The Association of Serum Erythroferrone, a Regulator of Erythropoiesis and Iron Homeostasis, with Cardiometabolic Risk Factors in Apparently Healthy Young Adults—A Preliminary Study

<b>Background</b>: Recent studies suggest that erythroferrone (ERFE), an iron-regulating protein whose primary role is to inhibit hepcidin synthesis, may affect glucose and lipid metabolism, and its serum concentration is reduced in obese and diabetic individuals. The aim of this study was to evaluate the association of ERFE concentration with selected cardiometabolic risk factors in apparently healthy young adults. <b>Methods</b>: This preliminary study consisted of 122 (63 females, 59 males) normoglycemic, non-smoking subjects aged 25-40 years. In all participants, anthropometric measurements and the following laboratory tests were performed: fasting plasma glucose, glycated hemoglobin (HbA1c) and serum iron, lipid profile, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein (CRP), ERFE and hepcidin. <b>Results</b>: The serum ERFE concentration was significantly lower in men compared to women (<i>p</i> = 0.009) and in subjects who were overweight (<i>p</i> < 0.001) and had abdominal obesity (<i>p</i> < 0.001). ERFE showed significant negative correlations with body mass index, waist-hip ratio, HbA1c, CRP, insulin, HOMA-IR and triglycerides. In the logistic regression analysis, ERFE was significantly associated with being overweight (OR = 0.051; <i>p</i> = 0.004), abdominal obesity (OR = 0.372; <i>p</i> < 0.001), HOMA-IR ≥ 2.0 (OR = 0.584; <i>p</i> = 0.013), CRP > 1 mg/L (OR = 0.648; <i>p</i> = 0.020) and triglycerides (OR = 0.521; <i>p</i> = 0.033). A relevant predominance in the prevalence of cardiometabolic risk factors was observed in subjects with ERFE levels in the first tertile (<1.35 ng/mL), compared to the third tertile (>2.19 ng/mL). <b>Conclusions</b>: Serum ERFE is inversely associated with being overweight, increased waist circumference, CRP, and markers of insulin resistance and lipid abnormalities, suggesting its potential relevance as a marker of early cardiometabolic risk in apparently healthy young adults.