Comparison of Peripheral and Portal (Via the Umbilical Vein) Routes of Insulin Infusion in IDDM Patients

Abstract

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 HbAIc 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 less than 0.05). The insulin plasma fasting levels were different (88 +/- 10.7 in the IPII group vs. 263 +/- 23 pM in CSII, P less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin Delivery Into the Peripheral Circulation: A Key Contributor to Hypoglycemia in Type 1 Diabetes

“…The effect of overinsulinizing the periphery (which increased R d ) was greater than the effect of underinsulinizing the liver (which increased R a ), thus explaining the greater hypoglycemia seen with Pe insulin infusion. A number of studies have examined differences between Pe and Po insulin delivery from the perspective of evaluating the efficacy of insulin delivery via intraperitoneal catheters (40–42). In general, slight improvements in glycemic control and glucose variability were seen.…”

Adjunct therapy for type 1 diabetes mellitus

“…5,6 When exo genous insulin is administered subcutaneously or intravenously, as in the treatment of patients with T1DM, this ratio is approximately 1:2. 5, 6 The administration of sufficient exogenously administered insulin to control the liver, therefore, results in peripheral hyperinsulinemia.…”

Intestinal receptor targeting for peptide delivery: an expert’s personal perspective on reasons for failure and new opportunities

“…Apart from this route being the more 'natural route', there are poten tial advantages of this route in controlling the weight gain and other undesirable sequelae that are seen with the 'nonnatural' subcutaneous route administration of insulin [122][123][124][125][126][127][128][129][130][131][132][133][134][135]. Thus, orally administered insulin would potentially reach the liver in a similar fashion to naturally secreted insulin.…”