Lack of association of liver fat with model parameters of beta-cell function in men with impaired glucose tolerance and type 2 diabetes.
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 beta-cell function.


METHODS
In 12 men with T2DM, 10 men with impaired glucose tolerance (IGT), and 14 age- and body mass index-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 beta-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 beta-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 beta-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 beta-cell dysfunction in susceptible humans.
Tushuizen
Maarten E
ME
Department of Endocrinology/Diabetes Centre, Institute of Biomedical Engineering, National Research Council, I-35127, Padova, Italy.
Bunck
Mathijs C
MC
Pouwels
Petra J W
PJ
Bontemps
Saskia
S
Mari
Andrea
A
Diamant
Michaela
M
D000273:Adipose Tissue / Q000473:pathology*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology* / Q000503:physiopathology; D018149:Glucose Intolerance / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008962:Models, Theoretical