‘Counterintuitive’ HAPO FUS findings challenge large baby metabolic concerns
medwireNews: The latest analysis of HAPO and HAPO FUS data indicates that, contrary to prior assumptions, a high birthweight and newborn adiposity are associated with good metabolic health in childhood.
Previous data from these population-based cohorts linked high maternal plasma glucose and BMI to high birthweight in the offspring, and maternal hyperglycemia to poor metabolic outcomes for the offspring in childhood.
The findings of the current analysis are therefore “somewhat counterintuitive,” write William Lowe Jr (Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA) and study co-authors in Diabetologia.
They say: “These findings stand in contrast to the hypothesis being addressed and suggest a complex interaction among maternal [plasma glucose] during pregnancy, size at birth and childhood metabolic outcomes.”
The conclusions are drawn from data on 4155 children, who were aged an average of 11.4 years at follow-up, and their mothers.
The researchers found that weight at birth significantly and inversely correlated with glucose measures in childhood, so that the higher birthweight was, the lower was fasting glucose, as well as measures derived from the oral glucose tolerance test. And the same was true for newborn adiposity, indicated by the sum of skinfolds.
These associations were independent of factors including child age and sex, and maternal variables including glucose levels during pregnancy.
Umbilical cord C-peptide level was not associated with childhood glucose measures; however, a higher level was significantly associated with poorer insulin sensitivity in childhood, as quantified on the Matsuda index. By contrast, higher birthweight and adiposity were significantly associated with greater insulin sensitivity, again independently of factors including maternal glucose levels.
“Greater newborn birthweight is typically associated with childhood obesity,” say the researchers, noting that this suggests a link to poor metabolic health in childhood, which is contrary to the findings in the current study.
“One potential explanation for our results is that newborns with higher birthweight may have more lean body mass during childhood, which would be associated with greater insulin sensitivity,” they speculate, but concede that this does not account for the observed association with sum of skinfolds.
As an alternative, Lowe and team suggest that genetic variants linked to both large birth size and good metabolic health might underpin the associations.
They say: “This would be consistent with the observation that some genetic variants associated with lower birthweight are also associated with greater risk of type 2 diabetes, while genetic variants associated with a higher disposition index are associated with greater birthweight.”
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