Understanding Bile Acid Signaling in Diabetes: From Pathophysiology to Therapeutic Targets

Ferrell, Jessica M.; Chiang, John Y.L.

doi:10.4093/dmj.2019.0043

Cited by 90 publications

(85 citation statements)

References 135 publications

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“…DCA, transformed by rectal taurocholate (TCA), increases GLP-1 secretion and insulin, leading to decreased serum glucose by activating intestinal bile acid receptors FXR and TGR5 [94,95]. Although UDCA is not used for T2DM directly, it has been used to treat obese patients [96]. Short-term UDCA administration activates FXR to stimulate bile acid and cholesterol synthesis, while circulation of FGF19 decreases.…”

Section: Bile Acid-based Therapy For T2dmmentioning

confidence: 99%

Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes

Zhou

Tang

et al. 2020

Journal of Diabetes Research

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Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and unclear pathogenesis, is a serious menace to human health. Bile acids are the end products of cholesterol catabolism and play an important role in maintaining cholesterol homeostasis. Furthermore, increasing studies suggest that bile acids may regulate glucose tolerance, insulin sensitivity, and energy metabolism, suggesting that bile acids may represent a potential therapeutic target for T2DM. This study summarizes the metabolism of bile acids and, more importantly, changes in their concentrations, constitution, and receptors in diabetes. Furthermore, we provide an overview of the mechanisms underlying the role of bile acids in glucose and lipid metabolism, as well as the occurrence and development of T2DM. Bile acid-targeted therapy may represent a valid approach for T2DM treatment.

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Section: Bile Acid-based Therapy For T2dmmentioning

confidence: 99%

Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes

Zhou

Tang

et al. 2020

Journal of Diabetes Research

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“…NAFLD is currently the most common cause of chronic liver disease globally, and its reported prevalence in the adult population is 20-30%; however, the prevalence can increases up to 70-90% in obese or diabetic patients [1,2]. NAFLD was previously considered an intra-hepatic phenotype of metabolic syndrome; however, it has since been revealed that NAFLD itself is an independent risk factor for various chronic 4 diseases such as cardiovascular disease (CVD) [3], hypertension [4], diabetes [5,6], and chronic kidney disease [7]. Additionally, because CVD is the most common cause of death among NAFLD patients, studies of the relationship between NAFLD and CVD and underlying mechanisms have been actively conducted [8].…”

Section: Introductionmentioning

confidence: 99%

Fatty liver index and development of cardiovascular disease in Koreans without pre-existing myocardial infarction and ischemic stroke: a large population-based study

Kim

Moon

Byun

et al. 2020

Preprint

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Background: Despite the known association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD), whether NAFLD predicts future CVD events, especially CVD mortality, remains uncertain. We evaluated the relationship between fatty liver index (FLI), a validated marker of NAFLD, and risk of major adverse cardiac events (MACEs) in a large population-based study. Methods: We identified 3,011,588 subjects in the Korean National Health Insurance System cohort without a history of CVD who underwent health examinations from 2009 to 2011. The primary endpoint was a composite of cardiovascular deaths, non-fatal myocardial infarction (MI), and ischemic stroke. A Cox proportional hazards regression analysis was performed to assess association between the FLI and the primary endpoint. Results: During the median follow-up period of 6 years, there were 46,010 cases of MACEs (7,148 cases of cardiovascular death, 16,574 of non-fatal MI, and 22,288 of ischemic stroke). There was a linear association between higher FLI values and higher incidence of the primary endpoint. In the multivariable models adjusted for factors, such as body weight and cholesterol levels, the hazard ratio for the primary endpoint comparing the highest vs. lowest quartiles of the FLI was 1.99 (95% confidence interval [CIs], 1.91–2.07). The corresponding hazard ratios (95% CIs) for cardiovascular death, non-fetal MI, and ischemic stroke were 1.98 (1.9-2.06), 2.16 (2.01-2.31), and 2.01 (1.90-2.13), respectively (p<0.001). The results were similar when we performed stratified analyses by age, sex, use of dyslipidemia medication, obesity, diabetes, and hypertension. Conclusions: Our findings indicate that the FLI, which is a surrogate marker of NAFLD, has prognostic value for detecting individuals at higher risk for cardiovascular events.

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“…This could explain why AA was identified as one of the top predictors of DM in our study. Alterations in GCDCA, amongst other bile acids, was previously shown to trigger diabetes [ 43 ], which could also explain why it appeared as one of the top predictors of DM in our study (Table 4 ). When…”

Section: Discussionmentioning

confidence: 54%

Metabolic profiling of pre-gestational and gestational diabetes mellitus identifies novel predictors of pre-term delivery

et al. 2020

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Background Pregnant women with gestational diabetes mellitus (GDM) or type 2 diabetes mellitus (T2DM) are at increased risks of pre-term labor, hypertension and preeclampsia. In this study, metabolic profiling of blood samples collected from GDM, T2DM and control pregnant women was undertaken to identify potential diagnostic biomarkers in GDM/T2DM and compared to pregnancy outcome. Methods Sixty-seven pregnant women (21 controls, 32 GDM, 14 T2DM) in their second trimester underwent targeted metabolomics of plasma samples using tandem mass spectrometry with the Biocrates MxP® Quant 500 Kit. Linear regression models were used to identify the metabolic signature of GDM and T2DM, followed by generalized linear model (GLMNET) and Receiver Operating Characteristic (ROC) analysis to determine best predictors of GDM, T2DM and pre-term labor. Results The gestational age at delivery was 2 weeks earlier in T2DM compared to GDM and controls and correlated negatively with maternal HbA1C and systolic blood pressure and positively with serum albumin. Linear regression models revealed elevated glutamate and branched chain amino acids in GDM + T2DM group compared to controls. Regression models also revealed association of lower levels of triacylglycerols and diacylglycerols containing oleic and linoleic fatty acids with pre-term delivery. A generalized linear model ROC analyses revealed that that glutamate is the best predictors of GDM compared to controls (area under curve; AUC = 0.81). The model also revealed that phosphatidylcholine diacyl C40:2, arachidonic acid, glycochenodeoxycholic acid, and phosphatidylcholine acyl-alkyl C34:3 are the best predictors of GDM + T2DM compared to controls (AUC = 0.90). The model also revealed that the triacylglycerols C17:2/36:4 and C18:1/34:1 are the best predictors of pre-term delivery (≤ 37 weeks) (AUC = 0.84). Conclusions This study highlights the metabolite alterations in women in their second trimester with diabetes mellitus and identifies predictive indicators of pre-term delivery. Future studies to confirm these associations in other cohorts and investigate their functional relevance and potential utilization for targeted therapies are warranted.

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Understanding Bile Acid Signaling in Diabetes: From Pathophysiology to Therapeutic Targets

Cited by 90 publications

References 135 publications

Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes

Bile Acids: Key Regulators and Novel Treatment Targets for Type 2 Diabetes

Fatty liver index and development of cardiovascular disease in Koreans without pre-existing myocardial infarction and ischemic stroke: a large population-based study

Metabolic profiling of pre-gestational and gestational diabetes mellitus identifies novel predictors of pre-term delivery

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