manipulating GDF15
action might disturb glucose homeostasis.
After a large postpartum reduction in circulating GDF15, there were no
changes between 6 and 18 months after pregnancy; glucose metabolism
followed a similar pattern. At 18 months after pregnancy GDF15 was
positively associated with HOMA-B for all women and NW and, in OB, with
HOMA-IR. The latter finding is in agreement with cross-sectional studies
linking insulin resistance and GDF15 in nonpregnant
OB17,
28. This association can be explained by
the higher release of GDF15 in inflammatory conditions such as insulin
resistance and obesity as discussed above.
The major strength of the current study is the longitudinal design
comprising three time points during pregnancy and three time points
after pregnancy, all involving identical study visits at a single
center. Our subjects were well characterized through blood sampling and
use of a reference method to measure body composition. However, oral
glucose tolerance testing in addition to HOMA calculations would have
provided a more extensive evaluation of glucose metabolism and insulin
release. As in all such studies, additional limitations include the
difficulty of proving causation in relationships, recruitment bias, and
generalizability. With a focus on health and anthropometric
measurements, recruited women are generally more inclined to keep
healthy habits. However, relationships among the various factors
measured should not be affected by this potential bias. A final
limitation was the reduced statistical power resulting from the number
of drop-outs in the OB group for the last visit at 18 months after
pregnancy.
In conclusion, we found that the serum level of GDF15 increases
throughout pregnancy, and does so to greater extent in NW than OB, and
is associated with increased insulin secretory function in normoglycemic
pregnancies. Adding to previous research in nonpregnant subjects, our
findings suggest that GDF15 has a beneficial effect on beta cell
function and may have implications for treatment to overcome insulin
resistance . More mechanistic studies will be needed to confirm the
effect of GDF15 on beta cells during pregnancy.
Acknowledgements We thank all the women who participated in the
study, and registered dietician Evelina Järvinen for expert caretaking
and measurements during study visits.
Ethical approval The study was approved by the Regional Ethical
Review Board in Gothenburg (Dnr 402-08). All women received oral and
written information about the study and gave informed written consent
before enrolment.
Author contributions Conception, data acquisition, or data
analysis and interpretation; UAH, PS, AH. Drafting or revising article
for intellectual content; UAH, LJ, CM, AH. Final appoval of article;
UAH, LJ, PS, CM, AH