Abstract
Six female diabetics, 14 to 31 years of age, had erratic control for years and developed resistance to subc. insulin (2.5-30.0 units/kg/day) but had normal response to I.V. insulin (0.35-0.9 units/kg/day). Three patients required continuous I.V. insulin infusion for 6 mos to 1 year. Euglycemia was achieved, when aprotinin (a protease inhibitor) and regular insulin (0.7-1.4 units/kg/day) was given subc. Plasma levels of free insulin rose and ketonuria subsided. Four patients had episodes of spontaneous severe hypoglycemia, before and during aprotinin therapy, requiring I.V. glucose for 2 to 60 days. Days and weeks after the last sub . injection of ins. hypoglycemia and hyperinsulinemia (50 to 2000 μU free insulin/ml) persisted, C-peptide was <0.5 ng/ml; counterregulatory hormones were normal; in one patient fat biopsy insulin (1090 μU/gm) and glutathione-insulin transhydrogenase in leukocytes and subc fat were higher than in 2 controls; 3H-insulin was absorbed and degraded normally during the hypoglycemic phase and not absorbed during the resistant phase. The findings suggest that insulin is sequestered (and may be degraded) at the injection site during the resistant phase and released during the hypoglycemic phase.
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Sotos, J., Freidenberg, G., White, N. et al. Diabetes unresponsive to subc. but responsive to I.V. insulin: Biphasic behavior. Pediatr Res 15, 1568 (1981). https://doi.org/10.1203/00006450-198112000-00196
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DOI: https://doi.org/10.1203/00006450-198112000-00196