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At least 19 recordsLinked to original sources
PubMed1979

Feedback control dynamics for glucose controlled insulin infusion system.

Miles Laboratories has developed a Glucose Controlled Insulin Infusion System (GCIIS) designated by the Trademark (BIOSTATOR) as a tool to investigate the physiologic control parameters of carbohydrate metabolism and regulatory deficiencies in diabetes. It consists, in principle, of a rapid on-line glucose analyzer, a computer/controller for the calculation and control of insulin or dextrose infusion, and a multichannel infusion system. A silent printer records, on a minute-by-minute basis, the glucose value measured, the insulin and/or dextrose infusion rates, and the cumulative total of the insulin infused. The on-line glucose analyzer employs an electrochemical sensor with immobilized glucose oxidase and measures the hydrogen peroxide produced. Its linearity extends beyond 700 mg/dl glucose; it permits a rapid two-point calibration of the sensor and the overall calibration of the on-line analyzer without disconnecting the catheter from the patient. The system's response time, including blood sample transport from the patient, is less than 90 seconds with a blood loss of approximately 50 ml per 24 h. The insulin and dextrose infusions are governed by control algorithms; various mathematical models have been developed and employed toward improved feedback control dynamics. The rapid glucose analyzer eliminates the need for the calculation of a "predicted" glucose value and permits, instead, the use of a derivative function for dynamic control. A multichannel infusion system combines the principles of a peristaltic pump with the advantages of a precision pump performance and individual computer control for each of the pump channels.

Blood Glucose↗
PubMed1978

Development and evaluation of a glucose analyzer for a glucose controlled insulin infusion system ((Biostator).

The Glucose-Controlled Insulin Infusion System (Biostator) is a modular, computerized, feedback control system for dynamic control of blood glucose concentrations in diabetics. This on-line glucose analyzer for use with whole blood utilizes a novel enzyme (glucose oxidase)-membrane configuration and an electrochemical cell to measure the H202 generated. The analyzer exhibits both short- and long-range stability, and instrument response and analyte concentration are linearly related over the full range of clinical interest. The response is fast, accurate, and precise, and permits determination of blood glucose within 2 min from the moment the blood leaves the patient. Correlation studies were completed to show the agreement between the Biostator Glucose Analyzer and the FDA's recommended hexokinase/glucose-6-phosphate dehydrogenase procedure on whole blood (e.g., average per cent recovered for 11 concentrations between 250 and 900 mg/liter was: hexokinase, 95.6%, Biostator Analyzer, 95.9%; bias and SDd, respectively, at low, normal, and high glucose values were: 12 and 41 mg/liter at the 500 mg/liter level; 4 and 52 mg/liter at the 1000 mg/liter level, and 4 and 128 mg/liter at the 4000 mg/liter level). No appreciable interference is observed with above-normal concentrations of bilirubin, uric acid, creatinine, sodium salicylate, or dextran. Platelet adhesion, which tends to decrease the useful life of the membrane, has been significantly decreased.

Autoanalysis↗
PubMed1979

Metabolic studies during normoglycaemic clamping of insulin-dependent diabetics using a glucose-controlled insulin infusion system.

Metabolic rhythms have been studied in six insulin-dependent diabetics during subcutaneous insulin therapy, and during control of blood glucose concentration by a glucose-controlled insulin infusion system (GCIIS). In none of the subjects was blood glucose concentration consistently within the normal range during subcutaneous insulin therapy. In contrast, blood glucose concentration was within the normal range after 3.5 h of insulin delivery by the glucose-controlled insulin infusion system and remained in the normal range for the following 8 h through lunch and dinner. Mean blood glucose concentration during this time ranged from 5.31 to 7.90 mM. Following normalisation of blood glucose concentration, blood lactate and pyruvate were similar with both the GCIIS and subcutaneous insulin therapy. Post-prandial lactate peaks were delayed with the GCIIS. Alanine levels were consistently higher during control with the GCIIS compared with subcutaneous therapy, while blood ketone body and plasma NEFA levels were lower, and the premeal peaks in the lipid metabolites were delayed. It is not possible to conclude that attainment of normoglycaemia with the present generation of glucose-controlled insulin infusion systems in insulin-dependent diabetics is accompanied by total normalisation of intermediary metabolism.

Adult↗
PubMed1978

A glucose-controlled insulin infusion system for diabetic women during labour.

A glucose-controlled insulin infusion system was used to control blood glucose concentration during labour or caesarean section in six insulin-dependent diabetics. The mean blood glucose concentration during the four hours of labour immediately before delivery was 4.6-5.2 mmol/1 (82.9-93.7 mg/100 ml). Feedback control of insulin delivery by blood glucose concentration should decrease the risk of postpartum hypoglycaemia in the infant and allow normal obstetric management for the insulin-dependent diabetic in labour.

Adult↗
PubMed1979

Use of glucose-controlled insulin infusion system for improvement of subcutaneous insulin regimen.

The use of an artificial pancreas for blood glucose monitoring and feedback correction for evaluation and improvement of subcutaneous insulin therapy facilitates the process of finding an optimal therapy regime for the individual patient. The frequency of hypoglycemic episodes can be reduced while maintaining good control, and hospital stays can be considerably shortened. This procedure is particularly useful in achieving tight control in pregnant diabetics.

Adolescent↗
PubMed1979

Comparison of a perfusion syringe (Mill Hill Infusor) and a glucose-controlled insulin infusion system in the regulation of diabetes mellitus.

In a preliminary study, three unstable, juvenile diabetics were first connected to a glucose-controlled insulin infusion system (Biostator), and subsequently to a portable infusor (Mill Hill Infuser) for continuous subcutaneous insulin application. The levels of glucose and several other metabolites as well as the insulin requirement were compared. As a tentative conclusion, continuous subcutaneous application is recommended (1) for long-term therapy when several daily doses are required and (2) after metabolic compensation with a Biostator, but before conventional therapy.

Adolescent↗
PubMed1979

Insulin treatment and state of control before, during, and after connection to a glucose controlled insulin infusion system (Biostator).

Nine insulin-dependent, juvenile-onset diabetics were treated for more than twenty four hours with an artificial beta cell (Biostator). Using the amounts and profile of the insulin delivered by the machine as a guide for subsequent subcutaneous therapy, a better state of control was obtained. However, with the algorithm constants used, we found the Biostator to deliver more insulin (average 36%) than needed for subcutaneous therapy. Repeated oral glucose tolerance tests show that constants used in the algorithms might be optimized.

Adolescent↗
PubMed1979

The external artificial pancreas: an instrument to induce remissions in severe recent juvenile diabetes. Comparison with a preprogrammed insulin infusion system.

Remission of juvenile insulin-dependent diabetes is a rare, temporary, and partial phenomenon which seems to be related to an improvement of the residual insulin secretion supported by prompt and rigorous insulin therapy. Thus, remissions allowing the replacement of insulin by oral drugs were attempted in 23 insulin dependent ketotic juvenile diabetics (age 10 +/- 2 years) of recent onset (apparent duration of diabetes 71 +/- 5 days) treated by an external artificial pancreas during 5 +/- 1 days and compared with 10 control diabetics treated by a less effective technique (preprogrammed insulin pump without feedback control) during 6 +/- 1 days. 18 (78%) remissions of long duration (1-26 months) occurred after artificial pancreas compared with 3 (30%) in the control group. Measurement of daily urinary C-peptide excretion confirmed the improvement of the residual insulin secretion in patients with insulin-induced remissions. Thus, the excellent blood glucose control given by an artificial pancreas seems necessary to lead to much more frequent remissions of diabetes than usually reported.

Acute Disease↗
PubMed1979

Optimal blood sugar control in labile diabetics using a portable open-loop insulin infusion system with a flexible program.

11 labile diabetics were well controlled after 2 days of an i.v., open-loop insulin infusion program consisting of constant, empirically determined, basal infusion rates (mean: 1.1 U/h) and superimposed rectangular one-hour insulin infusions between 2 and 8 U/h during the main meals. The steering unit switches automatically back to the basal infusion rate after one hour. An almost optimal blood sugar profile was already obtained on the third day of the infusion program. We believe that such a flexible, open-loop insulin infusion program would render long-term optimal blood sugar control in "labile" diabetics possible if the technological development ever allows implantation of the infusion pumps.

Adolescent↗
PubMed1976

Comparison of peripheral and portal routes of insulin infusion by a computer-controlled insulin infusion system (artificial endocrine pancreas).

This study was undertaken to determine the different consequences of portal and peripheral routes of insulin administration by the artificial endocrine pancreas. Intraportal glucose was infused (10 mg./min./kg. for 60 minutes) in anesthetized normal and pancreatectomized dogs while blood glucose concentrations were monitored continuously. During computer-controlled insulin administration normal glucose tolerance was restored by both portal and peripheral routes of insulin delivery. There were also no significant differences in (1) glycemic patterns, (2) insulin infusion patterns, (3) peripheral IRI levels, and (4) total insulin requirements between the two routes. It is apparent that the peripheral route, which is more readily accessible than the portal route, may be an appropriate infusion site for an implantable or portable prosthesis for controlling blood glucose concentration.

Animals↗
PubMed1979

A portable, pre-programmable insulin infusion system in diabetes mellitus.

A miniaturized portable pump has been developed in order to study the effects of pre-programmed insulin infusion patterns on the blood glucose levels in juvenile-onset, insulin-requiring diabetics. Six diabetics undergoing 7 insulin infusion periods of up to 4 days were studied. The mean blood glucose was 7.0 +/- 2.3 (SD) mmol/l and the mean amplitude of glycemic excursions was 5.0 +/- 1.4 mmol/l. Success in achieving normoglycemia will depend on choosing the correct dose of insulin for infusion.

Adult↗
PubMed1979

Use of a glucose controlled insulin infusion system (artificial beta cell) to control diabetes during surgery.

An artificial beta cell has been used to achieve and maintain a preset plasma glucose concentration in five diabetic patients undergoing surgery. These subjects were compared to control groups of normal subjects receiving either saline or glucose, and diabetics receiving glucose intraoperatively. Hyperglycaemia during surgery was seen in normals (mean plasma glucose +/- SEM: 185 +/- 16 mg/dl) and, to a greater degree, diabetics (247 +/- 36 mg/dl) receiving glucose. Insulin and C-peptide levels did not increase during 2 hours of operation in any of the control groups, suggesting beta cell suppression during surgery. As C-peptide levels declined similarly in normal subjects whether they received saline or glucose, the hyperglycaemia seems to be due to an inability to use exogenous glucose. This is confirmed by a correlation of maximal plasma glucose to glucose infusion rate (r = 0.78, p less than 0.01). The artificial beta cell was able to achieve the same plasma glucose after 2 hours of operation (128 +/- 21 mg/dl) as normal subjects receiving saline (110 +/- 7 mg/dl). The artificial beta cell proved to be a safe, convenient and effective way of monitoring and controlling the hyperglycaemia seen in diabetic patients undergoing surgery.

Blood Glucose↗
PubMed1979

A portable, Preprogrammable insulin infusion system with 16 rates.

An external, portable, programmable pump has been developed for long-term therapeutic i.v. insusion of drugs. The impulse-controlled system consists of a 250 g CMOS-electronic unit and an electromechanical infusor (200 g) containing a 10 ml disposable syringe. The infusion pattern during the 24-h cycle is manually programmed in 16 steps from 24 to 384 microliter per 0.5 h. The coefficient of variation of the infusate is less than 2% per 0.5 h. An alarm circuit monitors the pump speed and the reservoir volume. The infusion system can operate continuously for 7 days with a 1 Ah, 5.4 volt battery.

Artificial Organs↗
PubMed1992

Increased food intake following carotid and systemic insulin infusions.

In order to determine whether insulin receptors in the brain or in the periphery are more important for the control of food intake, four doses of insulin (0.1, 0.5, 1.0 and 2.0 U/day) were each infused continuously over 24 h into rats with chronic catheters in the common carotid artery (C) or the superior vena cava (VC). Daily food intake was unchanged from baseline levels by insulin doses of 0.1 to 1.0U. However, intake increased by 8.1 +/- 1.3 kcal for the C rats and by 10.2 +/- 1.8 kcal for the VC rats during the 2.0U infusion and was also increased on the subsequent day, by 10.9 +/- 1.9 kcal and 15.4 +/- 3.0 kcal for C and VC groups respectively. Rats were fed half an hour after insulin infusions began and measures of short-term intake made over the next 30 min were unaffected by any of the insulin doses. When injected into C catheters prior to sacrifice greater than 90% of 57Co labelled microspheres were recovered in arterioles of the brain, skull and facial regions. As brain blood flow is 1.8% of cardiac output, insulin levels in the brain blood supply would have been substantially greater for C rats. The similar increases in food intake for C and VC rats clearly show that insulin fails to produce greater effects when infused directly into the brain. Instead, these findings suggest that the effect of insulin on daily food intake is predominantly a function of insulin receptor activation in the periphery.

Animals↗
PubMed1992

Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus.

BACKGROUND: Glucagon-like peptide-1 (7-36) amide (glucagon-like insulinotropic peptide, or GLIP) is a gastrointestinal peptide that potentiates the release of insulin in physiologic concentrations. Its effects in patients with diabetes mellitus are not known. METHODS: We compared the effect of an infusion of GLIP that raised plasma concentrations of GLIP twofold with the effect of an infusion of saline, on the meal-related release of insulin, glucagon, and somatostatin in eight normal subjects, nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM), and eight patients with insulin-dependent diabetes mellitus (IDDM). The blood glucose concentrations in the patients with diabetes were controlled by a closed-loop insulin-infusion system (artificial pancreas) during the infusion of each agent, allowing measurement of the meal-related requirement for exogenous insulin. In the patients with IDDM, normoglycemic-clamp studies were performed during the infusions of GLIP and saline to determine the effect of GLIP on insulin sensitivity. RESULTS: In the normal subjects, the infusion of GLIP significantly lowered the meal-related increases in the blood glucose concentration (P less than 0.01) and the plasma concentrations of insulin and glucagon (P less than 0.05 for both comparisons). The insulinogenic index (the ratio of insulin to glucose) increased almost 10-fold, indicating that GLIP had an insulinotropic effect. In the patients with NIDDM, the infusion of GLIP reduced the mean (+/- SE) calculated isoglycemic meal-related requirement for insulin from 17.4 +/- 2.8 to 2.0 +/- 0.5 U (P less than 0.001), so that the integrated area under the curve for plasma free insulin was decreased (P less than 0.05) in spite of the stimulation of insulin release. In the patients with IDDM, the GLIP infusion decreased the calculated isoglycemic meal-related insulin requirement from 9.4 +/- 1.5 to 4.7 +/- 1.4 U. The peptide decreased glucagon and somatostatin release in both groups of patients. In the normoglycemic-clamp studies in the patients with IDDM, the GLIP infusion significantly increased glucose utilization (saline vs. GLIP, 7.2 +/- 0.5 vs. 8.6 +/- 0.4 mg per kilogram of body weight per minute; P less than 0.01). CONCLUSIONS: GLIP has an antidiabetogenic effect, and it may therefore be useful in the treatment of patients with NIDDM:

Adult↗