OBJECTIVE Bile acids (BAs) are signaling molecules controlling lipid and glucose metabolism. Since BA alterations are associated with obesity and insulin resistance, plasma BAs have been considered candidates to predict type 2 diabetes (T2D) risk. We aimed to determine (1) the association of BAs with glucose homeostasis parameters and (2) their predictive association with the risk of conversion from prediabetes to new-onset diabetes (NOD) in a prospective cohort study. DESIGN 205 patients with impaired fasting glucose (IFG) were followed each year during 5 years in the IT-DIAB cohort study. Twenty-one BA species and 7α-hydroxy-4-cholesten-3-one (C4), a marker of BA synthesis, were quantified by LC/MS-MS in plasma from fasted patients at baseline. Correlations between plasma BA species and metabolic parameters at baseline were assessed by Spearman's coefficients and the association between BAs and NOD was determined using Cox proportional-hazards models. RESULTS Among the analyzed BA species, total hyocholic acid (HCA) and the total HCA/total chenodeoxycholic acid (CDCA) ratio, reflecting hepatic BA 6α-hydroxylation activity, negatively correlated with BMI and HOMA-IR. The total HCA/total CDCA ratio also correlated negatively with HbA1C. Conversion from IFG to NOD occurred in 33.7% of the participants during the follow-up. Plasma BA species were not independently associated with the conversion to NOD after adjustment with classical T2D risk factors. CONCLUSIONS Fasting plasma BAs are not useful clinical biomarkers for predicting NOD in patients with IFG. However, an unexpected association between 6α-hydroxylated BAs and glucose parameters was found, suggesting a role for this specific BA pathway in metabolic homeostasis. IT-DIAB study registry number: NCT01218061.

中文翻译：

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胆汁酸与葡萄糖代谢有关，但不能预测空腹血糖受损会转化为糖尿病。

目的胆汁酸（BAs）是控制脂质和葡萄糖代谢的信号分子。由于BA变化与肥胖和胰岛素抵抗相关，因此血浆BA被认为是预测2型糖尿病（T2D）风险的候选药物。在一项前瞻性队列研究中，我们旨在确定（1）BA与葡萄糖稳态参数之间的关联，以及（2）它们与从糖尿病前期转变为新发糖尿病（NOD）的风险的预测关联。在IT-DIAB队列研究中，在5年中每年对205名空腹血糖受损（IFG）的患者进行随访。在基线时，通过LC / MS-MS对空腹患者血浆中的二十一种BA物种和BA合成的标志物7α-羟基-4-胆甾烯-3-酮（C4）进行了定量。通过Spearman系数评估血浆BA物种与基线代谢参数之间的相关性，并使用Cox比例风险模型确定BA与NOD之间的关联。结果在所分析的BA种类中，总胆酸（HCA）和总HCA /总鹅去氧胆酸（CDCA）之比反映了肝脏BA6α-羟基化活性，与BMI和HOMA-IR呈负相关。总HCA /总CDCA比值也与HbA1C负相关。在随访期间，有33.7％的参与者从IFG转换为NOD。用经典的T2D危险因素进行调整后，血浆BA物种与NOD的转化并不独立相关。结论空腹血浆BAs并不是预测IFG患者NOD的有用的临床生物标志物。然而，发现6α-羟基化BAs和葡萄糖参数之间存在意想不到的关联，表明该特定BA途径在代谢稳态中的作用。IT-DIAB研究注册号：NCT01218061。