Liver fat accumulation is associated with increased insulin secretion independent of total, visceral, and pancreatic fat.

Abstract

Studies in heterogenous groups of people with respect to sex, body mass index (BMI), and glycemic status (normoglycemia, impaired glucose tolerance, diabetes), indicate no relationship between liver fat accumulation and pancreatic insulin secretion. To better understand the association of liver fat with insulin secretion. Cross-sectional analysis of 61 men with abdominal obesity who had high liver fat (HLF, ≥5.6% by magnetic resonance spectroscopy, n=28) or low liver fat (LLF, n=33), but were balanced on BMI, total body fat, visceral adipose tissue (VAT), and pancreatic fat. A frequently sampled 5-hour oral glucose tolerance test with 11 samples, in conjunction with mathematical modeling, was used to compute indices of insulin sensitivity and insulin secretion (oral minimal model). Compared to subjects with LLF, those with HLF had significantly greater fasting glucose, insulin, C-peptide, and triglyceride; lower high-density lipoprotein-cholesterol; but similar glycated hemoglobin. Areas under the 5-hour curve for glucose, insulin, and C-peptide were greater in the HLF group than the LLF group (by ∼10%, ∼38%, and ∼28%, respectively); fasting and total postprandial insulin secretion rates were ∼37% and ∼50% greater, respectively (all P<0.05); whereas the insulinogenic index was not different. HLF subjects had lower whole-body and hepatic insulin sensitivity, disposition index, and total insulin clearance than LLF subjects (all P<0.05). Accumulation of liver fat is associated with increased insulin secretion independently of total adiposity, abdominal fat distribution, and pancreatic fat. Thereby, hyperinsulinemia in fatty liver disease is partly because of insulin hypersecretion and partly because of impaired insulin clearance.