Close relationship between high HbA1c levels and methemoglobin generation in human erythrocytes: The enhancement of oxidative stress in the process

J Diabetes Complications. 2023 Aug;37(8):108543. doi: 10.1016/j.jdiacomp.2023.108543. Epub 2023 Jun 13.

Abstract

Objective: This study aimed to investigate the effect of diabetic plasma on human red blood cells (RBCs) in order to highlight the amplification mechanisms of oxidative stress (OS) in relation to methemoglobin (metHb) production, a potential bio-indicator that could be related to diabetes disease.

Research design and methods: Normal RBCs were co-incubated with the diabetic plasma of 24 patients at different HbA1c levels, for 0, 24, and 48 h in order to assess cell turbidity and hemoglobin (Hb) stability. Hb and metHb production were quantified inside and outside RBCs. Malonaldehyde (MDA) level and cell morphology were concomitantly evaluated.

Results: The cell turbidity was significantly decreased in the group co-incubated with diabetic plasma at high HbA1c levels (0.074 ± 0.010 AU) compared to the control group (0.446 ± 0.019 AU). A significant decrease in intracellular Hb (0.390 ± 0.075 AU) and its stability (0.600 ± 0.001 AU) were revealed. Also, we found an important increase of metHb levels inside RBCs (0.186 ± 0.017 AU) and in its supernatant (0.086 ± 0.020 AU) after 48 h. Consequently, MDA absorbance increased significantly (0.320 ± 0.040 AU) in RBCs exposed to diabetic plasma with high HbA1c.

Conclusion: These findings suggest that poor glycemic control in diabetes leads to metHb generation which is the main factor of the OS amplification.

Keywords: Diabetic plasma; Hb; HbA(1c); MDA; Oxidative stress; RBCs; metHb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Erythrocytes*
  • Hemoglobins / metabolism
  • Humans
  • Methemoglobin* / metabolism
  • Methemoglobin* / pharmacology
  • Oxidative Stress

Substances

  • Methemoglobin
  • Hemoglobins