Serum Fibroblast Growth Factor 19 Levels Are Decreased in Chinese Subjects With Impaired Fasting Glucose and Inversely Associated With Fasting Plasma Glucose Levels

Abstract

OBJECTIVEFibroblast growth factor 19 (FGF19), a hormone secreted from the small intestine, has recently been shown to stimulate glycogen synthesis and inhibit gluconeogenesis through insulin-independent pathways. This study investigated the change of FGF19 in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM) and explored the association of serum FGF19 levels with parameters of glucose metabolism in Chinese subjects.RESEARCH DESIGN AND METHODSFasting serum FGF19 levels were determined by ELISA in 81 normal glucose tolerance (NGT), 91 impaired fasting glucose (IFG), 93 impaired glucose tolerance (IGT), and 104 newly diagnosed T2DM subjects, and their association with parameters of glucose metabolism was studied. An ordinal logistic regression analysis was performed in subjects with NGT, IFG, and T2DM. Serum FGF19 levels at 2 h after a 75-g oral glucose tolerance test in the different glucose tolerance categories were studied in a subgroup.RESULTSFasting serum FGF19 levels in subjects with IFG (210 pg/mL [142–327]) (median [interquartile range]) and T2DM (196 pg/mL [137–280]) were significantly lower than those in NGT subjects (289 pg/mL [224–393]) (both P < 0.001). However, no significant difference in fasting FGF19 levels was observed between IGT (246 pg/mL [138–379]) and NGT subjects. Fasting serum FGF19 levels were negatively associated with fasting plasma glucose and independently associated with the deterioration of glucometabolic status from NGT to IFG and T2DM.CONCLUSIONSFasting serum FGF19 levels were decreased in Chinese subjects with IFG and inversely associated with fasting glucose levels.

Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes

“…This may indicate that bile acid-induced FXR activation is impaired in T2D leading to decreased secretion of FGF-19, which could explain the higher bile acid concentrations as FGF-19 inhibits bile acid synthesis (30). Indeed, reduced FGF-19 concentrations in T2D patients have been reported in recent clinical studies (31)(32)(33). Although mechanisms independent of FXR could be at work in T2D (ie, altered synthesis, secretion and degradation of FGF-19, activation of the pregnane X and vitamin D receptors by bile acids (7)), the enterohepatic bile acid composition is a likely determinant of the degree of FXR activation.…”

Serum lipoprotein (a) concentrations are inversely associated with T2D, prediabetes, and insulin resistance in a middle-aged and elderly Chinese population

“…Second, bile acids had an Lp(a)-lowering effect via downregulated LPA gene expression ( 30 ). Meanwhile, fi broblast growth factor 19 (FGF19) was reportedly decreased in Chinese subjects with impaired fasting plasma glucose and inversely associated with fasting glucose levels ( 31 ). Therefore, one possible explanation might be that low levels of FGF19 in diabetic patients and the consequently high levels of bile acids may together infl uence the expression of LPA negatively.…”

Upregulation of hepatic bile acid synthesis via fibroblast growth factor 19 is defective in gallstone disease but functional in overweight individuals

“…12,13,15,36,37 Recently, in patients with idiopathic bile acid-induced diarrhoea, FGF19 and 7a-hydroxy-4-cholesten-3-one were shown to correlate negatively and FGF19 was proposed to serve as diagnostic marker for this disease. 16 Furthermore, in diabetic patients undergoing Roux-en-Y gastric bypass, lower FGF19 levels were significantly correlated with increased hepatic expression of the CYP7A1 gene, modulating bile acid production.…”