[Role of and current technical possibilities for intracorporeal determination of blood glucose in the treatment of insulin-dependent diabetes mellitus].
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Biomedical subjects
K Rebrin
Publications and source records attributed to K Rebrin.
[Continuous intracorporeal glucose measurement using enzyme electrodes].
An enzyme electrode (GOD, Pt-Ag/AgCl) is introduced for amperometric measurement of the intracorporal glucose concentration in the subcutaneous tissue. Changes of the glucose concentration in the peripheral blood (PG) were induced by glucose- respectively insulin-infusion in healthy dogs. PG was compared with values found by out means of a sensor implanted in the necks of the dogs (SG). The regression equation SG = 0.81 PG - 1.39 was calculated by analysing 62 steady state levels. The regression delta SG = 0.83 delta PG + 0.22 submitted for the deviation of the normoglycemic base-level. A sensibility loss of the sensor of about 10% appears after an implantation duration of 7.5 hours in medium. Conclusions for the further development of the sensors follows especially with the in vivo functions (biocompatibility, diminution, sterilisation).
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Automated feedback control of subcutaneous glucose concentration in diabetic dogs.
The subcutaneous tissue is generally considered as a potential site for the monitoring of intracorporal glucose concentration by means of implanted sensors. We studied the suitability of using the resulting signal from the interstitial glucose concentration as an input in a feedback-controlled system for insulin administration. Miniaturized glucose electrodes (amperometric glucose oxidase sensors for the measurement of hydrogen peroxide) were implanted in insulin-dependent diabetic dogs. The output of these sensors was fed into the controller of a bedside-type artificial B cell. Insulin was infused by the device intravenously on the basis of a proportional-differential algorithm. The glucose patterns were compared to identical experiments where feedback control was accomplished on the basis of paracorporal blood glucose measurement using the same algorithm. Normoglycaemia was restored and maintained in both sets of experiments and oral glucose loads were well compensated for. It is concluded that the apparent subcutaneous glucose concentration is appropriate as an input signal for an artificial B cell.
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Wick technique: reference method for implanted glucose sensors.
The control of function of experimentally implanted glucose sensors needs an independent reference method. Employing saline-impregnated cotton threads, an implanted wick-technique was adopted in dogs to obtain analytical specimen from the subcutaneous interstitial fluid compartment. By measuring the contents of potassium, calcium, and hemoglobin, the centrifuged wick fluid was validated to contain the interstitial concentrations of solutes after an equilibration time of approximately 15 min. Between 2 and 25 mmol/L, the steady state subcutaneous glucose concentration is nearly identical to circulating glycemia. Slow alterations, as during an oral glucose tolerance test, (OGTT) are well paralleled by the levels in the wick fluid. During alterations, however, a distinct delay is observed. The wick-based glucose levels are mirrored by the output of electrochemical sensors implanted at the same site. This method may be used in checking implanted sensors that can otherwise not be calibrated in situ.
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In situ calibration of implanted electrochemical glucose sensors.
A feasible and reliable method of in situ checking and calibration of implanted glucose sensors is required to compensate for alterations in the overall sensitivity of the "sensor plus subcutaneous fluid glucose compartment" system. In a study on nondiabetic dogs, the linear regression analysis of paired plasma glucose/sensor current data is validated as a potential basis of recalibration of intracorporal glucose sensors. These sensors were amperometric glucose oxidase/hydrogen peroxide electrodes of which the in vitro response time to square alterations in the ambient glucose concentration T95 was less than 5 min. The method presented may be incorporated into the data handling system of portable glucose monitors or of miniaturized artificial beta-cells. For its performance, no steady state glycaemia but a minimum alteration in the intracorporal glucose concentration is needed. The latter can be provided both by tests or by fluctuations as they occur spontaneously during the course of the day.
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Oxygen tension at the subcutaneous implantation site of glucose sensors.
To elucidate potential influences of the average tissue pO2 on the function of implanted glucose sensors, non-miniaturized polarographic oxygen electrodes and glucose oxidase/H2O2 glucose electrodes were implanted in the subcutaneous tissue of spontaneously breathing normal and diabetic dogs. There was no appreciable run-in phenomenon of oxygen sensors but normally a pronounced initial decrease in current after implantation of glucose sensors. The subcutaneous pO2 amounted to an average of 7 kPa in air-breathing animals with no difference between normal and insulin-dependent diabetic dogs. It showed oscillations of approximately +/- 2 kPa but the mean was stable over the maximum duration of experiments of 16 h. Induced alterations of tissue pO2 between less than 2 and greater than 20 kPa (as verified by measurements of arterial pO2) were not followed by alterations in the current of nearby implanted glucose sensors. It is concluded that the frequently observed instabilities and losses in sensitivity of the system "implanted glucose sensor in situ + tissue glucose compartment" are not caused by alterations in tissue pO2.
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Assessment of subcutaneous glucose concentration: validation of the wick technique as a reference for implanted electrochemical sensors in normal and diabetic dogs.
Employing saline-impregnated cotton threads, an implanted-wick technique was adopted in dogs to obtain specimen from the subcutaneous interstitial compartment in order to estimate its glucose concentration. By measuring the protein, potassium and haemoglobin contents, the centrifuged wick fluid was shown to contain the interstitial concentration of solutes after an equilibration time of approximately 15 min. In normal and in diabetic animals the steady state subcutaneous glucose concentration was almost identical to the circulating glucose level when ranged between 2 and 25 mmol/l. Slow alterations in the circulating glucose profile such as those which appear during an oral glucose tolerance test are closely mirrored by the respective levels in the wick fluid. Fast alterations, however, show deviations. The wick-based glucose levels are well paralleled by the current of Clark type glucose oxidase sensors implanted at the same site. Since, on the basis of in vitro calibrations the sensor outputs have only indicated apparent tissue glucose concentrations of between 70 and 90% of glycaemia, another reference is needed for calibration. Under steady state conditions, the wick method, and on this basis in routine measurements the blood glucose concentration, may be recommended as a reference of implanted sensors which can otherwise not be calibrated in situ.
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