Insulin Lispro is a newly FDA approved analog of human
insulin that exhibits rapid absorption and a short duration of action after sc injection. Although
Lispro insulin improves immediate postprandial glycemia compared to
Regular insulin, long term trials of
Lispro insulin have not shown improvement in overall
glycemic control, as determined by
glycosylated hemoglobin. We hypothesize that this lack of improvement is attributable to the development of late
postprandial hyperglycemia secondary to a waning of
Lispro insulin's effect in conjunction with continued meal absorption. This study was designed to evaluate the duration of
Lispro-induced reductions in plasma
glucose after a standardized meal when
Lispro insulin is incorporated into a regimen typically employed in
insulin-dependent diabetes mellitus. After establishment of euglycemia overnight, 12 healthy
IDDM patients received human
Ultralente insulin (0.2 U/kg) alone and in combination with each of the following treatments in random sequence immediately before ingesting a 750-Cal American Diabetes Association breakfast: 1) 0.15 U/kg
human Regular insulin (Regular 0.15 group), 2) 0.15 U/kg
Lispro insulin (
Lispro 0.15 group), 3) 0.1 U/kg
Lispro insulin (
Lispro 0.1 group), and 4) an equimolar (1:1) mixture of
Lispro and Regular
insulins (0.15 U/kg; 1:1 Mix group).
Glucose and hormonal parameters were assessed for 8 h after the meal. Peak postprandial
glucose was increased in the
Regular insulin group compared to that in all groups that incorporated
Lispro insulin (P < 0.001).
Glucose area under the curve (AUC) was decreased in the
Lispro 0.15 group compared to that in the
Lispro 0.1 group, and
glucose AUC was decreased in the
Lispro 0.15 and 1:1 Mix groups compared to that in the group given
Regular insulin (P < 0.001). Mean plasma
glucose concentrations during the final hour of study were increased in the Ultralente group compared with those in all other treatment groups and were increased in the
Lispro 0.1 group compared with those in the Regular,
Lispro 0.15, and 1:1 Mix groups (P < 0.05).
Insulin AUC was significantly reduced in the
Lispro 0.1 group compared to those in all other
short acting insulin groups (P < 0.001), and time to peak
insulin was more rapid in the two
Lispro groups than those in all other treatment groups (P < 0.01). The
glucagon response was significantly greater in the Ultralente group compared to those with all other treatments. There was no difference in the development of
hypoglycemia between the groups. This study demonstrates that the reductions in plasma
glucose effected by
Lispro insulin are consistent and stable for 8 h after meal ingestion when
Lispro insulin is used in combination with human
Ultralente insulin. These findings suggest that improvement in overall glycemia, as assessed by
glycosylated hemoglobin, may be achievable with
Lispro insulin if adequate doses are administered.