人工膵β細胞システムのためのパラメータ自己変換プログラムの開発:糖尿病性昏睡と血糖値適応制御
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概要
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In the computer algorithms of the bedside-type artificial beta cell system developed originally in the First Department of Medicine, Osaka University Medical School, insulin is infused in a proportional plus derivative control action to blood glucose concentrations in order to simulate the insulin secretion of healthy subjects. With this system the perfect physiological normalization of circadian profiles of blood glucose in diabetics has been established. However, in order to apply this artificial beta cell thus developed to diabetics in various conditions, such as those who have low insulin sensitivity, those who have supernormal insulin sensitivity, or brittle diabetics whose insulin sensitivity may change unpredictably, it is necessary to manually change parameters, deciding insulin infusion rate for the adaptive control of blood glucose in accordance with the individual ability to regulate blood glucose recognized after the specific period of its application.<BR>To cope with these situations, the author has developed a computer algorithm for the adaptive control of blood glucose, in which appropriate values of the parameters determining the rate of insulin infusion were established automatically on a moment-to-moment basis proportional to the changes in the ability of the subject to regulate blood glucose.<BR>First, as the marker of insulin sensitivity seen in normal situations, the projected rate of change in blood glucose [ΔBGp (t)] against blood glucose was determined by analyzing the relationship between the rate of change in blood glucose concentrations and blood glucose concentrations during declines from the peak values after 50 or 100g oral glucose loads in healthy subjects.Second, under glycemic regulation with the artificial beta cell, the real rate of change in blood glucose concentrations in each diabetic subject [ΔBG (t)] was calculated, and the index of insulin sensitivity was then estimated from the difference between ABG (t) and ΔBGp (t). According to the calculated insulin sensitivity, the computer automatically reset the parameters which regulated the insulin infusion rate.<BR>To fulfil the performance of software in the system, a filter system which could eliminate the noises generated from blood glucose sensors was included. The refractory period, in which the parameters should not be changed, was also provided in order to compensate the time-delay of the insulin action on blood glucose regulation.<BR>Validation of these algorithms was performed in diabetic ketotic or ketoacidotic animals and patients. <BR>Hyperglycemic depancreatized dogs were made to have protracted ketosis or keto-acidosis by constant iv infusion of sodium 3-hydroxybutyrate or 3-hydroxybutyric acid, respectively. Then blood glucose regulations were attempted with the aid of the artificial beta cell. In 5 ketotic or 5 ketoacidotic dogs, under the control of the artificial beta cell in which parameters regulating the rate of insulin infusion were fixed, the rate of fall in glycemia was smaller than that in 5 non-ketotic depancreatized dogs, showing that insulin resistance does exist in protracted ketosis or ketoacidosis.<BR>With the algorithm of self-adaptive control, the parameters were automatically changed several times in response to calculated insulin sensitivity; therefore, an adaptive blood glucose regulation which was indistinguishable from that in non-ketotic dogs was established. It was revealed that, for the adaptive blood glucose control, plasma concentrations of insulin should be raised to more than 33/μU/ml or 64μU/ml in protracted ketosis or ketoacidosis, respectively.<BR>Almost identical results were obtained clinically when the bedside-type artificial beta cell with the self-adaptive control algorithm was applied to 4 diabetic ketotic and 2 diabetic ketoacidotic patients.<BR>In summary,
- 日本内分泌学会の論文