Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD.

Colosimo, Santo; Miller, Hamish; Koutoukidis, Dimitrios A; Marjot, Thomas; Tan, Garry D; Harman, David J; Aithal, Guruprasad P; Manousou, Pinelopi; Forlano, Roberta; Parker, Richard; Sheridan, David A; Newsome, Philip N; Alazawi, William; Cobbold, Jeremy F; Tomlinson, Jeremy W

Abstract

Objectives
Currently, non-invasive scoring systems to stage the severity of non-alcoholic fatty liver disease (NAFLD) do not consider markers of glucose control (glycated haemoglobin, HbA1c); this study aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes.

Research design and methods
Data were obtained from 857 patients with liver biopsy staged NAFLD. Generalized-linear models and binomial regression analysis were used to define the relationships between histological NAFLD severity, age, HbA1c, and BMI. Paired biopsies from interventional studies (n = 421) were used to assess the impact of change in weight, HbA1c and active vs. placebo treatment on improvements in steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis.

Results
In the discovery cohort (n = 687), risk of severe steatosis, NASH and advanced fibrosis correlated positively with HbA1c, after adjustment for obesity and age. These data were endorsed in a separate validation cohort (n = 170). Predictive modelling using HbA1c and age was non-inferior to the established non-invasive biomarker, Fib-4, and allowed the generation of HbA1c, age, and BMI adjusted risk charts to predict NAFLD severity. Following intervention, reduction in HbA1c was associated with improvements in steatosis and NASH after adjustment for weight change and treatment, whilst fibrosis change was only associated with weight change and treatment.

Conclusions
HbA1c is highly informative in predicting NAFLD severity and contributes more than BMI. Assessments of HbA1c must be a fundamental part of the holistic assessment of patients with NAFLD and, alongside age, can be used to identify patients with highest risk of advanced disease.

Citation

Colosimo, S., Miller, H., Koutoukidis, D. A., Marjot, T., Tan, G. D., Harman, D. J., Aithal, G. P., Manousou, P., Forlano, R., Parker, R., Sheridan, D. A., Newsome, P. N., Alazawi, W., Cobbold, J. F., & Tomlinson, J. W. (in press). Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD. Diabetes Research and Clinical Practice, 217, Article 111820. https://doi.org/10.1016/j.diabres.2024.111820

• Journal Article Type: Article
• Acceptance Date: Aug 12, 2024
• Online Publication Date: Aug 13, 2024
• Deposit Date: Oct 29, 2024
• Publicly Available Date: Aug 14, 2025
• Journal: Diabetes research and clinical practice
• Print ISSN: 0168-8227
• Electronic ISSN: 1872-8227
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 217
• Article Number: 111820
• DOI: https://doi.org/10.1016/j.diabres.2024.111820
• Keywords: Liver fibrosis, Glucose control, Liver histology, Liver steatosis
• Public URL: https://nottingham-repository.worktribe.com/output/39159609
• Publisher URL: https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(24)00730-7/abstract