From the standpoint of clinical usefulness in cases of severe diabetes neither of the two standard insulins, soluble insulin and protamine zinc insulin, is ideal for routine day by day use. Because it is in solution, ordinary insulin is absorbed rapidly and within a short time exerts a strong effect which fades quickly. Hence it must be given frequently, and in excess it tends to cause violent hypoglycemic symptoms. With soluble insulin alone it is impossible to control severe diabetes in many cases unless multiple daily injections are given, including one during the normal sleeping hours. The same is true of solution of zinc insulin crystals, or crystalline insulin, the action of which is practically identical with that of ordinary insulin.1 Protamine zinc insulin eliminates some of these disadvantages because it releases insulin slowly. Its effects are slow in onset, weak until reenforced by repeated overlapping doses but slow
COLWELL AR, IZZO JL, STRYKER WA. INTERMEDIATE ACTION OF MIXTURES OF SOLUBLE INSULIN AND PROTAMINE ZINC INSULIN. Arch Intern Med (Chic). 1942;69(6):931–951. doi:10.1001/archinte.1942.00200180002001
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