OBJECTIVE To compare postprandial metabolic control after subcutaneous injection of a short-acting insulin analog [Lys(B289),Pro(B29)] (Lispro) or human regular insulin (Humulin R U-100 [Hum-R]) in insulin-dependent diabetes mellitus (IDDM) of short duration with residual β-cell function.

RESEARCH DESIGN AND METHODS Six IDDM patients (age 25 ± 2 years, diabetes duration 14 ± 2 months, HbA_1c 6.4 ± 0.5%) with residual pancreatic β-cell function (fasting plasma C-peptide 0.19 ± 0.02 nmol/l) were studied on three different occasions. Postbreakfast plasma glucose was maintained at ∼ 7.1 mmol/l by means of intravenous insulin until either 1200 when 0.1 U/kg Hum-R was injected or until 1225 when 0.1 U/kg of either Hum-R or Lispro was injected subcutaneously. Lunch (mixed meal, 692 Kcal) was served at 1230 (0 min). Six nondiabetic control subjects were also studied.

RESULTS After Lispro administration, the 120-min plasma glucose decreased more (6.1 ± 0.3 mmol/l) than after injection of Hum-R at −30 min (7.7 ± 0.3 mmol/l) or −5 min (9.9 ± 0.2 mmol/l). By the end of the study, plasma glucose was still lower after Lispro was injected (6.7 ± 0.3 mmol/l) than after Hum-R was injected at −30 min (7.6 ± 0.3 mmol/l) or −5 min (7.3 ± 0.2 mmol/l) (P < 0.05). Two IDDM patients required glucose to prevent hypoglycemia after being injected with Lispro, but four required glucose after being injected with Hum-R at −5 min (Lispro ∼ 27 mmol glucose infused between 90 and 240 min; Hum-R ∼ 80 mmol between 240 and 390 min). After Lispro, plasma insulin peaked earlier (at 30 min, 342 ± 29 pmol/l) than after Hum-R injection at −30 min (at 90 min, 198 ± 28 pmol/l) and was superimposable on that of nondiabetic subjects. In Hum-R injected at −5 min, plasma insulin peaked later (at 120 min) and subsequently remained > in the two other studies.

CONCLUSIONS Despite the lack of a time interval between injection and meal, Lispro controls postprandial plasma glucose concentration better than Hum-R given 30 min before meals and, to an even greater extent, better than Hum-R given 5 min before meals. In addition, Lispro minimizes the risk of postprandial hypoglycemia, thus closely mimicking the postprandial glucose homeostasis of nondiabetic subjects. IDDM patients with residual pancreatic β-cell function are the ideal candidates for prandial use of Lispro because they can maintain near-normoglycemia longer after subcutaneous analog injection because of residual endogenous insulin secretion.