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.

Keywords: Fatty liver; Ferritin; Insulin secretion in vivo; Insulin sensitivity.

Figure 1

Glucose (A) and insulin (B) values during the oral glucose tolerance test for control (solid circle, solid line: n=15) and NAFLD (open square, dash line: n=13) subjects. Fasting, 20, 30 and 60 minutes glucose values were higher in the NAFLD subjects compared to the controls. Fasting and 90 minute insulin values were higher in the NAFLD subjects. *p<0.05 by independent t-test

Figure 2

Glucose (A), insulin (B), free fatty acid levels (C) and whole body insulin sensitivity (M/I) (D) during the clamp (controls: solid circle, solid line; NAFLD: open square, dashed line). Both glucose (A) and insulin (B) levels achieved steady state and did not differ during the low and high dose clamp. Fasting free fatty acid levels (C) tended to be higher in NAFLD (p=0.06 by independent t-test) but the rate of fall and % suppression during the low dose clamp was similar between controls and NAFLD. Insulin sensitivity (D) was significantly lower in the NAFLD group compared to controls during both low and high dose insulin clamps (p<0.05 for both). M = the glucose infusion rate in mmol/minute adjusted for lean body mass.

Figure 3

Correlations between iron and liver fat measured by the liver/spleen ratio (A and B) and between iron and β-cell function as measured by the oral disposition index (C and D): controls (solid circle) and NAFLD (open square). There was a significant correlation between liver fat and (A) ln(ferritin) (r=0.59, p<0.001) and (B) iron saturation (r=0.45, p=0.01). There was a significant correlation between the ln(oral disposition index) and (C) ln(ferritin) (r=0.62, p=0.001), but not (D) iron saturation.