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Continuous monitoring of extracellular glucose concentrations in the striatum of freely moving rats with an implanted glucose biosensor.

We have used a glucose oxidase-based sensor implanted in the striatum of freely moving rats to determine the concentration of extracellular glucose in two distinct ways. With a modification of the zero net flux method, in which different concentrations of glucose are infused through a dialysis probe glued to the biosensor, we calculated the concentration at which there was no change in glucose current by regression analysis; this gave a concentration of 0.351 +/- 0.016 mM. Calculating the concentration from the basal current and the in vitro calibration of the biosensor was not significantly different from this. The basal extracellular glucose concentration determined by either method remained constant over a period of several days. Infusion of 50 microM veratridine through the adjacent dialysis probe caused a steep decrease in glucose current as soon as the drug reached the brain in contrast to the delayed fall (7.5 min) seen with microdialysis in previous experiments from this laboratory. These results demonstrate that this biosensor provides a direct, real-time measure of the extracellular concentration of glucose.

Animals↗

Continuous amperometric monitoring of glucose in a brittle diabetic chimpanzee with a miniature subcutaneous electrode.

The performance of an amperometric biosensor, consisting of a subcutaneously implanted miniature (0.29 mm diameter, 5 x 10(-4) cm2 mass transporting area), 90 s 10-90% rise/decay time glucose electrode, and an on-the-skin electrocardiogram Ag/AgCl electrode was tested in an unconstrained, naturally diabetic, brittle, type I, insulin-dependent chimpanzee. The chimpanzee was trained to wear on her wrist a small electronic package and to present her heel for capillary blood samples. In five sets of measurements, averaging 5 h each, 82 capillary blood samples were assayed, their concentrations ranging from 35 to 400 mg/dl. The current readings were translated to blood glucose concentration by assaying, at t = 1 h, one blood sample for each implanted sensor. The rms error in the correlation between the sensor-measured glucose concentration and that in capillary blood was 17.2%, 4.9% above the intrinsic 12.3% rms error of the Accu-Chek II reference, through which the illness of the chimpanzee was routinely managed. Linear regression analysis of the data points taken at t>1 h yielded the relationship (Accu-Chek) = 0. 98 x (implanted sensor) + 4.2 mg/dl, r2 = 0.94. The capillary blood and the subcutaneous glucose concentrations were statistically indistinguishable when the rate of change was less than 1 mg/(dl. min). However, when the rate of decline exceeded 1.8 mg/(dl.min) after insulin injection, the subcutaneous glucose concentration was transiently higher.

Animals↗

[Continuous monitoring for blood glucose after surgery of insulinoma and the use of insulin].

The changes of blood glucose in 60 patients after surgery of insulinoma were analysed. It was found that in more than half of the patients blood glucose was elevated to a standard level of total resection at 30' and in all patients at 24 hrs. More than 90% patients remained hyperglycemic for about 9 days. The higher the blood glucose level was elevated, the earlier the hyperglycemia developed. There was no relationship between the elevating speed of blood glucose and the severity of preoperative hypoglycemia, and the course of the disease. But there was positive relationship between the recovering time of hyperglycemia and the course of disease. Insulin is indicated in some patients during postoperative period to help safe recovery especially in a hyperglycemic state.

Adolescent↗

Application of transcutaneous microdialysis and continuous flow analysis for on-line glucose monitoring in newborn infants.

The combination of a transcutaneous microdialysis probe and continuous flow analysis was tested for continuous glucose monitoring in eight newborn infants who were fed intravenously. The probe was placed on the skin, which was first stripped with cellophane tape to increase the skin permeability. The skin was stripped until the transepidermal water loss reached values greater than 80 gm/m2/hr. Dialysate concentrations were monitored for 165 minutes while the blood glucose concentrations were manipulated by changing the infusion rate of glucose. Blood glucose concentration was linearly related to the dialysate concentration. Because the dialysate/blood glucose ratio varied among the infants, the dialysate concentration was calibrated to estimated blood values with a single-point and a multiple-point calibration method. The latter method yielded more accurate estimates of the blood values. We conclude that transcutaneous microdialysis may be used for glucose monitoring in newborn infants.

Blood Glucose↗

On line continuous monitoring of subcutaneous tissue glucose in men by combining portable glucosensor with microdialysis.

For the normalisation of blood glucose levels in diabetic patients by feedback controlled insulin delivery, a self-manageable and reliable method for continuous glucose estimation is still not available. By combining a commercially available needle type dialysis probe (molecular cutoff 20,000 Da) with a sensitive glucose sensor, we obtained a device for continuous glucose measurement in dialysate. This device was tested in healthy volunteers during a 75-g oral glucose tolerance test and in Type 2 (non-insulin-dependent) diabetic patients. Venous glucose and subcutaneous sensor signal were followed for 300 min (ten healthy subjects), 21 h (three healthy subjects) or 9 h (seven Type 2 diabetic patients). The recovery of the microdialysis was interindividually different, but after calibration, glucose levels in the dialysate and subcutaneous glucose sensor signal correlated well (r = 0.84-0.95). Under the assumption of a physiologic and technical delay between intravenous and subcutaneous glucose, correlation coefficient between intravenous glucose and subcutaneous sensor signal ranged from 0.60 to 0.93. We conclude that changes in blood glucose could be monitored in the subcutaneous tissue by the microdialysis technique in a continuous on line manner.

Adult↗

The glucose sensor: the missing link in diabetes therapy.

This review considers the present state of the implantable glucose sensor from the point of view of technical models available today. Chemical analysis behind the practical experiences under both in vitro and in vivo conditions are described (Abel, Fischer, Brunstein and Ertle 1988; Brückel, Kerner, Zier, Steinbach and Pfeiffer 1988a; Brückel, Kerner, Zier, Steinbach and Pfeiffer 1988b; Steinbach, Kerner, Zier, Dolderer and Pfeiffer 1987). Amperometric enzymatic glucose sensors are used by the majority of laboratories, providing satisfactory results of glucose determinan in solution and in the laboratory. Up to 4 days of reliable values were recorded by measuring glucose in vivo, in practical terms, in the subcutaneous tissue in animals. However, also in this first period of foreign-body reactions, enough encapsulation obviously occurs to neutralize the majority of the sensors implanted. In first experiments in humans, the results are even worse. Generally, decreasing activity was observed in less than 24 h. Therefore, continuous blood glucose monitoring by portable glucose sensors used the same principle in a flow-through chamber; the sensor of our own make was employed in a number of clinical conditions. When one of the available insulin pumps effecting continuous subcutaneous insulin infusions was connected, the algorithms worked out for the big AEP under bedside conditions were also of use in a slightly modified fashion for the subcutaneous insulin application. Renouncing the computer-mediated automated regulation of the insulin delivery is possible when the patient is constantly reading his blood glucose values and operates the insulin infusion pulses in association with meals. Continuous glucose monitoring by portable instruments is the only and irreplaceable prerequisite for unprejudiced evaluation of the various strategies for substitution of the insulin deficiency in any form of diabetes.

Biosensing Techniques↗

Methodological aspects of glucose monitoring with a slow continuous subcutaneous and intravenous ultrafiltration system in rats.

A method for the continuous ultrafiltration of venous blood or subcutaneous fluid is demonstrated with glucose monitoring in the living rat. Ultrafiltrate was withdrawn at a constant flow rate of approximately 100 nl/min. Glucose content of the ultrafiltrates was electrochemically determined with a flow injection analysis method and a bi-enzyme reactor. After glucose loading, the time course of glucose in the ultrafiltrate from the jugular vein was virtually identical, whereas that from the subcutaneous compartment was attenuated and the peaks blunted as compared to glucose levels in concomitantly assayed arterial blood. Our study demonstrates the potential of low rate ultrafiltration for monitoring metabolism with biosensor technology in vivo.

Animals↗

Ion-selective potentiometry in clinical chemistry. A review.

Ion-selective potentiometry is used more and more in clinical medicine for the determination of electrolytes in various body fluids. With regard to K+, Na+, Ca2+ and Cl- this technique has almost completely displaced flame photometry, atomic absorption spectrophotometry and coulometry. Moreover, reliable automated devices have facilitated routine analyses. Until now there are 6 different types of ion-selective sensors: glass membrane, solid phase, fluid membrane, carrier, gas-sensitive, and enzyme electrodes with immobilized enzymes. The latter are particularly used for in vivo monitoring, especially for continuous blood glucose monitoring. The essential fields of application in the clinical laboratory are the determinations of the cations H+, K+, Na+, Ca2+, Mg2+ and NH3+, and the anions F-, I-, Br-, Cl- and HCO3-. Despite the wide-spread application of ion-selective potentiometry a number of disturbing factors have to be taken into account by the user as well as by the manufacturer in order to get satisfactory results. For instance, there are differences between direct and indirect potentiometry. Moreover, the activities measured cannot be extrapolated readily to the desired concentrations. A careful and accurate calibration, a suitable sample preparation and an adjustment of the measuring conditions to the characteristics of the specimen and the matrix of the sample is necessary before each measurement. Therefore, a consequent internal and external quality control is necessary to achieve an optimal quality of these methods determining vital parameters in medicine. Thus, the technique of ion-selective potentiometry represents an important milestone in clinical chemistry. Moreover, being a very rapid procedure it is indispensable to clinical diagnostics.

Body Fluids↗

On line continuous monitoring of subcutaneous tissue glucose is feasible by combining portable glucosensor with microdialysis.

A new method for continuous measurement of subcutaneous tissue glucose content is introduced: by combining the microdialysis technique with a wearable amperometric glucose sensor, a device for continuous glucose measurement in the subcutaneous tissue was obtained. This device was applied to healthy volunteers (n = 10) over the period of an oral glucose load and to type I diabetic patients (n = 10) under the conditions of daily life. Glucose profiles in both healthy and diabetic persons were followed in the subcutaneous tissue up to 27 hours. This technique will certainly open new perspectives of monitoring and treating diabetic patients.

Biosensing Techniques↗