Association of Elevated Plasma FGF21 and Activated FGF21 Signaling in Visceral White Adipose Tissue and Improved Insulin Sensitivity in Gestational Diabetes Mellitus Subtype: A Case-Control Study

Wang, Ning; Sun, Bo; Guo, Haonan; Jing, Yingyu; Ruan, Qiuqi; Wang, Mengjun; Mi, Yang; Chen, Huan; Song, Lin; Cui, Wei

doi:10.3389/fendo.2021.795520

Cited by 3 publications

(4 citation statements)

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“…Next, we will continue to pay attention to such RCTs, and conduct further subgroup analyses of different GDM diagnoses. Finally, in combination with our previous studies (26,27,39), GDM subtypes should be considered as an important confounding factor that could affect the clinical efficacy of these oral hypoglycemic agents.…”

Section: Limitationmentioning

confidence: 79%

“…Metformin is regarded as an insulinsensitizing agent that is used as an oral hypoglycemic agent with limited power to control blood glucose levels during clinical practice (25). We have shown that there are three subtypes of GDM according to the heterogeneity in the physiological and pathological processes leading to hyperglycemia, which show different characteristics, risk factors, and insulin sensitivity alteration patterns (26,27). In the GDM-resistant subtype, metformin may improve blood glucose levels.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of hypoglycemic agents on gestational diabetes mellitus in women: A Bayesian network analysis of randomized controlled trials

Wang

Jing

Guo

et al. 2022

Front. Public Health

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ObjectiveTo compare the efficacy and safety of metformin, glyburide, and insulin for GDM, we conducted a subgroup analysis of outcomes for women with GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria.MethodsWe searched the NCBI, Embase, and Web of Science databases from inception to March 2022. Randomized controlled trials (RCTs) that compared the outcomes of hypoglycemic agents in women with GDM were included. Bayesian network analysis was employed.ResultsA total of 29 RCTs were included. Metformin was estimated to lead to a slight improvement in total gestational weight gain (WMD – 1.24 kg, 95% CI −2.38, −0.09), a risk of unmet treatment target in the sensitivity analysis (OR 34.50, 95% CI 1.18–791.37) than insulin. The estimated effect of metformin showed improvements in birth weight than insulin (WMD – 102.58 g, 95% CI −180.45 to −25.49) and glyburide (WMD – 137.84 g, 95% CI −255.31 to −25.45), for hypoglycemia within 1 h of birth than insulin (OR 0.65, 95% CI 0.47 to 0.84). The improvement in the estimated effect of metformin for hypoglycemia within 1 h of birth still existed when compared with glyburide (OR 0.41, 95% CI 0.26 to 0.66), whether in the IADPSG group (OR 0.33, 95% CI 0.12 to 0.92) or not (OR 0.43, 95% CI 0.20 to 0.98).ConclusionMetformin is beneficial for GDM women to control total GWG compared with insulin, regulate fetal birth weight more than insulin and glyburide, and increase the risk of unmet treatment targets compared with insulin. Compared to metformin, glyburide is associated with neonatal hypoglycemia.

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Section: Limitationmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of hypoglycemic agents on gestational diabetes mellitus in women: A Bayesian network analysis of randomized controlled trials

Wang

Jing

Guo

et al. 2022

Front. Public Health

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“…Both treatments upregulated FGF21 levels, an effect previously observed after ethinylestradiol–cyproterone acetate-based OC treatment in PCOS adolescents ( 35 ). The inverse correlation between circulating FGF21 levels and visceral fat only in spiomet-treated girls could reflect an increase in FGF21 signaling in visceral adipose tissue, followed by a more insulin-sensitive status ( 40 ). No significant associations were found between the on-treatment FGF21 changes and ALT and GGT concentrations.…”

Section: Discussionmentioning

confidence: 99%

Organokines and liver enzymes in adolescent girls with polycystic ovary syndrome during randomized treatments

Garcia-Beltran,

Peyrou,

Navarro-Gascon

et al. 2024

Front. Endocrinol.

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IntroductionPolycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function, systemic dysmetabolism, and abnormal circulating levels of signaling molecules called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage, which were assessed longitudinally in the aforementioned studies as safety markers.Materials and methodsLiver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) with those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 year. As a post hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI), and meteorin-like protein (METRNL) were assessed by ELISA after 6 months of OC (N = 26) or spiomet (N = 28). Auxological, endocrine-metabolic, body composition (using DXA), and abdominal fat partitioning (using MRI) were also evaluated. Healthy, age-matched adolescent girls (N = 17) served as controls.ResultsCirculating ALT and GGT levels increased during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 months of treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls than in controls and spiomet-treated girls; and (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels were directly correlated with circulating METRNL levels only in OC-treated girls (R = 0.449, P = 0.036 and R = 0.552, P = 0.004, respectively).ConclusionThe on-treatment increase in ALT and GGT levels occurring only in OC-treated girls is associated with circulating METRNL levels, suggesting enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment.Clinical Trial Registrationhttps://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.

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“…There is also different information about the direction of this relationship. Some authors report that this relationship is positive [ 25 , 28 ] while others report that it is negative [ 29 ]. It can be explained by the fact that fasting blood glucose in diabetic patients has high variability, which can affect the correlation between glycemia and FGF21 [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 21 in Gestational Diabetes Mellitus and Type 2 Diabetes Mellitus

Gawlik,

Milewicz,

Pawlica-Gosiewska

et al. 2023

Journal of Diabetes Research

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Objective. Women who develop GDM present a metabolic condition similar to that found in type 2 diabetes, characterized by impaired insulin response. Due to similar pathophysiologic mechanisms found between type 2DM and GDM, there is a great interest in finding markers that will lead to the understanding of a possible common origin to both diseases. The aim of this study was to determine serum FGF21 levels in 2DM and GDM and its correlation with selected metabolic parameters. Method. The study included 54 2DM patients and 52 nondiabetic individuals (control group 1) as well as 74 GDM women and 32 healthy pregnant controls (control group 2). Serum FGF21 was determined by enzyme-linked immunosorbent assay (ELISA), in all groups, and correlated with biochemical parameters of glucose metabolism and insulin resistance (HbA1c, HOMA index, TG, and HDL cholesterol). Results. FGF21 concentration was significantly higher in 2DM as compared with control group 1 ( p < 0.01 ). In the 2DM group, FGF21 was positively correlated with HOMA index ( p = 0.022 , R = 0.398 ). In the GDM group, the positive relationships with FGF21 were observed with glucose ( p = 0.020 , R = 0.264 ) and TG ( p = 0.013 , R = 0.283 ) while HDL-C levels were correlated negatively ( p = 0.004 , R = − 0.326 ). Conclusion. Serum FGF21 levels were significantly higher in 2DM patients than those without diabetes. Moreover, serum FGF21 levels were associated with selected metabolic parameters, suggesting that it may play acrolein glucose and lipid metabolism.

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Association of Elevated Plasma FGF21 and Activated FGF21 Signaling in Visceral White Adipose Tissue and Improved Insulin Sensitivity in Gestational Diabetes Mellitus Subtype: A Case-Control Study

Cited by 3 publications

References 43 publications

Efficacy and safety of hypoglycemic agents on gestational diabetes mellitus in women: A Bayesian network analysis of randomized controlled trials

Efficacy and safety of hypoglycemic agents on gestational diabetes mellitus in women: A Bayesian network analysis of randomized controlled trials

Organokines and liver enzymes in adolescent girls with polycystic ovary syndrome during randomized treatments

Fibroblast Growth Factor 21 in Gestational Diabetes Mellitus and Type 2 Diabetes Mellitus

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