Understanding the clinical implications of differences between glucose management indicator and glycated haemoglobin

Abstract

Laboratory measured glycated haemoglobin (HbA1c) is the gold standard for assessing glycaemic control in people with diabetes and correlates with their risk of long‐term complications. The emergence of continuous glucose monitoring (CGM) has highlighted limitations of HbA1c testing. HbA1c can only be reviewed infrequently and can mask the risk of hypoglycaemia or extreme glucose fluctuations. While CGM provides insights in to the risk of hypoglycaemia as well as daily fluctuations of glucose, it can also be used to calculate an estimated HbA1c that has been used as a substitute for laboratory HbA1c. However, it is evident that estimated HbA1c and HbA1c values can differ widely. The glucose management indicator (GMI), calculated exclusively from CGM data, has been proposed. It uses the same scale (% or mmol/mol) as HbA1c, but is based on short‐term average glucose values, rather than long‐term glucose exposure. HbA1c and GMI values differ in up to 81% of individuals by more than ±0.1% and by more than ±0.3% in 51% of cases. Here, we review the factors that define these differences, such as the time period being assessed, the variation in glycation rates and factors such as anaemia and haemoglobinopathies. Recognizing and understanding the factors that cause differences between HbA1c and GMI is an important clinical skill. In circumstances when HbA1c is elevated above GMI, further attempts at intensification of therapy based solely on the HbA1c value may increase the risk of hypoglycaemia. The observed difference between GMI and HbA1c also informs the important question about the predictive ability of GMI regarding long‐term complications.

Evaluation of continuous glucose monitoring‐derived person‐specific HbA1c in the presence and absence of complications in type 1 diabetes

“…For the older age group (>60 years), a significant increase in the spread was seen for k gly and AGR, which is consistent with a previous observation 22 . This suggests that some older individuals will have higher HbA1c for given average glucose, which may lead to overtreatment and precipitation of hypoglycaemia that can have detrimental effects on this population 23–25 . Clinically, knowing such a difference can have an immediate benefit.…”

Comparison of MiniMed 780G system performance in users aged younger and older than 15 years: Evidence from 12 870 real‐world users

“…The limitations of the analysis include the lack of demographic data, medical history (including HbA1c) and users' duration of diabetes, which are not available in the CareLink software platform. While there is a clinically important difference between HbA1c and the GMI, 35 the latter provides a validated correlation between CGM metrics and managed glycaemia over time 36 . As GMI has become a CGM‐derived standard for glycaemic control, it was used as a surrogate for HbA1c for determining treatment goal achievement.…”

The ambulatory glucose profile and its interpretation

“…A GMI lower than the HbA 1c level indicates that the individual’s BGLs are lower than would be typically associated with the HbA 1c level 21 . Aggressive up‐titration of hypoglycaemic agents can lead to increased risk of hypoglycaemia 28 . However, these individuals are more prone to glycation, with increased risk of diabetes‐related nephropathy, retinopathy and mortality despite the same glucose exposure 29 .…”