The impact of liver fat vs visceral fat in determining categories of prediabetes

Abstract

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.

Effects of a lifestyle intervention in metabolically benign and malign obesity

“…When estimated by the HOMA-IR, insulin resistance at follow-up was close to the cut-off of 2.5 that is associated with clamp-measured insulin resistance [5], indicating that OIR individuals remained essentially insulin resistant despite the intervention. The same trend was noted with regards to body fat distribution and ectopic fat deposition, which is a major determinant of the MHO vs the OIR status [6] and of prediabetes [17]. Certainly, it may well be that a longer duration of our relatively intense intervention may have yielded more positive results for the OIR individuals.…”

Gestational Diabetes and the Metabolic Syndrome

“…Elevated plasma Fetuin-A levels positively predict the incidence of T2DM independent of other established risk factors (Ix et al, 2008;Stefan et al, 2008). In a study of 330 adults at risk for T2DM, liver fat was the strongest predictor of prediabetes (Kantartzis et al, 2010) (Kantartzis et al, 2010). Among studied biochemical measures, serum Fetuin-A was a more significant predictor of fasting hyperglycemia than serum adiponectin (Kantartzis et al, 2010).…”

“…In a study of 330 adults at risk for T2DM, liver fat was the strongest predictor of prediabetes (Kantartzis et al, 2010) (Kantartzis et al, 2010). Among studied biochemical measures, serum Fetuin-A was a more significant predictor of fasting hyperglycemia than serum adiponectin (Kantartzis et al, 2010). In addition, individual liver enzymes, such as alanine aminotransferase, have varying positive associations with the components of the metabolic syndrome (Zhang et al, 2010).…”

Metabolically healthy and unhealthy obesity: differential effects on myocardial function according to metabolic syndrome, rather than obesity

“…Several studies have demonstrated that the quantity of liver fat is more closely linked to the metabolic complications of obesity than that of visceral fat [7][8][9] . However, there is conflicting evidence that suggests excess visceral fat and insulin resistance, but not general adiposity are associated with incident pre-diabetes and type 2 diabetes in obese individuals 10 .…”