Serum Cytokeratin-18 Fragment Levels Predict Development of Type 2 Diabetes Mellitus in Adult Patients With Nonalcoholic Fatty Liver Disease

Abstract

Introduction: Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for the development of type 2 diabetes (DM2). Whether the histologic severity of NAFLD correlates with higher risk of DM2 has not been investigated. Cytokeratin-18 (CK18) serum levels have been extensively validated as a reliable non-invasive marker of NAFLD severity and the presence of nonalcoholic steatohepatitis (NASH). We aimed to investigate baseline CK18 level as predictor of the development of DM2 in patients with NAFLD. Methods: Patients with biopsy-proven NAFLD who had serum CK18 fragment levels measured at the time of liver biopsy and were followed at our institution for at least 2 years were included in the current study. Charts were reviewed for the development of DM2 during the course of their follow-up. The diagnosis of DM was made using the American Diabetes Association (ADA) criteria. CK18 fragment levels at baseline were measured using the M30-Apoptosense ELISA kit. Student’s t tests were used to assess the association between the development of DM2 and CK-18 levels. A p< 0.05 was considered statistically significant. Results: Thirty-nine patients met the criteria for inclusion in the study, out of which 32 (82.1%) were white and 20 (51.3%) were female. At baseline, the mean age was 51.3±11.2 years and the mean BMI was 33.8±5.6 Kg/m2. Patients were followed for a median of 62.4 (38.8, 81.0) months. Fourteen patients had DM2 at baseline. Out of the remaining 25 patients, 6 (24.0%) developed DM during the course of the follow-up and had significantly higher mean values of CK-18 at baseline (768.8±821.4) as compared to the 19 that did not develop DM (285.1±166.5) (p =0.019) (Figure 1). Furthermore, there was a trend toward having higher baseline CK18 levels in patients that developed metabolic syndrome at last followup compared to those who did not (361.3±195.9 versus 195.4±103.1; p=0.077).Figure 1Conclusion: Baseline CK18 level may be a useful marker to predict the development of DM2 in adults with NAFLD. If these findings are validated in larger studies, having higher CK18 level may require a more aggressive approach to lifestyle modifications to prevent the development of DM2.