Serum fibroblast growth factor 21 was elevated in subjects with type 2 diabetes mellitus and was associated with the presence of carotid artery plaques

An, Soyeon; Lee, Min Suk; Yi, Sang-A; Ha, Eun Suk; Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Lee, Kwan‐Woo

doi:10.1016/j.diabres.2012.01.004

Cited by 65 publications

(35 citation statements)

References 28 publications

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“…The numerous positive effects of FGF-21 in vivo were proven somewhat later. Contrary to expectations, higher FGF-21 concentrations were found in patients with type 2 diabetes mellitus (T2DM), obesity and metabolic syndrome [2][3][4][5][6][7]. The results were explained by potential FGF-21 resistance [8,9] or compensatory protective elevation of FGF-21 [10,11].…”

Section: Introductioncontrasting

confidence: 49%

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

et al. 2014

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Section: Introductioncontrasting

confidence: 49%

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

et al. 2014

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“…In this regard, circulating FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes (DM2) (45,48,49,50,51,60) but decreased in type 1 diabetes and latent autoimmune diabetes in adults (61). FGF21 was also an independent predictor of DM2 in humans and its elevation is independent of the DM2 duration (62).…”

Section: Fgf21 Insulin Resistance and Type 2 Diabetesmentioning

confidence: 97%

“…The contribution from each tissue to plasma is not known. Several recent studies have analyzed circulating FGF21 levels in communitydwelling adults (47), as well as its role related to diabetes, insulin resistance, metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD), and weight status in humans (45,47,48,49,50,51,52,53,54,55) (Table 2).…”

Section: Fgf21 In Health and Human Diseasementioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21

Iglesias

Selgas

Romero

et al. 2012

European Journal of Endocrinology

100

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Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.

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“…On the other hand, raised FGF21 levels have been found in various cardiometabolic conditions in clinical studies, suggesting a reactive change to FGF21 resistance or the underlying metabolic disturbances 1. In population studies, we and others had previously shown that high circulating FGF21 levels predicted the development of type 2 diabetes mellitus (T2DM) and were associated with carotid atherosclerosis independent of established cardiovascular risk factors 5, 6, 7, 8, 9. Among subjects with T2DM, recently, we also demonstrated that serum FGF21 levels predicted nephropathy progression, in terms of decline in estimated glomerular filtration rate (eGFR), even in the stage of normoalbuminuria and relatively preserved renal function, highlighting its potential use as an early biomarker for diabetic kidney disease, a devastating diabetic complication 10…”

Section: Introductionmentioning

confidence: 99%

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

Lee

Woo

Chow

et al. 2017

JAHA

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BackgroundFibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross‐sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases.Methods and ResultsBaseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow‐up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow‐up of 4 years. Baseline serum log‐transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8–438.4] versus 151.1 pg/mL [75.6–274.6]; P<0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10–2.19; P=0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors.ConclusionsWe have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention.

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Serum fibroblast growth factor 21 was elevated in subjects with type 2 diabetes mellitus and was associated with the presence of carotid artery plaques

Cited by 65 publications

References 28 publications

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

MECHANISMS IN ENDOCRINOLOGY: Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

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