Iron Status during Pregnancy and the Risk of GDM

13 Dec, 16

Introduction

Studies in the past have indicated a link between larger iron stores and disturbed glucose metabolism in non-pregnant females. It is however unclear if such an association also holds true for the development of gestational diabetes mellitus (GDM) during pregnancy. Newer trials are needed to study this association using novel biomarkers such as hepcidin – that is known to be a better biomarker of iron status.

Aim

To prospectively investigate the maternal iron status during early to mid-pregnancy, and the risk of GDM, using both conventional and novel iron biomarkers including hepcidin, ferritin, soluble transferrin receptor (sTfR) and sTfR:ferritin ratio
To characterize the longitudinal changes in the iron biomarkers throughout the pregnancy

Patient Profile

Women with GDM (n=107; age: 18-40 years) who were a part of the prospective and multiracial ‘National Institute of Child Health and Human Development (NICHD) Fetal Growth’ Studies–Singleton Cohort
Age, race, ethnicity and gestational week-matched women without GDM (control group; n=214)

Methods

Study Design

A case-control, longitudinal study

Evaluations

Blood samples were collected at 4 visits: gestational weeks 10–14, 15–26, 23–31 and 33–39
Plasma concentrations of hepcidin (ng/ml), ferritin (pmol/l) and sTfR (nmol/l) were measured. The sTfR:ferritin ratio was derived by dividing the plasma concentration of sTfR (?g/l) by that of ferritin (?g/l)
A structured questionnaire was administered to the study participants to determine various GDM risk factors
Information on the use of supplements including iron supplements was derived from medical records and through self-reporting
The analysis was based on the values of biomarkers from the samples collected at weeks 10-14 and 15-26

Results

A decline through mid-pregnancy, followed by reaching a plateau was evident for hepcidin and ferritin concentrations. In contrast, there was an increase in the sTfR concentrations and the sTfR:ferritin ratio with the progression of pregnancy.
Women who developed GDM had almost 21% higher ferritin levels (at weeks 10-14) vs. the controls (Table 1).

Table 1: Plasma ferritin levels in the study groups at weeks 10-14

Parameter	GDM Group	Control Group	P value
Ferritin level	143.2 pmol/L	118.7 pmol/l	0.04

During gestational weeks 10-14, women in the highest quartile of ferritin level had more than two-fold greater odds for developing GDM {adjusted odds ratio (aOR) 2.43} vs. those in the lowest quartile.
On the contrary, the sTfR:ferritin ratio exhibited a significant inverse association with GDM risk at weeks 10–14 (aOR 0.33) when comparing the highest vs. the lowest quartile
At week 15-26, hepcidin as well as ferritin levels were significantly higher in GDM group vs. the control group (Table 2). These higher levels were significantly and positively associated with GDM risk (hepcidin – highest quartile vs. lowest quartile: aOR 2.61; ferritin – highest quartile vs. lowest quartile: aOR 3.95)

Table 2: Iron biomarker levels at weeks 15-26

Study Parameter	GDM Group	Control Group	P value
Hepcidin Levels	6.4 ng/ml	5.5 ng/ml	0.02
Ferritin Levels	94.5 pmol/L	78.1 pmol/L	0.007

The sTfR:ferritin ratio was inversely related to GDM risk even at weeks 15-26 (aOR 0.15)
No significant differences were evident for sTfR levels between the groups
Around 87% women reported the use of iron supplements (including iron-only supplements and prenatal or standard multivitamins that contain iron) during the second trimester (weeks 15-26); association between iron biomarkers and GDM risk didn’t reduce appreciably after adjustment for supplemental use of iron

Conclusions

Higher iron status during pregnancy (as indicated by higher hepcidin and ferritin concentrations and a lower sTfR:ferritin ratio) was significantly associated with an elevated risk of GDM in women without prepregnancy chronic disease, even after adjusting for major GDM risk factors
Although the increased risk was evident right from the first trimester, it was more robust during the second trimester, when GDM is generally diagnosed
The inverse association between the risk of GDM and sTfR:ferritin ratio in absence of an association between sTfR and GDM risk might be a result of increased ferritin levels and hence needs a cautious interpretation
The findings have important implications for public health and raise a potential concern about the routine practice of prescribing iron supplements among iron-replete pregnant females

Diabetologia 2016; DOI 10.1007/s00125-016-4149-3