Kristina M Utzschneider1, Anna Largajolli2, Alessandra Bertoldo2, Santica Marcovina3, James E Nelson4, Matthew M Yeh5, Kris V Kowdley6, Steven E Kahn7. 1. VA Puget Sound Health Care System, Department of Medicine, Division of Endocrinology and Metabolism, Seattle, WA; University of Washington, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, Seattle, WA. Electronic address: kutzschn@u.washington.edu. 2. University of Padua, Padua, Italy. 3. Department of Medicine, University of Washington and the Northwest Lipid Metabolism and Diabetes Research Laboratory, Seattle, WA. 4. Digestive Disease Institute, Virginia Mason Medical Center and Benaroya Research Institute, Seattle, WA. 5. University of Washington, Department of Pathology, Seattle, WA. 6. Digestive Disease Institute, Virginia Mason Medical Center and Benaroya Research Institute, Seattle, WA; University of Washington, Department of Medicine, Division of Gastroenterology/Hepatology, Seattle, WA. 7. VA Puget Sound Health Care System, Department of Medicine, Division of Endocrinology and Metabolism, Seattle, WA; University of Washington, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, Seattle, WA.
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
Entities:
Keywords:
Fatty liver; Ferritin; Insulin secretion in vivo; Insulin sensitivity
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