Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime

OBJECTIVE - To quantitate the contribution of postprandial blood glucose, which improves with the short-acting insulin analog lispro [Lys(B28),Pro(B29)] in type 1 diabetes, to the overall 24-h blood glucose concentration and the long-term HbA(1c) concentration under conditions of different postabsorptive blood glucose. RESEARCH DESIGN AND METHODS - A total of 24 type 1 diabetic patients on longterm intensive therapy with premeal human regular insulin (Hum-R) and bedtime NPH were randomly assigned to a continuation of Hum-R (group 1, n = 8), lispro (group 2, n = 8), or lispro + NPH tin variable proportions) administered at mealtime (group 3, n = 8) for 3 months. NPH administered at bedtime was continued in all three groups. Data from home blood glucose monitoring were collected, and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postprandial glucose curve (3.5 h after breakfast, 3.5 h after lunch, and 3.0 h after dinner for a total of 10.0 h) and the postabsorptive blood glucose curve (the remaining 14.0 h out of 24.0 h) (AUC). Eight nondiabetic subjects were also studied. RESULTS - The substitution of Hum-R with lispro (group 2) resulted in lower postprandial blood glucose, but greater postabsorptive blood glucose (P < 0.05 vs, group 1). The postprandial blood glucose AUC was lower (161 +/- 19 vs. 167 +/- 20 mg . 100 ml(-1) . h(-1)),but the postabsorptive blood glucose AUC was greater (155 +/- 22 vs. 142 +/- 19 mg . 100 ml(-1) . h(-1)) (P < 0.05). Therefore, the 24-h blood glucose AUC was no different (NS). Consequently, HbA(1c) was no different (NS). This occurred because in group 2, mealtime lispro resulted in normal prandial plasma insulin, but also resulted in lower interprandial concentration (P < 0.05 vs, group I). When NPH was added to lispro (30% at breakfast, 40% at lunch, 10% at dinner) in group 3, postabsorptive plasma insulin was similar to group 1 (NS). In group 3, the postprandial blood glucose AUC (153 +/- 17 mg . 100 ml(-1) . h(-1)) was lower and the postabsorptive blood glucose AUC was no different, as compared with group 1 (NS). Therefore, the 24-h blood glucose AUC was lower (147 +/- 17 vs. 155 +/- 21 and 158 +/- 20 mg . 100 ml(-1) . h(-1)), and HbA(1c) was lower (6.41 +/- 0.12 vs. 6.84 +/- 0.2 and 6.96 +/- 0.2% (groups 3, 1, and 2 respectively, P < 0.05). Frequency of hypoglycemia was greater in group 2 (P < 0.05),but not in group 3 (NS) vs. group 1. CONCLUSIONS - Lispro administered at mealtime, which improves postprandial blood glucose, should be associated with optimized replacement of basal insulin to prevent deterioration of postabsorptive blood glucose. NPH administered four times daily normalizes interprandial daily plasma insulin concentration and decreases mean daily blood glucose and HbA(1c), with no increase in hypoglycemia.