Ectopic Fat Storage in the Pancreas, Liver, and Abdominal Fat Depots: Impact on {beta}-Cell Function in Individuals with Impaired Glucose Metabolism.

N.J. van der Zijl, G.H. Goossens, C.C. Moors, D.H. van Raalte, M.H. Muskiet, P.J. Pouwels, E.E. Blaak, M. Diamant

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Context: Pancreatic fat content (PFC) may have deleterious effects on beta-cell function. Objective: We hypothesized that ectopic fat deposition, in particular pancreatic fat accumulation, is related to beta-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 beta-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 beta-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 beta-cell function.
Original languageEnglish
Pages (from-to)459-467
Number of pages9
JournalJournal of Clinical Endocrinology & Metabolism
Volume96
Issue number2
DOIs
Publication statusPublished - Feb 2011

Keywords

  • DEPENDENT DIABETES-MELLITUS
  • INSULIN-SECRETION
  • MAGNETIC-RESONANCE
  • ADIPOSE-TISSUE
  • OBESITY
  • LIPOTOXICITY
  • HUMANS
  • ACIDS
  • DYSFUNCTION
  • RESISTANCE

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