Insulin pump therapy: what is the evidence for using different types of boluses for coverage of prandial insulin requirements?

Abstract

Bolus infusion of insulin along with a meal is a standard procedure with continuous subcutaneous insulin infusion. Modern insulin pumps allow applying this bolus in four different ways: infusion of the total dose at once or splitting the dose into two boluses, infusion of a part of the bolus in the usual manner plus infusion of the other part over a prolonged period of time (with a higher infusion rate than the basal rate), or infusion of the total dose in the form of an elevated basal rate. Depending on the composition of the given meal and its glycemic index, this is an attempt to match the circulating insulin levels to the rate of glucose absorption from the gut in order to minimize postprandial glycemic excursions. However, in the framework of evidence-based medicine, the benefits of this approach should be proven in appropriately designed clinical studies. Performance of meal-related studies requires careful attention to many aspects in order to allow meaningful evaluation of a given intervention (i.e., type of bolus). Critical evaluation of the clinical experimental studies and the one clinical study published about the impact of different types of boluses on postprandial metabolic control revealed fundamental shortcomings in study design and performance in these studies. Insufficient establishment of comparable preprandial glycemia and insulinemia on the different study days within and between the patients studied is one key aspect. Therefore, the recommendation made in most of these studies (i.e., use of dual-wave bolus) has to be accepted with care, until we have better evidence.

Figure 1.

Subcutaneous infusion of insulin with respect to a meal with different types of bolus. The time interval between the two boluses or the time during which the delayed bolus (i.e., a high basal rate for a selected period of time) is applied can be selected by the patients themselves (between 1 and 8 h). The proportion of the insulin dose applied as a bolus or as a square wave can also be varied (in 10% steps between 20%/80% and 50/50%).

Figure 2.

Postprandial glycemic excursions with four different types of prandial insulin boluses in nine patients with type 1 diabetes on CSII.

Figure 3.

Best-fitting models for the behavior of blood glucose levels using the four methods of bolus administration. Please acknowledge that, in these figures, the preprandial glycemia is also presented.

Figure 4.

Mean average hourly glucose sensor values compared for 16 consecutive hours following each of the three combinations of meal and bolus.

Figure 5.

Postprandial glycemic excursions with a standard bolus or dual-wave bolus in 24 patients with type 1 diabetes.

Figure 6.

Relative mean ± SD of postprandial glycemic changes with a standard bolus or dual-wave bolus in 20 young patients with type 1 diabetes versus 10 healthy subjects (control) after consuming a meal with (A) low GI or (B) high GI.

Figure 7.

Mean postprandial glycemic changes with a dual bolus over 6 h, with a 15 min bolus–meal interval prior to consumption of a pizza margherita (dark blue line) or without a bolus–meal interval (light blue line); a dual-bolus over 6 h, with a 15 min bolus–meal interval prior to consumption of a pizza vegetable (dark green line) or without a bolus–meal interval (light green line); and regular bolus with a 15 min bolus–meal interval and a pizza margherita (light brown line) or without a bolus–meal interval (light red line) in 26 young patients with type 1 diabetes.

Figure 8.

Median change in blood glucose in 13 adolescent girls after a meal with 36% fat and three different types of boluses in comparison to a control group.

Figure 9.

Hemoglobin A1c in relation to the number of extended/dual-wave boluses.