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N Hakui

Publications and source records attributed to N Hakui.

9 recordsLinked to original sources

Closed-loop glycemic control with a wearable artificial endocrine pancreas. Variations in daily insulin requirements to glycemic response.

We succeeded in miniaturizing a needle-type glucose monitoring system with characteristics suitable for application in a wearable, closed-loop control system. A wearable artificial endocrine pancreas (12 X 15 X 6 cm, 400 g) consisting of a sensor, a microcomputer system that calculates insulin and glucagon infusion rates, and two roller pumps was developed. Continuous glucose monitoring by a glucose sensor inserted in the subcutaneous tissue of the forearm or abdomen of healthy and diabetic volunteers revealed that glucose concentrations in subcutaneous tissue were 10% lower than, but were highly correlated with, blood glucose concentrations in the range of 49-388 mg/dl. Glycemic control was established in diabetic patients by intravenously infusing insulin in response to measured glucose concentrations on a moment-to-moment basis for a period of several days. By comparing the glycemic control obtained in each patient treated with multiple insulin injections or open-loop subcutaneous insulin infusion, the superiority of feedback control with the system was clearly demonstrated. During continuous glycemic regulation, day-to-day variations of insulin requirements were recognized in both basal insulin infusion and postprandial insulin infusion rates in response to identical meals and exercise. These data suggest the feasibility of long-term glycemic control in diabetic subjects with a wearable artificial endocrine pancreas, and indicate that to overcome changes in individual metabolic characteristics on a moment-to-moment basis, a closed-loop glycemic control system may be essential for ambulatory diabetic patients.

Adult

The development of wearable-type artificial endocrine pancreas and its usefulness in glycaemic control of human diabetes mellitus.

We have succeeded in miniaturizing a glucose monitoring system into a needle-type which preserves the characteristics suitable for application in a wearable closed-loop control system. The wearable artificial endocrine pancreas (12 X 15 X 6 cm, 400 g) consists of the sensor, a microcomputer which calculates the insulin and glucagon infusion rates and of a 2-syringe driving system. The device succeeded in controlling glycaemia perfectly in depancreatized dogs for a period of 3 days, and with replacement of subcutaneously inserted sensor for up to 7 days. When glucose monitoring by a needle-type glucose sensor inserted into subcutaneous tissue of the forearm or abdomen of healthy and diabetic volunteers was attempted, the readings were about 10% lower than blood glucose concentrations, but good correlation between them was observed in the range of 60 to 400 mg/dl. Perfect glycaemic control was established by infusing insulin either intravenously or subcutaneously in response to measured glucose concentrations on a moment-to-moment basis in diabetics for a period of several days. These results might indicate the feasibility of long-term glycaemic control in ambulatory diabetic patients with a wearable closed-loop glycaemic control system.

Blood Glucose

Glycaemic control in pancreatectomized dogs with a wearable artificial endocrine pancreas.

A needle-type glucose sensor has been developed using a platinum electrode covered with immobilized glucose oxidase. Experiments with albumin-saline solution in vitro showed that at 5.5 mmol/l glucose concentration the output current generated was 1.2 +/- 0.4 nA (mean +/- SD). The current increased as a linear function of glucose concentration over the range (0-27.7 mmol/l). The response time to reach 90% of the final plateau value was 16.2 +/- 6.2s. The signal-to-noise ratio of the sensor was 15.8 +/- 2.6 decibels. The temperature coefficient in output was 2.3 +/- 1.0%/degrees C. The current output was not affected significantly by changes in oxygen tension of the solution in the range 25-150 mmHg. In vivo, the output current of sensors inserted into the subcutaneous tissues of dogs was directly related to blood glucose concentrations after oral glucose or meals. Daily checking of the sensors maintained in subcutaneous tissues in five dogs showed that the sensitivity decreased gradually to 87.2 +/- 7.6% at 72 h, and dropped significantly to 57.4 +/- 7.0% of the initial output by 96 h. A wearable artificial endocrine pancreas (18.0 x 17.7 x 7.9 cm, 700 g) was developed, consisting of a needle-type glucose sensor, a microcomputer system and a pump driving mechanism. Three pancreatectomized dogs were fitted with the system by inserting the sensor into subcutaneous tissue. By renewing the sensor every fourth day, the device could maintain the daily glucose variations in diabetic dogs within the range 5-9.5 mmol/l for 7 days.

Animals

Wearable artificial endocrine pancrease with needle-type glucose sensor.

Miniaturisation of the bedside artificial endocrine pancreas in necessary to provide a means of restoring physiological glycaemic excursions in diabetic patients in the long term. One of the remaining problems in producing such a sophisticated device is the difficulty in developing a sufficiently small glucose-monitoring system. A needle-type glucose sensor has been developed which is suitable for use in a closed-loop glycaemic control system. The wearable artificial endocrine pancreas, incorporating the needle-type glucose sensor, a computer calculating infusion rates of insulin, glucagon, or both, and infusion pumps, was tested in pancreatectomised dogs: the device produced perfect control of blood glucose for up to 7 days.

Animals

The effect of rectal administration of insulin on the short-term treatment of alloxan-diabetic dogs.

Six alloxan-diabetic dogs with fasting plasma glucose levels above 200 mg/100 mL were treated with rectal administration of insulin suppositories twice a day for 6--9 days. The effectiveness was compared with that of subcutaneous insulin injections. In three diabetic dogs with fasting plasma glucose levels below 300 mg/100 mL, both insulin suppository at a dose of 20 U (2.3 U/kg) and subcutaneous insulin at a dose of 0.2 U/kg showed a similar effect in reducing fasting glucose levels and daily urinary glucose amounts. In dogs with higher fasting glucose levels, 0.5 U of subcutaneous insulin/kg is less effective in reducing fasting glucose than 50 U (5.2 U/kg) suppositories, in spite of the same effects on daily urinary glucose output. Postprandial glucose responses were significantly lessened with rectal administration of insulin suppositories. The integrated area of increase in peripheral insulin concentration after subcutaneous infection of 0.2 or 0.5 U insulin/kg was significantly greater than that after rectal administration of an insulin suppository (2.3 or 5.2 U/kg, respectively). These results indicate that diabetes could be controlled by the daily rectal administration of an insulin suppository instead of the conventional subcutaneous injection.

Animals

The effectiveness of rectal administration of insulin suppository on normal and diabetic subjects.

The effectiveness of insulin administration by rectal suppository was examined in normal and non-insulin-dependent nonobese diabetic subjects. A 100-U insulin suppository (mean 1.8 U/kg) given to the diabetic subjects caused four times as great a fall in plasma glucose compared with the normal subjects given the same dose (mean 1.6 U/kg). The insulin response after suppository administration demonstrated a significantly positive correlation (r = 0.83, P less than 0.01) with the plasma glucose level before administration. Diabetic subjects given a 100-U insulin suppository (mean 1.7 U/kg) 15 min after meals three times daily showed a significant (P less than 0.05) improvement in postprandial hyperglycemia accompanied by a restoration of the normal circadian profile of plasma IRI and a reduction of urinary glucose from 26 +/- 5.9 to 2.0 +/- 1.0 g/day. No untoward reactions were observed. These data strongly imply a unique characteristic of the insulin suppository in spite of low bioavailability.

Adult