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

The DOI matches its Crossref record; 41 of the 43 references it cites were found in a registry or an index.

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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  1. Matsuda, 1997, Relationship between insulin sensitivity in adipose tissue, liver, muscle and components of the insulin resistance syndrome, Diabetes, 46, 68A

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Metadata

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
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
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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