Journal
DIABETES CARE
Volume 44, Issue 2, Pages 499-510Publisher
AMER DIABETES ASSOC
DOI: 10.2337/dc20-0884
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Funding
- Ministry of Science and Technology of China [2016YFC1305600, 2016YFC1305202, 2016YFC1304904, 2016YFC0901200, 2017ZX09304007, 2018YFC1311800]
- National Natural Science Foundation of China [81930021, 81970728, 81970691, 81670795, 81730023, 81621061]
- Shanghai Outstanding Academic Leaders Plan [18XD1402500, 20XD1422800]
- Clinical Research Plan of Shanghai Hospital Development Center [SHDC2020CR3064B]
- Shanghai Science and Technology Committee [20Y11905100]
- Shanghai Municipal Natural Science Foundation [18ZR1433100]
- Shanghai Medical and Health Development Foundation
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Aberrations in serum bile acids before the onset of diabetes may be associated with the risk of developing type 2 diabetes mellitus. Unconjugated primary and secondary bile acids were inversely associated with incident diabetes, while conjugated primary and secondary bile acids were positively related. This study suggests a potential role of bile acid metabolism in the pathogenesis of diabetes.
OBJECTIVE Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults. RESEARCH DESIGN AND METHODS We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression. RESULTS In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83-0.96) for cholic acid, 0.90 (0.84-0.97) for chenodeoxycholic acid, and 0.90 (0.83-0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset. CONCLUSIONS These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes.
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