EFFECTS OF INSULIN ADMINISTRATION ON BETA-CELL FUNCTION IN SUBJECTS AT HIGH-RISK FOR TYPE-I DIABETES-MELLITUS

The aim of the study was to determine the appropriate dose of subcutan eous insulin to induce ''beta-cell rest'' without any hypoglycemic ris k, as the first step in the investigation of its potential effect in p reventing or delaying clinical diabetes mellitus onset in high-risk su bjects. Four subjects at high risk for type I diabetes mellitus (first -degree relatives, islet cell antibodies (ICA)-positive, and with dimi nished first-phase insulin secretion) were compared with four healthy individuals. After hospitalization, urinary C-peptide excretion (UCP) and 24-hour serum profiles for glucose were measured before and after administration of NPH insulin 0.1, 0.2, and 0.3 U . kg body weight per day subcutaneously in a single dose on 4 consecutive days. After insu lin 0.1 U . kg body weight, a significant inhibition of endogenous ins ulin secretion was observed in high-risk subjects, but not in control subjects. There was no further inhibition when a higher insulin dose ( 0.2 and 0.3) was administered. A sustained beta-cell rest was obtained after 3, 6, and 12 months of treatment with 0.1 U . kg body weight pe r day as outpatient therapy in high-risk subjects. With this dose, no subject developed hypoglycemia (plasma glucose <50 mg/dL), whereas thi s adverse effect was detected after 0.2 and 0.3 U . kg body weight in both groups. In conclusion, our results indicate that administration o f NPH insulin 0.1 U . kg body weight per day induces beta-cell rest wi thout the undesirable effect of hypoglycemic episodes. This is a preli minary study to investigate the potential beneficial effect of insulin in preventing or delaying type I diabetes mellitus in subjects at hig h risk for the disease. Copyright (C) 1996 by W.B. Saunders Company