IMPROVED POSTPRANDIAL METABOLIC CONTROL AFTER SUBCUTANEOUS INJECTION OF A SHORT-ACTING INSULIN ANALOG IN IDDM OF SHORT-DURATION WITH RESIDUAL PANCREATIC BETA-CELL FUNCTION

OBJECTIVE - To compare postprandial metabolic control after subcutaneo us injection of a short-acting insulin analog [Lys(B289),Pro(B29)] (Li spro) or human regular insulin (Humulin R U-100 [Hum-R]) in insulin-de pendent diabetes mellitus (IDDM) of short duration with residual beta- 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 beta-cell function (lasting plasma C-peptide 0.19 +/- 0.02 nmol/l) were studied on three different occasions. Post breakfast plasma glucose was maintained at similar to 7.1 mmol/l by me ans of intravenous insulin until either 1200 when 0.1 U/kg Hum-R was i njected or until 1225 when 0.1 U/kg of either Hum-R or Lispro was inje cted 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 -3O min (7.7 +/ - 0.3 mmol/l) or -5 min (9.9 +/- O.2 mmol/l). By the end of the study, plasma glucose was still lower after Lispro was injected (6.7 i 0.3 m moVI) 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 gl ucose to prevent hypoglycemia after being injected with Lispro, but lo ur required glucose after bring injected with Hum-R at -5 min (Lispro similar to 27 mmol glucose infused between 90 and 240 min; Hum-R simil ar to 80 mmol between 240 and 390 min). After Lispro, plasma insulin p eaked earlier (at 30 min, 342 +/- 29 pmol/l) than after Hum-R injectio n al -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 insu lin peaked later (at 120 min) and subsequently remained greater than i n the two other studies.CONCLUSIONS - Despite the lack of a time inter nal between injection and meal, Lispro controls postprandial plasma gl ucose concentration better than Hum-R given 30 min before meals and, t o an even greater extent, better than Hum-R given 5 min before meals. In addition, Lispro minimizes the risk of postprandial hypoglycemia, t hus closely mimicking the postprandial glucose homeostasis of nondiabe tic subjects. IDDM patients with residual pancreatic beta-cell functio n are the ideal candidates for prandial use of Lispro because they can maintain near-normoglycemia longer after subcutaneous analog injectio n because of residual endogenous insulin secretion.