Gestational diabetes mellitus (GDM) can lead to short- and long-term health risks for both the mother and the infant, including increased risk of type 2 diabetes later in life. Recent evidence shows that excess iron stores are associated with an increased risk of diabetes. Moderately elevated ferritin levels, though well below those observed in iron overload disorders, have been associated with increased insulin secretion, decreased insulin sensitivity, and type 2 diabetes. However, the level of elevation at which this increased risk begins has not been established.

The proposed mechanisms for the association of an elevated ferritin level with increased diabetes risk include excess iron and inflammation. A randomized controlled trial in nonanemic pregnant women revealed that daily iron supplementation increased ferritin levels but did not increase the risk of GDM [Chan KKL et al. BJOG 2009]. Case-control studies that looked at the association of GDM in pregnant women and high ferritin levels have not indicated a clear association after controlling for inflammation [Sharifi F et al. Diabetes Metab Syndr Obes 2010; Chen X et al. Diabetes Care 2006]. Amina Khambalia, PhD, University of Sydney, Sydney, Australia, presented results of a retrospective study that aimed to determine whether an elevated serum ferritin level during the first trimester is associated with subsequent GDM when there is no evidence of inflammation.

Patients in the first trimester of pregnancy (n = 3143) had clinical and laboratory data collected. Women with preexisting diabetes, multiple pregnancies, or C-reactive protein (CRP) >5 mg/L were excluded. Stored blood samples were tested for serum ferritin, soluble transferrin receptor (sTfR), and CRP. Birth data and hospital data records on GDM were linked for the remaining 3045 pregnancies. Among these, 3.6% (n = 110) developed GDM.

The development of GDM was associated with maternal age ≥35 years (p <.004), gestational age >12 weeks (p = .06), weight ≥ 75th percentile (p = .05), and geography (p = .002). On univariate analysis, median ferritin levels were significantly higher among women with GDM (33.9 μg/L) compared with women without GDM (25.9 μg/L; p = .0007; Table 1). There was no significant difference in sTfR levels between the 2 groups. Fewer women with GDM were iron deficient (7.4%) compared with women without GDM (18.8%; p = .005). Women with GDM were more likely to have ferritin levels in the highest tertile (46.3% vs 32.6%; p = .005) and 75th percentile (33.7% vs 24.7%; p = .05) when compared to women without GDM.

Multivariate analysis adjusting for maternal age, parity, country of birth, weight, gestational age at blood collection, smoking, and CRP, revealed that ferritin was still associated with a statistically significant increased risk of developing GDM (adjusted odds ratio, 1.44; 95% CI, 1.10 to 1.90).

These results showed evidence of an association between elevated ferritin level and risk of developing GDM among women without evidence of inflammation. Transferrin receptor levels were not associated with the development of GDM. Future studies are needed to confirm these results, to determine if there is utility in the routine measurement of ferritin, and to identify other markers of iron and inflammation.