The clinical utility of glycated haemoglobin (HbA1c) in primary care in the U.K

Cheilari, Stamatina (2021) The clinical utility of glycated haemoglobin (HbA1c) in primary care in the U.K. Doctoral thesis, University of East Anglia.

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In the United Kingdom (U.K), the incidence and prevalence of type 2 diabetes mellitus (T2DM) and its complications are increasing. Glycated haemoglobin (HbA1c), a diagnostic and monitoring indicator of long-term glucose control has been pivotal for the management of individuals at high risk of, or with DM, with a strong correlation between increased HbA1c levels and adverse outcomes. However, the validity of HbA1c as a prognostic and diagnostic tool is affected by co-morbid conditions or other biological factors.

This thesis consists of three studies with the common aim of improving the interpretation of HbA1c values across different ethnic populations, and in patients with different types and severity of anaemia, and with or without renal impairment in primary care in the U.K. In the first part, a systematic review and meta-analyses were conducted and HbA1c levels were compared with fasting plasma glucose (FPG) or oral glucose tolerance test (OGTT), among participants from different race/ethnicity. The purpose was to identify whether the variability of HbA1c values in different racial/ethnic groups is present in patients who have not yet been diagnosed with T2DM, to describe the appropriate categorisation of ethnicity/race in a clinical setting, and to ascertain whether the common threshold to diagnose T2DM should be adjusted in diverse ethnic/racial groups. The results showed that white subjects without diagnosed T2DM appear to obtain lower HbA1c values than black, Hispanic, and South & East Asian subjects for similar levels of FPG or OGTT.

For the second and third part, electronic health records obtained from the Clinical Practice Research Datalink (CPRD) were analysed. The aim of part two, was to evaluate, using a regression analysis the direction and extent to which anaemia and renal failure affect HbA1c measurements when compared to FPG. Our conclusions indicated that there is an apparent impact of mild to moderate chronic kidney disease (CKD) on HbA1c (lower estimates), however, this impact does not appear to be clinically significant in primary care for individuals with good long-term glucose control or for T2DM diagnosis. Also, anaemia does not appear to be a mediator, however individuals with severe anaemia require further attention.

Finally, for the third part, a survival analysis was developed to test whether HbA1c,categorised into glycaemic groups, has an effect on the subsequent incidence and progression of CKD, and all-cause mortality in patients with non-diabetic hyperglycaemia (NDH) and newly diagnosed T2DM. This study revealed that over an average follow-up of 3 years pre-diabetic and newly diagnosed with DM participants of HbA1c groups over 48 mmol/mol (6・5%) have an increased risk of incident and progression of CKD 3b or above, and a higher risk of all-cause mortality compared to subjects in lower groups. Data were insufficient to estimate the effect of HbA1c on progression to end-stage renal disease.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > School of Health Sciences
Depositing User: Chris White
Date Deposited: 01 Dec 2021 14:13
Last Modified: 01 Dec 2021 14:13

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