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.

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.

Evaluation of Accuracy and Performance of isCGM Sensors during Experimentally Induced Glucose Excursions. Comment on Moser et al. Performance of the Intermittently Scanned Continuous Glucose Monitoring (isCGM) System during a High Oral Glucose Challenge in Adults with Type 1 Diabetes-A Prospective Secondary Outcome Analysis. Biosensors 2021, 11, 22.

A 2021 publication in Biosensors from Moser and colleagues [...].

Reductions in HbA1c with Flash Glucose Monitoring Are Sustained for up to 24 Months: A Meta-Analysis of 75 Real-World Observational Studies.

INTRODUCTION: Real-world evidence (RWE) confirms that reductions in HbA1c for children and adults with type 1 diabetes (T1DM) and adults with type 2 diabetes (T2DM) are associated with use of the FreeStyle Libre system. This current meta-analysis aims to investigate whether HbA1c benefits are sustained over 24 months and to identify patterns of change in HbA1c for users of the FreeStyle Libre system for people living with T1DM or T2DM. METHODS: A bibliographic search up to December 2020 identified 75 studies reporting data on change in lab HbA1c in 30,478 participants with type 1 (n = 28,063; 62 trials) or type 2 diabetes (n = 2415; 13 trials) using the FreeStyle Libre system, including observations on children, adolescents and adults. Meta-analysis was performed using a random effects model. RESULTS: Reductions in HbA1c at 3-4 months were similar for adults with T1DM (- 0.53%, 95% CI - 0.69 to - 0.38) or with T2DM (- 0.45%, 95% CI - 0.57 to - 0.33), continuing through 4.5-7.5 months in T1DM (- 0.42%, 95% CI - 0.58 to - 0.27) and in T2DM (- 0.59%, 95% CI - 0.80 to - 0.39). Meta-regression analysis shows that higher starting HbA1c is correlated with greater reductions in HbA1c in T1DM and in T2DM. These patterns of change in HbA1c were sustained for 24 months in T1DM and for at least 12 months in T2DM. CONCLUSIONS: Meta-analysis of RWE confirms that using the FreeStyle Libre system is associated with significant reductions in HbA1c for adults with T1DM or with T2DM. Reductions are greater for people with higher baseline HbA1c and are sustained for 24 and 12 months in T1DM and TD2M respectively.

Improving HbA1c Control in Type 1 or Type 2 Diabetes Using Flash Glucose Monitoring: A Retrospective Observational Analysis in Two German Centres.

INTRODUCTION: The aim of this study was to evaluate change in laboratory-measured HbA1c in patients with either type 1 diabetes (T1D) or type 2 diabetes (T2D) on insulin therapy following initiation of the FreeStyle Libre™ flash glucose monitoring system. METHODS: This was a retrospective observational study on adults with T1D or T2D on insulin, who were started on the FreeStyle Libre system as part of standard care. HbA1c was recorded at initiation and at 3-month intervals thereafter. RESULTS: The analysis included 131 patients with T1D and 176 patients with T2D on insulin. Mean HbA1c decreased significantly by 3 months following initiation of the FreeStyle Libre system, both in T1D (- 0.75%, p < 0.001) and in T2D (- 0.54%, p < 0.001). Reductions were maintained for 12 months. Change from 3 to 12 months was not significant either in T1D or T2D. Subgroup analysis showed significant reduction in patients with a baseline HbA1c > 7.5-10%, both in T1D (- 0.59%, p < 0.001) and in T2D on insulin (- 0.62%, p < 0.005) at 12 months. Reductions for subjects with HbA1c > 10% were - 4.66% in T1D and - 3.73% in T2D. No change was seen for subjects with a baseline HbA1c ≤ 7.5% (58 mmol/mol). Linear regression confirms that baseline HbA1c is strongly negatively correlated with subsequent change in HbA1c in T1D and in T2D. CONCLUSIONS: Patients with T1D or T2D show a reduction in HbA1c by 3 months following initiation of the FreeStyle Libre system. The mean fall in HbA1c at 3 months is strongly negatively correlated with starting HbA1c. This reduction is maintained over 12 months. The significant benefit is seen in patients with a starting HbA1c > 7.5% (58 mmol/mol).

Telemonitoring, Telemedicine and Time in Range During the Pandemic: Paradigm Change for Diabetes Risk Management in the Post-COVID Future.

People with diabetes are at greater risk for negative outcomes from COVID-19. Though this risk is multifactorial, poor glycaemic control before and during admission to hospital for COVID-19 is likely to contribute to the increased risk. The COVID-19 pandemic and restrictions on mobility and interaction can also be expected to impact on daily glucose management of people with diabetes. Telemonitoring of glucose metrics has been widely used during the pandemic in people with diabetes, including adults and children with T1D, allowing an exploration of the impact of COVID-19 inside and outside the hospital setting on glycaemic control. To date, 27 studies including 69,294 individuals with T1D have reported the effect of glycaemic control during the COVID-19 pandemic. Despite restricted access to diabetes clinics, glycaemic control has not deteriorated for 25/27 cohorts and improved in 23/27 study groups. Significantly, time in range (TIR) 70-180 mg/dL (3.9-10 mmol/L) increased across 19/27 cohorts with a median 3.3% (- 6.0% to 11.2%) change. Thirty per cent of the cohorts with TIR data reported an average clinically significant TIR improvement of 5% or more, possibly as a consequence of more accurate glucose monitoring and improved connectivity through telemedicine. Periodic consultations using telemedicine enables care of people with diabetes while limiting the need for in-person attendance at diabetes clinics. Reports that sustained hyperglycaemia and early-stage diabetic ketoacidosis may go untreated because of the lockdown and concerns about potential exposure to the risk of infection argue for wider access to glucose telemonitoring. Therefore, in this paper we have critically reviewed reports concerning use of telemonitoring in the acute hospitalized setting as well as during daily diabetes management. Furthermore, we discuss the indications and implications of adopting telemonitoring and telemedicine in the present challenging time, as well as their potential for the future.

The Impact of Flash Glucose Monitoring on Glycaemic Control as Measured by HbA1c: A Meta-analysis of Clinical Trials and Real-World Observational Studies.

INTRODUCTION: Glycated haemoglobin A1c (HbA1c) is the established standard measurement for assessment of glycaemic control in people with diabetes. Here we report on a meta-analysis of real-world observational studies on the impact of flash continuous glucose monitoring on glycaemic control as measured by HbA1c. METHODS: A total of 271 studies were identified in our search, of which 29 contained data reporting changes in HbA1c over periods from 1 to 24 months that could be used in a statistical analysis. Our meta-analysis focuses on observed change in HbA1c at either 2, 3 or 4 months, in adult or paediatric subjects, as well as a longitudinal analysis up to 12 months in adult subjects. These data were drawn from 25 of the studies identified in our initial search. These reported HbA1c data up to 12 months in a total of 1723 participants with type 1 diabetes (T1D) or type 2 diabetes (T2D) using the FreeStyle Libre® flash glucose monitoring system. RESULTS: Overall mean change in laboratory HbA1c across study subjects at 2-4 months was - 0.55% (95% CI - 0.70, - 0.39). Amongst the 1023 adults, mean change in HbA1c was - 0.56% (95% CI - 0.76, - 0.36); for the 447 children and adolescents, mean change in HbA1c was - 0.54% (95% CI - 0.84, - 0.23). Based on regression analysis, the degree of change in HbA1c correlated with the initial HbA1c of the study population. A longitudinal analysis in adult subjects (n = 1276) shows that HbA1c fell within the first 2 months and changes were sustained up to 12 months. No significant differences were detected between T1D and T2D. CONCLUSION: The meta-analysis reported here confirms that starting the FreeStyle Libre system as part of diabetes care results in a significant and sustained reduction in HbA1c for adults and children with T1D and for adults with T2D. FUNDING: Abbott Diabetes Care.