Abstract
Background: The present study aimed to assess the ability of serum bile acid profiles to predict the development of nonalcoholic fatty liver (NAFL) in type 2 diabetes mellitus (T2DM) patients. Methods: Using targeted ultraperformance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry (TQ/MS), we compared serum bile acid levels in T2DM patients with NAFL (n = 30) and age- and sex-matched T2DM patients without NAFL (n = 36) at the first time. Second, an independent cohort study of T2DM patients with NAFL (n = 17) and age- and sex-matched T2DM patients without NAFL (n = 20) was used to validate the results. The incremental benefits of serum biomarkers, clinical variables alone, or with biomarkers were then evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. The area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to evaluate the biomarker predictive abilities. Results: The serum bile acid profiles in T2DM patients with NAFL were significantly different from T2DM patients without NAFL, as characterized by the significant elevation of LCA, TLCA, TUDCA, CDCA-24G, and TCDCA, which may be potential biomarkers for the identification of NAFL in T2DM patients. Based on the improvement in AUC, IDI, and NRI, the addition of 5 bile acids to a model with clinical variables statistically improved its predictive value. Similar results were found in the validation cohort. Conclusions: These results highlight that the detected biomarkers may contribute to the progression of NAFL in T2DM patients, and these biomarkers particularly in combination may help in the diagnosis of NAFL and allow earlier intervention in T2DM patients.
Highlights
The prevalence of type 2 diabetes mellitus (T2DM) has increased in the world
It is urgent and important to find simple, non-invasive diagnostic biomarkers that can help early detect and understand the mechanism involved in the formation of Nonalcoholic fatty liver disease (NAFLD) in T2DM patients in order to prevent the occurrence of cardiovascular disease (CVD) and hepatocellular carcinoma (HCC)
According to the time of enrolment, the first 30 T2DM patients with nonalcoholic fatty liver (NAFL) and 36 T2DM patients without NAFL were included in the exploration cohort, while the subsequent 17 with NAFL and 20 without NAFL were included in the validation cohort
Summary
The prevalence of type 2 diabetes mellitus (T2DM) has increased in the world. Nonalcoholic fatty liver disease (NAFLD) has become the most frequent chronic liver disease in T2DM patients[1, 2]. Studies have shown that NAFLD may be present in up to 70% of patients with diabetes[4], the prevalence of biopsy-proven NASH was 20% in asymptomatic T2DM patients with normal liver function [5]. The presence of both NAFLD and T2DM increases the possibilities of the development of complications of diabetes (including both macro- and microvascular complications) and raises the risk of more severe NAFLD, including cirrhosis and HCC [6]. The present study aimed to assess the ability of serum bile acid profiles to predict the development of nonalcoholic fatty liver (NAFL) in type 2 diabetes mellitus (T2DM) patients
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