Cited by 629Liver Disease Diagnosis and TreatmentDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

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

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Gastaldelli, Amalia, Cusi, Kenneth, Pettiti, Maura, Hardies, Jean, Miyazaki, Yoshinori, Berria, Rachele, Buzzigoli, Emma, Sironi, Anna Maria, Cersosimo, Eugenio, Ferrannini, Ele, DeFronzo, Ralph A.·2007·Gastroenterology

DOI 10.1053/j.gastro.2007.04.068

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Abstract

Background and 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-(3)H-glucose) and GNG ((2)H(2)O) in the basal state and during 240 pmol/m(2)/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 micromol/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 micromol/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.

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Authors: Gastaldelli, A., Cusi, K., Pettiti, M., Hardies, J., Miyazaki, Y., Berria, R., Buzzigoli, E., Sironi, A. M., Cersosimo, E., Ferrannini, E., & DeFronzo, R. A.
Affiliations: The University of Texas at San Antonio Health Science Center (US)
Istituto di Fisiologia Clinica (IT)
University of Pisa (IT)
Corresponding author: Gastaldelli, Amalia
ORCID: Gastaldelli, Amalia
Cusi, Kenneth
Sironi, Anna Maria
Ferrannini, Ele
DeFronzo, Ralph A.
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2007-08
Volume: 133
Issue: 2
Pages: 496-506
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2007.04.068
OpenAlex: W2136226749
Cited by: 629
References: 43
Citations by year: 2026: 25 · 2025: 25 · 2024: 33 · 2023: 40 · 2022: 40 · 2021: 40 · 2020: 27 · 2019: 41 · 2018: 36 · 2017: 47 · 2016: 34 · 2015: 26 · 2014: 39 · 2013: 37 · 2012: 33
FWCI: 16.58
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (DK 24092)
National Center for Research Resources (M01RR01346, M01RR001346)
Topics: Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Keywords: hepatic insulin resistance, visceral fat, liver fat, abdominal fat accumulation, type 2 diabetes, obesity, hepatic glucose production, gluconeogenesis, hepatic steatosis, hyperinsulinemic-euglycemic clamp, subcutaneous adipose tissue, hepatic lipid accumulation, hepatic lipogenesis, hepatic lipolysis
MeSH terms: Adult, Aging, Blood Glucose, Diabetes Mellitus, Type 2, Female, Gluconeogenesis, Humans, Insulin, Insulin Resistance, Liver, Magnetic Resonance Imaging, Male, Middle Aged, Magnetic Resonance Spectroscopy, Obesity, Glucose Clamp Technique, Body Mass Index, Abdominal Fat, Glycogenolysis, Lipid Metabolism

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

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