Intermediate-acting Insulin Preparations: NPH and ... - Diabetes Care

INTERMEDIATE-ACTING INSULIN: NPH AND LENTE/TORSTEN DECKERT
per cent of initial
blood glucose (m* SEM )
100-
-
80-
x NPH (Retard RI®)
o Lente like (Monotard®)
n= 12
60-
40-
20-
T injection
^N-f+Hnu-——-—Hi
13 15 17 19 21
TIME
FIG. 2. Blood glucose lowering effect in percent
of initial capillary blood glucose (initial = mean
of blood glucose at 0700, 0800, and 0900 h)
after highly purified porcine NPH insulin (Retard
RI) and the highly purified porcine Ientelike
preparation (Monotard) given subcutaneous^
(at the arrow) in the femoral region.
Randomized crossover experiment.
ratio between lente and regular insulin in the syringe, 10 presumably
because the surplus of zinc in the supernatant of
lente insulin will react with regular insulin and change it to a
semilente-like preparation. This is not the case when mixing
regular insulin with NPH. Stable mixtures of regular and intermediate-acting
insulin can only be prepared with NPH insulin.
6
IMMUNOGENICITY
The immunogenicity of NPH and lente insulin depends
largely on the purity and species of the insulin
used. Preparations containing beef insulin are
more immunogenic than insulin preparations
made of porcine insulin of comparable purity. 11 However, by
using lente insulin of monocomponent purity (lente prepared
from highly purified beef and highly purified porcine insulin),
formation of antibodies can be avoided in some instances,
4 but not to the same extent as with highly purified
porcine insulin. 11 Highly purified porcine NPH insulin Leo
Retard RI (Nordisk) and the highly purified porcine lentelike
insulin preparation Monotard (Novo) are of very low
immunogenicity. Antibody formation against proinsulin, 12
glucagon, VIP, PP, and probably somatostatin can be
avoided. 13 Antibodies against protamine have not been described,
but in a few patients with insulin allergy, positive
cutaneous reactions were seen against highly purified insulin
as well as protamine. 14 It is not known whether the insulin
preparation plays a role in the development of late diabetic
complications; probably this cannot be substantiated.
From Steno Memorial Hospital, DK-2820, Gentofte, Copenhagen,
Denmark.
REFERENCES
1 Hagedorn, H. C, Jensen, B. N., Krarup, N. B., and Wodstrup,
I.: Protamine insulinate. JAMA 106: 177-80, 1936.
2 Krayenbiihl, C., and Rosenberg, T.: Crystalline protamine insulin.
Rep. Steno Hosp. (Kbh.) 1: 60-73, 1946.
3 Hallas-Mtfller, K., Jersild, M., Petersen, K., and Schlichtkrull,
J.: Zinc insulin preparations for single daily injection. JAMA 150:
1667-71, 1952.
4 Schlichtkrull, J., Pingel, M., Heding, L. G., Brange, J., and
J^rgensen, K. H.: Insulin preparations with prolonged effect. In Insulin
II. Hasselblatt, A., and Bruchhausen, F. v., Eds. Berlin,
Springer-Verlag, 1975, pp. 729-77.
5 Deckert, T., Andersen, O. O., and Poulsen, J. E.: The clinical
significance of highly purified pig-insulin preparations. Diabetologia
10: 703-08, 1974.
6 K«ilendorf, K., Aaby, P., Westergaard, S., and Deckert, T.:
Resorption, effect and side effects of highly purified porcine NPHinsulin
preparations (Leo®). Eur. J. Pharmacol. In press.
7 Binder, Chr.: Absorption of Injected Insulin. Copenhagen,
Munksgaard, 1969.
8 Faber, O. K., Lauritzen, T., Binder, Chr., Mouridsen, H. T.,
and V^lund, Aa.: Comparison of absorption and clinical effects of
Insulin Monotard® and Insulin Novo Lente®. Ugeskr. Laeg. 137:
2510-14, 1975.
9 Rasmussen, S. M., Heding, L. G., Parbst, E., and V«ilund,
Aa.: Serum IRI in insulin-treated diabetics during a 24/hour period.
Diabetologia JJ: 151-58, 1975.
10 Schlichtkrull, J.: The absorption of insulin. Acta Paediatr.
Scand. [Suppl.] 270: 97-102, 1977.
11 Chance, R. E., Root, M. A., and Galloway, J. A.: The immunogenicity
of insulin preparations. Acta Endocrinol. (Kbh.)
Suppl. 205: 185-99, 1976.
12 Falling, I., Jerwell, J., Aagenaes, 0., and Aarseth, S.: Antibodies
to insulin and proinsulin, metabolic control, and insulin
dose, in diabetics changing to highly purified insulins. Diabetologia
12: 390, 1976.
13 Bloom, S. R., West, A. M., Polak, J. M., Barnes, A. J., and
Adrian, T. E.: Hormonal Contaminants of Insulin from Gut Hormones.
Bloom, S. R., Ed. Edinburgh, Churchill Livingstone, 1978,
pp. 318-22.
14 Rosenthal, A.: Genetic control of insulin antibody formation.
Juvenile Diabetes Foundation International Workshop on Insulin.
New York, 1978.
626 DIABETES CARE, VOL. 3 NO. 5, SEPTEMBER-OCTOBER 1980