Comparison of plateau insulin levels achieved by intravenous or subcutaneous insulin infusion: evidence for low rates of subcutaneous degradation.

Continuous insulin infusion via the subcutaneous (s.c.) route is attractive for diabetes therapy because of its simplicity compared with other routes. Some insulin will be degraded locally before systemic absorption, although the magnitude of this degradation has not been established. We have performed in five normal subjects s.c. and intravenous (i.v.) insulin infusions (2.4 U/h) of sufficient duration to compare steady-state systemic appearance rates of exogenous insulin. A steady state was produced after 60-90 min (i.v.) and 6-8 h (s.c.). Blood glucose fell to approximately 2.7 mmol/L in both studies and a fall in C-peptide indicated suppression of endogenous insulin secretion. Plateau insulin levels attributable to systemic entry of exogenous insulin were 36 +/- 2.0 mU/L (i.v. route) and 29 +/- 1.8 mU/L (s.c. route). These indicate a rate of 2.c. degradation of insulin of 19 +/- 5% in the steady state. We conclude that there is a low rate of degradation of insulin during continuous s.c. infusion.