HbA1c Outperforms BMI in Predicting NAFLD Severity: Study Reveals

"HbA1c provides more precise insights into NAFLD severity than BMI," the researchers wrote in their study published in Diabetes Research and Clinical Practice. "Incorporating HbA1c assessments into the comprehensive evaluation of NAFLD patients is essential, as it, along with age, helps pinpoint those at the highest risk of advanced disease."

NAFLD, a condition characterized by excess fat accumulation in the liver independent of alcohol consumption, affects a significant portion of the global population and is often linked with metabolic disorders such as diabetes and obesity. Traditionally, BMI has been used as a primary indicator of NAFLD severity, but emerging research highlights HbA1c as a more robust predictor of disease advancement. Considering this, Santo Colosimo, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, and colleagues aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes (T2D).

For this purpose, the researchers collected data from 857 patients with liver biopsy-confirmed NAFLD, employing generalized-linear models and binomial regression analysis to explore the relationships between histological NAFLD severity, age, HbA1c, and BMI. Additionally, paired biopsies from 421 patients involved in interventional studies were analyzed to evaluate the effects of weight changes, HbA1c levels, and active versus placebo treatments on improvements in steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis.

The following were the key findings of the study:

• In the discovery cohort of 687 patients, the risk of severe steatosis, NASH, and advanced fibrosis showed a positive correlation with HbA1c levels, even after accounting for obesity and age. These findings were validated in a separate cohort of 170 patients.
• Predictive modeling incorporating HbA1c and age proved comparable to the established non-invasive biomarker Fib-4, enabling the creation of risk charts adjusted for HbA1c, age, and BMI to forecast NAFLD severity.
• Post-intervention, a reduction in HbA1c was linked to improvements in steatosis and NASH, independent of weight change and treatment.
• Changes in fibrosis were only associated with alterations in weight and treatment.

The team concluded HbA1c is "extremely informative" for predicting NAFLD severity and offers greater insight into disease status than BMI. Specifically, a one percent-point change in HbA1c carries the same risk to liver health as an 8 kg change in body weight.

Reference:

Colosimo S, Miller H, Koutoukidis DA, Marjot T, Tan GD, Harman DJ, Aithal GP, Manousou P, Forlano R, Parker R, Sheridan DA, Newsome PN, Alazawi W, Cobbold JF, Tomlinson JW. Glycated hemoglobin is a major predictor of disease severity in patients with NAFLD. Diabetes Res Clin Pract. 2024 Aug 13:111820. doi: 10.1016/j.diabres.2024.111820. Epub ahead of print. PMID: 39147101.