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

Amalia Gastaldelli, Kenneth Cusi, Maura Pettiti, Jean Hardies, Yoshinori Miyazaki, Rachele Berria, Emma Buzzigoli, Anna Maria Sironi, Eugenio Cersosimo, Ele Ferrannini, Ralph A Defronzo

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)496-506
Number of pages11
JournalGastroenterology
Volume133
Issue number2
DOIs
StatePublished - Aug 2007

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Intra-Abdominal Fat
Insulin Resistance
Glucose
Liver
Gluconeogenesis
Insulin
Body Mass Index
montirelin
Fasting
Glucose Clamp Technique
Adiposity
Type 2 Diabetes Mellitus
Magnetic Resonance Spectroscopy
Obesity

ASJC Scopus subject areas

  • Gastroenterology

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Relationship Between Hepatic/Visceral Fat and Hepatic Insulin Resistance in Nondiabetic and Type 2 Diabetic Subjects. / Gastaldelli, Amalia; Cusi, Kenneth; Pettiti, Maura; Hardies, Jean; Miyazaki, Yoshinori; Berria, Rachele; Buzzigoli, Emma; Sironi, Anna Maria; Cersosimo, Eugenio; Ferrannini, Ele; Defronzo, Ralph A.

In: Gastroenterology, Vol. 133, No. 2, 08.2007, p. 496-506.

Research output: Contribution to journalArticle

Gastaldelli, A, Cusi, K, Pettiti, M, Hardies, J, Miyazaki, Y, Berria, R, Buzzigoli, E, Sironi, AM, Cersosimo, E, Ferrannini, E & Defronzo, RA 2007, 'Relationship Between Hepatic/Visceral Fat and Hepatic Insulin Resistance in Nondiabetic and Type 2 Diabetic Subjects', Gastroenterology, vol. 133, no. 2, pp. 496-506. https://doi.org/10.1053/j.gastro.2007.04.068
Gastaldelli, Amalia ; Cusi, Kenneth ; Pettiti, Maura ; Hardies, Jean ; Miyazaki, Yoshinori ; Berria, Rachele ; Buzzigoli, Emma ; Sironi, Anna Maria ; Cersosimo, Eugenio ; Ferrannini, Ele ; Defronzo, Ralph A. / Relationship Between Hepatic/Visceral Fat and Hepatic Insulin Resistance in Nondiabetic and Type 2 Diabetic Subjects. In: Gastroenterology. 2007 ; Vol. 133, No. 2. pp. 496-506.
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abstract = "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.",
author = "Amalia Gastaldelli and Kenneth Cusi and Maura Pettiti and Jean Hardies and Yoshinori Miyazaki and Rachele Berria and Emma Buzzigoli and Sironi, {Anna Maria} and Eugenio Cersosimo and Ele Ferrannini and Defronzo, {Ralph A}",
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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

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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