PT  - JOURNAL ARTICLE
AU  - Arun Sanyal
AU  - Kenneth Cusi
AU  - Mark L Hartman
AU  - Shuyu Zhang
AU  - Edward J Bastyr III
AU  - Juliana M Bue-Valleskey
AU  - Annette M Chang
AU  - Axel Haupt
AU  - Scott J Jacober
AU  - Robert J Konrad
AU  - Qianyi Zhang
AU  - Byron J Hoogwerf
TI  - Cytokeratin-18 and enhanced liver fibrosis scores in type 1 and type 2 diabetes and effects of two different insulins
AID  - 10.1136/jim-2017-000609
DP  - 2017 Nov 23
TA  - Journal of Investigative Medicine
PG  - jim-2017-000609
4099  - http://hw-f5-jim.highwire.org/content/early/2017/11/23/jim-2017-000609.short
4100  - http://hw-f5-jim.highwire.org/content/early/2017/11/23/jim-2017-000609.full
AB  - 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.