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/m(2)) and 43 T2DM (24 nonobese, BMI = 26 +/- 1; 19 obese, BMI = 32 1 kg/m(2)) subjects, we measured endogenous (hepatic) glucose production (3-H-3-glucose) and GNG ((H2O)-H-2) in the basal state and during 240 pmol/m(2)/min euglycemic-hyperinsulinemic clamp, and liver (1,17) 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 mu mol/min/kg(ffm); P =.02) and basal GNG flux (NGT, 8.6 +/- 0.4; lean T2DM, 9.6 +/- 0.4; obese T2DM, 11.1 +/- 0.6 mu mol/min/kg(ffm); P= .02). Basal hepatic IR index (EGP X 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.
|Autori:||Gastaldelli A; Cusi K; Pettiti M; Hardies J; Miyazaki Y; Berria R; Buzzigoli E; Sironi AM; Cersosimo E; Ferrannini E; Defronzo RA|
|Titolo:||Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects|
|Anno del prodotto:||2007|
|Digital Object Identifier (DOI):||10.1053/j.gastro.2007.04.068|
|Appare nelle tipologie:||1.1 Articolo in rivista|