Association of Circulating TXNIP Levels with Fatty Liver in Newly Diagnosed Type 2 Diabetes Mellitus

Abstract

Background and Aims

Thioredoxin-interacting protein (TXNIP), a crucial modulator of the redox system, plays a crucial role in modulating lipid/glucose metabolism. Hence, this study aimed to explore whether circulating TXNIP is associated with non-alcoholic fatty liver disease (NAFLD) among patients with type 2 diabetes mellitus (T2DM).

Methods

We enrolled 110 new patients with T2DM. In this study, we determined hepatic fat fraction (HFF), which represents a hepatic fat level, by Dixon magnetic resonance imaging. TXNIP and the other biochemical profiles of the patients were measured using fasting plasma.

Results

Among the 110 patients with T2DM, 41 were classified as without fatty liver, whereas 34 and 35 were with mild and moderate-to-severe fatty liver, respectively. The patients with diabetes and advanced fatty liver had significantly higher TXNIP levels (P <0.001) than other patients. The prevalence of severe NAFLD showed an increasing trend with the increase in TXNIP quartiles (for all trends, P <0.05). HFF showed a positive correlation with TXNIP (r = 0.516, P <0.001). Even main risk factors were adjusted, TXNIP level was associated with NAFLD as analyzed by logistic regression.

Conclusion

TXNIP level remarkably increases among diabetics, which shows its positive relationship with the severity of NAFLD. TXNIP is a promising NAFLD biomarker that offers an efficient way to evaluate and monitor fatty liver progression among patients with T2DM.

Keywords:

• thioredoxin-interacting protein
• non-alcoholic fatty liver disease
• type 2 diabetes mellitus

Abbreviations

TXNIP, thioredoxin-interacting protein; NAFLD, nonalcoholic fatty liver disease; T2DM, type 2 diabetes mellitus; MRI, magnetic resonance imaging; HFF, hepatic fat fraction; NASH, nonalcoholic steatohepatitis; HCC, hepatocellular carcinoma; IR, insulin resistance; GDM, gestational diabetes mellitus; T1DM, type 1 diabetes mellitus; HC, hip circumference; WC, waist circumference; BP, blood pressure; WHR, waist/hip ratio; BMI, body mass index; FPG, fasting plasma glucose; hs-CRP, high-sensitivity C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; SUA, serum uric acid; TG, triglyceride; TC, total cholesterol; HDL-c/LDL-c, high/low-density lipoprotein cholesterol; FFAs, free fatty acids; CT, computed tomography.

Ethics Statements

The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University in accordance with the principles of the Helsinki Declaration and written informed consent was obtained from each subject.

Acknowledgments

This work was supported by grants from People’s Livelihood Science and Technology of Suzhou (grant no. SYS2020104 to Hong Sun, no. SS2020008 to Bimin Shi), National Natural Science Youth Foundation of China (grant no. 81700632 to Hong Sun), the Natural Science Youth Foundation of Jiangsu Province (grant no. BK20170366 to Hong Sun), and China Postdoctoral Science Foundation (2020M671559 to Juan Chen). Yuting Guo and Juan Chen are co-first authors for this study.

Disclosure

The authors have declared that no competing interest exists.