Medium-chain fatty acids increase glucose production in normal and low birth weight newborns.

To study the pathogenesis of hypoglycemia in low birth weight infants, glucose production was measured in five hypotrophic and four premature newborns with glycemia of 45 +/- 6 and 59 +/- 10 mg/dl, respectively. Hepatic glucose output averaged 5.7 +/- 0.4 and 5.3 +/- 0.5 mg.kg-1.min-1 in these neonates vs. 8.2 +/- 0.5 mg.kg-1.min-1 in five normal at term newborns and was correlated with glycemia (P less than 0.02). Despite normal plasma free fatty acids, the low birth weight infants had low ketone levels of 163 +/- 72 and 126 +/- 65 vs. 263 +/- 60 microM in normals. Oral administration of medium-chain triglycerides to the neonates increased their circulating ketones by two- to threefold and restored near-normal glycemia (51 +/- 9 and 76 +/- 8 mg/dl) and production of glucose (6.7 +/- 0.7 and 6.6 +/- 0.8 mg.kg-1.min-1) in the hypotrophic and premature vs. normals (8.7 +/- 0.7 mg.kg-1.min-1). Individual rates of glucose production correlated with ketone concentrations (P less than 0.02). We conclude that the hypoglycemia characterizing low birth weight neonates is primarily due to impaired glucose production. That exogenous lipids were able to increase glucose production indicates that fatty acid oxidation plays an important glucoregulatory role in the human newborn.