Pancreatic fat is negatively associated with insulin secretion in individuals with impaired fasting glucose and/or impaired glucose tolerance: a nuclear magnetic resonance study

Abstract

The pathogenesis of type 2 diabetes is characterized by insulin resistance and beta-cell dysfunction. Pancreatic fat load may add to the development of beta-cell dysfunction. The aim was to thoroughly quantify the fat content of pancreas sections (caput, corpus, and cauda) and to compare the impact of pancreatic, intrahepatic, and visceral fat on insulin secretion in humans. Fifty-one subjects were subjected to an oral glucose tolerance test (OGTT) with glucose, insulin, and C-peptide measurements [28 subjects displayed normal glucose tolerance, 23 impaired fasting glycemia (IFG)] and/or impaired glucose tolerance (IGT)], and also to whole-body magnetic resonance imaging (MRI), pancreas MRI, and liver magnetic resonance spectroscopy (MRS). After adjustment for gender and age, the mean pancreatic fat content was positively associated with body mass index (BMI), visceral adipose tissue (VAT), and waist circumference (all p < or = 0.0013). The mean pancreatic fat content was negatively associated with OGTT-based measures of insulin secretion (all p < or = 0.03). Analysis of the subgroups of glucose tolerance showed that this was restricted to subjects with IGT and/or IFG. Visceral fat also represented a determinant of beta-cell function in individuals with IGT and/or IFG (all p < or = 0.02), whereas intrahepatic fat did not. In a stepwise multivariate regression analysis, pancreatic fat turned out to be a stronger determinant of impaired insulin secretion than visceral fat. Pancreatic fat is negatively associated with insulin secretion in subjects with IGT/IFG and, therefore, might represent an additional pathogenetic factor leading to beta-cell dysfunction.