A semiclosed-loop algorithm for the control of blood glucose levels in diabetics

A theoretical analysis of the control of plasma glucose levels in diabetic individuals is undertaken using a simple mathematical model of the dynamics of glucose and insulin interaction in the blood system. Mathematical optimization techniques are applied to the mathematical model to derive insulin infusion programs for the control of blood levels in diabetic individuals. Based on the results of the mathematical optimization, a semiclosed-loop algorithm is proposed for continuous insulin delivery to diabetic patients. The algorithm is based on three hourly plasma glucose samples. A theoretical evaluation of the effectiveness of this algorithm shows that it is superior to two existing algorithms in controlling hyperglycemia. A glucose infusion term representing the effect of glucose intake resulting from a meal is introduced into the model equations. Various insulin programs for the control of plasma glucose levels following a meal are then assessed. The theoretical results suggest that the most effective short-term control is achieved by an insulin infusion program which incorporates an injection to coincide with the meal.<<ETX>>

[1]  R N Bergman,et al.  Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. , 1987, The Journal of clinical investigation.

[2]  Y. Z. Ider,et al.  Quantitative estimation of insulin sensitivity. , 1979, The American journal of physiology.

[3]  R N Bergman,et al.  Assessment of insulin sensitivity in vivo. , 1985, Endocrine reviews.

[4]  R. Bergman,et al.  Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. , 1981, The Journal of clinical investigation.

[5]  S. Genuth,et al.  Control of Hyperglycemia in Adult Diabetics by Pulsed Insulin Delivery , 1977, Diabetes.

[6]  G V Gill,et al.  Impaired subcutaneous absorption of insulin in 'brittle' diabetics. , 1982, Acta endocrinologica.

[7]  L C Gatewood,et al.  Model studies of blood-glucose regulation. , 1965, The Bulletin of mathematical biophysics.

[8]  H Keen,et al.  Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia. , 1978, British medical journal.

[9]  R. V. Gamkrelidze,et al.  Principles of optimal control theory , 1977 .

[10]  K. Teo,et al.  Optimal insulin infusion resulting from a mathematical model of blood glucose dynamics , 1989, IEEE Transactions on Biomedical Engineering.

[11]  E. Kraegen,et al.  Control of blood glucose in diabetics using an artificial pancreas. , 1977, Australian and New Zealand journal of medicine.

[12]  E. Kraegen,et al.  Timing of Insulin Delivery with Meals , 1981, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[13]  A M Albisser,et al.  Waveform Requirements for Metabolic Normalization With Continuous Intravenous Insulin Delivery in Man , 1981, Diabetes.

[14]  G. Grodsky,et al.  A threshold distribution hypothesis for packet storage of insulin and its mathematical modeling. , 1972, The Journal of clinical investigation.

[15]  R. Ollerton.  Application of optimal control theory to diabetes mellitus , 1989 .

[16]  C Cobelli,et al.  Stable-Label Intravenous Glucose Tolerance Test Minimal Model , 1989, Diabetes.

[17]  A H Clemens,et al.  The artificial beta cell--a continuous control of blood sugar by external regulation of insulin infusion (glucose controlled insulin infusion system). , 1974, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[18]  E. Pfeiffer,et al.  On the way to the automated (blood) glucose regulation in diabetes: the dark past, the grey present and the rosy future , 1987, Diabetologia.

[19]  G. W. Shaw,et al.  In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer , 1989, Diabetologia.

[20]  E. Kraegen,et al.  Blood Glucose Control by Intermittent Loop Closure in the Basal Mode: Computer Simulation Studies with a Diabetic Model , 1985, Diabetes Care.

[21]  B. Zinman,et al.  Normalization of Glycemia in Diabetics During Meals with Insulin and Glucagon Delivery by the Artificial Pancreas , 1977, Diabetes.

[22]  E W Kraegen,et al.  A semi‐closed loop computer‐assisted insulin infusion system , 1984, The Medical journal of Australia.

[23]  N. White,et al.  Practical closed-loop insulin delivery. A system for the maintenance of overnight euglycemia and the calculation of basal insulin requirements in insulin-dependent diabetics. , 1982, Annals of internal medicine.