Very low birth weight (VLBW) infants are dependent on total parenteral nutr
ition (TPN) to prevent hypoglycemia and provide a sufficient energy intake.
However, diminished tolerance for parenteral glucose delivered at high rat
es frequently provokes hyperglycemia. We hypothesized that when their gluco
se supply is reduced to prevent hyperglycemia, VLBW infants can maintain no
rmoglycemia via gluconeogenesis from glycerol and amino acids. Twenty infan
ts born at 27 +/- 0.2 (mean +/- SE) gestational weeks and having a birth we
ight of 996 +/- 28 g, received lipids (1.6 +/- 0.1 mg.kg(-1).min(-1)), prot
ein (2.2 0.1 mg.kg(-1).min(-1)), and glucose (3.1 +/- 0.1 mg.kg(-1).min(-1)
[17.1 +/- 0.2 mu mol.kg(-1).min(-1)]) parenterally over a period of 8-12 h
on day 5.0 +/- 0.2 of life. Gluconeogenesis was estimated using [U-C-13]gl
ucose (n = 8) or [2-C-13] glycerol (n = 6) and mass isotopomer distribution
analysis (MIDA), or (H2O)-H-2 (n = 6) and the rate of deuterium incorporat
ion in carbon 6 of glucose. Blood glucose averaged 3.0 +/- 0.1 mmol/l; plas
ma glucose appearance rate (glucose Ra), 28.8 +/- 1.1 mu mol.kg(-1).min(-1)
; and glucose production rate (GPR), 10.7 +/- 1.0 mu mol.kg(-1).min(-1) The
[U-C-13]glucose and [2-C-13]glycerol tracers provided similar estimates of
gluconeogenesis, averaging 28 +/- 2 and 26 +/- 2% of glucose Ra and 72 +/-
5 and 73 +/- 9% of GPR, respectively. Glycerol contributed 64 +/- 5% of to
tal gluconeogenesis. Gluconeogenesis measured by (H2O)-H-2, which does not
include the contribution from glycerol, was comparable to the nonglycerol f
raction of gluconeogenesis derived by the [2-C-13]glycerol MIDA. We conclud
e that in VLBW infants receiving TPN, normoglycemia was maintained during r
educed glucose infusion by glucose production primarily derived from glucon
eogenesis, and that glycerol was the principal gluconeogenic substrate.