Sex Differences in the Association Between Serum Ferritin and Fasting Glucose in Type 2 Diabetes Among South Asian Surinamese,African Surinamese,and Ethnic Dutch: The population-based SUNSET study

OBJECTIVE

Moderately elevated iron stores below the levels commonly associated with hemochromatosis have been implicated in the etiology of diabetes. Studies suggest that iron status (measured by serum ferritin) differs significantly according to sex, but inconsistent findings have been reported. Our aim is to test the association between serum ferritin and the prevalence of type 2 diabetes and fasting glucose concentrations in a population-based, multiethnic, cross-sectional study including men and women of African Surinamese, South Asian Surinamese, and ethnic Dutch origin.

RESEARCH DESIGN AND METHODS

We analyzed data on 508 ethnic Dutch, 597 African Surinamese, and 339 South Asian Surinamese aged 35–60 years. Type 2 diabetes was defined as a fasting plasma glucose level ≥7.0 mmol/L or a self-reported diagnosis.

RESULTS

Serum ferritin was positively associated with type 2 diabetes and fasting glucose, but differences in the associations according to sex were observed. Serum ferritin concentration was positively associated with type 2 diabetes among women in all ethnic groups (odds ratio OR] ethnic Dutch: 1.07 95% CI 1.01–1.13]; OR South Asian Surinamese: 1.05 1.00–1.10]; OR African Surinamese: 1.05 1.01–1.10]), but not among men. Serum ferritin was also more strongly associated with fasting glucose in women than in men. Moreover, the magnitude of sex differences in the association between serum ferritin and fasting glucose, but not type 2 diabetes, was more pronounced in the African Surinamese group than in the other ethnic groups (P for interaction ≤0.0001).

CONCLUSIONS

We found a positive association between serum ferritin and type 2 diabetes and fasting glucose in our multiethnic population, which appeared stronger among women than men. Further evaluation of the variation in sex differences between ethnic groups is warranted, particularly among the African Surinamese, to understand the mechanisms behind these sex differences.Moderately elevated iron stores below the levels commonly associated with hemochromatosis have been implicated in the etiology of type 2 diabetes (1–3). Although a mechanism linking iron concentrations and diabetes is yet to be established, it is known that iron is a catalyst in the formation of hydroxyl radicals (4), which may contribute initially to insulin resistance, subsequently to decreased insulin secretion, and ultimately to the development of type 2 diabetes (5). Animal models suggest that iron excess may result in β-cell oxidative stress and decreased insulin secretion (6). Levels of serum ferritin, a predominant iron-storage protein and a biomarker of iron stores, are elevated in persons with prevalent diabetes as compared with nondiabetic controls (7) and correlate with impaired fasting glucose levels (8), an early marker of type 2 diabetes. In addition, several cross-sectional or case-control studies and two prospective studies have identified an independent association between baseline elevations in iron stores and the occurrence of type 2 diabetes (2,5,9–12). However, several questions remain unanswered.It is yet unclear whether the association between serum ferritin and diabetes differs among men and women. Some have found that differences in iron status exist according to sex (8,13–16), which might have implications for the association with the etiology of diabetes (13). Others have suggested that sex differences might exist due to differences in iron accumulation in the peripheral muscles, which may cause derangement of muscle glucose uptake because of muscle damage (17,18). However, robust studies on the influence of sex on the association between serum ferritin and diabetes are rather inconsistent. Some have reported sex differences in the association (9,18), whereas others have not demonstrated this (19–21). Moreover, in those studies in which different associations between serum ferritin and type 2 diabetes were found for men and women, it appeared that the direction of the differences varied across studies (7–9).These discrepancies might be the result of differences in the ethnic composition of study populations. A first argument to support this is a study reporting variations in the serum ferritin and type 2 diabetes associations across men and women from different ethnic populations, including white, black, Hispanic, Asian, and Pacific Islander populations (9). This study reported that the association between serum ferritin and type 2 diabetes differed significantly between the ethnic groups among women but not among men. Unfortunately, other multiethnic studies have not considered differential sex effects across ethnic groups (10,19,20). Another argument for the potential role of ethnicity is a difference in body composition that may occur between ethnic groups. For instance, in the Netherlands, differences in waist circumference or waist-to-height ratio have been reported among ethnic Dutch, South Asian Surinamese, and African Surinamese (22,23). This is relevant, as body composition is suggested to affect the association between serum ferritin and the insulin resistance syndrome (17,18).The aim of this exploratory study is: 1) to test whether the association between serum ferritin and diabetes and fasting glucose differs between men and women of African Surinamese, South Asian Surinamese, and ethnic Dutch origin, and 2) to test whether the differences in the association between serum ferritin between men and women varies between these populations.