Abstract
Diminished insulin response to hyperglycemia has been thought to be the genetically determined prerequisite for the development of diabetes mellitus, best demonstrated in the insulin-deficient child with overt disease. Of eight children, with chemical diabetes mellitus, three and a half to 16 years of age, four had normal or increased plasma immunoreactive insulin responses to oral glucose loading on analysis for insulin-glucose ratios (microunits of insulin per milliliter over glucose, milligrams per 100 ml). In three of these patients the apparent insulin hypoactivity was ameliorated by tolbutamide, which diminished the insulinemia while either correcting or not markedly altering the glucose response. Thus, there appears to be a stage of essential diabetes mellitus in childhood that is characterized by a reduced effectiveness of circulating immunoreactive insulin. Tolbutamide may improve the glucose-insulin relation in certain patients and might prevent or delay progression to diabetes mellitus.