Healthy offsprings of T2DM patients were often considered as models for studying early metabolic aberrations in the development of Type 2 diabetes. Genetic predisposition of type 2 diabetes also accelerates the development of atherosclerosis and potentially increases the risk of coronary heart disease. Previous studies have reported that healthy adults with FHD exhibited a significant damage in beta cell function [
11]. Our results showed that the subjects in different categories of SF concentrations (SF main effect) had significantly different BMI, WC, SBP, FPG, PPG-2 h, FINS, and HOMA-IR. This suggested that the increased SF levels are associated with abdominal obesity, abnormal glucose metabolism, IR and elevated SBP. There was a significant difference in SBP, DBP, and FINS between the groups with FHD or without FHD (FHD main effect). This suggested that increased blood pressure and FINS are associated with FHD. Meanwhile, we speculated that the positive FHD increased the damage of islet function, leading to further increase of FINS and abnormal blood pressure. The interaction term between SF and FHD was significant for SBP, DBP, and PPG-2 h. Abnormal blood pressure and increased postprandial blood glucose are more obvious when there is a positive family history of diabetes and high SF levels at the same time. In our study, there were significant differences in the detection rate of cardiovascular risk factors components with ≥2 items and ≥ 3 items among the four groups. Logistic analysis after adjustment for age, showed that accumulation of CVD risk factors with ≥2 and ≥ 3 items in group D was 7.546 and 3.343 times higher compared with that in group A. The results showed that elevation of SF levels significantly increased the risk of cardiovascular risk factors together with a family history of diabetes.
Iron is an essential mineral in normal physiological processes, and ferritin is a specialized iron storage protein that reflects iron stores in the body [
12]. A cross-sectional study conducted among 123 men showed that the SF levels are independent predictors for IR, omitting the effect of BMI and WC [
7]. As known to all, IR is an important pathological basis for MetS and is associated with CVD. Excess body iron can impose oxidative injury that is associated with several cardiovascular risk factors including dyslipidemia, IR, and inflammation [
13]. SF is considered as a reliable tool, providing that the confounding effects by inflammatory, hepatic, or neoplastic diseases are excluded [
6]. It has been used as a surrogate variable to reflect the body iron stores in healthy individuals. Some recent researches from Asia shown that elevated SF levels may be a risk factor for T2DM [
14], IR, MetS [
15], and CVD [
16]. It’s also been observed in our study that increased SF levels are associated with abdominal obesity, abnormal glucose metabolism, IR and elevated SBP. In contrast, a recent large sample study from UK shown that low iron status was associated with CVD risk in T2DM, suggesting that low iron status seems to be harmful for cardiovascular health in T2DM. However, the underlying mechanisms are still unclear [
10]. The European Prospective Investigation into Cancer and Nutrition-Potsdam study concluded that high SF levels are associated with high risk of T2DM that is independent of established diabetes risk factors [
17]. SF levels are often elevated in MetS or associated with a true hepatic iron overload. Elevated iron stores are associated with increased risk of T2DM in a Mediterranean population who are at high risk of CVD, after adjusting for fasting glucose and other components of the MetS. Similar association was not evident with soluble transferrin receptor (sTfR) [
18]. sTfR levels could be spuriously elevated in subjects with IR and showed no association with MetS or its components [
19]. A recent meta-analysis study conducted to evaluated the associations between ferritin levels, MetS and its individual components, and the potential role of confounding, showed that high triglycerides and glucose are the components that are more strongly associated with ferritin. Hepatic injury and BMI influenced the association of ferritin-MetS, and a threshold effect of high ferritin concentration on ferritin-high triglycerides association was observed [
20]. The correlation between high triglycerides and ferritin is stronger, which was not observed in our study. This might be due to small sample size in our study. The difference in the detection rates of abdominal obesity and hypertension between the four groups showed no statistically significance, which was also related to the small sample size, and needs further confirmation by larger sample size study.
A recent study revealed that inflammatory cytokines may interact with MetS, obesity, IR, and T2DM [
21]. Elevated SF levels may comprise an inflammatory state like that of MetS. There are plenty evidences regarding a relevant relationship between SF levels and inflammation, and SF is considered as an acute phase reactant and increased during inflammation [
22]. And chronic inflammatory reaction may be considered to play an important role in the development and progression of IR. More studies are warranted to confirm this mechanism as it is becoming increasingly evident that excess iron is related to the incidence of MetS [
23].
Our study was a cross-sectional study. The limitations should be considered when interpreting our results. We cannot determine the causal relationship between SF and cardiovascular risk factors. Experimental and prospective studies are warranted to elucidate the role of SF in the risk factors associated with CVD in the first-degree relatives with FHD. Although several reports were put forwarded regarding the relationship between SF levels and MetS [
15,
16,
23], there has been no direct evidence whether SF is a predictor of accumulation of cardiovascular risk factors or not. In addition, small sample size and lack of data on women are also considered as limitations of this study. Therefore, a longitudinal relationship study between SF levels and accumulation of cardiovascular risk factors in larger samples size is warranted to confirm these results. Further studies are needed to confirm whether the correlation between SF and accumulation of cardiovascular risk factors also exists in women.