Comment on American Diabetes Association. Approaches to Glycemic Treatment. Sec. 7. In Standards of Medical Care in Diabetes—2015. Diabetes Care 2015;38(Suppl. 1):S41–S48

One of the difficult challenges for individuals with type 1 diabetes is trying to determine the optimum time to inject a bolus of rapid-acting insulin for meals. Therefore, we were surprised that the updated 2015 American Diabetes Association (ADA) Standards of Medical Care in Diabetes lacks a specific recommendation on this topic (1), especially given the contribution of postprandial hyperglycemia to achieved hemoglobin A_1c levels (2).

Although several recent publications have concluded that premeal bolusing 15–20 min ahead of time with currently available rapid-acting insulin analogs is advantageous to reducing postprandial hyperglycemia in people with type 1 diabetes without causing increases in hypoglycemia (2,3), the updated guidelines from the ADA are general, advising individuals to “match prandial insulin to carbohydrate intake, premeal blood glucose, and anticipated physical activity” (1). Moreover, they also suggest the use of rapid-acting insulin analogs administered “just before” eating without defining a time range (1).

Investigation into the optimal time of meal boluses for insulin analogs is not a new field of interest. The prescribing information for insulin lispro, available since 1996, does not define a specific time for meal bolusing, instead stating that it should be within 15 min before a meal or immediately after a meal. The labeling for insulin glulisine notes to administer it within 15 min before a meal or within 20 min after starting a meal, while insulin aspart is labeled to be given 5–10 min before meals. Despite different labeling, in clinical practice many patients and providers use these insulins interchangeably.

The availability of Afrezza (inhaled insulin human), now approved by the U.S. Food and Drug Administration, and its label stating that it should be given at, not before, mealtime further emphasize the need for detailed guidance from the ADA. We recently studied Afrezza and showed that when used as a priming bolus at mealtime to mimic first-phase insulin secretion, it reduced the median postprandial glucose peak by 33 mg/dL compared with control subjects during closed-loop insulin delivery (peak glucose 172 vs. 205 mg/dL, P = 0.004, n = 9 subjects) (4). The ability to provide effective first-phase insulin with a fast-acting delivery system fits the ADA guidelines to bolus at mealtime, but guidance should be given on the exact timing of the dose, as bolusing 15–20 min ahead of time with inhaled insulin may induce hypoglycemia.

The recent update to the International Society for Pediatric and Adolescent Diabetes (ISPAD) insulin treatment guidelines recognizes the delay to peak insulin action with subcutaneous injection of rapid-acting insulin analogs and now recommends that they “may need to be given 15–20 min before the meal to have full effect, especially at breakfast” (5). We would like to see the ADA reconsider this issue and provide more specific mealtime insulin bolusing guidelines for individuals with type 1 diabetes, at least until more rapid-acting subcutaneous insulins become available, as prebolusing for meals has the potential to significantly improve glycemic outcomes.