The Effect of Glucagon on the Blood Glucose Level and the Clinical State in the Presence of Marked Insulin Hypoglycemia 12

Abstract

The increasing evidence that glucagon is a naturally occurring hormone has led to considerable interest and speculation as to its possible metabolic roles. The possibility of obtaining glucagon in increasingly pure preparations and the final obtainment of a crystalline preparation (1) have added impetus to this interest.The presence of a hyperglycemic contaminant was one of the suggestions advanced to explain the initial rise in the blood sugar level which followed the administration of some preparations of insulin. There is general agreement that glucagon can cause at least a temporary rise in the blood sugar level in the presence of insulin. However, considerable interest still centers around the question of the relative effects of insulin and glucagon on the blood sugar level (2-5).It was believed that there would be some advantage in exploring the effect of glucagon in patients who had received massive doses of insulin. This situation obtains in the insulin coma treatment of psychiatric patients. It was also considered that glucagon could serve as a useful means of terminating insulin coma. The present report deals with these questions. MATERIALS AND METHODSThe patients used for this study were all hospitalized at The Henry Phipps Psychiatric Clinic and were diagnosed as exhibiting schizophrenic reactions. There were 11 patients, of whom 6 were women and 5 were men. They ranged in age from 16 to 48 years with an average age of 28 years. They were all in good physical health.All of these patients were receiving insulin coma therapy as part of the therapeutic regimen for their I This investigation, under the direction of Dr. John C.Whitehorn, was supported by a research grant (M-1085) from the National Institute of Mental Health of the Na- Insulin comas were terminated with glucagon in 141 instances. Of this total glucagon was administered intravenously 97 times, intramuscularly 22 times and subcutaneously on 22 occasions. Following 61 of these terminations of coma the response to glucagon was followed with blood sugar determinations. Blood was withdrawn from an antecubital vein several minutes before the administration of the glucagon and at 5, 10, 15, 20, 30, 40, and 50 minutes following the administration of the glucagon. A separate venipuncture was performed for each determination. There was some variation in the timing of the withdrawals for technical reasons. On two occasions more than one dose of glucagon was administered. The coma was considered clinically terminated when the patient was able to respond verbally to questions or was able to take fluids by mouth with minimal difficulty.In addition, seven of the patients had a series of three tests in which glucagon was administered on days when they had not received insulin. In each instance the first of the three tests was performed the day before insulin coma therapy was instituted, the second on the day after they had reached the highest insulin dose in the series of comas and the third on the day following the last insulin coma treatment. A fastin...

Treatment of insulin poisoning: A 100‐year review

“…The effect of glucagon had been examined in uncontrolled studies in psychiatric patients made hypoglycaemic during Sakel's insulin ‘therapy,’ 15 in adults patients with diabetes, 16 and in a study comparing glucose with glucagon in children with Type I diabetes, most of whom were only mildly hypoglycaemic 17 . Glucagon caused a dose‐dependent increase in blood glucose concentration.…”

“…14 In that study, a single intramuscular or intravenous dose of 1 mg glucagon roused 40% of 100 unconscious hypoglycaemic patients, but a second 1 mg dose only roused one of the remaining 60 patients. 14 The effect of glucagon had been examined in uncontrolled studies in psychiatric patients made hypoglycaemic during Sakel's insulin 'therapy,' 15 in adults patients with diabetes, 16 and in a study comparing glucose with glucagon in children with Type I diabetes, most of whom were only mildly hypoglycaemic. 17 Glucagon caused a dose-dependent increase in blood glucose concentration.…”

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

“…In contrast, at very high insulin levels (se/ba‐insulin > 3, IOB ≥ 3 U, IOB/TDD > 8%), the optimum glucagon doses exceeded the amount (1000 μg) normally used for treating severe hypoglycaemia. Nevertheless, the glucagon rescue dose may still be effective in treating severe hypoglycaemia regardless of ambient insulin levels, as shown in psychiatric patients undergoing insulin shock therapy but may not reach our pre‐defined success criteria. Further, at some point, the estimated optimum glucagon dose was, in our opinion, too high (>500 μg) as treatment option for mild hypoglycaemia, especially due to the increased risk of side effects.…”

Quantifying the risk of hypoglycaemia in children undergoing the glucagon stimulation test

“…First, available BG data were from hourly (rather than half hourly) sampling. As such, the true postglucagon BG peak at 30 min 10,21 as well as potentially important BG data at 150 min and beyond 180 min may be missed, thereby influencing the rate of hypoglycaemia and BG trends. Secondly, our testing protocol stipulates that children should be fasted from midnight before the morning of the test.…”