Portal systemic shunting of insulin does not lead to insulin resistance inpatients with extrahepatic portal vein obstruction

There is no clear relation between portal systemic shunting, reduced hepati c insulin extraction leading to an increased systemic delivery of insulin, and, resultant peripheral hyperinsulinemia and insulin resistance. Extrahep atic portal vein obstruction is a natural human model of portal systemic sh unting with essentially normal liver function. To investigate the role of p ortal systemic shunting of insulin in creating systemic hyperinsulinemia an d insulin resistance, we studied nine subjects with portal systemic shuntin g and nine controls matched for age (+/-2 years), body weight (+/-2 kg) and height (+/-5 cm). We carried out an oral glucose tolerance test and hyperi nsulinemic euglycemic clamp study at insulin infusion rate of 40 mU/m(2)/ m in. Comparable (p = 0.61) basal insulin concentrations in the two groups (M ean (SE): 21.0 (3.98) vs. 24.1 (4.28) mU/L) demonstrated a lack of hyperins ulinemia in the presence of portal systemic shunting. The lower (p = 0.03) insulin area under curve on oral glucose tolerance test in presence of port al systemic shunting (7.40 (0.95) vs. 10.83 (1.15) U/L . min) indicated tha t lower extraction of insulin by the liver leads to a lower requirements in the periphery. The coefficient of variation for plasma glucose between 60 and 120 min of the clamps was 4.44 (0.55)%. Comparable (p = 0.82) M-values (6.21 (0.67) vs. 6.38 (0.45) mg/kg/min) in the two groups proved a lack of significant insulin resistance in the presence of portal systemic shunting. We conclude that isolated portal systemic shunting leads to neither hyperi nsulinemia nor insulin resistance.