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

Abstract 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] at the Bungoma County Referral Hospital were recruited using simple random sampling. 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-9100K machine (Nihon Kohden Europe). Chi-square (c2) analysis was used to determine the differences between proportions. Mann-Whitney U test was used to compare laboratory characteristics between (T2DM) patients and non-diabetics. With HbA0 as the reference group, association between HbA1c and haemoglobin types was determined using multivariate logistic regression. Correlation between haemoglobin types and haematological parameters was determined using Pearson correlation. HbA1c is associated with reduced HbA0 [OR=0.949, 95% CI=0.914-0.986, p=0.007], reduced HbA2 [OR=0.275, 95% CI=0.146-0.489, p=0.001] and reduced HbF [OR=0.322, 95% CI=0.140-0.745, p=0.008]. Further, HCT had a negative correlation with HbAO and a positive correlation with HbAS in participants with controlled diabetes. MCV and MCH had a negative correlation with HbF. The MCH had a negative correlation with HbA2 in participant with uncontrolled diabetes. The study concluded that HbA1c is significantly associated with reduced haemoglobin types (HbA0, HbA2, HbSS, and HbF) in type 2 diabetes mellitus hence levels of various haemobglobin types should be considered in monitoring glycaemic control.