HbA1c may contribute to the development of non-alcoholic fatty liver disease even at normal-range levels

Biosci Rep. 2020 Jan 31;40(1):BSR20193996. doi: 10.1042/BSR20193996.


Previous clinical studies highlighted nonalcoholic fatty liver disease (NAFLD) as a hepatic facet of metabolic syndrome, which progresses toward Type 2 diabetes along with an elevation of HbA1c in the blood. Longitudinal observations were performed in a cohort of 2811 participants with no liver disease at inception. The rate of the conversion into NAFLD was 15.7% (440/2811), with a steady increase in prevalence observed in sub-cohorts with increasing HbA1c levels. Moreover, regression analysis indicated that HbA1c levels serve as the risk factors for NAFLD after multiple adjustments (odds ratio: 1.58, P-value < 0.004). When HbA1c-related molecular networks were investigated using natural language programming algorithms, multiple genetic/small molecular (SM) pathways were highlighted as connectors between the HbA1c levels and the development of NAFLD, including ones for nitric oxide, hypoxia and receptor for advanced glycation end products (RAGE). Our results suggest that increased levels of HbA1c may contribute to the progression of NAFLD either directly, by stimulating RAGE or indirectly, through the promotion of hypoxia and suppression of the release of NO. Further studies are needed to test the impact of HbA1c on the development of the chronic liver disease.

Keywords: HbA1c; RAGE; non-alcoholic fatty liver disease; pathway analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • China / epidemiology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Gene Regulatory Networks
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Incidence
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Non-alcoholic Fatty Liver Disease / blood*
  • Non-alcoholic Fatty Liver Disease / diagnosis
  • Non-alcoholic Fatty Liver Disease / epidemiology
  • Non-alcoholic Fatty Liver Disease / genetics
  • Prevalence
  • Protein Interaction Maps
  • Receptor for Advanced Glycation End Products / metabolism
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Up-Regulation


  • AGER protein, human
  • Biomarkers
  • Glycated Hemoglobin A
  • Receptor for Advanced Glycation End Products
  • hemoglobin A1c protein, human
  • Nitric Oxide