OBJECTIVE The objective of this study is to compare the effect of intraperitoneal versus subcutaneous insulin injection on hepatic glucose production (HGP) and systemic glucose utilization (R_d) in patients with NIDDM.

RESEARCH DESIGN AND METHODS Eight male volunteers with NIDDM, each of whom had a programmable-rate, implantable insulin pump, were given an injection of insulin (0.15 units/kg body wt) by intraperitoneal or subcutaneous injection on separate days in randomized order. Plasma glucose was kept constant for 5 h using the glucose clamp technique, and HGP and R_d were measured using isotope dilution.

RESULTS Intraperitoneal insulin injection resulted in higher and earlier peak systemic insulin concentrations (1,469 ± 245 vs. 454 ± 48 pmol/l, P < 0.01). Glucose R_d doubled within 1 h after intraperitoneal injection and was greater than that attained with subcutaneous injection (3.91 ± 0.27 vs. 2.60 ± 0.19 mg · kg⁻¹ · min⁻¹, P < 0.01). Intraperitoneal and subcutaneous injections suppressed HGP and plasma free fatty acid to a similar extent during the first 3 h, effects that persisted through 5 h after subcutaneous insulin injection but waned 3–4 h after intraperitoneal injection.

CONCLUSIONS In patients with NIDDM, intraperitoneal insulin injection achieves more rapid and greater peak values for stimulation of glucose R_d than subcutaneous insulin injection. With regard to HGP and lipolysis, intraperitoneal and subcutaneous injections achieve similar initial suppression but this is maintained for a more limited duration with intraperitoneal as compared with subcutaneous injection. These differences in insulin action seem directly related to the rapidity of insulin absorption with intraperitoneal injection.