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

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

Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol

Introduction: Hypoglycaemia is a significant burden to people living with diabetes and an impediment to achieving optimal glycaemic outcomes. The use of continuous glucose monitoring (CGM) has improved the capacity to assess duration and level of hypoglycaemia. The personal impact of sensor-detected hypoglycaemia (SDH) is unclear. Hypo-METRICS is an observational study designed to define the threshold and duration of sensor glucose that provides the optimal sensitivity and specificity for events that people living with diabetes experience as hypoglycaemia. Methods: We will recruit 600 participants: 350 with insulin-treated type 2 diabetes, 200 with type 1 diabetes and awareness of hypoglycaemia and 50 with type 1 diabetes and impaired awareness of hypoglycaemia who have recent experience of hypoglycaemia. Participants will wear a blinded CGM device and an actigraphy monitor to differentiate awake and sleep times for 10 weeks. Participants will be asked to complete three short surveys each day using a bespoke mobile phone app, a technique known as ecological momentary assessment. Participants will also record all episodes of self-detected hypoglycaemia on the mobile app. We will use particle Markov chain Monte Carlo optimization to identify the optimal threshold and duration of SDH that have optimum sensitivity and specificity for detecting patient-reported hypoglycaemia. Key secondary objectives include measuring the impact of symptomatic and asymptomatic SDH on daily functioning and health economic outcomes. Ethics and dissemination: The protocol was approved by local ethical boards in all participating centres. Study results will be shared with participants, in peer-reviewed journal publications and conference presentations