Associations between higher plasma ferritin and hepcidin levels with liver stiffness in patients with type 2 diabetes: An exploratory study

Abstract

BackgroundCurrently, 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).MethodsWe 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.ResultsAfter 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).ConclusionsHigher 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.

New Perspectives on Circulating Ferritin: Its Role in Health and Disease

“…Hyperferritinemia is associated with various metabolic and inflammatory disorders. sFT has been characterized as a possible biomarker for predicting the development of non-alcoholic fatty liver disease [100,101], type 2 diabetes mellitus [102], and obesity [103], and also for envisaging the progression of myalgic encephalomyelitis/chronic fatigue syndrome in COVID-19 patients [104]. Moreover, sFT levels were associated with the development of liver fibrosis in patients with autoimmune hepatitis [105], although these correlations were contradicted by another study published later in the same year [106].…”