- Publication date : 2018-07-18
Dong Y, Luo ZC, Nuyt AM, Audibert F, Wei SQ, Abenhaim HA, Bujold E, Julien P, Huang H, Levy E, Fraser WD; 3D cohort study group. Large-for-Gestational-Age May be Associated with Lower Fetal Insulin Sensitivity and β-Cell Function Linked to Leptin. J Clin Endocrinol Metab. 2018 Jul 18. doi: 10.1210/jc.2018-00917. [Epub ahead of print] PubMed PMID: 30032199.
CONTEXT:Fetal overgrowth is associated with increased risk of type 2 diabetes in adulthood. It is unclear whether there are alterations in insulin sensitivity and β-cell function in early life.OBJECTIVE:We sought to determine whether large-for-gestational-age (LGA, birth weight >90th percentile), an indicator of fetal overgrowth, is associated with altered fetal insulin sensitivity and β-cell function.STUDY DESIGN, POPULATION,
OUTCOMES:In the 3D (design, development and discover) birth cohort in Canada, we studied 106 pairs of LGA and optimal-for-gestational-age (OGA, birth weight 25-75th percentiles) infants matched by maternal ethnicity, smoking status and gestational age. Cord plasma glucose-to-insulin ratio was used as an indicator of fetal insulin sensitivity, and proinsulin-to-insulin ratio as an indicator of β-cell function. Cord plasma leptin and high-molecular-weight (HMW) adiponectin concentrations were measured.
RESULTS:Comparing LGA vs. OGA infants adjusted for maternal and newborn's characteristics, cord blood insulin, proinsulin and leptin concentrations were significantly higher, while HWM adiponectin concentrations were similar. Glucose-to-insulin ratios were significantly lower (15.4±28.1 vs. 22.0±24.9, P=0.004), while proinsulin-to-insulin ratios significantly higher (0.73±0.82 vs. 0.60±0.78, P=0.005) in LGA vs. OGA newborns, indicating lower insulin sensitivity and β-cell function in LGA newborns. These significant differences were virtually unchanged further adjusting for cord blood adiponectin levels, but disappeared further adjusting for cord blood leptin levels.
CONCLUSIONS:This is the first study demonstrating that LGA may be associated with decreases in both fetal insulin sensitivity and β-cell function. The alterations appear to be linked to elevated leptin levels.