Circulating Glucagon Antibodies in Children Who Have Insulin-dependent Diabetes Mellitus: Clinical Significance and Characterization

Abstract

A substance present in the sera of diabetic children that interferes with the radioimmunoassay for glucagon was found in six of 66 children who were participating in an inpatient study of diabetic control. Detailed studies documented unequivocally that this glucagon-binding substance is a specific antibody to glucagon and is located in the immunoglobulins. In a survey of diabetic children in the outpatient diabetes clinic and in a diabetes summer camp, antibodies to glucagon were found in about 12% of those evaluated. However, no children who had had diabetes for less than three years were found to have antibodies, and there appeared to be an increase with increasing duration of disease of up to greater than 20% at eight years' duration. The presence of glucagon antibodies may be of pathologic significance in that the patients have a greater tendency to develop hypoglycemia than do diabetic children without glucagon antibodies.

Glucagon‐reactive islet‐infiltrating CD8 T cells in NOD mice

“…There are some reports that an immune response to proglucagon may occur in both NOD mice, as shown here, and in T1D patients . Indeed, glucagon‐specific antibodies have been demonstrated in some patients with T1D .…”

“…There are some reports that an immune response to proglucagon may occur in both NOD mice, as shown here, and in T1D patients . Indeed, glucagon‐specific antibodies have been demonstrated in some patients with T1D . Although attributed to ‘immunization’ by glucagon contaminants present in exogenously administered insulin, a spontaneous autoimmune response should also be considered in light of our findings in the NOD mouse.…”

“…Indeed, glucagon‐specific antibodies have been demonstrated in some patients with T1D . Although attributed to ‘immunization’ by glucagon contaminants present in exogenously administered insulin, a spontaneous autoimmune response should also be considered in light of our findings in the NOD mouse. Furthermore, autoantibodies against islet cells other than β cells (presumed to be α cells) have been reported in children before the onset of T1D and without exogenous insulin treatment .…”

Insulin Treatment for the Early 80s: Facts and Questions About Old and New Insulins and Their Usage

“…Clearly, in some patients antibodies to glucagon develop, which may impair the action of endogenous glucagon secreted in response to hypoglycemia. 79 Antibodies to other pancreatic hormones, such as PP, VIP, and somatostatin, occur in patients treated with unchromatographed insulin and probably single-peak insulins, 80 but not in patients receiving the purified pork insulins. Immunocytochemical examinations have disclosed that plasmas from diabetic patients with increased titers of these substances (PP, VIP, and somatostatin) react to their respective hormone-producing cells.…”