Cytokeratin-18 and Enhanced Liver Fibrosis Scores in Type 1 and Type 2 Diabetes and Effects of Two Different Insulins

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.

Cytokeratin 18 can help predict liver fibrosis in HCV infected patients with type 2 diabetes mellitus

“…However, only a few studies investigated the correlations about CK18 in patients infected with HCV [ 10 , 11 ], and limited data confirmed the strong relationship between serum CK18 and HCV-related fibrosis. Sanyal et al [ 10 ] also found CK18 associated with insulins in CHC complicated with T2DM.…”

“…However, only a few studies investigated the correlations about CK18 in patients infected with HCV [ 10 , 11 ], and limited data confirmed the strong relationship between serum CK18 and HCV-related fibrosis. Sanyal et al [ 10 ] also found CK18 associated with insulins in CHC complicated with T2DM. Additionally, there have been many developed noninvasive serum biomarkers for predicting liver fibrosis in CHC patients without any other metabolic diseases [ 12 ], but no marker was specially developed for CHC-T2DM patients.…”

Delving Deep into the Structural Aspects of the BPro28-BLys29 Exchange in Insulin Lispro: A Structural Biophysical Lesson

“…Another insulin analogue, peglispro [28,29,30,31] was derived by covalent attachment of a linear 20 kD polyethylene polymer to the LysB28 side chain in insulin lispro.…”