HEPATIC GLUCOSE-PRODUCTION DURING INTRAPERITONEAL AND INTRAVENOUS CLOSED-LOOP INSULIN REGULATION OF BLOOD-GLUCOSE IN TYPE-1 (INSULIN-DEPENDENT) DIABETIC-PATIENTS

Intraperitoneal infusion of insulin should be more physiological than intravenous insulin since part of the insulin is directed toward the p ortal vein, which allows the liver to retain its major role in glucose homeostasis. The regulation of hepatic glucose production during the intraperitoneal and intravenous infusions of insulin were compared in eight Type 1 (insulin-dependent), C-peptide-deficient diabetic patient s. Primed, continuous infusions of [6,6-H-2] glucose were given in the postabsorptive state and during continuous infusion of unlabelled glu cose at 1.5 and 4 mg/kg . min, while normoglycaemia was maintained by closed-loop intraperitoneal and intravenous insulin delivery. During a ll three periods, plasma glucose concentrations remained near normal ( variations 3.8-6.1%). The insulin infusion rates required for normal p lasma glucose concentrations were essentially the same for the intrave nous and intraperitoneal routes in all cases, although the variations were greater with intraperitoneal insulin. Plasma free-insulin levels were only slightly, non-significantly lower with intraperitoneal infus ion than with intravenous infusion. Hepatic glucose production was sig nificantly lower with intraperitoneal insulin during all three conditi ons: basal: 1.71 +/- 0.14, i. p. vs 2.37 +/- 0.26 mg/kg . min, i.v.; 1 .5 mg/kg . min glucose infusion: 0.49 +/- 0.23, i.p. vs 0.88 +/- 0.18 mg/kg . min, i.v.; 4 mg/kg . min glucose infusion: 0.31 +/- 0.10, i.p. vs 0.56 +/- 0.12 mg/kg . min, i.v.. These results, obtained with stea dy-state conditions for plasma glucose, isotopic plasma glucose enrich ments and unlabelled glucose infusion rates, suggest that better contr ol of hepatic glucose production leading to normoglycaemia was achieve d with the intraperitoneal infusion.