Relationship Between Hepatic/Visceral Fat and Hepatic Insulin Resistance in Nondiabetic and Type 2 Diabetic Subjects

Background & Aims: Abdominal fat accumulation (visceral/hepatic) has been associated with hepatic insulin resistance (IR) in obesity and type 2 diabetes (T2DM). We examined the relationship between visceral/hepatic fat accumulation and hepatic IR/accelerated gluconeogenesis (GNG). Methods: In 14 normal glucose tolerant (NGT) (body mass index [BMI] = 25 ± 1 kg/m2 ) and 43 T2DM (24 nonobese, BMI = 26 ± 1; 19 obese, BMI = 32 ± 1 kg/m2 ) subjects, we measured endogenous (hepatic) glucose production (3-3 H-glucose) and GNG (2 H2 O) in the basal state and during 240 pmol/m2 /min euglycemic-hyperinsulinemic clamp, and liver (LF) subcutaneous (SAT)/visceral (VAT) fat content by magnetic resonance spectroscopy/magnetic resonance imaging. Results: LF was increased in lean T2DM compared with lean NGT (18% ± 3% vs 9% ± 2%, P < .03), but was similar in lean T2DM and obese T2DM (18% ± 3% vs 22% ± 3%; P = NS). Both VAT and SAT increased progressively from lean NGT to lean T2DM to obese T2DM. T2DM had increased basal endogenous glucose production (EGP) (NGT, 15.1 ± 0.5; lean T2DM, 16.3 ± 0.4; obese T2DM, 17.2 ± 0.6 μmol/min/kgffm ; P = .02) and basal GNG flux (NGT, 8.6 ± 0.4; lean T2DM, 9.6 ± 0.4; obese T2DM, 11.1 ± 0.6 μmol/min/kgffm ; P = .02). Basal hepatic IR index (EGP × fasting plasma insulin) was increased in T2DM (NGT, 816 ± 54; lean T2DM, 1252 ± 164; obese T2DM, 1810 ± 210; P = .007). In T2DM, after accounting for age, sex, and BMI, both LF and VAT, but not SAT, were correlated significantly ( P < .05) with basal hepatic IR and residual EGP during insulin clamp. Basal percentage of GNG and GNG flux were correlated positively with VAT ( P < .05), but not with LF. LF, but not VAT, was correlated with fasting insulin, insulin-stimulated glucose disposal, and impaired FFA suppression by insulin (all P < .05). Conclusions: Abdominal adiposity significantly affects both lipid (FFA) and glucose metabolism. Excess VAT primarily increases GNG flux. Both VAT and LF are associated with hepatic IR.