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March 7, 1977

The Primacy of Insulin

JAMA. 1977;237(10):959-960. doi:10.1001/jama.1977.03270370031008

To the Editor.—  The editorial entitled "The Primacy of Insulin" (236:1274, 1976) reflects a misunderstanding of the recently advanced bihormonal abnormality hypothesis1 concerning the contribution of glucagon to the metabolic derangements of diabetes mellitus. The editorial incorrectly implies that the primacy of insulin in diabetes has been challenged. On the contrary, our hypothesis views a defect in insulin secretion or response as the sine qua non of diabetes mellitus, without which no amount of glucagon can produce either hyperglycemia or increased ketogenesis.2What we have proposed is that, in the presence of a defect in insulin secretion, the presence of glucagon (either in absolute excess or in excess relative to the amount of available insulin) can cause a rate of endogenous glucose production that exceeds the limited capacity of the diabetic to clear it. Obviously this will result in a rise in glucose concentration. If insulin secretion is