery system is attainable, although substantial research remains to be conducted prior to such a system being available for home patient use.