Aims/hypothesis: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are risk factors for type 2 diabetes and cardiovascular disease; however, their impact on these endpoints differs. Because liver fat and visceral fat are important determinants of glucose and lipid metabolism, we investigated whether these fat compartments and their humoral products, the adipokine adiponectin and the hepatokine fetuin-A, differ in their impact on the glucose categories.
Methods: In 330 individuals at risk of type 2 diabetes, glucose tolerance status was determined by a 2 h 75 g OGTT. Total-body and visceral fat were precisely quantified by magnetic resonance (MR) tomography and liver fat by (1)H-MR spectroscopy.
Results: A total of 210 individuals had normal glucose tolerance (NGT), 41 isolated IFG, 43 isolated IGT and 36 IFG+IGT. Total-body fat was not different (p = 0.51), although a small but continuous increase in visceral fat was found among the categories after adjustment for age and sex (NGT: 3.07 +/- 0.10 kg; IFG: 3.11 +/- 0.21 kg; IGT: 3.61 +/- 0.21 kg; IFG+IGT: 3.84 +/- 0.23 kg [SEs], p = 0.03). A larger difference was found for liver fat (NGT: 4.73 +/- 0.42%; IFG: 5.86 +/- 0.92%; IGT: 8.65 +/- 0.92%; IFG + IGT: 11.11 +/- 1.01%, p < 0.0001). The differences among the categories were small for adiponectin (p = 0.14), but larger for fetuin-A (p = 0.015). Among fat compartments, liver fat (p < 0.0001) and among circulating variables fetuin-A (p = 0.016) were the strongest determinants of the categories.
Conclusions/interpretation: Liver fat, more than visceral fat, strongly increases when glycaemia and glucose tolerance move from NGT to isolated IFG, isolated IGT and IFG+IGT. Because liver-derived circulating fetuin-A determines, although weakly, prediabetes categories, it is worth searching for hepatokines more strongly predicting prediabetes.