Elevated Serum Cytokeratin-18 Levels in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease

Background: Cytokeratin-18 (CK-18) is a caspase-cleaved fragment released by injured hepatocytes, and serum levels of CK-18 were believed to be a marker of hepatic cell damage such as inflammation. Patients with type 2 diabetes (T2DM) were well known to have a high prevalence of the fatty liver condition. However, rare studies had been reported the serum CK-18 level in patients with T2DM and investigated the association between the levels with metabolic biomarkers. Material and Methods: Healthy participants and T2DM patients who followed in the specialized diabetes polyclinic were enrolled. Physical and metabolic factors were collected,and NAFLD was screened by abdominal ultrasound and fatty liver index. Cytokeratin 18 level was detected by commercially available immunoassay. Results: There were 22.8% (29/127) and 35.9%(42/117) participants were diagnosedwith NAFLD in the non-DM group and T2DM group, respectively. Both serum levels of CK-18 M30 and CK-18 M65 were significantly higher in patients with T2DM as compared with those of the non-DM group. Patients with nonalcoholic fatty liver disease (NAFLD) had higher serum CK-18 M30 level whatever withT2DM (205.8±135.1 vs. 108.4±66.19 U/L; P<0.001) or without (177.69±70.53 vs. 87.07±34.57 U/L; P003C0.001). Similarly, serum CK-18 M65 was also higher in patients with NAFLD in theT2DM group (513.9±271.2 vs. 285.4±115.3 U/L; P<0.001)and in the non-DM group (353.5±162.4 vs. 248.51±111.3 U/L; P<0.001).Multi-variate regression analyses demonstrated that fasting plasma glucose was independently and significantly associated with CK-18 M30 (β coefficient: 0.002; P=0.011)) and CK-18 M65 (β coefficient:0.003; P<0.001). These results suggested that CK-18 level was closely connected with diabetes mellitus. Conclusions: Independent of NAFLD, our result suggests that CK-18 level was closely associated with the hyperglycemic milieu. The association between serum CK-18 and T2DM may worth for further investigation. Disclosure T. Lee: None.