SMALL DOSES OF SUBCUTANEOUS INSULIN AS A STRATEGY FOR PREVENTING SLOWLY PROGRESSIVE BETA-CELL FAILURE IN ISLET-CELL ANTIBODY-POSITIVE PATIENTS WITH CLINICAL-FEATURES OF NIDDM

We report a pilot study to determine the preventive effect of small do ses of insulin injected subcutaneously on slowly progressive beta-cen damage in islet cell antibody (ICA)-positive patients with apparent NI DDM. Ten NIDDM patients who were ICA(+) were divided into two groups o f five. In the insulin group (age: 51 +/- 8 years [mean +/- SD], sex: 3 men and 2 women), intermediate-type insulin (3-16 U/day) was given o nce or twice daily as a subcutaneous injection. The sulfonylurea (SU) group (age: 48 +/- 11 years, sex: 3 men and 2 women) was initially tre ated with a SU agent. Changes in beta-cen function, as indicated by se rum C-peptide responses and blood glucose values during a 100-g oral g lucose tolerance test, as well as ICA and GAD antibody status, were ev aluated for up to 30 months in both groups. IGA status became negative in four of five patients in the insulin group. ICA status did not bec ome negative in any of the patients in the SU group (P = 0.047 vs. ins ulin group). ICA status was persistently positive in two patients whos e beta-cen function eventually progressed to an insulin-dependent stat e and fluctuated in the remaining three patients. In the insulin group , GAD antibody status became negative in one of four initially GAD ant ibody-positive NIDDM patients. In the SU group, GAD antibody status wa s persistently positive in three NIDDM patients (NS vs. insulin group) . The serum C-peptide response improved significantly within 6 and 12 months in the insulin group, whereas it decreased progressively in the SU group. The changes in C-peptide response were significantly differ ent between the two groups at 6, 12, 24, and 30 months. Two-hour blood glucose and HbA(1) values were unchanged in the insulin group, but th ey increased in the SU group. Subcutaneous small doses of insulin, res ulting in a high rate of negative conversion of ICA and an improved se rum C-peptide response, may be effective in treating ICA(+) NIDDM pati ents who are at high risk for slowly progressive beta-cen failure.