Glucose Concentration In Interstitial Fluid Research Articles

Continuous Glucose Monitor Shows Potential for Early Hypoglycemia Detection in Hospitalized Patients

This study shows the potential of continuous glucose monitoring (CGM) for the detection of hypoglycemia in hospitalized patients. A Medtronic Diabetes (Northridge, CA) CGMS iPro continuous glucose recorder was inserted into the subcutaneous tissue of a hospitalized orthopedic surgery patient with type 1 diabetes the day after a moderate hypoglycemia event. The interstitial fluid glucose concentration was recorded every 5 min. Both the patient and the hospital staff were blinded to the CGM data. Bedside capillary blood glucose measurements were performed per hospital protocol. The CGM recorded a repeat severe episode of hypoglycemia the next day. The hospital-defined threshold for hypoglycemia (70 mg/dL) was crossed 4.5 h prior to the patient being found unconscious by the nursing staff. Data from the CGMS iPro Recorder illustrate the potential benefit of using a real-time CGM in the hospital to detect hypoglycemia in a more timely fashion compared to infrequent point-of-care glucose meter measurements.

Delays in Minimally Invasive Continuous Glucose Monitoring Devices: A Review of Current Technology

Through the use of enzymatic sensors-inserted subcutaneously in the abdomen or ex vivo by means of microdialysis fluid extraction-real-time minimally invasive continuous glucose monitoring (CGM) devices estimate blood glucose by measuring a patient's interstitial fluid (ISF) glucose concentration. Signals acquired from the interstitial space are subsequently calibrated with capillary blood glucose samples, a method that has raised certain questions regarding the effects of physiological time lags and of the duration of processing delays built into these devices. The time delay between a blood glucose reading and the value displayed by a continuous glucose monitor consists of the sum of the time lag between ISF and plasma glucose, in addition to the inherent electrochemical sensor delay due to the reaction process and any front-end signal processing delays required to produce smooth traces. Presented is a review of commercially available, minimally invasive continuous glucose monitors with manufacturer reported device delays. The data acquisition process for the Medtronic MiniMed (Northridge, CA) continuous glucose monitoring system-CGMS Gold-and the Guardian RT monitor is described with associated delays incurred for each processing step. Filter responses for each algorithm are examined using in vitro hypoglycemic and hyperglycemic clamps, as well as with an analysis of fast glucose excursions from a typical meal response. Results demonstrate that the digital filters used by each algorithm do not cause adverse effects to fast physiologic glucose excursions, although nonphysiologic signal characteristics can produce greater delays.

The Clinical Research Tool: A High-Performance Microdialysis-Based System for Reliably Measuring Interstitial Fluid Glucose Concentration

A novel microdialysis-based continuous glucose monitoring system, the so-called Clinical Research Tool (CRT), is presented. The CRT was designed exclusively for investigational use to offer high analytical accuracy and reliability. The CRT was built to avoid signal artifacts due to catheter clogging, flow obstruction by air bubbles, and flow variation caused by inconstant pumping. For differentiation between physiological events and system artifacts, the sensor current, counter electrode and polarization voltage, battery voltage, sensor temperature, and flow rate are recorded at a rate of 1 Hz. In vitro characterization with buffered glucose solutions (c(glucose) = 0 - 26 x 10(-3) mol liter(-1)) over 120 h yielded a mean absolute relative error (MARE) of 2.9 +/- 0.9% and a recorded mean flow rate of 330 +/- 48 nl/min with periodic flow rate variation amounting to 24 +/- 7%. The first 120 h in vivo testing was conducted with five type 1 diabetes subjects wearing two systems each. A mean flow rate of 350 +/- 59 nl/min and a periodic variation of 22 +/- 6% were recorded. Utilizing 3 blood glucose measurements per day and a physical lag time of 1980 s, retrospective calibration of the 10 in vivo experiments yielded a MARE value of 12.4 +/- 5.7. Clarke error grid analysis resulted in 81.0%, 16.6%, 0.8%, 1.6%, and 0% in regions A, B, C, D, and E, respectively. The CRT demonstrates exceptional reliability of system operation and very good measurement performance. The ability to differentiate between artifacts and physiological effects suggests the use of the CRT as a reference tool in clinical investigations.

Decreasing concentration of interstitial glucose in REM sleep in subjects with normal glucose tolerance

Sleep is divided into two major stages, non-rapid eye movement (NREM) and rapid eye movement (REM), which are distinct in various neuroendocrine respects. NREM/REM cycles influence insulin and glucagon secretion; however, glucose concentrations in REM compared with NREM have not been directly explored. The aim was to investigate the differences in glucose concentrations in interstitial fluid (IGC) between NREM/REM cycles using a continuous glucose monitoring system (CGMS). Thirteen subjects were eligible for analysis out of the 28 enrolled. All underwent standard polysomnography for the assessment of sleep stages and the exclusion of sleep apnoea syndrome with CGMS and subsequent morning oral glucose tolerance test (exclusion of glucose intolerance or diabetes). The IGC in REM fell in 12 out of the 13 subjects, whereas the IGC in NREM increased in eight out of the 13 subjects. Therefore, the mean change of IGC differed in direction between sleep stages: -0.028 (-0.045 to -0.011) for REM vs. 0.005 (-0.012 to 0.017) for NREM [median (QR), P = 0.007, n = 13], with the mean difference of 0.038 mmol/l x 5 min(-1) (95% confidence interval 0.012, 0.064). The mean glucose concentration in REM sleep was lower than in NREM: 4.29 +/- 1.00 vs. 4.53 +/- 0.90 mmol/l (mean +/- sd, P = 0.003, n = 13). The decrease in IGC in REM compared with NREM sleep, with lower absolute values, may arise from different physiological events observed in these sleep stages. The REM-related decline in glucose concentrations may be a risk factor for nighttime hypoglycaemia.

Insulin release and daily glucose change in polycystic ovary syndrome women with normal glucose tolerance

To evaluate the characteristics of daily glucose change, insulin sensitivity, and insulin release in polycystic ovary syndrome (PCOS) women with normal glucose tolerance. Oral glucose tolerance test (OGTT) with 75 g glucose was conducted on 20 PCOS women with normal glucose tolerance and 20 age-matched healthy women with normal menstruation. Before the glucose uptake and 30, 60, and 120 min after samples of venous blood were collected to detect the blood glucose and insulin. Continuous glucose monitoring system (CGMS) was used to monitor the glucose concentration of subcutaneous interstitial fluid so as to reflect the blood glucose level. Mean blood glucose level (MBG) and its standard deviation (SDBG), mean amplitude of glycemic excursion (MAGE), peak level of postprandial plasma glucose as well as its peaking time during a 48-hour period CGMS were calculated. Stumvoll first-phase and second-phase (1st PH and 2nd PH) insulin release during OGTT were evaluated by Stumvoll formula, whereas baseline insulin release by HOMA-B. Insulin sensitivity index (ISI) was evaluated by Cederholm formula. (1) The 1-hour and 3-hour plasma glucose levels during OGTT of the PCOS group were higher than those of the control group (P < 0.01 and P < 0.05 respectively). The fasting insulin level and insulin levels 30, 60, 120, and 180 min after the glucose uptake during OGTT of the PCOS group were all significantly higher than those of the control group (all P < 0.01). (2) The daily MBG, SDBG, and MAGE of the PCOS group were (5.43 +/- 0.44), (0.66 +/- 0.24), and (1.46 +/- 0.47) mmol/L respectively, all similar to those of the control group [(5.3 +/- 0.5), (0.67 +/- 0.27), and (1.7 +/- 0.7) mmol/L respectively, all P > 0.05]. The peaking time of post-breakfast plasma glucose level of the PCOS group was (40 +/- 18) min, significantly longer than that of the control group [(30 +/- 10) min, P < 0.05]. (3) The ISI of the PCOS group was 64 (59 - 81), significantly lower than that of the control group [95 (78 - 102), P < 0.01]. The Stumvoll 1st PH and 2nd PH insulin release levels of the PCOS group were 1779 (1411 - 2194) mU/L and 440 (361 - 545) mU/L respectively, both significantly higher than those of the control group [1217 (1056 - 1477) and 320 (283 - 375) mU/L respectively, P < 0.01 and P < 0.05]. With normal glucose tolerance, the PCOS women show (1) a backwardly-shifted peak of glucose -stimulated insulin secretion, (2) an abnormal mode of daily glucose change characterized by a delayed peak of post-breakfast plasma glucose level, and (3) significant decrease of peripheral insulin sensitivity with compensated increase of insulin secretion.

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.

OCCURENCE OF ADVERSE EVENTS DUE TO CONTINUOUS GLUCOSE MONITORING

Continuous glucose monitoring (CGM) using transcutaneous sensors is becoming a sophisticated method to control and regulate glucose metabolism. The transcutaneous sensor of the CGM system (CGMS Medtronic Minimed, Northridge, CA, USA) is chosen to measure glucose concentration in interstitial fluid up to three days after insertion even though its function remains stable for a longer period. The question arises, which factors really limit the period of sensor insertion without unnecessary risk. The aim of this study was to assess any adverse events occurring in the course of 9 days after the sensor insertion. In a group of 22 healthy volunteers aged 21.8+/-1.30 y (mean +/- SE) a total of 26 sensors was inserted subcutaneously in gluteal or lumbar region for 9 days. Before insertion the site was sprayed with an antiseptic (Cutasept F, Bode Chemie, Hamburg, Germany). Local adverse reactions and disturbances in general condition were examined. In the course of 184 sensor-days, there were only minor local adverse events: hypersensitivity, itching, pain, redness, burning, subcutaneous hemorrhage. Additionally, sleep disturbances, attention deficits, problems related to the CGMS monitor, to adhesive tape and/or sensor were found. None of these resulted in sensor withdrawal. In 12 volunteers (55 %) no complications were observed. The sensor function measured according to electrical signals (ISIG) failed (always on day 1-2) in 4 cases (16 %). The present FDA approved 3-day insertion period for Medtronic transcutaneous sensor does not seem to limit its use and appears to be worth a careful revision.

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.

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.

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 …

Function and Accuracy of Glucose Sensors Beyond Their Stated Expiry Date

The sensor of the Continuous Glucose Monitoring System (CGMS, Medtronic Minimed, Northridge, CA) is labeled to expire 6 months following its production and to measure the glucose concentration in interstitial fluid up to 3 days after insertion. The purpose of this study was to demonstrate potential possibilities of sensors when used beyond their expiry date. Twenty sensors, each between 3 to 18 months after the expiry date, were assessed in a 7-day period after insertion. Twenty healthy volunteers 23.4 +/- 2.92 (mean +/- SD) years old were trained in handling the CGMS and the Hypoguard (Woodbridge, UK) Advance glucometer system to measure their capillary plasma glucose concentration 18 times a day. Sensor function was estimated according to the number of readings per day, the accuracy according to the mean absolute difference (MAD), and correlation coefficient (r) between glucometer and sensor resulting from paired values. Uninterrupted sensor function was found in 117 of 140 sensor-days (83.6%). A reduction of readings in 23 sensor-days (16.4%) was caused by user error (5 sensor-days, 3.6%), connecting cable (7 sensor-days, 5%), sensor failure (8 sensor-days, 5.7%), or uncertain factors (3 sensor-days, 2.1%). MAD was always < 28%, and r = 0.79. Neither the expiry date nor the 3-day period of use limits the reliable function of a CGMS sensor. Sensors were found to function as long as 18 months after the expiry date, mostly for at least 7 days. There were no serious local adverse reactions. Prolongation of shelflife label and insertion time appears to be reasonable. Further studies are in progress.

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.

Continuous Glucose Monitoring - A Novel Approach to the Determination of the Glycaemic Index of Foods (DEGIF 1)

The glycaemic index (GI) is a measure of the food power to raise plasma glucose (PG) concentration after a meal. For its determination, classical methods register the development of glucose concentration in capillary plasma or whole blood. The aim of this prospective open-label trial was to compare the GI of selected foods obtained by means of the Continuous Glucose Monitoring System (CGMS) (Minimed Medtronic, Northridge, USA) which has not been applied for this purpose until now, with the respective GI determined by a conventional method using the Glucometer Advance System (GAS) (Hypoguard, Woodbridge, United Kingdom), and to assess the advantages of each approach. Portions of tested foods containing 50 g of carbohydrates were eaten for breakfast and for dinner after 10 and 4 h fast, respectively, by 20 healthy volunteers. Using GAS, PG-curves were constructed from 9 PG values at time 0, 15, 30, 45, 60, 75, 90, 105 and 120 min after the meal, and, using CGMS, from 25 values of interstitial fluid glucose concentration (ISFG) stored within 120 min in 5-minute intervals in CGMS memory. The GI was calculated (for GAS and CGMS separately) by dividing the incremental area under the curve for the tested food by the average area of 3 tests performed with the standard. Having excluded tests with missing glucose values, there remained 285 GAS- and 290 CGMS tests for further analysis. In each volunteer, each food was tested 3 times within one week so that 1 to 3 GI's were obtained and averaged. The GI for each tested food was calculated as the mean from the respective average GI's of 20 volunteers. The GI-variability was assessed according to the respective SD. The preference of GAS vs. CGMS in the persons tested was explored by means of a questionnaire. MS Excel and the statistical program SPSS v. 10.1 were used to analyze the data. The GI values (mean +/- SD) measured by GAS/CGMS were for dark chocolate 43.6 +/- 22.13 %/44.0 +/- 21.71 % (p > 0.01); for apple baby food 46.1 +/- 21.38 %/53.8 +/- 37.69 % (p > 0.01); for puffed rice squares 76.5 +/- 20.24 %/76.9 +/- 27.62 % (p > 0.01); for yogurt 43.2 +/- 20.17 %/37.7 +/- 21.55 % (p > 0.01). The GI's of dark chocolate, apple baby food and yogurt, determined by either method, were significantly lower than the GI of puffed rice squares (p < 0.01). CGMS was preferred by 12 of 20 volunteers (60 %). No significant difference could be seen between the GI's determined by conventional method (GAS) and by CGMS (p > 0.01). The method with CGMS is reliable and comfortable for both tested persons and investigators. Hence, it appears to become a sophisticated approach to determine the GI.

Glucose measurements with sensors and ultrasound

Accurate monitoring of the blood glucose level in diabetics is essential in preventing complications. Generally, conventional over-the-counter glucose meters require frequent painful finger punctures to obtain samples, which makes a noninvasive method preferable. The purpose of this study was to demonstrate that glucose levels can be measured transdermally with the combination of the low-profile cymbal array and an electrochemical glucose sensor consisting of amperometric electrodes and a novel glucose oxidase hydrogel. Interstitial fluid glucose concentrations can be determined with the electrochemical glucose sensor after the skin is made permeable to glucose by ultrasound (US) (20 kHz) with the thin (< 7 mm) and light (< 22 g) cymbal array. Using this array to deliver insulin into hyperglycemic rats, our previous experiments demonstrated that blood glucose levels would decrease 233.3 mg/dl with 5 min of US exposure. With the sensor and array, our goal was to determine the glucose levels of hyperglycemic rats noninvasively and evaluate the possible bioeffects. A total of 12 anesthetized rats were placed into two groups (US exposure group and control group) and the array (I SPTP = 100 mW/cm 2) with a saline reservoir operating for 20 min was affixed to the abdomen. The array was removed and an electrochemical glucose sensor was placed on the exposed area to determine the glucose concentrations through the skin. Comparison was made using a commercial glucose meter with the blood collected from a jugular vein. The average blood glucose level determined by the sensor was 356.0 ± 116.6 mg/dl, and the glucose level measured by the commercial glucose meter was 424.8 ± 59.1 mg/dl. These results supported the use of this novel system consisting of the electrochemical glucose sensor and the cymbal array for glucose monitoring. (E-mail: nbs@engr.psu.edu)

Minimally Invasive Extraction of Dermal Interstitial Fluid for Glucose Monitoring Using Microneedles

Compliance with glucose monitoring by patients with diabetes is poor because of the pain and inconvenience of conventional blood collection using lancets. To improve compliance, and thereby reduce morbidity and mortality associated with poor glucose control, this study sought to develop and test minimally invasive microneedles to extract dermal interstitial fluid (ISF) for glucose monitoring. We used a thermal puller to fabricate individual or multi-needle arrays of glass microneedles with tip radii of 15-40 microm to penetrate 700-1,500 microm deep into the skin of anesthetized hairless rats or conscious, normal, adult, human subjects. After applying a vacuum of 200-500 mm Hg for 2-10 min, we extracted ISF and measured glucose concentration. These measurements were compared with glucose levels in blood collected from the tail vein of rats or finger stick on humans. Using this procedure, 1-10 microL of ISF was extracted out of holes punctured in the skin using microneedles. Human subjects generally reported the procedure as painless. ISF glucose concentration correlated well with blood levels based on 140 measurements on 15 rats and six measurements on six human subjects, where 95% of rat data and 100% of human data fell within the clinically acceptable A + B region in Clarke Error Grid analysis. A linear calibration factor was needed to correlate ISF and blood glucose concentrations using our standard procedure. Modifying the procedure to prevent ISF evaporation during extraction provided a one-to-one correlation that eliminated the need for calibration. ISF glucose measurements tracked rapidly changing blood glucose levels following insulin injection with a time lag of less than 20 min. These results suggest that microneedle devices can be used to extract ISF for painless glucose monitoring.

Evaluation of a continuous glucose monitoring system in diabetic dogs

The generation of a blood glucose curve is important for assessing the response to insulin therapy in diabetic dogs. Disadvantages of this technique include patient discomfort and the potential for missing transient hypo- or hyperglycaemic episodes. The aim of the current study was to evaluate a continuous glucose monitoring system (CGMS) for use in diabetic dogs. Interstitial fluid glucose concentrations were recorded in 10 diabetic dogs, every five minutes for up to 48 hours, using a subcutaneous sensor attached to the CGMS device. Blood glucose concentrations were measured simultaneously using a glucometer. The correlation between interstitial fluid and blood glucose values was 0.81 (P < 0.01). The largest discrepancies between the two sets of data were seen during the one- to three-hour period following feeding, suggesting that postprandial hyperglycaemia might not be reflected in the interstitial fluid. The authors conclude that the CGMS is a potentially valuable tool in the management of canine diabetic patients.

Continuous glucose monitoring and haemoglobin A(1c).

Measurement of HbA(1c) is the standard test for assessment of glycaemic control in diabetic subjects. Using new glucose sensing technology we re-evaluated the significance of HbA(1c) in terms of the aspects of the blood profile it measures in patients with diabetes. In a group of 27 patients with type 1 diabetes, interstitial fluid glucose concentrations were monitored for a mean of 2.6 days using the Continuous Glucose Monitoring System trade mark (MiniMed Inc, CA, USA). Results were correlated with an HBA(1c) measurement taken at the time of sensor insertion. Results were available in 25 subjects, two datasets being lost due to patient error. There was a correlation between mean sensor glucose value, and the HbA(1c) value (r = 0.59, P = 0.002). The correlation with standard deviation of the readings was weaker (r = 0.3, P = 0.15). No other descriptor of the sensor glucose concentration correlated with HbA(1c). The mean interstitial glucose concentration recorded with the Continuous Glucose Monitoring System correlates with HbA(1c) level recorded at the time, but with no other marker of glucose control in diabetic subjects. These results have implications for the interpretation of HbA(1c) concentrations in type 1 diabetes.

Correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue evaluated with microdialysis during intensive care

Background: Hyper- as well as hypoglycemia may be detrimental for brain energy metabolism and even a moderate increase in blood glucose concentration can affect outcome adversely. During physiological conditions, glucose concentration obtained from microdialysis of subcutaneous adipose tissue adequately reflects plasma glucose concentration. This study examines whether this correlation is also obtained during intensive care in patients with severe injuries. Methods: The study included 62 patients with severe traumatic brain injuries. All patients received one 30 mm microdialysis catheter (CMA 60, CMA Microdialysis) inserted into periumbilical subcutaneous adipose tissue. The probe was perfused (0.3 w l/min) with a Ringer solution from a microinfusion pump and analyzed for glucose, lactate, and glycerol. The study included 2.434 simultaneous analyses of glucose concentration in arterial blood and subcutaneous adipose tissue. Results: The correlation coefficient for glucose concentration in blood and interstitial fluid was 0.743 for the whole material. The correlation was relatively poor for 1-6 h after insertion of the probes. During this period, a continuous increase in the subcutaneous level of glucose and decreases in lactate and glycerol were noted. Conclusions: The correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue was not as good during intensive care as in normal humans. The poor correlation during the first 6 h probably reflects a stress reaction (and possibly local vasoconstriction). Microdialysis of subcutaneous adipose tissue permits frequent bedside analyses of the biochemical composition of the extracellular fluid and may be of value during routine intensive care provided the methodological limitations are recognized.

Determination of Time Delay between Blood and Interstitial Adipose Tissue Glucose Concentration Change by Microdialysis in Healthy Volunteers

For the development and use of subcutaneous glucose sensors it is important to know the time lag between changes in blood glucose and subcutaneous interstitial glucose concentration. To determine the time lag we inserted a microdialysis probe into the abdominal subcutaneous adipose tissue of healthy volunteers (n = 19) and performed oral glucose tolerance tests (n = 39) over a 7-day period. After correction for the microdialysis system time lag, we compared the change in dialysate glucose concentration with the capillary blood glucose concentration. We found no significant delay time between a change in capillary blood glucose concentration and subcutaneous interstitial fluid glucose concentration using the Mann-Whitney test. The substantial interindividual variation of glucose recovery and the changing recovery in time makes it difficult to draw unambiguous conclusions about the exact physiological time lag. Based on the present experimental findings and theoretical calculations of glucose transport in adipose tissue, the physiological lag time is short and negligible compared to the system delay time of a glucose sensor.

Measurement of interstitial muscle glucose and lactate concentrations during an oral glucose tolerance test.

To study the relationship between blood flow rate and muscle metabolism, muscle microdialysis was performed in nine human subjects (5 females and 4 males) after an oral glucose load (75 g). Two microdialysis probes were inserted into the medial femoral muscle for estimation of glucose and lactate concentrations in the interstitial fluid, and the muscle blood flow was measured concomitantly with strain-gauge plethysmography. After subjects fasted overnight, their glucose concentration in arterial plasma and interstitial fluid was 4.6 +/- 0.13 vs. 3.8 +/- 0.23 mmol/l (P < 0.05), and the corresponding lactate concentrations were 0.60 +/- 0.07 vs. 0.83 +/- 0.07 mmol/l (P < 0.05). Muscle blood flow was 5.2 +/- 0.7 and 7.5 +/- 1.4 ml.100 g-1.min-1 (P < 0.05) at 0 and 90 min after oral glucose, respectively. The arterial-interstitial concentration differences of glucose increased after oral glucose [at 0 min 0.73 +/- 0.24 vs. 2.19 +/- 0.60 mmol/l at 90 min (P < 0.001)]. The corresponding values for lactate were -0.23 +/- 0.10 at 0 min vs.-0.26 +/- 0.18 mmol/l at 90 min (not significant). The data show that 1) the capillary wall is partly rate limiting for glucose uptake, and 2) after oral glucose, the glucose concentration gradient over the capillary wall increases despite a limited increase in blood flow rate, which then mediates approximately 10-20% of total enhancement of glucose uptake in muscle.