Serum ferritin is associated with non-alcoholic fatty liver disease and decreased Β-cell function in non-diabetic men and women

Abstract

Aims We sought to determine whether NAFLD is associated with poorer β-cell function and if any β-cell dysfunction is associated with abnormal markers of iron or inflammation. Methods This was a cross-sectional study of 15 non-diabetic adults with NAFLD and 15 non-diabetic age and BMI-matched controls. Insulin sensitivity was measured by isotope-labeled hyperinsulinemic-euglycemic clamps and β-cell function by both oral (OGTT) and intravenous glucose tolerance tests. Liver and abdominal fat composition was evaluated by CT scan. Fasting serum levels of ferritin, transferrin-iron saturation, IL-6, TNFα and hsCRP were measured. Results Compared to controls, subjects with NAFLD had lower hepatic and systemic insulin sensitivity and β-cell function was decreased as measured by the oral disposition index. Fasting serum ferritin and transferrin-iron saturation were higher in NAFLD and were positively associated with liver fat. Serum ferritin was negatively associated with β-cell function measured by both oral and intravenous tests, but was not associated with insulin sensitivity. IL-6, TNFα and hsCRP did not differ between groups and did not correlate with serum ferritin, liver fat or measures of β-cell function. Conclusions These findings support a potential pathophysiological link between iron metabolism, liver fat and diabetes risk.

The effect of alpha-lipoic acid on inflammatory markers and body composition in obese patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial

“…Ferritin has been found to be increased in NAFLD, which may reflect the inflammation within the steatotic liver contributing to insulin resistance . Nevertheless, there is limited evidence of the effect of ALA supplementation on serum ferritin levels.…”

“…Moreover, serum levels of ferritin—an acute‐phase protein—has been suggested as an independent biomarker for advanced fibrosis and may be a beneficial adjunctive biomarker for assessment of patients with NAFLD . Hyperferritinemia observed in NAFLD may be associated with increased inflammation and hepatic fat deposition …”

“…13 Hyperferritinemia observed in NAFLD may be associated with increased inflammation and hepatic fat deposition. 14 A number of studies have pointed out the importance of adipose tissue and its secreted adipokines in pathogenesis of metabolic and inflammatory-related diseases such as NAFLD. 15 One of the most abundant adipose tissue-specific adipocytokines, adiponectin, has been shown to not only have inflammatory effects by reducing production of inflammatory mediators, but also prevent lipid accumulation in the liver by increasing β-oxidation and decreasing free fat synthesis in hepatocytes.…”

Hyperferritinemia in Nonalcoholic Fatty Liver Disease: Iron Accumulation or Inflammation?

“…A wide range of indirect and direct inflammatory parameters were found to be significantly higher in NAFLD or NASH patients when compared with control subjects (e.g., aspartate aminotransferase, thioredoxin, C-reactive protein, α-2-macroglobulin, ceruloplasmin, malondialdehyde, hepatic 8-oxodG, nitric oxide, interleukin-6, interleukin-8, and tumor necrosis factor-α). Most studies also found ferritin levels to be significantly higher in NASH patients compared with control subjects and/or patients with HS and NAFLD patients compared with control subjects 27,36,37,42,[45][46][47][48][49] (►Supplementary Table S2 [online only]). Most of the studies showed no signs of biochemical or histological iron overload to explain the higher ferritin levels.…”

Serum ferritin levels predict histological severity in patients with nonalcoholic fatty liver disease in India

“…Univariate analyses showed lower hemoglobin, higher Fibroscan values, and greater fibrosis in patients with serum ferritin levels ≥48 ng/mL. [4] showed that fasting serum ferritin and transferrin iron saturation were higher in NAFLD and were positively associated with liver fat. Polyzos et al [5] concluded that serum ferritin, ferritin/adiponectin ratio, and ferritin by homeostatic model assessment Insulin resistance (HOMA-IR) product escalade from controls to NAFL and NASH patients and ferritin/ adiponectin ratio and ferritin by HOMA-IR product may be promising in noninvasive assessment of portal inflammation in NAFLD.…”