All physicians who treat diabetes mellitus have long been interested in the perfecting of some type of delayed action insulin which would adequately control the level of sugar in the blood when injected once in each twenty-four hours. It was hoped that protamine zinc insulin, introduced in 1936 by Hagedorn and his associates1 would be the answer to the problem of a depot of insulin. However, further experience with this type of insulin revealed that a single injection in each twenty-four hours was incapable of giving satisfactory control of the blood sugar in many cases of severe diabetes. In such cases it was often not possible to give sufficient protamine zinc insulin to control postprandial hyperglycemia during the day without producing nocturnal insulin reactions. Consequently, most authors have agreed that for satisfactory control of severe diabetes mellitus protamine zinc insulin must be supplemented by unmodified insulin.2 In this
HILDEBRAND AG, RYNEARSON EH. CLINICAL EXPERIENCE WITH MIXTURES OF PROTAMINE ZINC AND UNMODIFIED INSULINS: A PRELIMINARY REPORT. Arch Intern Med (Chic). 1943;72(1):37–45. doi:10.1001/archinte.1943.00210070045004
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