Eleven brittle diabetics, mean duration 11.5 years, all treated with highly purified porcine NPH insulin twice daily, were placed on highly purified porcine regular insulin 4 times daily for 2 days. Thereafter pre-planned intravenous insulin infusion was started. Insulin in an amount corresponding to the daily insulin requirement was infused by a mobile electric infusion pump at precalculated rates between 30 and 7 ml/hour during 2 days. The patients were ambulatory. Capillary blood glucose was taken every 30 min after meals and every two hours during the night. After an equilibration period of 7 hours, blood glucose fluctuations were in the physiological range in nearly all patients during the infusion period. [Only 1.3% of the blood samples showed glucose levels lower than 2.5 mmol/l and 2.9% levels exceeding 10.0 mmol/l during the infusion days]. Mean blood glucose (MBG) was 6.0 +/- 0.9 mmol/l (mean +/- s.d.), the standard deviation of MBG was 1.8 +/- 0.5 mmol/l, the mean amplitude of blood glucose excursions (MAGE) 4.7 +/- 1.4 mmol/l, and glucosuria 3.1 +/- 3.9 g/day. All these data of glucose homeostasis were significantly lower during the infusion days. The incidence of hypoglycaemic attacks was low (0.32/patient/day) and not significantly higher than during NPH treatment. It is concluded that near normal blood glucose fluctuations can be achieved in brittle diabetics by preplanned insulin infusion without blood glucose monitoring.

The blood glucose/urinary glucose relationship was studied in 23 patients with Type 1 (insulin-dependent) diabetes. Glucose was infused intravenously in order to increase blood glucose concentration slowly and gradually. The renal threshold was recorded at the slightest trace of glycosuria and varied by a factor of 2 (from 6.0 to 14.3 mmol/l). The rise in blood glucose required to change the urinary output (0-1.1 mmol glucose/20 min) varied by a factor of 7 (1.1-7.6 mmol/l). The maximal rate of tubular glucose reabsorption varied by a factor of 2 (0.93-1.98 mmol/min). The renal threshold was negatively correlated with the creatinine clearance (r = -0.052, p less than 0.05), but was not correlated with diabetic control, age or duration of diabetes. The maximal rate of glucose reabsorption was negatively correlated with age (r = 0.47, p less than 0.05) and duration of diabetes (r = -0.54, p less than 0.05). In conclusion, urinary glucose excretion is dependent on both renal threshold and the splay and the slope of the blood glucose/urinary glucose excretion curve. Thus, the degree of glycosuria is of value as an index of diabetic control only when the blood glucose/urinary glucose relationship is known. The inverse correlation between renal threshold and creatinine clearance limits the usefulness of measuring glycosuria in patients with nephropathy.

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Glucose homeostasis was studied in nine longstanding insulin-dependent diabetic patients using a portable pump for intravenous insulin infusion. The 24 h infusion dose was calculated from the conventional SC insulin treatment. The range of basal infusion rates was 2.5 to 15 mU/min and peak delivery rates were raised up to 16-fold from start of main meals for 30-60 minutes. Mean blood glucose improved from 12.0 +/- 2.4 to 6.4 +/- 1.0 mmol/l (SD) during infusion (p less than 0.01). Glucose excretion decreased from 23 g/24 h (range 1-42) to 4 g/24 h (range 0-14) (p less than 0.01). Mean amplitude of glycaemic excursions was significantly improved during infusion (from 8.9 +/- 4.8 to 4.7 +/- 0.9 mmol/l; p less than 0.01). No severe hypoglycaemic episodes or other adverse reactions were seen.

Ten patients with unstable insulin-dependent diabetes mellitus, mean duration 17.5 yr, all treated with highly purified porcine NPH insulin twice daily, were placed on highly purified porcine regular insulin subcutaneously four times daily for 2 days. Thereafter a preplanned intravenous insulin infusion was given for 54 h. Insulin in an amount corresponding to 24-h insulin requirement was infused by a portable infusion pump. Immediately before the main meals the prandial infusion program was released by the patients by pushing a button. Capillary blood glucose was taken every 30 min during the day and every 2 h during the night. Endogenous insulin secretion was calculated by measuring the C-peptide response after 1 mg of glucagon intravenously. Insulin antibodies were measured in all patients.Insulin antibody concentration was low in most cases, and only one patient reacted to glucagon by a significant but low rise of C-peptide. After an equilibration period of 5 h, mean blood glucose (MBG) was in the physiologic range in 6 of 10 patients during the infusion period. MGB in the 10 diabetics averaged 5.5 ± 1 . 0 mmol/L (mean ± SD) compared with 4.4 ± 0.4 mmol/L in nondiabetic controls. The mean amplitude of glycemic excursions (MAGE) was 4.1 ± 1 . 4 mmol/L (mean ± SD) against 1.8 ± 0.6 mmol/L in control subjects. MBG, MAGE, and glucosuria were significantly reduced on the infusion days compared with the days on subcutaneous insulin.It is concluded that near-normal blood glucose fluctuations can be obtained in unstable diabetics by a preplanned prandial insulin infusion program activated by diabetic patients themselves. DIABETES S ubcutaneous insulin therapy cannot produce physiologic postprandial fluctuations of plasma insulin because of slow 1 and variable 2 absorption of insulin from subcutaneous tissue. To keep the concentration of blood glucose and other metabolites and hormones in the narrow physiologic range (which probably significantly reduces the incidence of late diabetic complications such as blindness, uremia, and neuropathy 3 ), patients with insulin-dependent diabetes mellitus (IDDM) have to follow a rigid regimen including regular meals, snacks, physical activity, and frequent examinations of urine and/or blood for glucose and ketone bodies. Furthermore, unpredictable attacks of hypoglycemia, especially during and after muscular exercise, trouble the patient and his family, and often lead to huge blood glucose oscillations.Other methods of insulin therapy therefore need to be investigated. Several groups have shown that mean blood glucose (MBG) and mean amplitude of glycemic excursions (MAGE) 4 in ambulant patients with unstable IDDM can be reduced significantly when insulin is infused intravenously (i.v.) at different rates, 5 " 9 without glucose sensoring. However, to obtain these results, either the infusion rate had to be varied during the day from time to time, or the patients had to adhere strictly to a preplanned program of meals, exercise, etc. One of us (J.B.) has constructed a portable insu...