The Ambulatory Glucose Profile Opportunities For Enhancement

Diabetes Technology and Therapeutics
Page 1 of 27
© Mary Ann Liebert, Inc.
DOI: 10.1089/dia.2020.0524
1
10-16-2020 Revision R1
current: The Ambulatory Glucose Profile: Opportunities for Enhancement previous: The Ambulatory Glucose-, Insulin-, Physical Activity- Profile (AGIP): Proposals for Refinement (DOI: 10.1089/dia.2020.0524)
REVIEW
This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
The Ambulatory Glucose Profile: Opportunities for Enhancement
Short Title: Ambulatory Glucose Profile (AGP) Enhancements
David Rodbard MD1)

Downloaded by AUT UNIVERSITY (Auckland University of Tech) from www.liebertpub.com at 10/28/20. For personal use only.
1)
Biomedical Informatics Consultants LLC
10113 Bentcross Dr.
Potomac MD 20854
Tel: 301-983-8088
drodbard@comcast.net
Keywords
Ambulatory Glucose Profile (AGP)

Continuous Glucose Monitoring (CGM)
Self-Monitoring of Blood Glucose (SMBG)
Data Visualization
Diabetes
Glucose
Insulin
Physical Activity
Exercise
Diet
Statistical analysis
Computer programs
Page 2 of 27
2
Abbreviations
AGP Ambulatory Glucose Profile

Gmax Glucose maximum of a post prandial glucose excursion

%TAR Time above range (percentage)
%TBR Time below range (percentage)
%TIR Time in range (percentage)
%R %Recovery from apex of prandial glucose excursion towards baseline a specified
period of time
Gmax Amplitude of a post-prandial glucose excursion
Tmax Time interval between onset of meal and maximum prandial glucose excursion
(Gmax)
Word count:
Title: 7 words (61 characters including spaces)
Short title: 45 characters including spaces
Abstract: 276 words
Main body of text: 4,257 words

Page 3 of 27
3
Abstract (276 words)
The Ambulatory Glucose Profile (AGP) and the frequency distribution for glucose by ranges
are well established as standard methods for display, analysis and interpretation of
glucose data arising from self-monitoring, continuous glucose monitoring and automated
insulin delivery systems. In the present review we consider several refinements that may
further improve the utility of the AGP. These include: 1) Display of the AGP together with
information regarding dietary intake, medication administration (e.g., insulin), glucose
lowering (pharmacodynamic) activity of medications, and physical activity measured by

accelerometers or heart rate; 2) Display of average Time Below Range (%TBR), Time above
Range (%TAR), and Time in Range (%TIR) by time of day to indicate timing of hypo- and
hyperglycemic episodes; 3) Detailed analysis of post-prandial excursions for each of the
major meals after synchronizing by onset of meals and adjusting for the premeal glucose
levels, enabling comparisons of magnitude, shape and patterns; 4) Methods to

characterize distinct patterns on different days of the week; 5) Display of glucose on a
non-linear scale to improve the balance between deviations associated with hypo- vs
hyperglycemia; 6) Use of time scales other than midnight-to-midnight to facilitate analysis
of time segments of particular interest (e.g., overnight); 7) Options to display individual
glucose values to assist in the identification of dates and times of outliers and episodes of
hypo- and hyperglycemia; and 8) Methods to compare AGPs obtained from different
individuals or groups receiving alternative interventions in terms of therapy or technology.
These refinements, individually or collectively, can potentially further enhance the
effectiveness of the AGP for assessment of glucose levels, patterns, and variability. We
discuss several questions regarding implementation and optimization of these methods.
Page 4 of 27
4
Introduction
The Ambulatory Glucose Profile (AGP) is now well established for analysis of Continuous
Glucose Monitoring data (1-13) both for clinical and research purposes. The AGP is also
applicable to Self- Monitoring-of-Blood-Glucose (SMBG) data and was originally introduced
for that purpose (1). It was based on the principles underlying Exploratory Data Analysis
(EDA) of Tukey (6), as applied previously to glucose data using a discrete set of the 8 time
points commonly used for SMBG (5). Construction of separate AGPs for different days of
the week was proposed in 1988 (7). The display of a simplified frequency distribution for
glucose in terms of discrete categories from Very Low to Very High was proposed in 2009
(14) (rather than as a histogram for glucose on a continuous linear scale), and is generally
presented as part of or together with the AGP in the form of a stacked bar chart (13,14).
Many articles have appeared to assist clinicians in the use and interpretation of the AGP
(13-20) . There have been several consensus conferences and other collaborative efforts to
select which statistics should accompany the AGP and glucose distribution (8,9,21-25).
We propose several potential improvements to the AGP (Table 1).
1. Display major determinants of glucose levels: To facilitate interpretation of the

glucose patterns by time of day and of the patterns for %TBR, %TIR and %TAR, it is
important to show several of the major factors influencing glucose levels: diet,
medications (especially insulin when applicable), and physical activity. Figure 1 shows
a schematic example. This type of display is in common usage for display of data for a
single day from insulin pumps and hybrid closed loop systems. We propose to display
the combination of glucose and insulin data, pooling data from multiple days and
displaying insulin and derived measures (calculated Insulin on Board, plasma insulin
levels, and insulin pharmacodynamics), meals, and physical activity as individual data
points, individual datapoints combined with percentiles, or using the percentiles alone
as in common displays of the AGP for glucose. A schematic illustration is shown in
Supplementary Materials (Figure S1). Results for glucose, insulin delivery, insulin
bioactivity, meals, physical activity and heart rate from multiple days can be pooled
Page 5 of 27
5
th
and averaged, with display of data points, a series of percentiles (usually 5 though
95th), or data points and percentiles superimposed.
a. Meals. It is important to show the time of onset of meals and ideally their duration
as well. It would also be desirable to display the amounts and nature of foodstuffs
consumed during the meal at least in semi-quantitative terms or in terms of
carbohydrates, fat, protein, fiber, and calories when such data are available (26-
28). If accurate dietary composition data are available, one can use a color-coded
stacked bar chart to show the relative or absolute composition of carbohydrate,

protein, saturated and unsaturated fat, and fiber.
b. Medications: When insulin is being used, it would be desirable to show both the
timing and dosage for basal and bolus insulin (Figure S1), for a single day and as
average values after pooling data from multiple days. In addition to the insulin
injection doses or infusion rates, one can calculate three key aspects of insulin
action: i) the model-predicted level of insulin-on-board; ii) model-predicted profile

for plasma insulin; iii) and the model-predicted pharmacodynamic effectiveness of
insulin (rate of glucose disposal from the extracellular space based on parameters
obtained in studies of multiple individuals) (29-32). The doses and timing of other
medications can also be shown.
c. Physical Activity: It is desirable to show physical activity on the same time scale,
e.g. as detected by accelerometers or pedometers, or by heart rate (33,34). In
studies of the effects of exercise on glucose, the time series for glucose and insulin
can be analyzed after synchronization to either the onset or offset of strenuous
physical activity.
2. Display of %TAR, %TBR, and (optionally) %TIR on the AGP using the same time axis at
the glucose data: It can be very difficult to evaluate the risks of hypo- or
hyperglycemia at any specified time of day when displaying only the 25 th and 75th
percentiles for glucose. Use of a series of several percentiles (e.g. the 5th, 10th, 90th, and
95th percentiles) can considerably improve the graphical estimate of %TBR and %TAR.
It is preferable to show the %TBR (both <54 mg/dL and <70 mg/dL) and %TAR (both
>180 mg/dL and >250 mg/dL) by time of day. This avoids the need to make crude visual
Page 6 of 27
6
estimates, and greatly facilitates the identification of the times of onset and offset,
duration, and maximal levels.
3. Detailed Analysis of postprandial glucose excursions by type of meal: The AGP shows
glucose elevations following the usual times for the major meals. However, the
resolution of the post-prandial excursions is usually limited because meals are
consumed at different times on different days and the pre-meal (baseline) glucose also
varies considerably from day to day. When data are pooled from multiple days (or from
multiple subjects), these two factors result in shifting along the horizontal (time axis)
and vertical (glucose axis) directions, respectively. Accordingly we recommend that the
post-prandial segments of the glucose vs time curves be “normalized” by: 1)
synchronization with respect to the time of onset of the meals, and b) subtraction of
the premeal baseline glucose to show only the excursion above baseline. In some
cases, it may be strongly desirable to make an additional correction for the slope of
glucose versus time at the onset of the meal. This makes it possible to analyze glucose
excursions for the major meals and snacks. Individual glucose values may be show as
discrete dots or connected with line segments. Pooled data from multiple days can be
summarized using selected percentiles (e.g., 25th, 50th, and 75th percentiles), shading
the area between the 25th and 75th percentiles, and (optionally) showing the individual
glucose data points. If data from multiple days are superimposed, then it is usually best
to dispense with line segments between consecutive data points.
It would be helpful to show the frequency distributions of the timing of onset of meals
(either as a histogram or as a Box chart parallel to the time axis). Similarly, when
accurate data for administration of a meal-related insulin bolus and also for the time of
onset of the meal, it is helpful to show this as a histogram shown in immediate
proximity to the display of the prandial excursion.
Comment: Since use of “normalizing” of the curves results in loss of information, it is

desirable to display frequency distributions for: a) times of onset of the meals; b)
premeal baseline glucose; c) maximum glucose (Gmax); d) amplitude of glucose
excursion (Gmax); e) time lag between onset of the meal and time when the apex of
the glucose peak is achieved (Tmax); f) %Recovery to baseline after a specified period
Page 7 of 27
7
of time (e.g. 2, 3, or 4 hours) (35,36); g) other metrics to describe the shape of the
prandial excursions such as half-times (t1/2) for the upstrokes and downstrokes of
prandial excursions; h) time lag between onset of the meal and the first readily
detectable rise in plasma glucose. These normalized post-prandial excursion patterns
for a specified time interval (e.g., 4 hours following the median time of onset of given
type of meal) can be superimposed on the full 24-hour AGP, together with graphical
representations of several of the above descriptive metrics. The average glycemic
patterns following each of the three major meals can be obtained. One can test for
heterogeneity of peak shapes for any one type of meal, compare the patterns from the
three types of major meals to determine if they can all be characterized by a single
pattern or shape with individual magnitudes, or whether a different pattern must be
used for one or another meal type.
4. Analysis by Day of the Week. Many methods have been used to display differences in
glucose patterns between different days of the week. The simplest is show the mean ±
1 SD or ± 1 sem or 95% confidence interval for mean glucose by day of the week. A
second approach is to show the Box plot (consisting of the 0 th-, 25th-, 50th-, 75th-, and
100th percentiles) by day of the week (5). A third approach is to show the glucose
distribution by times in categories or ranges, also by day of week (14). Another is to
show the AGPs constructed separately for each day of the week (7). We previously
proposed to analyze a CGM record of four-weeks duration, showing the median
glucose by time of day for each of the days of the week individually, together with the
median glucose for all days of the week combined (16). One can then examine the
correlations of the glucose patterns for any one day of the week with the overall
pattern for all days, to identify days that are consistent (or inconsistent) with the
typical pattern. By calculating the pairwise correlation coefficients for the 21 possible
pairs of the 7 days of the week, one can identify days with similar or distinct patterns
(16). A cross-correlation analysis can be useful to evaluate time delays (horizontal
shifts) in the glucose patterns from day to day or by day of the week.
Sandig et al. used two alternative approaches to compare glucose patterns for
weekdays and weekends (defined as Friday 6 PM to Sunday 11:59 PM (37). They
Page 8 of 27
8
th th th
compared the 10 , 50 and 90 percentiles of glucose vs time of day for a group of
subjects on weekdays vs weekends. The AGPs for weekends and weekdays showed
considerable overlap and only a suggestion of a difference in patterns (cf. Figure 3 of

(37)). However, by re-analyzing the data for each subject individually, calculating the
mean difference between glucose levels on weekdays vs weekends for every possible
time of day, it became clear that there was a dramatic, highly statistically significant, ~
20 mg/dL increase in glucose on weekends, especially during the midnight to 3:00 AM
time period (cf. Figure S3 in Supplementary materials to (37).

5. Display of glucose on a nonlinear scale to expand the hypoglycemic region and
compress the hyperglycemic region: A change of 10 mg/dL has a completely different
clinical significance depending on whether the glucose level is 64 mg/dL or 190 mg/dL.
To date nearly all graphical displays of glucose have utilized a linear scale. This makes it
difficult to appreciate small changes in the hypoglycemic range and inadvertently
places an undue emphasis on the much larger variation seen in the hyperglycemic
region. Accordingly, it should be helpful to use a nonlinear scale in order to expand or
stretch the glucose scale in the hypoglycemic region while compressing it in the
hyperglycemic region (38). A simple, standard approach, well known to most scientists
and clinicians, is the use of a logarithmic scale, i.e, a “semi-log” graph.
Comment: Alternative scales could also be used: a) A “root” transformation of glucose,
(e.g., the cube-root of glucose (G1/3) or the fourth-root of glucose (G1/4), and similar
functions of glucose could be used to expand the glucose scale in the hypoglycemic
range; or b) one can stretch the scale for glucose by a factor of 2 for glucose levels
below 100 mg/dL while compressing it by a factor of two in the range above 200
mg/dL. Similarly, one can expand the scale by another factor of 2 for glucose values
below 50 mg/dL while compressing the scale by another factor of two for glucose
levels above 400 mg/dL. The logarithmic scale provides simplicity and is likely to be
easier to use than several short ranges for glucose with abrupt changes in scaling
factor. The log scale can be applied equally whether expressing glucose levels in terms
of mg/dL or mmol/L. People with difficulty using or understanding a logarithmic scale
might still prefer use of linear segments with abrupt changes in the scaling factor at
arbitrary places along the scale, e.g., at 50, 100, 200 and 400 mg/dL. A different set of
Page 9 of 27
9
breaks in the scale might be preferable when glucose is expressed as mmol/L, e.g. 3.0,
6.0, 12.0 and potentially 24.0 mmol/L.
6. Choice of timescale: A midnight-to-midnight time scale for the AGP has nearly always
been used. In a few studies, e.g., in studies examining hybrid closed loop for periods
less than 24 hours, shorter time scales have been used. One can also examine the AGP
over 24-hour periods starting at times other than midnight (e.g., 6 AM or 7 AM) to
examine a typical daily pattern. When examining glucose changes in the late evening -
overnight - early morning periods, it may be desirable to display the AGP using a Noon-
to-Noon times scale. It may also be helpful to use a 48-hour time period for display: a
48-hour time interval was previously used to display motor activity and food
consumption in studies of circadian rhythms in animals.
7. Display of individual glucose values: It can be helpful to show individual glucose data
points by time of day (5,7). This approach may help identify outliers. This will show
data density -- and allows one to identify outliers and glucose values corresponding to
severe hypo- or hyperglycemia. When using an interactive display, one can select an
individual point to generate a pop-up window showing the time and glucose values,
and any associated information.
8. Methods to compare AGPs from people receiving different forms of therapy, devices,
or other kinds of interventions. The AGP has facilitated the comparison of patterns in
people receiving different forms of therapy, e.g. hybrid closed loop vs predictive low
glucose suspend vs sensor augmented pump. It is customary to superimpose displays
of the AGP using different colors or shading to distinguish groups of subjects receiving
different forms of intervention or treatment, typically showing the 25 th, 50th, and 75th
percentiles. One can examine the differences in mean or median for glucose by time of
day for two treatment groups (39). Alternatively, one can characterize differences in
times-in-ranges within- or between-subjects either for the full 24-hour period or for
several narrow time windows spread throughout the day (37,40).
Discussion
Since its introduction in 1987 (1) for SMBG and since 2008 as it has been applied to CGM
(2-4), the AGP has proven to be extremely useful to patients, physicians, other members of
Page 10 of 27
10
the health care team, and to researchers. Numerous variations have been utilized in the
ensuing years. The AGP is almost always accompanied by the now-ubiquitous frequency
distribution for glucose values in multiple segments of glucose (14) and several associated
’statistics’ (8-17, 21-25). The present report summarizes a number of proposals for
improvement of the effectiveness and informativeness of the AGP, some that had been
presented years ago (e.g., log scale (38), display of data points (5,7), risks or rates of hypo-
and hyperglycemia (9,17), analysis by day of the week (7)), and some relatively recently
(e.g., normalizing and synchronizing prandial excursions (28,33) The ability to visualize
glucose patterns simultaneously with the major factors controlling plasma glucose levels
(e.g., dietary intake (26-28, 33-34), medications (especially insulin)(29-32), and physical
activity/exercise (33,34)) can enhance the effectiveness of the AGP.
We will now discuss several questions regarding these potential enhancements to the
AGP:
1) Who is the intended Target Audience? To whom would these additional features
be of interest and assistance? In principle, several of these enhanced features could be of
interest to many or most of the current users of the AGP, including patients and their
families and health care professionals engaged in the care of people with diabetes.
However, not all users will be interested in all of the enhancements. If people are
experiencing difficulties achieving their goals for adequate control of prandial glucose
excursions, then a detailed analysis of the postprandial period (with synchronization and
correction for premeal glucose) might be of highest priority. For people experiencing hypo-
or hyperglycemia, simple displays of %TBR (using both <70 and <54 mg/dL), and %TAR
(using both >180 and >250 mg/dL) by time of day might be of most interest.
Some people have difficulty understanding non-linear scales while others may find that
use of a “semi-log” scale for glucose is immediately helpful because it makes it easier to
see and to analyze glucose values in the hypoglycemic range.
Features that would be adopted may vary for every patient and HCP, and may change as
the patient’s ‘chief complaint’ or principal clinical problem changes over a period of time.
2. How can these features be implemented in practice? These kinds of features would
need to be made available instantly and effortlessly if they are to be used by extremely
Page 11 of 27
11
time-pressed care givers. It would be desirable to incorporate these features into the
software provided by manufacturers of CGM sensors and of insulin pumps, closed-loop
systems, connected pens, fitness-trackers, and ‘apps’ to eliminate barriers that would arise
if it were necessary to employ a separate program or ‘app’. Alternatively, they could be
incorporated into centralized systems for data integration.
There are multiple options that could be used for graphs, tables, statistics, layout and
format of output, use of colors and icons, on-screen instructions and advice, and aids to
interpretation and education. It would be important to optimize these displays using the
principles and practice of usability laboratories and cognitive laboratories, to evaluate the
extent to which additional information is desired, being provided, understood, and utilized
(41). Such evaluations might also consider the nature and extent of user training that
might be desirable to obtain maximal benefit from the use of these enhanced features.
3. Would an enhanced AGP become too complex for people to use? The currently
well-established AGP can be difficult to comprehend for many users. Will the addition of
several additional types of information (insulin and other medications, dietary intake, and
physical activity) make the system so complex that it becomes intimidating? Do the
‘enhancements’ result in a level of complexity that becomes intimidating or
insurmountable? Could analyses and displays of this degree of ‘sophistication’ be utilized
in a practical manner during a brief patient-physician encounter? These are legitimate
concerns.
First, To the extent that we are modifying or adding a few graphs to the AGP report, users
who are already comfortable and experienced with the interpretation of graphs should be
able to absorb the information rather quickly. Some of these graphics may be useful for
education of the patient, the patient’s family, personal caregivers, and healthcare
providers. For instance, the simple display of %TBR and %TAR vs time of day may provide
insights that are not readily appreciated even when the 5th, 10th, 90th and 95th percentiles
for glucose are displayed.
Second, the software that generates graphs and statistics for the enhanced AGP can also
provide a basic level of interpretation, as some programs for CGM sensors and insulin
pumps do currently, e.g., identifying and prioritizing the major problems (15, 16, 42) and
Page 12 of 27
12
identifying “best days” and “worst days”. Much of the interpretation can be done by
computer as soon as the data become available, so that useful results can be available at
the onset of a clinic visit.

Third, the interpretation of the multivariate data set can be generated using artificial
intelligence and various forms of statistical analyses to identify patterns and interactions
among the several streams of data, e.g., to examine relationships between hypoglycemia,
physical activity and dietary intake over periods of hours or days. The level of complexity
of the outputs can and should be customizable. One can introduce new features in a
sequential manner as the users gain more experience. Some features can be selected a
priori by default or by personal choice, e.g. a) options to use a logarithmic or other
nonlinear scale for glucose, or b) to display the original glucose data points, percentiles, or
both superimposed – and whether to allow the user to rotate through these three types of
display interactively. Some aspects of the analysis can be presented only when there is an
interesting and potentially clinically-relevant finding to display, e.g., whether some days of
the week have similar patterns for glucose by time of day while other days have
consistently distinct patterns (7,9,16)
4. Will the input data be sufficiently available, accurate, and reliable to be useful?
Glucose data are now generally quite accurate and often very abundant. Insulin data are
reliable if captured from an insulin pump or a connected pen. Physical activity data can be
accurate and reliable if captured from a pedometer or accelerometer, or from an array of
multiple accelerometers (34), e.g., using sensors on arms, legs, and trunk. It remains to be
seen what percentage of the time a person will wear these sensors and how this depends
on their degree of motivation. Data regarding diet are often unavailable and have been
notoriously unreliable except in the content of research studies. However, some non-
invasive passive methods may permit sensitive detection of eating behaviors (43), and
these can be complimented with automated methods for analysis of photographs of food
obtained both before and after the meal (44) or by use of bar-code readers for individual
packaged foods. The relative availability, accuracy, and importance of different types of
dietary data is likely to improve, perhaps in conjunction with automated insulin delivery
systems.
Page 13 of 27
13
5. Is there a need for Scoring Systems in addition to the AGP and the frequency
distribution of glucose by ranges? Should the multi-stream data be used to generate one
or more scores to evaluate the quality of glycemic control? Multiple scoring systems to
evaluate an overall quality of glycemic control have been proposed. (45-59). Some are
based on the original glucose values without need for calculation of intermediary metrics:
Schlichtkrull’s M (or MR) (48), BGRI and its two subcomponents (LBGI and HBGI)(49,50),
IGC and its two subcomponents (Hypoglycemia Index and Hyperglycemia Index) (15),
GRADE and its three subcomponents for hypo-, eu- and hyperglycemia (51). Others are
based on use of between 2 and 5 intermediary scores or metrics: summations of scores for
mean glucose, variability, hypoglycemia, hyperglycemia, and adequacy of data (45), Q-
Score (54), the Glycemic Pentagon (53) and its revised version, the Comprehensive
Glucose Pentagon (CGP) (55), and the Personal Glycemic State (PGS) (56). In view of the
mathematical complexity of some of the scoring systems (especially those based on the
original glucose data), there has been a marked trend toward use of %TIR as the principal
score for quality of glycemic control (21-25,57,58). [Interestingly, %TAR has a slightly
higher correlation and greater range of linearity with mean glucose and A1C than does
%TIR] (57,58).] It is essential to combine information from at least two metrics – one that
reflects mean glucose level (A1C, mean glucose, %TIR, or %TAR)] and one that reflects
hypoglycemia (%TBR [T <70 mg/dL and/or T<54 mg/dL], LBGI, GRADEHYPOGLYCEMIA, Hypoglycemia
Index).(58,59) The relationship of risk of hypoglycemia (or its proxys) to mean glucose (or
A1C) is an ideal way to compare alternative modalities of therapy. (45, 60, 61)
Leelarathna et al. (62) proposed a scoring system combing three metrics (%TIR, TBR, SD)
based on expert opinion and illustrative cases. It remains to be seen to what extent this
improves upon the use of just two input metrics (45,60,61), and whether scoring systems
utilizing 5 metrics (45,46,52-56) can improve upon scores that use only two or three
metrics. Scores, and changes in scores, may be most helpful in identifying situations where
a drill-down with additional analyses would be important to the care of an individual
patient.
We expect that at least a few of the enhancements to the AGP discussed in this review will
prove to be useful to patients and health care professionals. Some users may need
Page 14 of 27
14
instructional materials to help them maximize the utility of the available information.
Others may rely progressively on automated artificial intelligence systems for
interpretation of the data. These approaches can be used to make comparisons of the
quality of glycemic control for a person at different points in time. It will be usually be
informative to provide a comparison of any one person with a reference group (2,51,53-
55), expressed in terms of percentiles. This will make it possible to provide guidance such
as “When compared to other people with similar clinical characteristics, this patient ranks
in the [specified percentile] in terms of risk of hypoglycemia”, rather than a “raw score”
such as %TBR or a numerical score on an unfamiliar parameter (e.g., LBGI,
GRADEHYPOGLYCEMIA, Hypoglycemia Index).
One can expect that there will be need for customization for different situations and
continuing exploration and experimentation to optimize each of the many complementary
forms of analysis now available (graphical, statistical, scoring, artificial intelligence,

machine learning).
Conclusion
Several methods have been proposed for enhancement of the Ambulatory Glucose Profile
– perhaps most importantly the combination of glucose data with data regarding
medications (especially insulin), dietary intake, and physical activity. Possibilities for
improved graphic displays include display of %TBR and %TAR by time of day, nonlinear
scales (log scales) for glucose, display of glucose data points together with the series of
percentiles, use of limits for the time-of-day axis other than midnight-to-midnight, display
of insulin not only in terms of dose and time administered but also in terms of expected
plasma insulin levels and pharmacodynamic (glucose disposal) activities. One can utilize
statistical criteria to identify days of the week with similar or markedly dissimilar patterns
by time of day provided that sufficient data are available. Several of these approaches
should be suitable for incorporation into software for analysis of data obtained from CGM,
insulin pumps and closed loop systems, for use by patients and healthcare professionals.
Page 15 of 27
15
Acknowledgements
The author thanks several colleagues for many helpful suggestions regarding use, display
and modifications of the AGP. Development of the original AGP was primarily a
collaborative effort with Roger Mazze. Figure 1 is based in part on collaboration with Dr.
Howard Wolpert, Jie Xue, and Xuanyao He, of Eli Lilly & Co., and Sara Krugman of
Healthmade Design. Jie Xue developed software for display of the AGP showing percentiles
and glucose data points alone or combined including the ability to interactively display
date, time, glucose levels, and ancillary information for any datapoint. The smoothing
algorithm for percentiles in the original AGP were developed by David Lucido.
Funding
This study was funded by Biomedical Informatics Consultants LLC.

Disclosures: None.
Prior presentations:
Wolpert H, Rodbard D, Polonsky W, Johnson J., He X, Xue J, Krugman S. Call to Action:

Insulin Dosing Metrics - Preparing to Leverage the Potential of Connected Insulin Pens.
ATTD 2020, February 21, 2020, Madrid, Spain, symposium sponsored by Eli Lilly and Co.
Rodbard D. New Enhancements to the Ambulatory Glucose Profile, in ATTD 2017, Paris,
Abstract 137, Diabetes Technology & Therapeutics Feb 2017.A-56.
http://doi.org/10.1089/dia.2017.2525.abstracts
Page 16 of 27
16
References
1. Mazze RS., Lucido D, Langer O., Hartmann K. and Rodbard D. Ambulatory Glucose
Profile: Representation of Verified Self-Monitored Blood Glucose Data. Diabetes Care,

10 (1): 111-117, 1987
2. Mazze RS, Strock E, Wesley D, Borgman S, Morgan B, Bergenstal R, Cuddihy R.
Characterizing glucose exposure for individuals with normal glucose tolerance using
continuous glucose monitoring and ambulatory glucose profile analysis. Diabetes
Technol Ther. 2008 Jun;10(3):149-59. doi: 10.1089/dia.2007.0293.PMID: 18473688

3. Mazze R, Strock E, Cuddihy R, Wesley D. Ambulatory glucose profile (AGP):
development of a common, web-based application to record and report continuous
glucose monitoring data. Can J Diabetes. 2009;33(3):215. doi: 10.1016/S1499-
2671(09)33083-X. Epub 2012 Dec 10.
4. Mazze R, Akkerman B, Mettner J. An overview of continuous glucose monitoring and

the ambulatory glucose profile. Minn Med. 2011 Aug;94(8):40-4. PMID: 21957816
5. Pernick NL, Rodbard D. Personal computer programs to assist with self-monitoring of
blood glucose and self-adjustment of insulin dosage. Diabetes Care. 1986 Jan-
Feb;9(1):61-9. PubMed PMID: 3 512210.
6. Tukey, John W. (1977). Exploratory Data Analysis. Pearson. ISBN 978-0201076165
7. Rodbard D. Potential role of computers in clinical investigation and management of
diabetes mellitus. Diabetes Care. 1988 Nov-Dec;11 Suppl 1:54-61. Review. PubMed
PMID: 3069391
8. Bergenstal RM, Ahmann AJ, Bailey T, Beck RW, Bissen J, Buckingham B, Deeb L, Dolin
RH, Garg SK, Goland R, Hirsch IB, Klonoff DC, Kruger DF, Matfin G, Mazze RS, Olson BA,
Parkin C, Peters A, Powers MA, Rodriguez H, Southerland P, Strock ES, Tamborlane W,
Wesley DM. Recommendations for standardizing glucose reporting and analysis to
optimize clinical decision making in diabetes: the Ambulatory Glucose Profile (AGP).
Diabetes Technol Ther. 2013 Mar;15(3):198-211. doi: 10.1089/dia.2013.0051. Epub
2013 Feb 28.PMID: 23448694
9. Rodbard D. Standardization versus customization of glucose reporting. Diabetes
Technol Ther. 2013 May;15(5):439-43. doi: 10.1089/dia.2013.0116.PMID: 23634672
Page 17 of 27
17
10. Carlson AL, Mullen DM, Bergenstal RM. Clinical Use of Continuous Glucose Monitoring
in Adults with Type 2 Diabetes. Diabetes Technol Ther. 2017 May;19(S2):S4-S11. doi:
10.1089/dia.2017.0024.PMID: 28541137
11. Mullen DM, Bergenstal R, Criego A, Arnold KC, Goland R, Richter S. Time Savings Using
a Standardized Glucose Reporting System and Ambulatory Glucose Profile. J Diabetes
Sci Technol. 2018 May;12(3):614-621. doi: 10.1177/1932296817740592. Epub 2017
Nov 24. PMID: 29169243
12. Carlson AL, Mullen DM, Mazze R, Strock E, Richter S, Bergenstal RM. Evaluation of
insulin glargine and exenatide alone and in combination: a randomized clinical trial
with continuous glucose monitoring and ambulatory glucose profile analysis. Endocr
Pract. 2019 Apr;25(4):306-314. doi: 10.4158/EP-2018-0177.PMID: 30995433
13. Johnson ML, Martens TW, Criego AB, Carlson AL, Simonson GD, Bergenstal RM.
Utilizing the Ambulatory Glucose Profile to Standardize and Implement Continuous
Glucose Monitoring in Clinical Practice. Diabetes Technol Ther. 2019 Jun;21(S2):S217-

S225. doi: 10.1089/dia.2019.0034.PMID: 31169432
14. Rodbard D. Display of glucose distributions by date, time of day, and day of week: new
and improved methods. J Diabetes Sci Technol. 2009 Nov 1;3(6):1388-94. PMID:
20144393
15. Rodbard, D. Interpretation of Continuous Glucose Monitoring Data: glycemic variability
and quality of glycemic control. Diabetes Technology and Therapeutics, 11
(Supplement 1): S55 – S67, June, 2009.
16. Rodbard D. New and improved methods to characterize glycemic variability using
continuous glucose monitoring. Diabetes Technol Ther. 2009;11(9):551-565.
doi:10.1089/dia.2009.0015
17. Rodbard D. Glucose Variability: A Review of Clinical Applications and Research
Developments. Diabetes Technol Ther. 2018 Jun;20(S2):S25-S215. doi:
10.1089/dia.2018.0092.PMID: 29916742 (cf. especially Table 3)
18. Ekhlaspour L, Tabatabai I, Buckingham B. 2019. A Review of Continuous Glucose
Monitoring Data Interpretation in the Age of Automated Insulin Delivery. Journal of
Diabetes Science and Technology 13:4, 645-663
Page 18 of 27
18
19. Borot S, Benhamou PY, Atlan C, et al. Practical implementation, education and
interpretation guidelines for continuous glucose monitoring: A French position
statement. Diabetes Metab. 2018;44(1):61-72. doi:10.1016/j.diabet.2017.10.009

20. Kröger J, Reichel A, Siegmund T, Ziegler R. Clinical Recommendations for the Use of the
Ambulatory Glucose Profile in Diabetes Care. J Diabetes Sci Technol. 2020;14(3):586-
594. doi:10.1177/1932296819883032
21. Maahs DM, Buckingham BA, Castle JR, Cinar A, Damiano ER, Dassau E, DeVries JH,
Doyle FJ 3rd, Griffen SC, Haidar A, Heinemann L, Hovorka R, Jones TW, Kollman C,
Kovatchev B, Levy BL, Nimri R, O'Neal DN, Philip M, Renard E, Russell SJ, Weinzimer SA,
Zisser H, Lum JW. Outcome Measures for Artificial Pancreas Clinical Trials:
A Consensus Report. Diabetes Care. 2016 Jul;39(7):1175-9. doi: 10.2337/dc15-
2716.PMID: 27330126
22. Danne T, Nimri R, Battelino T, Bergenstal RM, Close KL, DeVries JH, Garg S, Heinemann
L, Hirsch I, Amiel SA, Beck R, Bosi E, Buckingham B, Cobelli C, Dassau E, Doyle FJ 3rd,
Heller S, Hovorka R, Jia W, Jones T, Kordonouri O, Kovatchev B, Kowalski A, Laffel L,
Maahs D, Murphy HR, Nørgaard K, Parkin CG, Renard E, Saboo B, Scharf M, Tamborlane
WV, Weinzimer SA, Phillip M. International Consensus on Use of Continuous Glucose
Monitoring. Diabetes Care. 2017 Dec;40(12):1631-1640. doi: 10.2337/dc17-
1600.PMID: 29162583
23. Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, Buckingham
BA, Cefalu WT, Close KL, Cobelli C, Dassau E, DeVries JH, Donaghue KC, Dovc K, Doyle FJ
3rd, Garg S, Grunberger G, Heller S, Heinemann L, Hirsch IB, Hovorka R, Jia W,
Kordonouri O, Kovatchev B, Kowalski A, Laffel L, Levine B, Mayorov A, Mathieu C,
Murphy HR, Nimri R, Nørgaard K, Parkin CG, Renard E, Rodbard D, Saboo B, Schatz D,
Stoner K, Urakami T, Weinzimer SA, Phillip M. Clinical Targets for Continuous Glucose
Monitoring Data Interpretation: Recommendations From the
International Consensus on Time in Range. Diabetes Care. 2019 Aug;42(8):1593-1603.
doi: 10.2337/dci19-0028. Epub 2019 Jun 8.PMID: 31177185
Page 19 of 27
19
24. Bailey TS, Grunberger G, Bode BW, Handelsman Y, Hirsch IB, Jovanovič L, Roberts
VL, Rodbard D, Tamborlane WV, Walsh J; American Association of Clinical
Endocrinologists (AACE); American College of Endocrinology (ACE). American

Association of Clinical Endocrinologists and American College of Endocrinology 2016
Outpatient Glucose Monitoring Consensus Statement. Endocr Pract. 2016
Feb;22(2):231-61. doi: 10.4158/EP151124.CS. Epub 2016 Jan 27.PMID: 26848630
25. Fonseca VA, Grunberger G, Anhalt H, Bailey TS, Blevins T, Garg SK, Handelsman Y,
Hirsch IB, Orzeck EA, Roberts VL, Tamborlane W; Consensus Conference Writing
Committee. Continuous Glucose Monitoring: A Consensus Conference of the American
Association of Clinical Endocrinologists and American College of Endocrinology. Endocr
Pract. 2016 Aug;22(8):1008-21. doi: 10.4158/EP161392.CS. Epub 2016 May
23.PMID: 27214060
26. Wolpert HA, Atakov-Castillo A, Smith SA, Steil GM. Dietary fat acutely increases
glucose concentrations and insulin requirements in patients with type 1 diabetes:

implications for carbohydrate-based bolus dose calculation and
intensive diabetes management. Diabetes Care. 2013 Apr;36(4):810-6. doi:
10.2337/dc12-0092. Epub 2012 Nov 27.PMID: 23193216
27. Papakonstantinou E, Papavasiliou K, Maouri C, et al. Postprandial glucose response
after the consumption of three mixed meals based on the carbohydrate counting
method in adults with type 1 diabetes. A randomized crossover trial. Clin Nutr ESPEN.
2019;31:48-55. doi:10.1016/j.clnesp.2019.03.002
28. Gillingham M, Li Z, Beck RW, Calhoun P, Castle JR, Clements MA, Dassau E, Doyle Iii FJ,
Gal R, Jacobs PG, Patton SR, Rickels M, Riddell M, Martin C. Assessing Mealtime
Macronutrient Content: Patient Perceptions versus Expert Analyses via a Novel Phone
App. Diabetes Technol Ther. 2020 Aug 24. doi: 10.1089/dia.2020.0357. Online ahead of
print. PMID: 32833544
29. Berger M, Rodbard D. Computer simulation of plasma insulin and glucose dynamics
after subcutaneous insulin injection. Diabetes Care. 1989;12(10):725-736.
doi:10.2337/diacare.12.10.725
Page 20 of 27
20
30. Berger MP, Rodbard D. A pharmacodynamic approach to optimizing insulin

therapy. Comput Methods Programs Biomed. 1991;34(4):241-253. doi:10.1016/0169-
2607(91)90107-5
31. Visentin R, Campos-Náñez E, Schiavon M, et al. The UVA/Padova Type 1 Diabetes
Simulator Goes From Single Meal to Single Day. J Diabetes Sci Technol. 2018;12(2):273-
281. doi:10.1177/1932296818757747
32. Ma X, Chien JY, Johnson J, Malone J, Sinha V. Simulation-Based Evaluation of Dose-
Titration Algorithms for Rapid-Acting Insulin in Subjects with Type 2 Diabetes Mellitus
Inadequately Controlled on Basal Insulin and Oral Antihyperglycemic
Medications. Diabetes Technol Ther. 2017;19(8):483-490. doi:10.1089/dia.2016.0361
33. DuBose SN, Li Z, Sherr JL, Beck RW, Tamborlane WV, Shah VN. Effect of Exercise and
Meals on Continuous Glucose Monitor Data in Healthy Individuals Without Diabetes
[published online ahead of print, 2020 Feb 17]. J Diabetes Sci Technol.
2020;1932296820905904. doi:10.1177/1932296820905904
34. Turksoy K, Hajizadeh I, Hobbs N, Kilkus J, Littlejohn E, Samadi S, Feng J, Sevil M, Lazaro
C, Ritthaler J, Hibner B, Devine N, Quinn L, Cinar A. Multivariable Artificial Pancreas for
Various Exercise Types and Intensities. Diabetes Technol Ther. 2018 Oct;20(10):662-
671. doi: 10.1089/dia.2018.0072. Epub 2018 Sep 6. PMID: 30188192
35. Service FJ, O'Brien PC, Rizza RA. Measurements of glucose control. Diabetes Care. 1987
Mar-Apr;10(2):225-37. doi: 10.2337/diacare.10.2.225.PMID: 3582083
36. Service FJ. Glucose variability. Diabetes. 2013;62(5):1398-1404. doi:10.2337/db12-1396
37. Sandig D, Grimsmann J, Reinauer C, et al. Continuous Glucose Monitoring in Adults
with Type 1 Diabetes: Real-World Data from the German/Austrian Prospective
Diabetes Follow-Up Registry. Diabetes Technol Ther. 2020;22(8):602-612.
doi:10.1089/dia.2020.0019
38. Rodbard D. A semilogarithmic scale for glucose provides a balanced view of
hyperglycemia and hypoglycemia. J Diabetes Sci Technol. 2009 Nov 1;3(6):1395-401.
PubMed PMID: 20144394; PubMed Central PMCID: PMC2787040. [Comment: Includes
comparison of LBGI, HBGI (Kovatchev et al.), Index of Glycemic Control (IGC) (Rodbard),
and GRADE (N.R. Hill et al.)]
Page 21 of 27
21
39. Henry RR, Strange P, Zhou R, Pettus J, Shi L, Zhuplatov SB, Mansfield T, Klein D, Katz A.
Effects of Dapagliflozin on 24-Hour Glycemic Control in Patients with Type 2 Diabetes:
A Randomized Controlled Trial. Diabetes Technol Ther. 2018 Nov;20(11):715-724.

40. Brown SA, Beck RW, Raghinaru D, et al. Glycemic Outcomes of Use of CLC Versus PLGS
in Type 1 Diabetes: A Randomized Controlled Trial. Diabetes Care. 2020;43(8):1822-
1828. doi:10.2337/dc20-0124
41. Wiklund MED and Wilcox SB (Eds.). Designing Usability into Medical Products. Taylor
and Francis, 2015. ISBN 0 8493 2843 8.

42. Rodbard D. Optimizing display, analysis, interpretation and utility of self-monitoring of
blood glucose (SMBG) data for management of patients with diabetes. J Diabetes Sci
Technol. 2007 Jan;1(1):62-71. doi: 10.1177/193229680700100111. PMID: 19888382;
PMCID: PMC2769603.
43. Chun KS, Jeong H, Adaimi R, Thomaz E. Eating Episode Detection with Jawbone-
Mounted Inertial Sensing. Annu Int Conf IEEE Eng Med Biol Soc. 2020 Jul;2020:4361-
4364. doi: 10.1109/EMBC44109.2020.9175949. PMID: 33018961.43.
44. Bell BM, Alam R, Alshurafa N, Thomaz E, Mondol AS, de la Haye K, Stankovic JA, Lach J,
Spruijt-Metz D. Automatic, wearable-based, in-field eating detection approaches for
public health research: a scoping review. NPJ Digit Med. 2020 Mar 13;3:38. doi:
10.1038/s41746-020-0246-2. PMID: 32195373; PMCID: PMC7069988.
45. Rodbard, D., Berger, M., and Pernick, N. Computer, networking, and information
systems to facilitate delivery of health care to patients with diabetes. In: Baba, S., and
Kaneko, T. (Eds.), Diabetes 1994, Proceedings of the 15th International Diabetes
Federation Congress, Kobe, 6 - 11 November 1994. Elsevier, Amsterdam, pp. 800-803,
1995.
46. Nguyen M, Han J, Spanakis EK, Kovatchev BP, Klonoff DC. A Review of Continuous
Glucose Monitoring-Based Composite Metrics for Glycemic Control. Diabetes Technol
Ther. 2020 Aug;22(8):613-622. doi: 10.1089/dia.2019.0434. Epub 2020 Mar 4. PMID:
32069094.
47. Moscardó V, Herrero P, Reddy M, Hill N, Georgiou P, Oliver N. Assessment of Glucose
Control Metrics by Discriminant Ratio. Diabetes Technol Ther. 2020 Mar 12. doi:
10.1089/dia.2019.0415. Epub ahead of print. PMID: 32163723.
Page 22 of 27
22
48. Schlichtkrull J, Munck O, Jersild M. The M-Value, An Index of Blood-Sugar Control in

Diabetics. Acta Med Scand. 1965 Jan;177:95-102. doi: 10.1111/j.0954-
6820.1965.tb01810.x. PMID: 14251860.

49. Kovatchev BP, Otto E, Cox D, Gonder-Frederick L, Clarke W. Evaluation of a new
measure of blood glucose variability in diabetes. Diabetes Care. 2006 Nov;29(11):2433-
8. doi: 10.2337/dc06-1085. PMID: 17065680.
50. Clarke W, Kovatchev B. Statistical tools to analyze continuous glucose monitor data.
Diabetes Technol Ther. 2009 Jun;11 Suppl 1(Suppl 1):S45-54. doi:

10.1089/dia.2008.0138. PMID: 19469677; PMCID: PMC2903980.
51. Hill NR, Hindmarsh PC, Stevens RJ, Stratton IM, Levy JC, Matthews DR. A method for
assessing quality of control from glucose profiles. Diabet Med. 2007 Jul;24(7):753-8.
doi: 10.1111/j.1464-5491.2007.02119.x. Epub 2007 Apr 19. PMID: 17459094.
52. Rodbard, D. Interpretation of Continuous Glucose Monitoring Data: glycemic variability
and quality of glycemic control. Diabetes Technology and Therapeutics, 11

(Supplement 1): S55 – S57, June, 2009.
53. Thomas A, Schönauer M, Achermann F, Schnell O, Hanefeld M, Ziegelasch HJ,
Mastrototaro J, Heinemann L. The "glucose pentagon": assessing glycemic control of
patients with diabetes mellitus by a model integrating different parameters from
glucose profiles. Diabetes Technol Ther. 2009 Jun;11(6):399-409. doi:
10.1089/dia.2008.0119. PMID: 19459770.
54. Augstein P, Heinke P, Vogt L, Vogt R, Rackow C, Kohnert KD, Salzsieder E. Q-Score:
development of a new metric for continuous glucose monitoring that enables
stratification of antihyperglycaemic therapies. BMC Endocr Disord. 2015 May 1;15:22.
doi: 10.1186/s12902-015-0019-0. PMID: 25929322; PMCID: PMC4447008.
55. Vigersky RA, Shin J, Jiang B, Siegmund T, McMahon C, Thomas A. The Comprehensive
Glucose Pentagon: A Glucose-Centric Composite Metric for Assessing Glycemic Control
in Persons With Diabetes. J Diabetes Sci Technol. 2018 Jan;12(1):114-123. doi:
10.1177/1932296817718561. Epub 2017 Jul 27. PMID: 28748705; PMCID:
PMC5761978.
Page 23 of 27
23
56. Hirsch IB, Balo AK, Sayer K, Garcia A, Buckingham BA, Peyser TA. A Simple Composite
Metric for the Assessment of Glycemic Status from Continuous Glucose Monitoring
Data: Implications for Clinical Practice and the Artificial Pancreas. Diabetes Technol
Ther. 2017 Jun;19(S3):S38-S48. doi: 10.1089/dia.2017.0080. PMID: 28585873; PMCID:
PMC5467104.
57. Beck RW, Bergenstal RM, Cheng P, Kollman C, Carlson AL, Johnson ML, Rodbard D. The
Relationships Between Time in Range, Hyperglycemia Metrics, and HbA1c. J Diabetes
Sci Technol. 2019 Jul;13(4):614-626. doi: 10.1177/1932296818822496. Epub 2019 Jan

13. PMID: 30636519; PMCID: PMC6610606.
58. Rodbard D. Glucose Time In Range, Time Above Range, and Time Below Range Depend
on Mean or Median Glucose or HbA1c, Glucose Coefficient of Variation, and Shape of
the Glucose Distribution. Diabetes Technol Ther. 2020 Jul;22(7):492-500. doi:
10.1089/dia.2019.0440. Epub 2020 Feb 18. PMID: 31886733.
59. Rodbard D. Evaluating quality of glycemic control: graphical displays of hypo- and
hyperglycemia, time in target range, and mean glucose. J Diabetes Sci Technol. 2015
Jan;9(1):56-62. doi: 10.1177/1932296814551046. Epub 2014 Oct 14. PMID: 25316714;
PMCID: PMC4495532.
60. Little S, Shaw J, Home P. Hypoglycemia rates with basal insulin analogs. Diabetes
Technol Ther. 2011 Jun;13 Suppl 1:S53-64. doi: 10.1089/dia.2011.0022. PMID:
21668338.
61. Danne T, Pettus J, Giaccari A, Cariou B, Rodbard H, Weinzimer SA, Bonnemaire M,
Sawhney S, Stewart J, Wang S, Castro RC, Garg SK. Sotagliflozin Added to Optimized
Insulin Therapy Leads to Lower Rates of Clinically Relevant Hypoglycemic Events at Any
HbA1c at 52 Weeks in Adults with Type 1 Diabetes. Diabetes Technol Ther. 2019
Sep;21(9):471-477. doi: 10.1089/dia.2019.0157. PMID: 31335194; PMCID:
PMC6708262.
62. Leelarathna L, Thabit H, Wilinska ME, Bally L, Mader JK, Pieber TR, Benesch C, Arnolds
S, Johnson T, Heinemann L, Hermanns N, Evans ML, Hovorka R. Evaluating Glucose
Control With a Novel Composite Continuous Glucose Monitoring Index. J Diabetes Sci
Technol. 2020 Mar;14(2):277-283. doi: 10.1177/1932296819838525. Epub 2019 Mar
31. PMID: 30931606; PMCID: PMC7196869.
Page 24 of 27
24
Table Legend
Table 1. Enhancements to the Ambulatory Glucose Profile (AGP)

Enhancements of the Ambulatory Glucose Profile (AGP)
1. Show multiple factors with major effects on glucose levels by time of day,
for individual days or for data pooled over multiple days.

 Medications: insulin administration (basal, bolus) by time, dose, calculated
Insulin on Board (IOB), plasma insulin levels (pharmacokinetics), glucose
disposal activity (pharmacodynamics) by time of day, for individual days or
pooled over multiple days.
 Meals: timing, food quantity and content

 Physical activity (accelerometer) and (optionally) heart rate
2. Show %Time Below Range (%TBR: %T <54 mg/dL and %T <70 mg/dL) and %Time
Above Range ( %TAR: %T >180 mg/dL and %T >250 mg/dL) by time of day, for
individual days or pooled over multiple days.
3. Analyze patterns following major meals, pooling data from multiple days, after
“normalizing” glucose data by subtracting the pre-meal glucose and synchronizing
with respect to the onset of meals, displaying glucose values and 25th, 50th, and 75th
percentiles by time after meals. Characterize patterns in terms of maximal glucose
achieved (Gmax Gmax), time of maximum glucose (Tmax), % Recovery
toward pre-meal baseline after a specified number of hours (e.g., 2-4)
Compare magnitude and shape of the prandial excursions for the three major
meals
Combine or merge the displays of post-prandial excursions with the overall 24-hour
AGP.
4. Analyze patterns by day of the week, with separate AGP for each day of week.
Identify days of week with similar patterns and those with distinct patterns using
objective criteria.
Page 25 of 27
25
5. Display glucose levels using a nonlinear scale (e.g., semi-log scale) to expand the
hypoglycemic region and compress the hyperglycemic region.
6. Provide options to examine 24-hour periods starting at times other than midnight
(e.g. 6 AM) or utilize 48 hour displays to facilitate analysis of the overnight period.
7. Enable interactive analysis to display the date, time, glucose value, and ancillary
data for individual data points.
8. Methods to compare AGPs from persons or groups receiving different forms of
therapy or other interventions.
Enhancements of the Ambulatory Glucose Profile (AGP)
9. Show multiple factors with major effects on glucose levels by time of day,
for individual days or for data pooled over multiple days.

 Medications: insulin administration (basal, bolus) by time, dose, calculated
Insulin on Board (IOB), plasma insulin levels (pharmacokinetics), glucose
disposal activity (pharmacodynamics) by time of day, for individual days or
pooled over multiple days.
 Meals: timing, food quantity and content
 Physical activity (accelerometer) and (optionally) heart rate
10. Show %Time Below Range (%TBR: %T <54 mg/dL and %T <70 mg/dL) and %Time
Above Range ( %TAR: %T >180 mg/dL and %T >250 mg/dL) by time of day, for
individual days or pooled over multiple days.
11. Analyze patterns following major meals, pooling data from multiple days, after
“normalizing” glucose data by subtracting the pre-meal glucose and synchronizing
with respect to the onset of meals, displaying glucose values and 25 th, 50th, and 75th
percentiles by time after meals. Characterize patterns in terms of maximal glucose
achieved (Gmax Gmax), time of maximum glucose (Tmax), % Recovery
toward pre-meal baseline after a specified number of hours (e.g., 2-4)
Compare magnitude and shape of the prandial excursions for the three major
meals
Page 26 of 27
26
Combine or merge the displays of post-prandial excursions with the overall 24-hour
AGP.
12. Analyze patterns by day of the week, with separate AGP for each day of week.
Identify days of week with similar patterns and those with distinct patterns using
objective criteria.
13. Display glucose levels using a nonlinear scale (e.g., semi-log scale) to expand the
hypoglycemic region and compress the hyperglycemic region.
14. Provide options to examine 24-hour periods starting at times other than midnight
(e.g. 6 AM) or utilize 48 hour displays to facilitate analysis of the overnight period.
15. Enable interactive analysis to display the date, time, glucose value, and ancillary
data for individual data points.
16. Methods to compare AGPs from persons or groups receiving different forms of
therapy or other interventions.
Page 27 of 27
glucose disposal.
with model-based simulations of insulin pharmacodynamic activity in terms of rate of
Figure 1. Display of Glucose, Insulin, Meals, and Physical Activity by time of day for one
person for one day (schematic drawing). Insulin bolus dose and timing are shown together
27

The Ambulatory Glucose Profile Opportunities For Enhancement

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

The Ambulatory Glucose Profile Opportunities For Enhancement

Uploaded by

Copyright:

Available Formats

Diabetes Technology and Therapeutics

The Ambulatory Glucose Profile: Opportunities for Enhancement

Short Title: Ambulatory Glucose Profile (AGP) Enhancements

David Rodbard MD1)

10113 Bentcross Dr.

Ambulatory Glucose Profile (AGP)

AGP Ambulatory Glucose Profile

Gmax Glucose maximum of a post prandial glucose excursion

Title: 7 words (61 characters including spaces)

Short title: 45 characters including spaces

Abstract: 276 words

Main body of text: 4,257 words

Abstract (276 words)

lowering (pharmacodynamic) activity of medications, and physical activity measured by

levels, enabling comparisons of magnitude, shape and patterns; 4) Methods to

We propose several potential improvements to the AGP (Table 1).

1. Display major determinants of glucose levels: To facilitate interpretation of the

stacked bar chart to show the relative or absolute composition of carbohydrate,

action: i) the model-predicted level of insulin-on-board; ii) model-predicted profile

Comment: Since use of “normalizing” of the curves results in loss of information, it is

considerable overlap and only a suggestion of a difference in patterns (cf. Figure 3 of

time period (cf. Figure S3 in Supplementary materials to (37).

the onset of a clinic visit.

forms of analysis now available (graphical, statistical, scoring, artificial intelligence,

This study was funded by Biomedical Informatics Consultants LLC.

Wolpert H, Rodbard D, Polonsky W, Johnson J., He X, Xue J, Krugman S. Call to Action:

Profile: Representation of Verified Self-Monitored Blood Glucose Data. Diabetes Care,

Technol Ther. 2008 Jun;10(3):149-59. doi: 10.1089/dia.2007.0293.PMID: 18473688

4. Mazze R, Akkerman B, Mettner J. An overview of continuous glucose monitoring and

Glucose Monitoring in Clinical Practice. Diabetes Technol Ther. 2019 Jun;21(S2):S217-

statement. Diabetes Metab. 2018;44(1):61-72. doi:10.1016/j.diabet.2017.10.009

Endocrinologists (AACE); American College of Endocrinology (ACE). American

glucose concentrations and insulin requirements in patients with type 1 diabetes:

30. Berger MP, Rodbard D. A pharmacodynamic approach to optimizing insulin

A Randomized Controlled Trial. Diabetes Technol Ther. 2018 Nov;20(11):715-724.

and Francis, 2015. ISBN 0 8493 2843 8.

48. Schlichtkrull J, Munck O, Jersild M. The M-Value, An Index of Blood-Sugar Control in

6820.1965.tb01810.x. PMID: 14251860.

Diabetes Technol Ther. 2009 Jun;11 Suppl 1(Suppl 1):S45-54. doi:

and quality of glycemic control. Diabetes Technology and Therapeutics, 11

Sci Technol. 2019 Jul;13(4):614-626. doi: 10.1177/1932296818822496. Epub 2019 Jan

Table 1. Enhancements to the Ambulatory Glucose Profile (AGP)

Enhancements of the Ambulatory Glucose Profile (AGP)

for individual days or for data pooled over multiple days.

 Meals: timing, food quantity and content

therapy or other interventions.

Enhancements of the Ambulatory Glucose Profile (AGP)

for individual days or for data pooled over multiple days.

You might also like