A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 1. Metabolic and hormonal consequences and scheme for a prompt return to adequate control

Abstract

Summary. Interruption of a continuous subcutaneous insulin infusion, most often due to technical problems occurring during the night, is a not uncommon event whose metabolic consequences have received relatively little attention until now. We have therefore investigated the changes in blood glucose, plasma non-esterified fatty acids, 3-hydroxybutyrate, glucagon and free insulin in eight C-peptide negative Type 1 diabetic patients whose pumps were deliberately stopped between 23.00 h and 05.00 h. A control test with the pump functioning normally was carried out in each patient and the studies were randomized. Considering the values at 23.00 h as reference, interruption of the insulin infusion resulted in (1) a rapid decrease in plasma free insulin significant after 1 h and reaching a nadir of 6 + 2 mU/l after 6 h; (2) a rise in blood glucose which was significant at hour3 and reached 17.4+ 1.9 mmol/l at hour 6; (3) a moderate increase in plasma nonesterified fatty acids which remained in the range of 700-800 ~tmol/1; (4) an early and linear rise in plasma 3-hydroxybutyrate, significant after 1 h and averaging 1290_+ 140 gmol/1 after 6 h; (5) a late increase (hour 5) in plasma glucagon. The second aim of our study was to provide for the patient a precise scheme of insulin supplements administered via the pump and based on blood glucose monitoring (Dextrostix -Glucometer) and semi-quantitative evaluation of ketonuria (Acetest). Resetting the pump at its basal rate at 05.00h and giving insulin supplements (2-8 U) at 06.45 h (with the usual breakfast dose) and again at 10.00h have proved efficacious in restoring satisfactory metabolic control by noon the day after starting the experiment. These results form practical recommendations to patients undergoing this type of accident.

Comparison of Metabolic Deterioration between Insulin Analog and Regular Insulin after a 5-Hour Interruption of a Continuous Subcutaneous Insulin Infusion in Type 1 Diabetic Patients1

“…This is consistent with the lower plasma free insulin levels during LP treatment and consequently less inhibition of plasma glucagon by insulin. Krzentowski et al, who studied the hormonal consequences of nocturnal interruption of CSII with regular insulin (13), demonstrated that plasma glucagon was above baseline only 6 h after stopping the pump and remained significantly elevated until 4 h after restarting the pump. The lack of a significant change in glucagon in our study was probably due to the shorter interruption of CSII.…”

“…However, technical problems with CSII (pump failure, catheter occlusion, and skin infection) may reduce insulin delivery or insulin absorption and cause diabetic ketoacidosis (12). A rapid drop in plasma free insulin and an increase in blood glucose and plasma 3␤-hydroxybutyrate (␤-OHB) occurred when CSII with regular insulin was interrupted for 6 h during the night (13). Given the pharmacokinetic characteristics of LP, the interruption of CSII may result in a more rapid metabolic deterioration in type 1 diabetic patients (14).…”

A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 2. Marked attenuation of the metabolic deterioration by somatostatin

“…Interruption of continuous subcutaneous insulin infusion (CSII) in diabetic patients without residual insulin secretion is followed by a rapid and sustained increase in blood glucose and plasma 3-hydroxybutyrate levels [1][2][3]. These metabolic alterations occur in conjunction with an early decrease in plasma free insulin concentrations [2,3] and a later rise in plasma glucagon levels [3].…”

Metabolic Control Targets for Patients with Type 1 Diabetes in Clinical Practice

“…Advantages of CIIS Interruption of insulin delivery by mechanical failure in the system of infusion leads quickly to hypoglycaemia and ketoacidosis due to the absence of a subcutaneous deposit of insulin (Krzentowski et al, 1983). This and other similar circumstances are preventable by training the individual to identify a potential episode, to warn and to treat the elevated levels of glycaemia (Guilhem et al, 2006).…”