TY - JOUR
T1 - Relationship Between Hepatic/Visceral Fat and Hepatic Insulin Resistance in Nondiabetic and Type 2 Diabetic Subjects
AU - Gastaldelli, Amalia
AU - Cusi, Kenneth
AU - Pettiti, Maura
AU - Hardies, Jean
AU - Miyazaki, Yoshinori
AU - Berria, Rachele
AU - Buzzigoli, Emma
AU - Sironi, Anna Maria
AU - Cersosimo, Eugenio
AU - Ferrannini, Ele
AU - DeFronzo, Ralph A.
N1 - Funding Information:
Supported by a National Institutes of Health grant (DK-24092), a General Clinical Research Center grant (M01-RR-01346), a Veterans Administration Merit Award, and funds from the Veterans Administration Medical Research Service.
PY - 2007/8
Y1 - 2007/8
N2 - 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 (3-3H-glucose) and GNG (2H2O) 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.
AB - 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 (3-3H-glucose) and GNG (2H2O) 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.
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U2 - 10.1053/j.gastro.2007.04.068
DO - 10.1053/j.gastro.2007.04.068
M3 - Article
C2 - 17681171
AN - SCOPUS:34547514221
SN - 0016-5085
VL - 133
SP - 496
EP - 506
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -