Abstract
Objective Obesity in pregnancy bears unique maternal and fetal risks. Obesity has also been
associated with chronic inflammation, including elevated serum levels of interleukin-6
(IL-6) and tumor necrosis factor-α (TNF-α). Higher serum lipopolysaccharide (LPS)
levels have been implicated in driving this inflammation, a phenomenon called metabolic
endotoxemia (ME). GLP-2, a proglucagon-derived peptide, is believed to be integral
in maintaining the integrity of the intestine in the face of LPS-mediated endotoxemia.
We hypothesized that obesity and/or excess weight gain in pregnancy would be associated
with an increase in maternal and neonatal markers of ME, as well as GLP-2.
Study Design Paired maternal and neonatal (cord blood) serum samples (n = 159) were obtained from our pregnancy biobank repository. Serum levels of LPS,
endotoxin core antibody-immunoglobulin M (EndoCAb-IgM), and GLP-2 were measured by
ELISA. IL-6 and TNF-α were measured using a Milliplex assay. Results were stratified
by maternal body mass index (BMI), maternal diabetes, and gestational weight gain
(GWG).
Results Maternal IL-6 is significantly decreased in the obese, diabetic cohort compared with
the nonobese, nondiabetic cohorts (95.28 vs. 99.48 pg/mL, p = 0.047), whereas GLP-2 is significantly increased (1.92 vs. 2.89 ng/mL, p = 0.026). Neonatal TNF-α is significantly decreased in the obese cohort compared
with the nonobese cohort (12.43 vs. 13.93 pg/mL, p = 0.044). Maternal GLP-2 is significantly increased in women with excess GWG compared
with those with normal GWG (2.27 vs. 1.48 ng/mL, p = 0.014). We further found that neonatal IL-6 and TNF-α are negatively correlated
with maternal BMI (–0.186, p = 0.036 and –0.179, p = 0.044, respectively) and that maternal and neonatal IL-6 showed a positive correlation
(0.348, p < 0.001).
Conclusion Although we observed altered levels of markers of inflammation (IL-6 and TNF-α) with
maternal obesity and diabetes, no changes in LPS or endoCAb-IgM were observed. We
hypothesize that the increased GLP-2 levels in maternal serum in association with
excess GWG may protect against ME in pregnancy.
Key Points
-
Maternal serum levels of GLP-2, a proglucagon-derived peptide, are increased in obese,
diabetic gravidae.
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Maternal serum GLP-2 levels are also increased in association with excess gestational
weight gain compared with normal gestational weight gain.
-
GLP-2 may be increased in association with obesity and weight gain to protect against
metabolic endotoxemia in pregnancy.
Keywords
gestational weight gain - gestational diabetes - obesity - metabolic endotoxemia
