Optimal prandial timing of bolus insulin in diabetes management: a review

Abstract

The inability to achieve optimal diabetes glucose control in people with diabetes is multifactorial, but one contributor may be inadequate control of postprandial glucose. In patients treated with multiple daily injections of insulin, both the dose and timing of meal-related rapid-acting insulin are key factors in this. There are conflicting opinions and evidence on the optimal time to administer mealtime insulin. We performed a comprehensive literature search to review the published data, focusing on the use of rapid-acting insulin analogues in patients with Type 1 diabetes. Pharmacokinetic and pharmacodynamic studies of rapid-acting insulin analogues, together with postprandial glucose excursion data, suggest that administering these 15-20 min before food would provide optimal postprandial glucose control. Data from clinical studies involving people with Type 1 diabetes receiving structured meals and rapid-acting insulin analogues support this, showing a reduction in post-meal glucose levels of ~30% and less hypoglycaemia when meal insulin was taken 15-20 min before a meal compared with immediately before the meal. Importantly, there was also a greater risk of postprandial hypoglycaemia when patients took rapid-acting analogues after eating compared with before eating.

Figure 1

Review flow diagram.

Figure 2

Pharmacokinetics of bolus insulins. Panels (a), (b) and (c) are reproduced from Home et al. Diabetes Obes Metab 2012; 14: 780–788. Panel (d) is reproduced with permission from Andersen et al. EASD 2016; ePoster #931. Panels (e) and (f) are reproduced from Heise et al. Diabetes Obes Metab 2015; 17: 682–688 25, under a Creative Commons licence. s.c., subcutaneous.

Figure 3

(a): Serum insulin levels before and after subcutaneous (s.c.) injection (at 0 min) of insulin aspart or insulin lispro in seven patients with Type 1 diabetes. (b) Glucose infusion rate (GIR) needed to prevent hypoglycaemia in the same seven patients. (c) Plasma glucose concentrations before and after s.c. injection of insulin aspart or insulin lispro in the same seven patients. Figure reproduced from Homko et al. Diabetes Care 2003; 26: 2027–2031 33.

Figure 4

Mean blood glucose levels after meal initiation in three treatment arms: Pre: delivering an insulin glulisine bolus by insulin pump 20 min prior to a meal (−20 min); Start: immediately before the meal (0 min); and Post: 20 min after meal initiation (+20 min). Figure reproduced from Cobry et al. Diabetes Technol Ther 2010; 12: 173–137 33.