High Iron Levels Linked With Gestational Diabetes

Marcia Frellick

November 10, 2016

High levels of iron are linked with a higher risk of developing gestational diabetes (GDM), which calls into question routine recommendations for iron     supplements for pregnant women, new research indicates.

Results from a study by Shristi Rawal, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health in Bethesda, Maryland, and colleagues, were published online in    Diabetologia on November 10.

They found that women who were in the top quartile for iron biomarkers in the second trimester of pregnancy had about 2.5 times the risk of developing GDM     compared with those in the bottom quartile.

Asked to comment, Joel Zonszein, MD, director of the Clinical Diabetes Center at Montefiore Health System in the Bronx, New York, said he thinks it is more     likely that iron supplements are a contributor to gestational diabetes, rather than the cause of it.

Nevertheless, he says that pregnant women should be screened for iron levels and given supplements only if they are deficient.

Iron Levels Are "Double-edged Sword"

Too much iron as well as too little can cause harm, and pregnant women are often susceptible to low iron levels and related adverse outcomes, according to     background information in the article.

But different guidelines vary on recommendations for iron in pregnancy.

Those from the American College of Obstetricians and Gynecologists (ACOG) recommend screening and treatment only as necessary for iron deficiency.

But other groups, including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend routine iron     supplementation for pregnant women, the authors point out.

The results of the few prior studies on iron status in pregnancy and the risk of GDM have been inconsistent, they add.

In their case-control study, they compared 107 women with GDM and 214 pregnant women without gestational diabetes as controls who were matched by age,     race/ethnicity, and gestational week of blood collection.

The women studied were part of a 2009–2013 prospective and multiracial pregnancy cohort within the    NICHD Fetal Growth Studies.

Strengths of the study included longitudinal blood collection, which allowed a unique opportunity to look at the iron biomarkers hepcidin and ferritin     across pregnancy and GDM risk by trimester.

The markers were longitudinally measured four times during pregnancy, twice before GDM diagnosis (gestational weeks 10–14 and 15–26), and twice afterward     (gestational weeks 23–31 and 33–39). GDM diagnosis was ascertained from medical records based on oral glucose-tolerance test results.

Hepcidin concentrations during weeks 15–26 of gestation were 16% higher among women with GDM vs controls (P = .02) and were positively associated     with GDM risk — the odds ratio (OR) for highest vs lowest quartile was 2.61 (adjusted for prepregnancy body mass index [BMI] and other demographic and     major risk factors).

Similar results were observed for ferritin levels — ORs for gestational diabetes for highest vs lowest quartile were 2.43 for the first trimester and 3.95     at weeks 15–26.

Along with those two biomarkers, researchers looked at soluble transferrin receptor (sTfR), and the combined data were used to calculate the sTfR:ferritin     ratio — which captures both cellular iron need and availability of body iron stores — and this was inversely related to GDM risk.

The authors conclude that"higher maternal iron stores may play a role in the development of GDM starting as early as the first trimester.

"These findings are of clinical and public-health importance as they extend the observation of an association between high body iron stores and elevated     risk of glucose intolerance among nonpregnant individuals to those who are pregnant," they note.

This raises "potential concerns about the recommendation of routine iron supplementation among pregnant women who already have sufficient iron."

Iron a More Likely Contributor Than Cause

Dr Zonszein says if iron were directly related to diabetes risk, it would have a progressively worsening effect, rather than having an inconsistent effect     over different trimesters.

The study "doesn't show that every woman who got iron got more gestational diabetes. There was an association both early and late in pregnancy, which also     doesn't make sense, because when there is causation of a medication or a vitamin, the longer they are exposed to it and the more doses they get, the more     chance they have of getting gestational diabetes. You don't have this effect when they get it early in pregnancy and late in pregnancy."

He said its likely iron plays a role in developing GDM, "but this study doesn't show that."

At his institution, Montefiore Health System in the Bronx, women are screened for iron levels when pregnant and given supplements only if they are     deficient, he noted.

        The research was supported by National Institute of Child Health and Human Development intramural funding and included American Recovery and         Reinvestment Act funding. The authors declare no relevant financial relationships. Dr Zonszein has served on advisory boards for Novo Nordisk, Sanofi,         and Merck.    

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Diabetologia. Published online November 10, 2016. Abstract

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