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Serum Fibroblast Growth Factor 21 Is Associated with Adverse Lipid Profiles and -Glutamyltransferase But Not Insulin Sensitivity in Chinese Subjects

Department of Endocrinology and Metabolism (H.Li., Y.B., X.P., J.L., H.W., H.Lu., K.X., W.J.), Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai 200233, China; Department of Medicine (H.Li.), Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; and Department of Medicine and Department of Pharmacology (A.X.), Research Centre of Heart, Brain, Hormone, and Healthy Aging (A.X.), University of Hong Kong, Hong Kong 999077, China

Address all correspondence and requests for reprints to: Weiping Jia, M.D., Ph.D., Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China. E-mail: wpjia{at}sjtu.edu.cn.

Objective: Fibroblast growth factor (FGF) 21, a hormone primarily secreted by liver, has recently been shown to have beneficial effects on glucose and lipid metabolism and insulin sensitivity in animal models. This study investigated the association of serum FGF21 levels with insulin secretion and sensitivity, as well as circulating parameters of lipid metabolism and hepatic enzymes in Chinese subjects.

Design: Serum FGF21 levels were determined by ELISA in 134 normal glucose tolerance (NGT), 101 isolated-impaired fasting glucose, and 118 isolated-impaired glucose tolerance (I-IGT) Chinese subjects, and their association with parameters of adiposity, glucose, and lipid profiles, and levels of liver injury markers was studied. In a subgroup of this study, the hyperglycemic clamp technique was performed in 31 NGT, 17 isolated-impaired fasting glucose, and 15 I-IGT subjects to measure insulin secretion and sensitivity to test the associations with serum FGF21.

Results: The serum FGF21 levels in I-IGT were significantly higher than NGT subjects [164.6 pg/ml (89.7, 261.0) vs. 111.8 pg/ml (58.0, 198.9); P < 0.05], and correlated positively with several parameters of adiposity. Multiple stepwise regression analysis showed an independent association of serum FGF21 with serum triglycerides, total cholesterol, and -glutamyltransferase (all P < 0.05). However, FGF21 did not correlate with insulin secretion and sensitivity, as measured by hyperglycemic clamp and a 75-g oral glucose tolerance test.

Conclusions: Serum levels of FGF21 are closely related to adiposity, lipid metabolism, and biomarkers of liver injury but not insulin secretion and sensitivity in humans.

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