Haemoglobin types and variant interference with HbA1c and its association with uncontrolled HbA1c in type 2 diabetes mellitus

Diabetes mellitus is among the leading global health concerns, causing over 1.5 million deaths alongside other significant comorbidities and complications. Conventional diagnosis involves estimating fasting, random blood glucose levels and glucose tolerance test. For monitoring purposes, long-term glycaemic control has been achieved through the measurement of glycated haemoglobin (HbA1c) which is considered reliable and preferred tool. However, its estimation could be affected by haemoglobin types like HbA0, HbA2, and HbF concentrations whose magnitude remains unclear as well as other haematological parameters. As such, the current study determined the association between HbA1c and haemoglobin types and determined correlation between haemoglobin types and haematological parameters among patients with type 2 diabetes mellitus (T2DM) compared to healthy non-diabetic participants. In this cross-sectional study, participants [n = 144 (72 per group), ages 23-80 years] were recruited and the desired parameter measured. HbA1c and other Haemoglobin variants were measured using ion-exchange high-performance liquid chromatography (HPLC) by the Bio-Rad D-10 machine (Bio-Rad Laboratories, Inc). Haematological parameters were measured using the Celtac G MEK-i machine (Nihon Kohden Europe). SPSS version 27 (IBM Corporation, Chicago, Illinois, United States) was used for the analysis. Chi-square (χ²) analysis, Mann-Whitney U test, Binary logistic regression and Pearson correlation were used to determine the differences between proportions, compare laboratory characteristics, associations and correlations respectively. With non-diabetics as the reference group, HbA1c was associated with increased HbA0 [OR = 1.509, 95% CI = 1.020-1.099, p = 0.003] and increased HbA2 [OR = 3.893, 95% CI = 2.161-7.014, p = 0.001]. However, there was no significant association between HbA1c and HbF [OR = 2.062, 95% CI = 0.873-4.875, p = 0.099]. Further, haematocrit (HCT) had a negative correlation with HbAO and a positive correlation with HbAS in participants with controlled diabetes. Mean cell volume (MCV) and mean cell haemoglobin (MCH) had a negative correlation with HbF. MCHC (mean cell haemoglobin concentration) had a negative correlation with HbA2 in participant with uncontrolled diabetes. The study concluded that levels of various haemoglobin types should be considered while monitoring glycaemic control through HbA1c. Additionally, MCHC should be considered in individuals with high concentration of HbA2 among T2DM patients while interpretating results for HbA1c.