Three normal, three stable diabetic, and eight unstable diabetic subjects were investigated, with continuous automated blood glucose analysis for forty-eight-hour periods, during metabolic balance studies of six days' duration under near normal conditions (fed and ambulatory) after the attainment of clinically optimal diabetic regulation. The studies on unstable diabetics were performed during constant dietary intake, with one or two daily injections of intermediate-acting insulin and then repeated with four daily injections of short-acting insulin. A characteristic of blood glucose behavior, the mean amplitude of glycemic excursion (MAGE), was measured. MAGE was small for normals (range, 22 to 60 mg./100 ml.), larger for stable diabetics (67 to 82 mg./100 ml.), and largest for unstable diabetics (119 to 200 mg./100 ml.). Associated with a significant decrease (p = 0.004) in the mean diurnal glycemic level (from 146 to 244 mg,/100 ml. to 101 to 152 mg./100 ml.) achieved through the use of four daily doses of short-acting insulin there was a significant increase (p = 0.006) in hypoglycemic episodes (from 0 to 4/48 hr. to 3 to 6/48 hr.) without significant change in MAGE. The persistently large value of MAGE despite therapy with multiple injections of short-acting insulin appears to be a characteristic of unstable diabetes.

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