Authors’ reply re: Maternal lipids are associated with newborn
adiposity independent of GDM status, obesity and insulin resistance: a
prospective observational cohort study
Sir,
We thank Muggleton et al) Muggleton, 2020, Re: Maternal Lipids are
associated with newborn adiposity independent of GDM status‘, obesity
and insulin resistance: a prospective observational cohort
study(1 for their interest in our paper.
We concur with Muggleton et al1 that our
study2 reveals only an association (as indicated by
the title of our paper) between maternal hypertriglyceridemia and
neonatal anthropometrics and cannot provide proof of
causality2. Studies in Caucasian populations have
revealed a similar association between maternal triglyceride and newborn
adiposity both in mothers with Gestational Diabetes Mellitus(GDM) and in
Normal Glucose Tolerance mothers2. Hence, while it is
true that a high carbohydrate diet can result in hypertriglyceridemia
and may have partially contributed to elevated triglycerides in our
Malaysian mothers, given similar associations found in Western
populations we do not believe this to be solely modulated by a uniquely
‘Malaysian diet’ but rather a consequence of obesity and associated
maternal insulin resistance. We did not however collect data on dietary
intake and therefore cannot objectively confirm the role of a
high-carbohydrate diet in our sample population.
We do not however think that based on present published literature that
there is sufficient evidence to definitively support the hypothesis that
high carbohydrate induced maternal insulin secretion directly increases
neonatal adiposity. It is well-established that endogenous fetal
hyperinsulinemia as reflected by elevated cord-blood c-peptide
correlates strongly with fetal overgrowth and fetal fat accretion
secondary to increased fetal triglyceride synthesis/deposition and
stimulation of white adipocyte growth.3 By contrast,
it has not however been conclusively established that maternal
hyperinsulinemia plays a direct causative role in fetal overgrowth. The
presence of insulin receptors on the placenta has led some to
hypothesize that maternal insulin affects transplacental nutrient
transport in women with GDM4. Although maternal
insulin itself does not cross the placenta, it has been postulated that
placental insulin resistance results in abnormal insulin signaling
pathways in the placenta thus perhaps influencing placental metabolism.
Exogenous insulin treatment of GDM mothers however has been found to be
beneficial. Langer et al have demonstrated macrosomia rates were lower
in insulin-treated GDM mothers compared with diet-treated controls
despite equivalent glycemic control, indicating that exogenous insulin
has no adverse impact on the fetus at least in the short term and rather
results in improved neonatal outcomes5. It is also
important to note that high levels of maternal insulin are a consequence
of the maternal insulin resistance in adipose tissue/skeletal muscle,
which plays a significant role in the pathophysiology of GDM. Therefore
increased circulating maternal insulin per se which has been
associated with increased fetal adiposity4, may not
necessarily be directly causative. All these variables are part of a
complex inter-connected metabolic web with feedback loops that make it
difficult to pinpoint one particular element as the definitive prime
mover or underlying cause.
Syahrizan Samsuddin
Shireene R Vethakkan
(On behalf of the authors)