Cytokeratin-18 and Enhanced Liver Fibrosis Scores in Type 1 and Type 2 Diabetes and Effects of Two Different Insulins. (March 2018)

• Record Type: Journal Article
• Authors: Sanyal, Arun; Cusi, Kenneth; Hartman, Mark L; Zhang, Shuyu; Bastyr, Edward J; Bue-Valleskey, Juliana M; Chang, Annette M; Haupt, Axel; Jacober, Scott J; Konrad, Robert J; Zhang, Qianyi; Hoogwerf, Byron J
• Is Part Of: Journal of investigative medicine. Volume 66:Number 3(2018)
• Page Start: 661
• Page End: 668
• Publication Date: 2018-03
• Subjects: magnetic resonance imaging -- insulin -- fatty liver -- diabetes mellitus; Clinical medicine -- Periodicals; Medicine -- Research -- Periodicals; Medicine; Research -- United States; Clinical medicine; Medicine -- Research; Periodicals; 616.075
• DOI: 10.1136/jim-2017-000609
• Languages: English
• ISSNs: 1081-5589

Abstract

Data on cytokeratin-18 (K-18) and enhanced liver fibrosis (ELF) score in insulin-treated diabetes patients with non-alcoholic fatty liver disease (NAFLD) are limited. This study analyzed phase III data comparing basal insulin peglispro (BIL) and insulin glargine in type 1 (T1D), and type 2 diabetes (T2D) (insulin-naïve and insulin-treated). Alanine aminotransferase (ALT), K-18, ELF scores and liver fat content (LFC), measured by MRI, were obtained longitudinally. Baseline K-18 (U/L) was higher in T2D (range: 207-247) than T1D (range: 148-183), correlated with ALT in all populations (r (range) 0.264-0.637, p<0.05), but with LFC only in T2D (r (range) 0.474-0.586, p<0.05). K-18 increased significantly from baseline in BIL-treated, but not glargine-treated patients. Change from baseline (CFB) K-18 was significantly correlated with CFB in ALT in BIL-treated T2D populations. Baseline ELF scores were higher in T2D (range: 9.12-9.20) than T1D (range: 8.24-8.36), correlated with ALT in T1D only (0.209, p<0.05), and not correlated with LFC in any population. ELF scores increased significantly from baseline in BIL-treated but not glargine-treated patients. There were no correlations between CFB in LFC and ELF score at week 52 in any treatment group/population. In all BIL-treated populations, CFB in ALT and CFB in ELF score at week 52 were positively correlated. These data characterize associations of K-18 and ELF score with ALT and LFC in insulin-treated patients with T1D and T2D. Hepatopreferential insulins may be associated with increased K-18 and ELF scores but mechanisms and clinical significance are unknown. ClinicalTrials.gov identifiers are NCT01481779, NCT01435616, NCT01454284 and NCT01582451.