Among 603 patients over the age of 18, with insulin-treated diabetes mellitus, a questionnaire identified 98 patients who during a 12-month period had experienced severe hypoglycaemia, defined as an event which required the help of another person. Twenty of these patients had repeatedly suffered from such episodes, without any obvious reason, for a period of at least three years. The capacity to counter-regulate a standardized, insulin-infusion test (0.034 U.kg-1.h-1 given for 3 h unless severe neuroglucopenia developed) was evaluated in 14 of these patients. In 12, an impaired glucose counter-regulation was registered, defined as blood-glucose values below -2 SD of healthy subjects. In all but one of these patients, a combined deficiency of glucagon and adrenaline was documented, and was believed to be the likely cause of their inclination towards hypoglycaemia. In patients with severe hypoglycaemia, but not in diabetic patients without severe hypoglycaemia or in healthy subjects, a significant relationship between insulin disappearance and glucose rise was found. It is concluded that in insulin-treated diabetic patients, the prevalence of recurrent attacks of severe hypoglycaemia amounts to about 4%. In such patients, a combined deficiency of adrenaline and glucagon responses to hypoglycaemia is the predominant finding and the disappearance rate of insulin becomes critical for recovery of blood glucose after hypoglycaemia.
In order to enlighten the controversy on whether human and pork insulin result in different hormonal responses to insulin-induced hypoglycaemia, eight C-peptide negative, diabetic patients without measurable circulating insulin-binding antibodies were exposed to insulin-induced hypoglycaemia in random order with highly purified pork insulin (Actrapid) and semisynthetic human insulin (Actrapid Human). Hypoglycaemia was provoked by a constant rate IV infusion of insulin (0.034 U kg-1 h-1) for 3 h after which the blood glucose recovery was assessed for an additional period of 60 min. Both insulin preparations gave close to identical responses for glucose, glucagon, growth hormone, adrenaline, and somatostatin. The circulating noradrenaline levels were higher during the infusion of pork insulin which also yielded a more prominent response of pancreatic polypeptide and, after cessation of the insulin infusion, plasma cortisol was also higher following pork insulin. It is concluded that human and pork insulin induce close to identical responses of the important counter-regulatory hormones during hypoglycaemia in Type 1 diabetic patients.
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