Albumin Abundance and Its Glycation Status Determine Hemoglobin Glycation

Diabetes
diagnosis and management majorly depend upon the measurement
of glycated hemoglobin (HbA1c) levels. Various factors influence HbA1c
levels such as the use of various analytical methods and the presence
of various clinical conditions. Plasma albumin levels were known to
be negatively associated with HbA1c. However, the precise mechanism
by which they affect HbA1c is not well understood. Therefore, we have
studied the influence of albumin levels and its glycation status on
hemoglobin glycation using erythrocyte culture experiments. Erythrocytes
maintained at low albumin concentration exhibited relatively increased
albumin and hemoglobin glycation as compared to that in those maintained
at higher albumin concentration. Increase in albumin glycation may
decrease its ability to protect hemoglobin glycation. This was demonstrated
by treatment of erythrocytes with N(ε)-(carboxymethyl)­lysine-modified
serum albumin (CMSA), which failed to protect hemoglobin glycation;
instead, it increased hemoglobin glycation. The inability of CMSA
to reduce hemoglobin glycation was due to the lack of free lysine
residues of albumin, which was corroborated by using N(ε)-(acetyl)­lysine serum albumin (AcSA) and clinical diabetic
plasma. This is the first study which demonstrates that the modification
of lysine residues of albumin impairs its ability to inhibit hemoglobin
glycation. Furthermore, correlation studies between HbA1c and albumin
levels or relative albumin fructosamine from clinical subjects supported
our experimental finding that albumin abundance and its glycation
status influence hemoglobin glycation. Therefore, we propose albumin
level and its glycation status to be quantified in conjunction with
HbA1c for better management of diabetes.