Impaired Insulin Clearance as the Initial Regulator of Obesity-Associated Hyperinsulinemia: Novel Insight Into the Underlying Mechanism Based on Serum Bile Acid Profiles

Abstract Background ICP pregnant women have a unique profile of serum bile acid metabolis, early and accurate identification of ICP patients is beneficial to early appropriate treatment and improvement of pregnancy outcomes. In this study, ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to analyze the 15 types of serum bile acid profiles of ICP in third trimester, patients with cholelithiasis, and patients with hepatitis B virus. The ICP diagnostic model established by partial least squares-discriminant analysis (PLS-DA) was used to screen the differential bile acids for clinical subtypes of ICP. 144 cases of ICP patients were involved in this study, and were divided into four subgroups according to serum levels of TBA, DBIL, and ALT. Results ①The differential serum bile acid profiles of ICP group and normal pregnant women were DCA, TDCCA, TCA, GDCA and GLCA.②The differential serum bile acid profiles of the ICP1 group (ICP with jaundice) and normal pregnant women were TCDCA, TCA, GCA, GCDCA, TUDCA and GUDCA.③The differential serum bile acid profiles of the ICP3 group (hyperbiliary acidemia of pregnancy) and normal pregnant group was GUDCA, LCA, GLCA, UDCA, TUDCA, CDCA, and TLCA (P <0.05).④The differential serum bile acid profiles of ICP4 group (idiopathic aminotransferase abnormality during pregnancy) and normal pregnant group was UDCA, GUDCA, TUDCA, GCA and GLCA (P <0.05).⑤The occurrence of meconium-stained amniotic fluid, premature delivery and cesarean section in ICP1 group was significantly higher than normal group,ICP2 group,ICP3 group,and ICP4 group (P <0.05); The occurrence of meconium-stained amniotic fluid, premature delivery and cesarean section in ICP2 group, ICP3 group,and ICP4 group was significantly higher than normal group (P <0.05), but no difference was found among ICP2 group, ICP3 group,and ICP4 group (P> 0.05). Conclusion: Maternal serum bile acid profiles are useful to differentiate the four subtypes of ICP. ICP with jaundice could be an important predictor of adverse pregnancy outcomes of ICP.

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Maternal bile acid profile and subtype analysis of intrahepatic cholestasis of pregnancy

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01887-1 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Yong Shao ◽

Siyu Chen ◽

Huan Li ◽

Qin Tang ◽

Di Xu

Keyword(s):

Mass Spectrometry ◽

Bile Acid ◽

Cesarean Section ◽

Amniotic Fluid ◽

Pregnant Women ◽

Pregnancy Outcomes ◽

Premature Delivery ◽

Serum Bile Acid ◽

Bile Acid Profiles ◽

Meconium Stained Amniotic Fluid

Abstract Background ICP pregnant women have a unique profile of serum bile acid metabolism, thus the early and accurate identification of ICP patients is beneficial to early appropriate treatment and improvement of pregnancy outcomes. In this study, ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to analyze the 15 types of serum bile acid profiles among patients with ICP in third trimester, patients with cholelithiasis, and patients with hepatitis B virus. The ICP diagnostic model established by partial least squares-discriminant analysis (PLS-DA) was used to screen the differential bile acids for clinical subtypes of ICP. 144 cases of ICP patients were involved in this study, and divided into four subgroups according to serum level of TBA, DBIL, and ALT. Results (1) The differential serum bile acid profiles of ICP group and normal pregnant women were DCA, TDCA, TCA, GDCA and GLCA. (2) The differential serum bile acid profiles of the ICP1 group (ICP with jaundice) and normal pregnant women were TCDCA, TCA, GCA, GCDCA, TUDCA and GUDCA. (3) The differential serum bile acid profiles of the ICP3 group (Hyperchoicemia of pregnancy) and normal pregnant group was GUDCA, LCA, GLCA, UDCA, TUDCA, CDCA, and TLCA (P < 0.05). (4) The differential serum bile acid profiles of ICP4 group (idiopathic aminotransferase abnormality during pregnancy) and normal pregnant group was UDCA, GUDCA, TUDCA, GCA and GLCA (P < 0.05). (5) The occurrence of meconium-stained amniotic fluid, premature delivery and cesarean section in ICP1 group was significantly higher than normal group, ICP2 group, ICP3 group, and ICP4 group (P < 0.05); The occurrence of meconium-stained amniotic fluid, premature delivery and cesarean section in ICP2 group, ICP3 group, and ICP4 group was significantly higher than normal group (P < 0.05), but no difference was found among ICP2 group, ICP3 group, and ICP4 group (P > 0.05). Conclusion Maternal serum bile acid profiles are useful to differentiate the four subtypes of ICP. ICP with jaundice could be an important predictor of adverse pregnancy outcomes of ICP.

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Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients

Journal of Proteome Research ◽

10.1021/acs.jproteome.1c00104 ◽

2021 ◽

Author(s):

Tao Wu ◽

Ming Yang ◽

Hanchen Xu ◽

Lei Wang ◽

Huafeng Wei ◽

...

Keyword(s):

Bile Acid ◽

Fatty Liver ◽

Serum Bile Acid ◽

Clinical Prediction ◽

Nonalcoholic Fatty Liver ◽

Bile Acid Profiles

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Serum bile acid profiles in cerebrotendinous xanthomatosis

Clinica Chimica Acta ◽

10.1016/0009-8981(82)90004-3 ◽

1982 ◽

Vol 118 (2-3) ◽

pp. 167-175 ◽

Cited By ~ 14

Author(s):

Tomoe Beppu ◽

Yousuke Seyama ◽

Takeshi Kasama ◽

Shigeo Serizawa ◽

Tamio Yamakawa

Keyword(s):

Bile Acid ◽

Cerebrotendinous Xanthomatosis ◽

Serum Bile Acid ◽

Bile Acid Profiles

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Impaired Insulin Clearance as the Initial Regulator of Obesity-Associated Hyperinsulinemia: Novel Insight Into the Underlying Mechanism Based on Serum Bile Acid Profiles

10.2337/figshare.17004016.v1 ◽

2021 ◽

Author(s):

Zhenzhen Fu ◽

Qinyi Wu ◽

Wen Guo ◽

Jingyu Gu ◽

Xuqin Zheng ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Insulin Clearance ◽

Serum Bile Acid ◽

Intravenous Glucose ◽

Impaired Insulin ◽

Obese Subjects

OBJECTIVE <div>To investigate the roles of insulin clearance and insulin secretion in the development of hyperinsulinemia in obese subjects and to reveal the association between insulin clearance and bile acids (BAs). RESEARCH DESIGN AND METHODS In cohort 1, insulin secretion, sensitivity and endogenous insulin clearance were evaluated with an oral glucose tolerance test (OGTT) in 460 recruited participants. In cohort 2, 81 participants underwent an <a>intravenous glucose tolerance test</a> (IVGTT) and a hyperinsulinemic-euglycemic clamp to assess insulin secretion, endogenous and exogenous insulin clearance, and insulin sensitivity. Based on insulin resistance levels ranging from mild to severe, nondiabetic obese participants were further divided into 10 quantiles in cohort 1 and into tertiles in cohort 2. Forty serum BAs were measured in cohort 2 to examine the association between BAs and insulin clearance. RESULTS All obese participants had impaired insulin clearance, and it worsened with additional insulin resistance in nondiabetic obese subjects. However, insulin secretion was unchanged from quantile 1 to 3 in cohort 1, and no difference was found in cohort 2. After adjustments for all confounding factors, serum conjugated BAs, especially glycodeoxycholic acid (GDCA, β=-0.335, P=0.004) and taurodeoxycholic acid (TDCA, β=-0.333, P=0.003), were negatively correlated with insulin clearance<a>. The ratio of </a><a></a><a>unconjugated to conjugated BAs (UnconBA/ConBA</a>, β=0.335, P=0.002) was positively correlated with insulin clearance. CONCLUSIONS Hyperinsulinemia in obese subjects might be primarily induced by decreased insulin clearance rather than increased insulin secretion. Changes in circulating conjugated BAs, especially GDCA and TDCA, might play an important role in regulating insulin clearance.</div>

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