Cited by 390Fibroblast Growth Factor ResearchAdipokines, Inflammation, and Metabolic DiseasesDiabetes, Cardiovascular Risks, and Lipoproteins

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Circulating Fibroblast Growth Factor-21 Is Elevated in Impaired Glucose Tolerance and Type 2 Diabetes and Correlates With Muscle and Hepatic Insulin Resistance

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Chavez, Alberto O., Molina-Carrion, Marjorie, Abdul-Ghani, Muhammad A., Folli, Franco, DeFronzo, Ralph A., Tripathy, Devjit·2009·Diabetes Care

DOI 10.2337/dc09-0684PMC PMC2713625

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Abstract

OBJECTIVE: Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates hepatic glucose production and lipid metabolism in rodents. However, its role in the pathogenesis of type 2 diabetes in humans remains to be defined. The aim of this study was to quantitate circulating plasma FGF-21 levels and examine their relationship with insulin sensitivity in subjects with varying degrees of obesity and glucose tolerance. RESEARCH DESIGN AND METHODS: Forty-one subjects (8 lean with normal glucose tolerance [NGT], 9 obese with NGT, 12 with impaired fasting glucose [IFG]/impaired glucose tolerance [IGT], and 12 type 2 diabetic subjects) received an oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp (80 mU/m2 per min) combined with 3-[3H] glucose infusion. RESULTS: Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT. Plasma FGF-21 levels progressively increased from 3.9 ± 0.3 ng/ml in lean subjects with NGT to 4.9 ± 0.2 in obese subjects with NGT to 5.2 ± 0.2 in subjects with IGT and to 5.3 ± 0.2 in type 2 diabetic subjects. FGF-21 levels correlated inversely with whole-body (primarily reflects muscle) insulin sensitivity (r = −0.421, P = 0.007) and directly with the hepatic insulin resistance index (r = 0.344, P = 0.034). FGF-21 levels also correlated with measures of glycemia (fasting plasma glucose [r = 0.312, P = 0.05], 2-h plasma glucose [r = 0.414, P = 0.01], and A1C [r = 0.325, P = 0.04]). CONCLUSIONS: Plasma FGF-21 levels are increased in insulin-resistant states and correlate with hepatic and whole-body (muscle) insulin resistance. FGF-21 may play a role in pathogenesis of hepatic and whole-body insulin resistance in type 2 diabetes.

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Authors: Chavez, A. O., Molina-Carrion, M., Abdul-Ghani, M. A., Folli, F., DeFronzo, R. A., & Tripathy, D.
Affiliations: From the Division of Diabetes, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
The University of Texas at San Antonio Health Science Center (US)
Corresponding author: Tripathy, Devjit
ORCID: Folli, Franco
DeFronzo, Ralph A.
Tripathy, Devjit
Venue: Diabetes Care
Publisher: American Diabetes Association
Published: 2009-06-01
Volume: 32
Issue: 8
Pages: 1542-1546
ISSN: 0149-5992 (ISSN-L)
1935-5548
DOI: 10.2337/dc09-0684
PMC: PMC2713625
OpenAlex: W2131044927
Cited by: 390
References: 29
Citations by year: 2026: 5 · 2025: 12 · 2024: 24 · 2023: 32 · 2022: 22 · 2021: 30 · 2020: 30 · 2019: 24 · 2018: 30 · 2017: 27 · 2016: 32 · 2015: 33 · 2014: 17 · 2013: 22 · 2012: 18
FWCI: 6.72
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 4475 d)
Locations: Diabetes Care (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: FGF21, type 2 diabetes, impaired glucose tolerance, insulin resistance, hepatic insulin resistance, skeletal muscle insulin sensitivity, obesity, impaired fasting glucose, glycemia, hyperinsulinemic-euglycemic clamp
MeSH terms: Adult, Blood Pressure, Diabetes Mellitus, Type 2, Fibroblast Growth Factors, Glucose Tolerance Test, Humans, Insulin Resistance, Liver, Middle Aged, Obesity, Reference Values, Glucose Clamp Technique, Body Mass Index, Glucose Intolerance, Muscle, Skeletal

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Circulating Fibroblast Growth Factor-21 Is Elevated in Impaired Glucose Tolerance and Type 2 Diabetes and Correlates With Muscle and Hepatic Insulin Resistance

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