Twelve subjects with insulin-dependent diabetes mellitus were treated using continuous subcutaneous insulin infusion (CSII) and intraportal insulin infusion (IPII) via the umbilical vein for 4 mo. Glucose control improved in both CSII and IPII groups, but a decrease in glucose and HbA1c was more rapid and more significant in the IPII group than in CSII, even though insulin requirement was lower during IPII than CSII (40 ± 2 vs. 50 ± 2 U/day, P < 0.05). The insulin plasma fasting levels were different (88 ± 10.7 in the IPII group vs. 263 ± 23 pM in CSII, P < 0.001). High plasma levels of lactate, pyruvate, alanine, cortisol, and growth hormone were decreased in both groups, with their full normalization only in the IPII group. Glucagon concentrations were low in both groups at the beginning of the study (30.0 ± 4.1 in the CSII group and 32.3 ± 1.8 ng/L in IPII); they were equalized to control values in the IPII group and were low in the CSII group at the study's end (46.0 ± 3.7 in IPII vs. 31.7 ± 3.1 ng/L in CSII, P < 0.05. We conclude that intraportal administration of insulin via the umbilical vein at rates of 0.01–0.05 U · kg−1 hr−1 reduces plasma levels of glucose, three carbon precursors, cortisol, and growth hormone by a direct action on the liver, and the hepatic action of peripherally administered insulin is manifested only when the infusion rate is increased to 0.1–0.3 U · kg−1 · hr−1. Thus the intraportal route via the umbilical vein may offer improved physiological insulin delivery over the subcutaneous route.

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