d i a b e t e s r e s e a r c h a n d c l i n i c a l p r a c t i c e 187 (2022) 109867

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Diabetes Research and Clinical Practice

journal homepage: www.journals.elsevier.com/diabetes-research-and-clinical-practice

A guide for the use of LibreView digital diabetes platform in clinical

practice: Expert paper of the Italian Working Group on Diabetes
and Technology
Sergio Di Molfetta a, 1, Antonio Rossi b, 1, Roberta Assaloni c, Valentino Cherubini d,
Agostino Consoli e, Paolo Di Bartolo f, Vincenzo Guardasole g, Andrea Laurenzi h,
Fortunato Lombardo i, Claudio Maffeis j, Andrea Scaramuzza k, Concetta Irace l, AMD-SID-SIEDP
Working group on Diabetes and Technology
a
Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro,
Bari, Italy
b
Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy
c
Diabetes Unit ASS2 Bassa-Friulana Isontina, Udine, Monfalcone, GO, Italy
d
Department of Women’s and Children’s Health, G. Salesi Hospital, Ancona, Italy
e
Endocrinology and Metabolic Diseases, University of Chieti-Pescara, Chieti, Italy
f
AUSL Diabetes Unit Romagna, Ravenna, Italy
g
Department of Translational Medical Sciences, University Federico II, Naples, Italy
h
San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
i
Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Messina, Italy
j
Pediatric Diabetes and Metabolic Disorders Unit, Regional Center for Pediatric Diabetes, University City Hospital of Verona, Verona, Italy
k
Division of Pediatrics, ASST Cremona, “Ospedale Maggiore di Cremona”, Cremona, Italy
l
Department of Health Science, University Magna Graecia, Catanzaro, Italy

A R T I C L E I N F O A B S T R A C T

Keywords: Wider access to continuous glucose monitoring systems, including flash glucose monitoring, has enabled people
Continuous glucose monitoring with diabetes to achieve lower HbA1c levels and reduce the amount of time they spend in hypoglycaemia or
CGM hyperglycaemia, and has improved their quality of life. An International Consensus Panel proposed different
LibreView
target glucose ranges and recommendations according to different ages and situations (adults, young people and
Diabetes management system
Flash glucose monitoring
children with type 1 or type 2 diabetes, as well as elderly people who are at higher risk of hypoglycaemia, and
Time in range women with diabetes during pregnancy).
Hypoglycaemia In this expert opinion, we interpret the international recommendations in the context of established clinical
Glycaemic variability practice for diabetes care, and propose three different step-by-step algorithms to help the healthcare pro­
fessionals use the most innovative glucose metrics, including time in glucose ranges, glucose management in­
dicator, coefficient of variation, and ambulatory glucose profile. In detail, we focus on glucose metrics as
measured by the FreeStyle Libre system and as visualized on the LibreView digital diabetes platform to support
appropriate interpretation of flash glucose monitoring data. This is specifically structured for healthcare pro­
fessionals and general practitioners who may have a low level of confidence with diabetes technology, with the
aim of optimizing diabetes management, ensuring effective use of healthcare resources and to maximise out­
comes for people with diabetes.

1. Introduction Currently, two types of CGM systems are available for personal use: real-
time CGM (rtCGM) and intermittently scanned CGM, also labeled flash
Continuous glucose monitoring (CGM) is an effective technology to glucose monitoring (FGM), both of which measure glucose in the
enable people with diabetes to achieve better glucose control [1,2]. interstitial fluid (ISF) [3]. Both systems measure glucose every few

1
These authors equally contributed to the manuscript.

https://doi.org/10.1016/j.diabres.2022.109867
Received 13 December 2021; Received in revised form 16 March 2022; Accepted 4 April 2022
Available online 9 April 2022
0168-8227/© 2022 Elsevier B.V. All rights reserved.

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S. Di Molfetta et al. Diabetes Research and Clinical Practice 187 (2022) 109867

minutes, and while rtCGM actively transmits data wirelessly from the More recently, the FreeStyle Libre 2 sensor has become available that
sensor to a reader or smartphone app, FGM systems transmit data only includes high and low glucose alarm functionality, not previously an
when users scan their sensors with a reader or smartphone app. option for first-generation FreeStyle Libre sensors. Whether this can
Currently, one of the most widely used glucose monitoring systems is have additional impact on outcomes will require further studies.
the FreeStyle Libre FGM system (Abbott, Alameda CA), which consists of In this expert opinion, we interpret the International Consensus
a small glucose sensor usually applied to the back of the upper arm, with recommendations in the context of established clinical practice for
a 5 mm sensor filament that is inserted into the subcutaneous space and diabetes care. In doing so, we provide step-by-step algorithms to help the
measures glucose in the ISF. The FreeStyle Libre has a 14-day wear time, HCPs use the most innovative glucose metrics including time in glucose
during which it measures and displays on demand glucose every minute. ranges, GMI, and CV, and the ambulatory glucose profile (AGP) as
All the data are continuously stored and available for retrospective represented in the standardized report format. To provide relevant and
calculation of glucose metrics at intervals of 15 min. practical examples, we focus on glucose metrics as measured by the
The sensors are factory calibrated, eliminating the need for users to FreeStyle Libre system, and visualized with the LibreView digital dia­
self-calibrate using capillary-blood fingerprick tests, and are accurate, betes platform. Ultimately, our goal is to support appropriate interpre­
with a mean absolute relative difference (MARD) of 9.2% for adults and tation of FGM data in order to optimize diabetes management, ensure
9.7% for children and adolescents [4], which indicates a level of effective use of healthcare resources, and maximise outcomes for people
concurrence with reference blood-glucose measurements sufficient for with diabetes.
clinical decision making. For this reason, the FreeStyle Libre system is
approved for making insulin dosing decisions without the need for 2. Application of time in glucose ranges in diabetes clinical care
adjunctive fingerpick testing. The system requires that users scan their
sensors to see a glucose reading and the associated trend arrow that As use of glucose monitoring systems becomes widespread in dia­
indicates the rate of change (ROC) of glucose. The need to scan with betes management, it is important to acknowledge the need to move
FGM is also emphasized by the fact that if the sensor is not scanned every beyond using HbA1c as the predominant marker of glucose control and
8 h, then glucose data that is collected outside of the most-recent 8 h can to support the application of more dynamic and comprehensive mea­
be lost. sures of diabetes health. A number of metrics have been adopted for
The sensor can transmit glucose values either to the LibreLink interpreting the wealth of glucose data provided by FGM (Table 1).
smartphone app or to a dedicated reader. Data collected by the LibreLink Time in glucose ranges indicates the proportion of each day that a
app are automatically uploaded to the cloud every time the phone is person with diabetes spends with glucose readings in each of three
connected to the internet, whereas the data stored in the reader have to ranges that have been defined by the international consensus group
be uploaded following connection to an internet-connected computer. (Supplementary Table 1) [1]. TIR indicates the amount of time that
Once uploaded, all glucose data are available to view in the LibreView glucose readings are within a defined target glucose range of 70–180
digital diabetes system, from where glucose management reports are mg/dL (or 63–140 mg/dL during pregnancy). TBR refers to the amount
automatically collated to be examined by healthcare professionals of time spent below the target glucose range (<70 mg/dl, or < 63 mg/dL
(HCPs) or by patients. Available reports include summaries of the user’s during pregnancy), and TAR refers to the amount of time above the
percentage time in range (TIR), time below range (TBR) and time above target range (>180 mg/dL, or > 140 mg/dL during pregnancy). TBR and
range (TAR), as well as calculated metrics for glycemic variability using TAR can be divided into low/very low and high/very high ranges,
the coefficient of variation (CV) and the overall glucose exposure using depending on the profile of the person with diabetes. As a focus for
the mean sensor glucose, and the glucose management indicator (GMI). assessing glucose control, TIR is easily understandable by people with
[5,6]. diabetes and by their HCPs. More importantly, TIR is immediately
Use of the FGM system is associated with lowered HbA1c, in adults responsive to changes in medication, diet and lifestyle that can be
and in children with type 1 diabetes [7–10] and in adults with type 2
diabetes treated either with insulin [10–13] or non-insulin therapy
[14,15]. A meta-analysis of 25 real-world studies indicates that HbA1c Table 1
falls by a mean of − 0.56% in adult users and by − 0.54% for children and Objective measures of glycaemic control derived from FGM and rtCGM systems.
adolescents [7]. Use of the FGM system is also associated with less time Metric What does it measure?
spent in hypoglycaemia, including nocturnal hypoglycaemia, in type 1
% of sensor data captured The proportion of possible readings captured by the
and type 2 diabetes [16,17], improved quality of life [11,18–20], and
rtCGM or FGM device. Provides a measure of
reduction in hospital admissions for acute diabetes events (ADEs) such confidence in the other data-derived outcomes.
as diabetic ketoacidosis (DKA) and severe hypoglycaemia [21–23]. The Time in Ranges
RELIEF study [21] showed a 56.2% and a 52.1% fall of admissions for Time In Range (TIR) Measures the % of time spent in the target glucose
range set on the rtCGM or FGM system – defined as
DKA in type 1 diabetes and type 2 diabetes patients, respectively, once
70–180 mg/dL (63–140 mg/dL in pregnancy)
reimbursement for FGM was approved in France, and a 43% drop in Time Below Range (TBR) Measures the % of time spent below the target glucose
admissions for severe hypoglycaemia was reported in Israel in the 12 range set on the rtCGM or FGM system – defined as
months after FGM was initiated for people with T1DM [24]. The Free­ below 70 mg/dL (63 mg/dL in pregnancy)
Style Libre system has been CE marked for use in pregnancy with dia­ Time Above Range (TAR) Measures the % of time spent above the target glucose
range set on the rtCGM or FGM system – defined as
betes since 2017. In a cohort of 74 participants with type 1, type 2, or
above 180 mg/dL (140 mg/dL in pregnancy)
gestational diabetes mellitus (GDM) from 13 sites in Europe, clinical Mean Glucose A measure of the average 24-hour glucose
accuracy of sensor readings versus self-monitoring blood glucose concentration calculated across all of the recorded
(SMBG) was demonstrated, with 88.1% and 99.8% of results within glucose readings in a day
Glucose Management A measure of short-term glucose exposure that can be
Zone A and Zones A and B of the Consensus Error Grid, respectively [25].
Indicator (GMI) used in conjunction with long-term HbA1c making
More recently, FGM has been demonstrated to be as effective as SMBG in treatment decisions
lowering the HbA1c level in a cohort of 40 women with pregestational Coefficient of Variation A measure of variability. Expressed as %CV
diabetes, with additional benefit in terms of TBR and glucose variability (CV)
reduction. Notably, in this cohort, the number of daily FGM scans was Each of these measures of glucose control or variability can be derived and re­
positively associated with HbA1c reduction [26]. ported by FGM (Flash Glucose Monitoring and rtCGM (real-time Continuous
The majority of the outcomes data reported in the studies above was Glucose Monitoring) systems. They are all endorsed by international consensus
substantially generated from the first generation FreeStyle Libre sensor. guidance on use of CGM systems in management of diabetes [5,53].

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visualized in day-to-day diabetes management. paper will be of benefit.

HbA1c is the gold-standard for understanding population-based risks
for developing macrovascular and microvascular complications [27,28]; 3.1. Step 1: Evaluate data sufficiency
however, TIR is becoming a reference for the treatment of diabetes. With
the aim to assess any relationship between TIR and long-term compli­ Fundamental to accurate and meaningful interpretation of FGM data
cations, SMBG data from the Diabetes Control and Complications Trial is ensuring that enough glucose data have been collected. Studies have
(DCCT) have been reanalyzed to calculate the TIR 70–180 mg/dL of shown that 14 consecutive days of FGM, if ≥ 70% of data are available,
participants with and without microvascular complications [29]. Study correlate satisfactorily with 3 months of glycaemic data for the assess­
subjects who developed complications had a 10–12% (2.5–3.0 h/day) ment of mean glucose, TIR and measures of hyperglycaemia, and addi­
lower TIR when compared to participants who did not develop com­ tional days of data do not substantially increase this correlation [37,38].
plications. For each 10% decrease in TIR (2 h 24 mins less each day), the It is worth noting that the association between the mean glucose and the
risk of progression of retinopathy was increased by 64% and risk of laboratory-measured HbA1c is stronger when using the 14 days that
developing microalbuminuria was increased by 40%. In a separate study immediately precede the time of the HbA1c test reading [38]. This is
that used retrospective CGM to measure glucose control in 3,262 people important in the context of Step 2, below.
with type 2 diabetes, TIR was again inversely correlated with the Since adequate wear time can be an issue it should be discussed in
prevalence and severity of diabetic retinopathy, so that a higher TIR was the consultation. When the patient can’t ensure adequate wear time, the
associated with less, and less severe, retinopathy [30]. Increased TIR clinician should investigate potential issues regarding sensor adhesion
also correlates with improved peripheral nerve function [31,32]. Most or adverse reactions, as well as insufficient skills or psychological
notably, analyses of blinded CGM in 2,983 people with type 2 diabetes distress, provide suggestions for increasing FGM wear time, for instance
demonstrated a relationship between TIR and carotid intimal thickness providing tips to help sensor adhesion [39] or motivating the patient to
[33], and a 10-year follow up of 6,225 adult patients with type 2 dia­ increase the frequency of daily scans (e.g., before and 1–2 h after meals,
betes has shown that TIR is correlated with the hazard ratio for all-cause at bedtime, before, during and after exercise, and in case of symptoms of
mortality and for cardiovascular mortality [34]. hypoglycaemia), and evaluate psychological well-being with validated
In terms of implementing these metrics in day-to-day clinical prac­ tests [40,41]. If necessary, professional psychological support may be
tice, the International Consensus on Time in Range [5] has defined a needed and encouraged.
series of clinical targets for TIR, TBR and TAR that can be applied to Similarly, while confirming the importance of the 70% data capture
people with type 1 or type 2 diabetes. Separate recommendations have to use the proposed algorithm, a quick evaluation of daily glucose pro­
also been made for pregnant women with type 1 diabetes and for people files may be valuable in order to assess whether occurrences of very low
who are at higher risk of hypoglycaemia because of age, duration of (i.e. < 54 mg/dL) or very high (i.e. > 250 mg/dL) glucose episodes are
diabetes, duration of insulin therapy or impaired awareness of hypo­ evident and whether these need to be discussed.
glycaemia (IAH), irrespective of diabetes type. Because of the lack of
evidence to guide CGM targets for pregnant women with type 2 diabetes 3.2. Step 2: Evaluate the glucose management indicator (GMI)
or GDM, firm recommendations for TIR, TBR and TAR have not been
established yet. However, recent data suggest that very strict glycemic The GMI, either expressed as a % or as mmol/mol, is a measure of
control [35] and reduction of nocturnal hyperglycaemia may be short-term glucose control which is intended to convey information
required to normalize outcomes in pregnant women with GDM [36]. about overall glucose exposure over the 14-day assessment period [6].
Specific targets for these groups of people with diabetes are detailed GMI is calculated from CGM-derived mean glucose and can be compared
in Supplementary Table 1. The international consensus recommenda­ alongside laboratory-tested HbA1c, but it is important to note that the
tions also emphasise the importance of setting individual goals for time two measures are not expected to be identical in value and are likely to
spent within any defined glycaemic range, which is an essential part of differ in at least 81% of cases [6]. GMI can be used in clinical practice to
implementing TIR, TBR and TAR in clinical practice [5]. evaluate the overall glucose control in the short term or when HbA1c is
unavailable or unreliable. HbA1c is produced by a post-translational
3. Treatment algorithms to navigate LibreView digital diabetes modification of hemoglobin when glucose reacts with the amino
platform group on a hemoglobin molecule, forming a ketoamine. Although
HbA1c formation is proportional to average blood glucose concentra­
We have developed three separate algorithms that each identify a tion, it is also influenced by a range of non-glycemic factors, such that an
possible 6-step treatment path for different groups of people with dia­ HbA1c test reading may be higher or lower than that predicted by
betes: (1) non-fragile, non-pregnant adults with either type 1 or type 2 average glucose alone, showing the so-called “glycation gap” [42].
diabetes; (2) fragile adults with type 1 or type 2 diabetes; (3) pregnant These non-glycemic factors are both analytical and biological and are
women with type 1, type 2 or GDM. The term ‘fragile’ adults refers to the summarized in Supplementary Table 2, along with their influence on
older/high-risk as reported in the consensus, i.e. people at higher risk for HbA1c accuracy.
severe hypoglycaemia due to age, duration of diabetes, hypoglycaemia
unawareness and/or people who are particularly vulnerable to adverse 3.3. Step 3: Identify the appropriate target glucose range and evaluate
events associated with hypoglycaemia due to comorbid conditions like time in different glucose ranges
cognitive deficits, renal disease, cardiovascular disease [5]. These visual
treatment algorithms are presented in Figs. 1-3 and are self-explanatory Each person with diabetes must have the target glucose range and
when used in conjunction with the defined treatment interventions time in ranges requirements that apply to his/her status. For non-fragile
indicated in boxes 1-5, therefore we will not describe each treatment and fragile adults, the glucose ranges are the same, but the consensus
option in detail. However, we will clarify the general 6-step approach targets differ. For fragile adults, the TIR target has been lowered from >
that is common among the three algorithms. An easy-to-use tool for 70% to > 50%, and the TBR reduced to < 1%. For diabetes in pregnancy,
reporting FGM data-informed clinical evaluation is also provided the target glucose range must be changed from the default setting for the
(Fig. 4). With the greater use of FGM system amongst people with type 1 FreeStyle Libre system (70–180 mg/dL) to 63–140 mg/dL. This can be
diabetes or type 2 diabetes, healthcare professionals and general prac­ done in the LibreView platform.
titioners who have low level of confidence with diabetes technology will Each of the targets for TIR, TBR and TAR and the patient’s specific
increasingly be required to manage their patients using FGM metrics and metrics against these targets is provided in the top part of the AGP
AGP reports. We believe that the algorithms presented in this expert Report that is compiled by the LibreView data platform (Fig. 5).

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Fig. 1. Non-fragile, non-pregnant T1DM and T2DM adult patients.

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Fig. 2. Fragile adult T1DM and T2DM patients.

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Fig. 3. Pregnant T1DM, T2DM or GDM patients.

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Box 1
Enhanced Management Plan.

• Suggest increasing the frequency of daily scans.

• Suggest inserting notes on carbohydrate intake and insulin doses.
• Consider aiming at more-stringent treatment targets for TIR.
• Encourage patient’s self-monitoring of TIR.
• Encourage patient’s retrospective review of FGM data.
• Intensify ongoing treatment without increasing the risk of hypoglycaemia.
• Discuss bolus insulin adjustments based on trend arrows.
• Consider insulin bolus calculations for fat and protein.

Box 2
Possible interventions for reduction of glycaemic variability.

• Review the insulin injection technique.

• Identify areas of lipodystrophy.
• Discuss the importance of appropriate timing of bolus insulin administration.
• Discuss bolus insulin adjustments based on trend arrows.
• Improve management of physical activity.

Box 3
Possible interventions for hypoglycaemia reduction.

• Consider de-intensification of insulin therapy.

• Switch to a second-generation long-acting insulin analogues [59,60].
• Reinforce the proper hypoglycaemia treatment protocol.
• Suggest increasing the frequency of daily scans with FGM system.
• Review carbohydrate-counting principles and insulin sensitivity factor.
• Ask about prior episodes of severe hypoglycaemia and activities of daily life (physical activity, alcohol intake, etc..).
• Investigate the presence of hypoglycaemia unawareness [61].
• Consider switching to second-generation FGM system with threshold alerts.
• Review the low glucose alert threshold if using second-generation FGM system.
• If TBR is consistently > 4% at follow-up, consider switching to rtCGM with predictive low-glucose alerts, hybrid closed-loop or low-glucose
suspend pumps [62].

Box 4
Possible interventions for hyperglycaemia reduction.

• Consider intensification of insulin therapy.

• Suggest increasing the frequency of daily scans with FGM system.
• Review carbohydrate-counting principles.
• Review hyperglycaemia correction principles with insulin sensitivity factor.
• Ask about prior episodes of severe hypoglycaemia and fear of hypoglycaemia (using the FH-15 scale [63]).
• Reinforce principles for diabetic ketoacidosis (DKA) prevention and early detection in patients whose time in hyperglycaemia >250 mg/dL is
> 5%.
• Consider adding non-insulin treatment if applicable or implement ongoing non-insulin treatment.

However, note that when reviewing TIR, TBR and TAR for any glucose which is associated with severe adverse events, risk of developing IAH,
range that is different from the default, the necessary metrics for TIR, reduced quality of life and poor adherence with diabetes therapy [43].
TBR and TAR must be viewed in the ‘Snapshot’ report screen rather than Likewise, lower TIR is associated with an increased risk of microvascular
the AGP Report screen, which always shows the default glucose ranges. and macrovascular complications of diabetes [29,30,32–34,44]. How­
In Step 3, three alternative pathways are suggested depending on: (1) ever, this evidence has not yet been fully validated in a prospective
TBR and TIR are at the target levels (green pathway); (2) high TBR is a randomized clinical trial (RCT) with TIR as the primary outcome. TAR is
concern (red pathway); (3) low TIR is a concern (yellow pathway). at a slightly lower priority for assertive management in many patients
Exceeding the target for TBR creates a risk of recurrent hypoglycaemia, since improvements in TIR typically come as a consequence of reduced

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Box 5
Possible interventions for hyperglycaemia and glycemic variability reduction.

• Same as box 4, but be more cautious with intensification of insulin therapy.

• Reinforce the proper hypoglycaemia treatment protocols.
• Review patient’s daily habits and screen for diabetes distress.

Fig. 4. Tool for reporting FGM data-informed clinical evaluation.

TAR, when TBR is stably low. Following adjustments to therapy, band, typically shaded in lighter blue. These are described in detail in
changes in TAR should help assess the efficacy of the intervention. For Fig. 6. Each of the defined features of the AGP graph tell a clear story
women with diabetes during pregnancy, there is evidence that hyper­ about glucose control across each day and between different days and
glycaemia may be a contributing factor to adverse perinatal outcomes, can be used in a systematic and straightforward way to identify trends in
such as macrosomia [45], emphasising the need to reduce TAR as much glucose control on which clinical decisions can be taken [46,47].
as possible. When the median line or the 25th percentile falls close to or below
70 mg/dL, or the 5th percentile falls close to or below 54 mg/dL
3.4. Step 4: Evaluate the ambulatory glucose profile (AGP) and patterns regardless the value of TIR, a high priority hypoglycaemic pattern exists
of hypoglycaemia and hyperglycaemia and an immediate action is required. Conversely, when the median line
or the 75th percentile rises close to or above 180 mg/dL, or the 95th
In patients who are not hitting their targets of TIR and/or TBR, the percentile rises close to or above 250 mg/dL, correction of hyper­
AGP graph (Fig. 6) helps to identify the time of occurrence (i.e. during glycaemia is urgently required.
the night, before or after meals) and the severity of any hypoglycaemic These thresholds for hypoglycaemia or hyperglycaemia are tighter
or hyperglycaemic pattern. for diabetes in pregnancy (Fig. 3) but the assessment need is the same. It
The AGP graph provides a visually impactful summary that allows is important to note that, for people who are older or more-fragile
the HCPs to identify patterns and trends in daily glucose control. The (Fig. 2), avoiding hypoglycaemia is mandatory and interventions to
AGP graph comprises four key features: the target glucose range; the lower glucose should be more cautious. As indicated, patients who are
median line; the dark-blue shaded 25th-75th percentile band, also meeting their recommended targets for TIR and TBR, Step 4 is not
known as the interquartile range (IQR); the outer 5th- 95th percentile essential and their assessment can move from Step 3 to Step 5.

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Fig. 5. Time in range statistics and measures as provided in the AGP Report. The AGP Report is compiled and downloaded from the LibreView diabetes data
platform. The default setting is to show time in range for the target glucose range 70–180 mg/dL. For visualizing metrics for time in range 63–140 mg/dL in
pregnancy, use the ‘Snapshot’ report.

Fig. 6. The essential features of an AGP graph explained, 1) Two parallel lines – the Target Glucose Range, typically 70–180 mg/dL except in pregnancy. 2)
Median line – this dark blue line shows the average glucose at each point in the day. It provides a visual trace of whether average glucose is within the target glucose
range and how much oscillates during the day. 3) Inner blue-shaded band – this is 25th to 75th percentile band, also called the interquartile range (IQR). It shows
the 50% of all glucose readings that are closest to the median line and their variability from day-to-day. This blue IQR band shows more-consistent daily trends in
glucose levels and indicates how medication and mealtimes are influencing glucose control. The wider this darker-blue shaded band is, the more variable are these
day-to-day readings. 4) Outside grey-shaded band – this is the 5th-95th percentile. This shows glucose readings that reflect ‘occasional’ departures from the daily
average glucose. This is glucose variation that is happening on some days but not others and can indicate how behaviour and lifestyle issues are impacting on glucose
control. The wider this grey band is, the more variable are these occasional readings. (For interpretation of the references to colour in this figure legend, the reader is
referred to the web version of this article.)

3.5. Step 5: Assess glucose variability within each day or among days coefficient of variation of the 24-hour mean glucose values (CV) [53]. A
threshold for CV of ≤ 36% is currently set as differentiating between
Measurable glucose variability is now associated with an increased stable and unstable glucose profile, based on the observation that the
risk of microvascular and macrovascular complications of diabetes frequency of hypoglycaemic events rose significantly if this value was
[48–52]. Therefore, an essential component of any evaluation of FGM exceeded [54]. Thus, Step 5 indicates that any patient with CV of > 36%
glucose metrics in a person with diabetes is the assessment of glucose is at a higher risk of hypoglycaemia, and that the source of excess
variability. Glucose fluctuations within a day (intraday) and from one variability should be examined by moving on to Step 6, i.e. looking at
day to another (interday) must both be considered here. Intraday the daily glucose profiles that cover the period of the AGP in question.
glucose variability is often associated with the specifics of treatment and For patients with a CV of ≤ 36%, further evaluation is not mandatory.
can be targeted by adjusting treatment parameters as indicated. Interday Review of daily glucose profiles is suggested irrespective of %CV value
variability may prompt a discussion with the patient about the causes of in cases where concerns may emerge during the consultation or when a
high or low glucose traces occurring on some days but not on others. deeper educational intervention is required, namely in the first period
The parameter defined as representing glucose variability is the after FGM initiation. In selected individuals (e.g. pregnant women,

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Fig. 3) with either TIR, TBR, and CV at the target level, an enhanced 5. Conclusions
management plan (box 1) could be pursued to achieve even tighter
glucose outcomes. However, this is not the first choice for fragile pa­ In this expert opinion we have set out the core process for adhering
tients (Fig. 2). These caveats are indicated by dashed lines in each case. the international recommendations [5] in the context of the LibreView
digital diabetes platform. We highlighted the important use of the
3.6. Step 6: Navigate using daily glucose profiles consensus targets for TIR, TBR, TAR and CV combined with the elements
of the visual AGP format that provides insight into the dynamic changes
When glucose variability is calculated to be high (CV > 36%), the in glucose control across a typical day. We propose treatment algorithms
aim of reviewing daily glucose printouts is to double-check when pat­ based on consensus targets for non-fragile, non-pregnant adults with
terns of low/high glucose occur (hour of the day or day in the week). The either type 1 or type 2 diabetes, fragile adults with type 1 or type 2
individual daily profiles are shown either in the bottom of LibreView diabetes, and pregnant women with diabetes. These algorithms can
AGP Report, in the Daily Logs and Weekly Summary reports. guide HCPs through six steps, from assessing if there is sufficient glucose
Importantly, the interpretation of daily glucose variability is facili­ data for a clinically effective diabetes review, through to deciding on
tated if the patient has used the features of the FreeStyle Libre system to potential interventions. At each step, essential checkpoints are identified
add notes on insulin doses, exercise, mealtimes and meals composition. along with the requirements for managing care for patients not meeting
Addressing the causes of glucose variability can mean making changes to one or more of the consensus targets.
standard treatment parameters, but for all causes of variability the value Although these algorithms are intended to clarify and consolidate the
of organized diabetes education should be emphasized. practice of using FGM glucose metrics and the associated consensus
targets at the heart of diabetes care, we must emphasize the importance
4. Pediatrician’s point of view of individualized care and the skills of each HCP in optimizing outcomes
for each person with diabetes.
FGM is widely used in children and adolescents treated either with
multiple daily injections or insulin pump therapy due to its convenience 6. Perspectives
and practicality [55]. Randomized controlled trials and real world data
suggest that FGM improves quality of life, satisfaction for patients and FGM improves HbA1c and enables people with diabetes to achieve
care givers, self-efficacy, and frequency of glucose monitoring in a pe­ the recommended time in glucose ranges. Some cross-sectional and
diatric population with type 1 diabetes. HbA1c and glucose metrics are retrospective research has also indicated the potential of FGM to reduce
improved by using FGM compared to SMBG in some studies but not in the chronic complications of diabetes. More-robust prospective data are
others. However, the recent report published in the Canadian Journal of certainly needed to confirm the efficacy of increasing TIR to reduce
Health Technology, reviewing all data available in pediatric population diabetes complications. The use of FGM contributes to improve the
with type 1 diabetes, generally suggest that the use of FGM is associated quality of life of patients with diabetes. The FreeStyle Libre system is
with improved clinical outcomes [56]. In general, more emphasis must user-friendly, does not require self-calibration and the FreeStyle Libre 2
be placed on education of children and adolescents with diabetes and system provides optional alarms for hypoglycaemia and
their families when using the FreeStyle Libre system. hyperglycaemia.
For some years, continuous monitoring of interstitial glucose levels The LibreView platform allows health care providers and patients to
has become the first choice for glucose monitoring in pediatric clinical be continuously connected, and it is effective for picturing and evalu­
practice, replacing traditional SMBG testing. The transition to this new ating the glucose control and glucose variability.
way of assessing glycemic control poses new challenges for families, The systematic addition of insulin data, amount of carbohydrates,
children and adolescents who are required to interpret all the informa­ duration, and type of physical activity or exercise is a comprehensible
tion gathered from the FGM sensor and use it to adapt insulin and burden for patients with diabetes. However, the lack of these data might
nutritional therapy. It is therefore necessary that HCPs in the pediatric limit the efficacy of appropriate changes to diabetes therapy, and
diabetes team acquire the knowledge and skills to provide adequate therefore we strongly suggest adding these information at least few days
education. This is of primary importance, as people treated in the pe­ before the planned visit.
diatric diabetes outpatient clinic come from diverse socioeconomic, Funding
cultural and ethnic backgrounds and in most cases are newly diagnosed The authors received no funding from an external source.
patients who are unfamiliar with glucose measuring. Authorship
Education on the use and interpretation of glucose results is therefore All named authors meet the International Committee of Medical
a pillar for maximizing clinical outcomes and should be provided prior Journal Editors (ICMJE) criteria for authorship for this article, take re­
to initiation of FGM and periodically during follow-up. Specifically, sponsibility for the integrity of the work as a whole, and have given their
before starting FGM it is suggested to set appropriate expectations and approval for this version to be published.
discuss both with children and their families how the system works, Author Contributions
including the possible differences in glycemic values compared to fin­ All named authors contributed to the concept and design of the
gerprick blood glucose tests, the time-lag of sensor readings compared to manuscript and worked collaboratively to review and prepare the final
fingerprick tests, and the practical interpretation of the results. After manuscript.
initiation and during follow-up visits, it is useful to discuss the AGP Medical writing/Editorial Assistance
graph and the meaning of FGM-derived glucometrics, and how to use Editorial assistance in the preparation of this manuscript was pro­
these tools to optimize insulin therapy and improve metabolic control. vided by Dr Robert Brines of Bite Medical Consulting.
Notably, children and adolescents with type 1 or type 2 diabetes have Compliance with ethical standards
the same glycaemic targets as adults [57]. Although there is evidence This article is based on previously conducted studies and does not
that it is difficult for children and adolescents with diabetes to achieve contain any new studies with human participants or animals performed
the recommended goals, except with automated insulin delivery [58], by any of the authors.
we believe that adopting the algorithms proposed in this expert paper Data availability
may help the pediatrician optimize diabetes therapy in children and Data sharing is not applicable to this article as no new data sets were
adolescents using the FreeStyle Libre system. generated during the current study.

10

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S. Di Molfetta et al. Diabetes Research and Clinical Practice 187 (2022) 109867

Declaration of Competing Interest glucose: A prospective observational cohort study. Diabetes Res Clin Pract 2022;
183:109172. https://doi.org/10.1016/j.diabres.2021.109172.
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D.M. has received speaker fees from Roche Diabetes Care Italy and has [13] Kröger J, Fasching P, Hanaire H. Three European Retrospective Real-World Chart
Review Studies to Determine the Effectiveness of Flash Glucose Monitoring on
provided advisory services to Alpha-Pharma Service Srl and Roche HbA1c in Adults with Type 2 Diabetes. Diabetes Ther 2020;11:279–91.
Diabetes Care Italy. A.R. has received speaker fees and provided advi­ [14] Wada E, Onoue T, Kobayashi T, Handa T, Hayase A, Ito M, et al. Flash glucose
sory board services for Sanofi, Novo Nordisk, Becton Dickinson Italia, monitoring helps achieve better glycemic control than conventional self-
monitoring of blood glucose in non-insulin-treated type 2 diabetes: a randomized
Menarini Diagnostics. V.C. has received research grant support from controlled trial. BMJ Open Diabetes Res Care 2020;8(1):e001115.
Astra Zeneca, Novo Nordisk, Eli Lilly, Theras, Movi, Dompè, and [15] Wright EE, Kerr MSD, Reyes IJ, Nabutovsky Y, Miller E. Use of Flash Continuous
Menarini. He has received fees from Eli Lilly, Tandem Diabetes Care, Glucose Monitoring Is Associated With A1C Reduction in People With Type 2
Diabetes Treated With Basal Insulin or Noninsulin Therapy. Diabetes Spectr 2021;
and Insulet as speaker and participation in scientific advisory boards. A. 34:184–9.
C. has received grants from Astra Zeneca, Lilly, Novo-Nordisk. He has [16] Bolinder J, Antuna R, Geelhoed-Duijvestijn P, Kröger J, Weitgasser R. Novel
also received speaker fees and provided advisory board services for glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre,
non-masked, randomised controlled trial. Lancet 2016;388(10057):2254–63.
Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Lilly, [17] Haak T, Hanaire H, Ajjan R, Hermanns N, Riveline J-P, Rayman G. Flash Glucose-
Merck Sharp & Dhome, Menarini, Novo-Nordisk, Sanofi, Sigma-Tau, Sensing Technology as a Replacement for Blood Glucose Monitoring for the
Takeda. P.D.B. has received speaker fees and provided advisory board Management of Insulin-Treated Type 2 Diabetes: a Multicenter. Open-Label
Randomized Controlled Trial Diabetes Ther 2017;8(1):55–73.
services for Novo Nordisk, Lilly, Novartis, Sanofi, Merck Sharp &
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Sigma Tau. F.L. has received speaker fees from Lilly, Sanofi, Menarini, Study. Diabetes Ther 2020;11(7):1551–62.
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Glucose Monitoring System on Diabetes Distress Among Individuals with Type 1
neca, Abbott, Aboca, Eli Lilly, Ypsomed, Novo Nordisk, Roche, Sanofi, Diabetes: A Prospective Study. Diabetes Ther 2020;11(4):927–37.
and Theras. A.S. has received a personal fee as a speaker for Sanofi and [20] Tyndall V, Stimson RH, Zammitt NN, Ritchie SA, McKnight JA, Dover AR, et al.
Abbott. He has also received grant support from Medtronic and Movi. C. Marked improvement in HbA1c following commencement of flash glucose
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Menarini, and Senseonics, and has received speaker fees for Novo Nor­ Important Drop Rate of Acute Diabetes Complications in People With Type 1 or
disk, Abbott, Senseonics, Lilly, and Boehringer Ingelheim Type 2 Diabetes After Initiation of Flash Glucose Monitoring in France: The RELIEF
Study. Diabetes Care 2021. dc201690.
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