Ectopic fat storage in the pancreas, liver, and abdominal fat depots: impact on β-cell function in individuals with impaired glucose metabolism

J Clin Endocrinol Metab. 2011 Feb;96(2):459-67. doi: 10.1210/jc.2010-1722. Epub 2010 Nov 17.

Abstract

Context: Pancreatic fat content (PFC) may have deleterious effects on β-cell function.

Objective: We hypothesized that ectopic fat deposition, in particular pancreatic fat accumulation, is related to β-cell dysfunction in individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT).

Design, setting and participants: This was a cross-sectional study in 64 age- and body mass index-matched individuals, with normal glucose tolerance (NGT; n = 16, 60% males), IFG (n = 29, 52% males), or IFG/IGT (n = 19, 63% males) was conducted.

Intervention and main outcome measures: Participants underwent the following: 1) a combined hyperinsulinemic-euglycemic and hyperglycemic clamp, with subsequent arginine stimulation to quantify insulin sensitivity and β-cell function; 2) proton-magnetic resonance spectroscopy to assess PFC and liver fat content (LFC); and 3) magnetic resonance imaging to quantify visceral (VAT) and sc (SAT) adipose tissue. The disposition index (DI; insulin sensitivity adjusted β-cell function) was assessed.

Results: IFG and IFG/IGT were more insulin resistant (P < 0.001) compared with NGT. Individuals with IFG/IGT had the lowest values of glucose- and arginine-stimulated C-peptide secretion (both P < 0.03) and DI (P < 0.001), relative to IFG and NGT. PFC and LFC gradually increased between NGT, IFG, and IFG/IGT (P = 0.02 and P = 0.01, respectively), whereas VAT and SAT were similar between groups. No direct associations were found between PFC, LFC, VAT, and SAT and C-peptide secretion. The DI was inversely correlated with PFC, LFC, and VAT (all P < 0.05).

Conclusions: PFC was increased in individuals with IFG and/or IGT, without a direct relation with β-cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat / metabolism*
  • Abdominal Fat / pathology
  • Aged
  • Blood Glucose / metabolism
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Fasting / metabolism
  • Fats / metabolism*
  • Female
  • Glucose Clamp Technique
  • Glucose Intolerance / metabolism*
  • Glucose Intolerance / pathology
  • Humans
  • Insulin Resistance / physiology
  • Insulin-Secreting Cells / physiology*
  • Liver / metabolism*
  • Liver / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Overweight / metabolism
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Pancreatic Function Tests
  • Prediabetic State / metabolism
  • Subcutaneous Fat / metabolism

Substances

  • Blood Glucose
  • Fats