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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.