Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age

Abstract

OBJECTIVE. In addition to neonatal hypoglycemia, infants who are born large for gestational age are at risk for developing obesity, cardiovascular disease, and diabetes later in life. The aim of this study was to investigate glucose production, lipolysis, and insulin sensitivity in infants who were born large for gestational age to mothers without diabetes. The effect of glucagon administration on production of energy substrates was also investigated. METHODS. Ten healthy term infants who were born large for gestational age to mothers without diabetes were studied 16 ± 8 hours postnatally after a 3-hour fast. Rates of glucose production and lipolysis were analyzed by gas chromatography–mass spectrometry following constant rate infusion of [6,6-2H2]glucose and [2-13C]glycerol. Insulin sensitivity was assessed by the Homeostasis Assessment Model. In 8 of the infants, the effect of an intravenous injection of 0.2 mg/kg glucagon was also analyzed. RESULTS. Plasma glucose and glycerol averaged 3.8 ± 0.5 mmol/L and 384 ± 183 μmol/L, respectively. The glycerol production rate, reflecting lipolysis, was 12.7 ± 2.9 μmol/kg per min. Mean rate of glucose production was 30.2 ± 4.6 μmol/kg per min. Homeostasis Assessment Model insulin sensitivity corresponded to 82% ± 19%, β-cell function to 221% ± 73%, and insulin resistance to 1.3 ± 0.3. After glucagon administration, rate of glucose production increased by 13.3 ± 8.3 μmol/kg per min and blood glucose by 1.4 ± 0.5 mmol/L. Glycerol production decreased from 12.8 ± 3.0 to 10.7 ± 2.9 μmol/kg per min. Mean insulin concentration increased from 10.9 ± 3.0 to 30.9 ± 10.3 mU/L. There was a strong inverse correlation between the decrease in lipolysis and increase in insulin after glucagon administration. CONCLUSIONS. Infants who are born large for gestational age show increased lipolysis and a propensity for decreased insulin sensitivity already at birth. The simultaneous increase in plasma insulin correlated strongly with the noted decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants.