Gluconeogenesis in Very Low Birth Weight Infants Who Are Receiving Nutrition By Intravenous Infusion

Overview

RATIONALE: Very low birth weight infants have problems maintaining normal blood sugar levels. Gluconeogenesis is the production of sugar from amino acids and fats. The best combination of amino acids, fat, and sugar to help very low birth weigh infants maintain normal blood sugar levels is not yet known. PURPOSE: Clinical trial to study how very low birth weight infants break down amino acids, fat, and sugar given by intravenous infusion, and the effect of different combinations of nutrients on the infants' ability to maintain normal blood sugar levels.

PROTOCOL OUTLINE: Patients are assigned to one of 6 study groups. Patients receive infusions of stable isotope tracers: \[15N\]urea IV beginning at -12 hours and continuing over 22 hours to measure protein oxidation; \[U-13C\]glucose IV beginning at zero hour and continuing over 10 hours to measure glucose appearance rate and gluconeogenesis; \[2-13C\]glycerol IV over 10 hours to measure lipolysis; and \[1-C\]leucine IV over 10 hours to measure proteolysis. Blood samples are obtained before the start of the urea tracer infusion; before the start of the glucose, glycerol, and leucine tracer infusions; and at study hours 4, 4.5, 5, 9, 9.5, and 10. Blood glucose is measured hourly, and patients receive glucose IV if blood glucose falls below 40 mg/dL. Group I: Patients are randomized to one of two study arms. Arm I: Patients receive standard total parenteral nutrition (TPN), except the \[U-13C\]glucose is substituted for a portion of the glucose. Arm II: The infusions of lipids (Intralipid) and amino acids (TrophAmine) are discontinued at study hour zero. The infusion rate of natural glucose will be reduced during the first hour, and thereafter discontinued. Group II: Patients are randomized to receive either TrophAmine or Intralipid IV over the last 5 hours of the study. Group III: Patients are randomized to receive one of two different doses of glycerol IV over the last 5 hours of the study. Group IV: Patients are randomized to receive either glutamine or alanine IV over the last 5 hours of the study. Group V: Patients receive glucagon IV for 24 hours prior to study. Patients are then randomized to receive glucagon IV with either IV glucose alone or with Intralipid and TrophAmine IV. Group VI: Patients who are hyperglycemic receive TPN and \[U-13C\]glucose as in group I, arm I, over 14 hours, and regular insulin IV at 10 hours, followed by an IV infusion of carbohydrate. Blood samples obtained between hours 4 and 5 are omitted, and are drawn instead between hours 13 and 14.