Plasma Fibroblast Growth Factor 21 Is Associated With Severity of Nonalcoholic Steatohepatitis in Patients With Obesity and Type 2 Diabetes.
Adipose Tissue
/ metabolism
Adult
Aged
Body Mass Index
Cross-Sectional Studies
Diabetes Mellitus, Type 2
/ blood
Fasting
/ blood
Female
Fibroblast Growth Factors
/ blood
Glucose Clamp Technique
Glycated Hemoglobin
/ metabolism
Humans
Insulin
/ metabolism
Insulin Resistance
Liver
/ metabolism
Male
Middle Aged
Non-alcoholic Fatty Liver Disease
/ blood
Obesity
/ blood
Severity of Illness Index
Triglycerides
/ blood
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
07
11
2018
accepted:
04
03
2019
pubmed:
9
3
2019
medline:
26
5
2020
entrez:
9
3
2019
Statut:
ppublish
Résumé
The relationship between plasma fibroblast growth factor 21 (FGF21), insulin resistance, and steatohepatitis has not been systematically assessed. To determine if higher plasma FGF21 is associated with worse steatohepatitis on liver biopsy in patients with nonalcoholic fatty liver disease (NAFLD). Cross-sectional study in a university hospital. Patients with a body mass index >25 (n = 187) underwent: (i) euglycemic hyperinsulinemic clamp to assess tissue-specific insulin resistance (IR); (ii) liver magnetic resonance spectroscopy for intrahepatic triglyceride quantification, (iii) liver biopsy (if NAFLD present; n = 146); and (iv) fasting plasma FGF21 levels. Patients were divided into three groups: (i) No NAFLD (n = 41); (ii) No nonalcoholic steatohepatitis (NASH) (patients with isolated steatosis or borderline NASH; n = 52); and (iii) NASH (patients with definite NASH; n = 94). Groups were well-matched for age/sex, prevalence of type 2 diabetes mellitus, and hemoglobin A1c. During euglycemic hyperinsulinemic insulin clamp, insulin sensitivity in skeletal muscle and adipose tissue worsened from No NAFLD to NASH (both P < 0.001). Plasma FGF21 levels correlated inversely with insulin sensitivity in adipose tissue (r = -0.17, P = 0.006) and skeletal muscle (r = -0.23, P = 0.007), but not with liver insulin sensitivity. Plasma FGF21 was higher in patients with NASH (453 ± 262 pg/mL) when compared with the No NASH (341 ± 198 pg/mL, P = 0.03) or No NAFLD (325 ± 289 pg/mL, P = 0.02) groups. Plasma FGF21 increased with the severity of necroinflammation (P = 0.02), and most significantly with worse fibrosis (P < 0.001), but not with worsening steatosis (P = 0.60). Plasma FGF21 correlates with severity of steatohepatitis, in particular of fibrosis, in patients with NASH. Measurement of FGF21 may help identify patients at the highest risk of disease progression.
Identifiants
pubmed: 30848827
pii: 5371245
doi: 10.1210/jc.2018-02414
pmc: PMC7453039
doi:
Substances chimiques
Glycated Hemoglobin A
0
Insulin
0
Triglycerides
0
fibroblast growth factor 21
0
Fibroblast Growth Factors
62031-54-3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3327-3336Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK079626
Pays : United States
Organisme : NIH HHS
ID : S10 OD021726
Pays : United States
Informations de copyright
Copyright © 2019 Endocrine Society.
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