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This Article Accepted manuscript (PDF) All Versions of this Article: EJE-08-0424v1 159/3/251    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tushuizen, M. Articles by Diamant, M. PubMed PubMed Citation Articles by Tushuizen, M. Articles by Diamant, M.

Lack of Association of Liver Fat with Model Parameters of Beta-Cell Function in Men with Impaired Glucose Tolerance and Type 2 Diabetes

M Tushuizen, Department of Endocrinology / Diabetes Centre, VU University Medical Centre, Amsterdam, Netherlands
M Bunck, Department of Endocrinology / Diabetes Center, VU University Medical Center, Amsterdam, Netherlands
P Pouwels, Department of Physics & Medical Technology, VU University Medical Centre, Amsterdam, Netherlands
S Bontemps, Department of Endocrinology / Diabetes Centre, VU University Medical Centre, Amsterdam, Netherlands
A Mari, National Research Council, Institute of Biomedical Engineering, Padova, Italy
M Diamant, Endocrinology, VU University Medical Center, Amsterdam, Netherlands

Correspondence: Maarten Tushuizen, Email: m.tushuizen{at}vumc.nl

Abstract

Objective: Hepatic steatosis and obesity are components of the metabolic syndrome and risk factors for developing type 2 diabetes (T2DM). We studied how liver fat and body fat distribution relate to various aspects of β-cell function.

Methods: In 12 men with T2DM, 10 men with impaired glucose tolerance (IGT) and 14 age- and BMI-matched controls, we measured body fat distribution and liver fat by magnetic resonance imaging and spectroscopy. An oral glucose tolerance test was performed to calculate insulin secretory rate (ISR) by C-peptide deconvolution, and β-cell function, using a mathematical model that describes ISR as a function of absolute glucose levels (insulin secretory tone and glucose sensitivity), the glucose rate of change (rate sensitivity), and a potentiation factor.

Results: Waist circumference and the various body fat compartments did not differ among groups. IGT had the highest total and late phase insulin secretion (P<0.001), whereas patients had the lowest insulinogenic index adjusted for insulin resistance (P=0.006). In spite of the hypersecretion, IGT had β-cell glucose sensitivity, rate sensitivity and potentiation similar to controls. Liver fat content was highest in diabetic patients (P=0.004) and showed the strongest association with total and late phase of insulin secretion in the IGT group (r=0.657; P=0.039 and r=0.732; P=0.016, respectively). Model β-cell function variables showed no association with liver fat or body fat compartments.

Conclusions: These data suggest that, in spite of the association of central adiposity and liver fat with T2DM risk, additional, hitherto unknown factors may contribute to β-cell dysfunction in susceptible humans.