MEAL COMPOSITION IS A DETERMINANT OF LISPRO-INDUCED HYPOGLYCEMIA IN IDDM

OBJECTIVE - Lispro is a newly FDA-approved analog of human insulin tha t will be widely used in patients with IDDM. This insulin, however, ma y have an increased potential for hypoglycemia because of its very rap id subcutaneous absorption, especially in a setting of decreased carbo hydrate intake. Using a short-term prospective randomized parallel gro up-study design, we studied the incidence of hypoglycemia when lispro was given before breakfast compared with regular human insulin. Since carbohydrate intake is a determinant of postprandial glycemia, we admi nistered three isocaloric meals characterized by low, average, and hig h carbohydrate content. RESEARCH DESIGN AND METHODS - Two groups of si x IDDM subjects were randomized to receive 0.15 U/kg of lispro or regu lar human insulin subcutaneously before the ingestion of three 500-kca l breakfast meals of differing carbohydrate content on separate days. Lispro was administered at mealtime, and regular insulin was administe red 30 min before mealtime. RESULTS - Postprandial plasma glucose conc entrations were decreased in the lispro group compared with the regula r-insulin group for all three meal types (P < 0.05), and hypoglycemia developed more frequently and rapidly in the lispro group, compared wi th the regular-insulin group by survival analysis. Additionally, peak insulin concentrations were higher (P < 0.001) and peaked more rapidly (P < 0.05) in the lispro group, compared with the regular-insulin gro up. CONCLUSIONS - We conclude that lispro has a tendency for early pos tprandial hypoglycemia compared with regular insulin in the setting of reduced carbohydrate intake. This fact should be told to patients who decide to switch from regular insulin to lispro. Health care professi onals should instruct their IDDM patients to monitor glucose levels fr equently after switching to lispro since adjustments in their carbohyd rate intake and/or their lispro dosage may be necessary to avoid hypog lycemia.