Intravenous tolbutamide was administered to three groups of children with diabetes mellitus: (A) those with newly diagnosed disease, (B) those diabetic for less than two and one-half years, and (C) those diabetic for more than three years. Children in Groups A and B were found to respond to tolbutamide with a drop in blood glucose which differed from the response of normal children in that it was slow in onset and persisted throughout a three-hour period of observation. Children in Group C were unresponsive to tolbutamide. Children in Groups A and B showed an interference with the expected starvation-induced rise in nonesterified fatty acids over the period of observation, while children in Group C showed gradually increasing levels. The effect of tolbutamide on nonesterified fatty acids was less striking and showed more individual variation than did the effect on blood glucose. A few children with early diabetes mellitus developed hypoglycemia which appeared resistant to the usual counter-regulatory mechanisms. The fall in blood glucose was not accompanied by increased levels of insulin in peripheral blood.

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