Comparison of two ultralente insulin preparations with protamine zinc insulin in clinically normal cats

The absorption kinetics and glycemic effects of 3 long-acting insulin preparations (protamine zinc beef-pork insulin, ultralente beef-pork insulin, and ultralente human insulin) were evaluated in 9 healthy, adult, domestic shorthair cats (6 males, 3 females). A triple crossover study was performed, in which the serial serum concentrations of insulin and glucose were determined over a 24-hour period after sc administration of the 3 insulin preparations (dosage, 1.0 U/kg of body weight) at 3-week intervals. A control study was also performed in 4 of the cats by serially collecting samples for insulin and glucose determinations after administration of insulin diluent. After administration of protamine zinc insulin (PZI), mean (+/- SEM) serum insulin concentration increased significantly (P < 0.05) above baseline, reached a peak value (484 +/- 287 pmol/L) at 1 hour, and remained significantly (P < 0.05) higher than baseline at 24 hours. After administration of ultralente human insulin, the serum insulin curve was similar to that obtained after PZI administration, but mean serum insulin concentration took longer to peak (538 +/- 177 pmol/L at 4 hours). After administration of ultralente beef-pork insulin, mean peak serum insulin concentration was lower (220 +/- 54 pmol/L, not statistically significant) than that obtained after administration of PZI and ultralente human insulins; it then decreased to values statistically indistinguishable from baseline by 16 hours. The area under the serum insulin concentration curve for PZI (5,063 +/- 681 pmol.h/L) and ultralente human insulin (4,138 +/- 439 pmol.h/L) was significantly (P < 0.05) larger than that for ultralente beef-pork insulin (2,378 +/- 561 pmol.h/L). Serum glucose concentration decreased after administration of all 3 insulins, but the decrease was not different from that observed after diluent (control) administration. Results of this study indicate that differences may exist between absorption of PZI, ultralente human, and ultralente beef-pork insulins. Of the 2 ultralente insulin preparations, human insulin appears better absorbed than beef-pork insulin, but these findings need to be confirmed in cats with naturally acquired diabetes mellitus.