Insulin aspart (Novolog) and insulin lispro (Humalog) are rapid-acting insulin analogs suitable for mealtime use in an intensive insulin therapy regimen of multiple daily injections (MDIs). Insulin analogs administered just before meals improve postprandial glycemic control as compared with regular human insulin administered 30 min before meals (1,2). These rapid-acting analogs are soluble insulins and are effective in continuous subcutaneous insulin infusion (CSII) (3,4).
P.L. is a 12-year-old male with a 4-year history of type 1 diabetes. Initial treatment with a mixed-split regimen of NPH insulin and insulin lispro in MDI therapy was reasonably well accepted, given the necessity of lifestyle modifications (patient was then 9 years old). However, P.L. had to follow a meal-snack schedule to minimize hypoglycemic episodes related to the duration of NPH insulin. HbA1c was maintained at 8.1% during this time.
After 4 months of MDI therapy, P.L. initiated CSII therapy with insulin lispro administered by a Disetronic Pump. After 6 months of CSII therapy, P.L. had remarkable improvements in perceived lifestyle: freely adjusted eating schedule, freedom from previously required snacks, notably fewer hypoglycemic episodes, and reduced HbA1c to 5.4%. However, his blood glucose became more difficult to control and his insulin requirements progressively increased, perhaps related to leaving a “honeymoon phase” of his evolving type 1 diabetes. His response to therapy showed a pattern that was related to the infusion site duration.
Day 1: P.L. was exquisitely sensitive to boluses and minor basal rate dosage changes.
Day 2: There was less sensitivity to minor dosage changes.
Day 3: The infusion site showed signs of erythema and swelling, and P.L. experienced mild hyperglycemia, conditions requiring a new infusion site. The same insulin dose could not be maintained over the 3-day cycle without an increased frequency of hypoglycemic episodes on day 1 followed by an increased frequency of unacceptable hyperglycemia on day 3.
A partial solution was to change the infusion site every 1.5–2 days. During this period of increased treatment difficulties, his HbA1c was maintained at 6.2%.
After another 8.5 months, P.L.’s family visited the Insulin Pumpers Web site. They learned that other patients were adding Velosulin (buffered regular insulin) to insulin lispro to increase site duration in CSII. When they used a ratio of 1:4 (Velosulin:lispro), P.L.’s infusion sites consistently lasted up to 3 days. This practice was continued for 2.5 years, during which P.L.’s average HbA1c was 7.2%.
In July 2001 P.L. started using insulin aspart in his pump. His HbA1c has since been maintained at ≤7%. In June 2002, his HbA1c was 6.2%. The infusion site has been changed every 4–5 days (only when the insulin cartridge is empty).
Although the mechanism for improved infusion site duration with insulin aspart is not known, the response is consistent over the lifetime of the infusion site, and has not been accompanied by an increased frequency of hypoglycemia. The improved predictability of insulin aspart has encouraged P.L. and his family to more confidently adjust the insulin pump settings to maintain tighter glycemic control without increasing the risk of hypoglycemia.
Address correspondence to Denis I. Becker, MD, FACE, Raleigh Endocrine Associates, 3410 Executive Dr., Raleigh, NC 27609. E-mail: email@example.com.
D.I.B. has received honorarium from Eli Lilly and Novo Nordisk.