Assessment of Hepatic Disorders in Patients with Type 2 Diabetes by Means of a Panel of Specific Biomarkers for Liver Injury.

Abstract

Modern biomarkers for the assessment of liver cell damage are indicative for distinct hepato-cellular deteriorations. We investigated the prevalence of these markers in healthy subjects and patients with early stage type 2 diabetes mellitus (T2DM) on metformin monotherapy. The study was performed with blood from 36 healthy subjects (17 females, age: 43 ± 12.4 years, BMI: 22.6 ± 1.5 kg/m2) and 32 T2DM patients (15 females, age: 57 ± 7.9 years, BMI: 35.0 ± 6.3 kg/m2, HbA1c: 7.3 ± 0.8%). Parameters for liver cell damage included ALT and AST and alpha-glutathione-S-transferase (α-GST, acute liver injury), keratin 18 (K18, cell necrosis), caspase-cleaved K18 (ccK18, cell apoptosis), and collagen IV (C-IV, fibrosis). In addition, insulin, intact proinsulin, and hsCRP were determined for staging insulin resistance, β-cell dysfunction, and chronic systemic inflammation. Differences were seen for mean ALT (T2DM: 36 ± 19 U/L vs. control: 20 ± 8 U/L, p < 0.001) but not for mean AST (26 ± 15 U/L vs. 25 ± 5 U/L, n.s.). All other biomarkers but insulin were higher in the T2DM group (intact proinsulin: 10 ± 6 pmol/L vs. 2 ± 1 pmol/L; hsCRP: 4.8 ± 2.7 mg/L vs. 1.1 ± 0.8 mg/L, α-GST: 17.3 ± 12.2 μg/L vs. 9.5 ± 0.2 μg/L, K18: 235 ± 125 U/L vs. 100 ± 33 U/L, ccK18: 280 ± 158 U/L vs. 167 ± 35 U/L, C-IV: 114 ± 28 μg/L vs. 92 ± 20 μg/L, all p < 0.001). Elimination of seven T2DM patients with elevated ALT or AST values did not change the overall results, which were also independent from the stage of the underlying diabetes disorders. Potential indications of liver cell damage were detected in T2DM patients with more specific biomarkers, which would not have been detected by ALT and AST alone.