The effect of large carbohydrate or protein meals upon plasma glucagon was compared in 14 nondiabetic and 24 diabetic patients. In nondiabetic subjects carbohydrate suppressed mean glucagon concentration from 126 ± 15 μμg (S.E.M.) to 90 ± 11 μμg (S.E.M.) per milliliter. In adult-type and juvenile-type diabetes, however, glucagon did not fall despite marked hyperglycemia. In nondiabetic subjects protein increased mean glucagon from 121 ± 11 (S.E.M.) to a peak of 203 ± 18 μμg (S.E.M.) per milliliter. In diabetes of both types protein induced a similar rise in glucagon despite fasting plasma glucose levels averaging above 215 mg per 100 ml. In nondiabetic subjects made hyperglycemic by glucose infusion, protein ingestion failed to stimulate glucagon.

In normal persons glucagon falls after carbohydrate and rises after protein, unless hyperglycemia is induced. In diabetic patients glucagon is not suppressed by carbohydrate and rises normally after protein despite hyperglycemia. Inappropriate hyperglucagonemia appears to be a common feature of human diabetes that must exaggerate the metabolic consequences of insulin lack and unfavorably influence diabetic control.