SummaryThe effects of semi-synthetic human insulin (IHSS) and monocomponent porcine insulin (IPMC) were compared in a double blind study carried out in 9 totally insulin dependent diabetic patients in hospital. Short-acting preparations of these insulins were administered subcutaneously 4 times per day at an identical dose in each subject. Plasma glucose and plasma free insulin were measured 28 times on the 3rd day of each insulin treatment. At none of the 28 time points were the mean plasma glucose and free insulin levels significantly different. In the 5 patients without or with only a low titer of anti-insulin antibodies (AIA—), the mean circadian glycemia was markedly higher (under IHSS or IPMC) and the glycemic fluctuations were more pronounced (with IPMC) than in the 4 other subjects with a higher titer of anti-insulin antibodies (AIA +). This observation could be explained by a reduced half-life of circulating insulin in patients AIA—, leading to low levels of plasma free insulin, and, thus, to glycemic escapes, several hours after the insulin injection.In conclusion, the administration of identical doses of IHSS or IPMC to totally insulindependent diabetics (with or without anti-insulin antibodies) results in undistinguishable plasma glucose and free insulin circadian profiles. The presence of anti-insulin antibodies could improve the glycemic control by curtailing the fluctuations of plasma free insulin between insulin injections.