Associations between higher plasma ferritin and hepcidin levels with liver stiffness in patients with type 2 diabetes: An exploratory study |
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| Authors: | Alessandro Mantovani Alessandro Csermely Annalisa Castagna Elisa Antinori Elisa Danese Chiara Zusi Elena Sani Federico Ravaioli Antonio Colecchia Claudio Maffeis Luca Valenti Domenico Girelli Giovanni Targher |
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| Affiliation: | 1. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy;2. Department of Medicine, Section of Internal Medicine, EuroBloodNet Center, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy;3. Section of Clinical Biochemistry, Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy;4. Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgical Sciences, Dentistry, Pediatrics and Gynaecology, University Hospital of Verona, Verona, Italy;5. Gastroenterology Unit, Department of Medical Specialities, University Hospital of Modena, University of Modena & Reggio Emilia, Modena, Italy;6. Precision Medicine—Biological Resource Center, Transfusion Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, Milan, Italy |
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| Abstract: | Background Currently, there is no information about the association between circulating levels of ferritin and hepcidin and liver fibrosis in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Methods We enrolled 153 patients with T2DM with no known liver diseases, who consecutively attended our diabetes outpatient service and who underwent liver ultrasonography and liver stiffness measurement (LSM) by vibration-controlled transient elastography (Fibroscan® for the non-invasive assessment of liver fibrosis). Plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. Results After stratification of patients by LSM tertiles [1st tertile median LSM: 3.6 (interquartile range: 3.3–4.0) kPa, 2nd tertile: 5.3 (4.9–5.9) kPa and 3rd tertile: 7.9 (6.7–9.4) kPa], we found that plasma ferritin and hepcidin concentrations increased across LSM tertiles [median ferritin: 68.7 (interquartile range: 25.1–147) vs. 85.8 (48.3–139) vs. 111 (59.3–203) μg/L, p = 0.021; median hepcidin: 2.5 (1.1–5.2) vs. 4.4 (2.5–7.3) vs. 4.1 (1.9–6.8) nmol/L, p = 0.032]. After adjustment for age, sex, diabetes duration, waist circumference, haemoglobin A1c, HOMA-insulin resistance score, triglycerides, haemoglobin, presence of hepatic steatosis on ultrasonography and patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genetic variant, higher plasma ferritin levels were associated with greater LSM values (adjusted-odds ratio 2.10, 95% confidence interval 1.23–3.57, p = 0.005). Higher plasma hepcidin levels were also associated with greater LSM values (adjusted-odds ratio 1.90, 95% confidence interval 1.15–3.13, p = 0.013). Conclusions Higher levels of plasma ferritin and hepcidin were associated with greater NAFLD-related liver fibrosis (assessed by LSM) in patients with T2DM, even after adjustment for established cardiometabolic risk factors, diabetes-related variables and other potential confounders. |
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| Keywords: | fatty liver ferritin hepcidin liver stiffness measurement non-alcoholic fatty liver disease type 2 diabetes |
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