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.
- magnetic resonance imaging
- fatty liver
- diabetes mellitus
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Contributors AS, KC, MLH, SZ and BJH contributed to data analysis and interpretation, and in reviewing and editing the manuscript. SZ and QZ designed and conducted the statistical analyses, and participated in the interpretation of the results and writing the manuscript. AMC, EJB, SJJ and JMB-V contributed to the design and medical oversight of trials, data analysis and interpretation and reviewing and editing of the manuscript. AH contributed to design of the MRI studies, data analysis and interpretation, and in reviewing and editing the manuscript. All authors approved the final version of the article, including the authorship list.
Funding The studies and writing of this paper were funded in full by Eli Lilly and Company.
Competing interests AS has stock options in Genfit, is President of Sanyal Biotechnologies, has served as a consultant to Merck, Eli Lilly and Company, Bristol Myers, Novartis, AbbVie, AstraZeneca, Gilead, Intercept, Genfit, Zafgen, Enanta, Immuron, Galmed, Nitto Denko, Durect, Ikaria, Echosens and Salix. His institution receives grant support from Intercept, Merck, AstraZeneca, Bristol Myers and Gilead. EJB was an employee and shareholder of Eli Lilly and Company during the trials and results analyses; he is currently a consultant to Viacyte. MLH, SZ, JMB-V, AMC, AH, SJJ, RJK, QZ and BJH are employees and stockholders of Eli Lilly and Company.
Patient consent Obtained.
Ethics approval The data from the four studies came from the larger data sets of multicenter and international studies. Thus, there were multiple ethics committees across sites and countries involved for each of these four studies. We believe there are too many to list individually in this manuscript. Each of the four studies from which these data derive have been previously published (and are referenced in this manuscript) and the role of the ethical review boards in each study is noted in the primary manuscripts.
Provenance and peer review Not commissioned; externally peer reviewed.