Effects of exogenous hyperglucagonemia in insulin-treated diabetics

This study was designed to determine if hyperglucagonemia approximating that believed to be present in the portal vein of poorly controlled diabetics can exert metabolically deleterious effects in insulin-treated diabetics. Three juvenile-type diabetics and one maturity-onset-type patient were given glucagon intravenously at a dose of 6 ng./kg./min. for 24 hours while receiving a continuous infusion of insulin. This raised their plasma IRG levels from an average of 122 ± 15 pg./ml. on the control day to 594 ± 60 pg./ml. Mean plasma glucose concentration, measured at two-hour intervals around the clock, averaged 200 ± 20 mg./dl. on the control day and increased significantly in all four patients to 293 ± 18 mg./dl. (p<0.05) during glucagon administration; fasting glucose rose from 138 ± 10 mg./dl. to 201 ± 17 (p < 0.05). Glucose excretion rose significantly from the control value of 36 ± 14 gm. per 24 hours to 152 ± 19 gm. per 24 hours (p < 0.05). The excretion of both urea nitrogen and ketones also increased significantly (p<0.05) during glucagon administration. The three juvenile-diabetic patients also received a glucagon infusion at a rate of only 3 ng./kg./min., and in each evidence of deterioration in metabolic control was observed. In every experiment, termination of the glucagon infusion was followed by a recession in the metabolic abnormalities. These data indicate that exogenous hyperglucagonemia of the magnitude believed to be present in the portal vein of uncontrolled diabetics can cause metabolic deterioration in diabetics receiving continuous insulin treatment.