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Lehn-Stefan, A. ; Peter, A. ; Machann, J. ; Schick, F. ; Randrianarisoa, E. ; Heni, M. ; Wagner, R. ; Birkenfeld, A.L. ; Fritsche, A. ; Häring, H.-U. ; Staiger, H. ; Stefan, N.

Elevated circulating glutamate associates with subclinical atherosclerosis independently of established risk markers: A cross-sectional study.

J. Clin. Endocrinol. Metab. 106, e982-e989 (2021)
Postprint DOI PMC
Open Access Green
OBJECTIVE: Elevated plasma glutamate levels associate with an increased risk of cardiovascular disease (CVD). Because plasma glutamate levels also strongly associate with visceral adiposity, NAFLD, insulin resistance and high circulating levels of branched-chain amino acids (BCAA), it is unknown to what extent elevated circulating glutamate is an independent marker of an increased risk of atherosclerosis. METHODS: Plasma levels of glutamate and BCAA were measured in 102 subjects who were precisely phenotyped for body fat mass and distribution (MR tomography), liver fat content ( 1H-MR spectroscopy), insulin sensitivity [oral glucose tolerance test and hyperinsulinemic, euglycemic clamp (N=57)] and carotid intima-media thickness (cIMT). RESULTS: Plasma glutamate levels, adjusted for age, sex, body fat mass and visceral fat mass, correlated positively with liver fat content and cIMT (all std.-ß≥0.22, all p≤0.023) and negatively with insulin sensitivity (std.-ß≤-0.31, p≤0.0019). Glutamate levels also associated with cIMT, independently of additional adjustment for liver fat content, insulin sensitivity and BCAA levels (std.-ß≥0.24, p≤0.021). Furthermore, an independent positive association of glutamate and IL-6 levels was observed (N=50; std. ß=0.39, p=0.028). While glutamate, adjusted for age, sex, body fat mass and visceral fat mass, also correlated positively with cIMT in this subgroup (std. ß=0.31, p=0.019), after additional adjustment for the parameters liver fat content, insulin sensitivity, BCAA or IL-6 levels, adjustment for IL-6 most strongly attenuated this relationship (std. ß=0.28, p=0.05). CONCLUSIONS: Elevated plasma glutamate levels are associated with increased cIMT, independently of established CVD risk factors and this relationship may in part be explained by IL-6-associated subclinical inflammation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Carotid Intima-media Thickness ; Endothelial Cells ; Insulin Resistance ; Non-alcoholic Fatty Liver Disease ; Plasma Glutamate ; Visceral Obesity
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Zeitschrift Journal of Clinical Endocrinology & Metabolism, The
Quellenangaben Band: 106, Heft: 2, Seiten: e982-e989 Artikelnummer: , Supplement: ,
Verlag Endocrine Society
Verlagsort Bethesda, Md.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen Heisenberg professorship from the Deutsche Forschungsgemeinschaft
EIT Health
German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD eV)