DIABETES TECHNOLOGY & THERAPEUTICS

Volume 11, Supplement 1, 2009

Mary Ann Liebert, Inc.
DOI: 10.1089=dia.2009.0004

Clinical Experience with Continuous Glucose

Monitoring in Adults

Kristin Fabiato, M.D.,1 John Buse, M.D., Ph.D.,1 Michelle Duclos, M.P.H.,1
Joseph Largay, P.A.C., C.D.E.,1 Camille Izlar, M.S., R.D., L.D.N., C.D.E.,1 Thomas OConnell, M.D.,1
Jennifer Stallings, R.D., L.D.N., C.D.E.,1 and Kathleen Dungan, M.D.2

Abstract
Despite recent advances in therapy, achieving adequate glycemic control may be difficult for a large number of
patients with diabetes. Real-time (RT)-continuous glucose monitoring (CGM) has the potential to improve
glycemic control through immediate feedback to the properly trained patient. However, limitations exist both in
interpreting the results of published randomized clinical trials on CGM use and in extrapolating the results to the
diabetes population at large. This review summarizes the evidence for use, identifies suitable candidates, de-
scribes optimal implementation, and employs case scenarios in order to emphasize practical aspects of RT-CGM
use in adults. Establishment of expectations and comprehensive education in intensive insulin therapy and RT-
CGM use are necessary for successful implementation. Because the technology has been shown to be most useful
in patients who are actively viewing and responding to RT data, patients should receive explicit instructions for
active self-adjustment of insulin and lifestyle elements. While the technology is improving, false alarms remain a
significant barrier to optimal use. The utility of RT-CGM for patients with severe hypoglycemia or hypoglycemia
unawareness has not been established. Finally, studies are needed to determine the sustainability of improve-
ments in glycemic control, as well as cost-effectiveness and practicality of implementation into busy real-world
practice.

Introduction
D espite recent advances in diabetes therapy, many
patients still fail to achieve the minimal glycosylated
hemoglobin (A1c) target of less than 7.0% set forth by the
American Diabetes Association.1 Observational studies have
shown that glycemic control is linked to frequency of self-
monitored blood glucose (SMBG) testing in insulin-treated
patients.2 The link between frequency of SMBG and glycemic
control in patients with type 2 diabetes not treated with in-
sulin is not so clear.3,4 A recent panel concluded that SMBG
should be performed once or twice per day in most non
insulin-requiring patients.5 It has not been disputed, how-
ever, that even SMBG performed four to six times per day can
miss important hyperglycemic and hypoglycemic events.6,7
This has, therefore, spurred a growing interest in continuous
glucose monitoring (CGM). Retrospective CGM systems
(CGMSs) were approved for use by the Food and Drug Ad-
ministration (FDA) in June 1999.8 The first real-time (RT)
CGM, the GlucoWatch
Biographer (Cygnus Inc., Redwood
City, CA), was approved by the FDA in 2001.9 Controlled
trials indicate that only frequent intensive use leads to im-
provement in glycemic control or reduction in hypoglyce-
mia in insulin-treated patients.1013 RT-CGM, however, has
greater potential to improve glycemic control through im-
mediate feedback to the properly trained patient and there-
fore serves as the focus of the current review. In this review,
we will summarize the evidence for use, identify suitable
candidates, describe optimal implementation, and employ
case scenarios in order to emphasize practical aspects of
RT-CGM use. We will focus on adults with type 1 diabetes
mellitus (T1DM), based on the available evidence, unless
otherwise specified.
Evidence
Interpretation of studies
In general there are several limitations in interpreting the
current CGM literature and extrapolating to the general adult
population. Initial studies were uncontrolled, making it dif-
ficult to interpret whether benefit originated from a true effect
of CGM or resulted from the Hawthorne effectpatients who

1
UNC Highgate Diabetes and Endocrinology Clinic, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
2
The Ohio State University, Columbus, Ohio.

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know they are being observed alter their behavior consciously
or subconsciously enough to affect glycemic control. In ad-
dition, blinding is difficult because subjects must use RT data
to make adjustments in insulin therapy. Many of the early
trials were also conducted in pediatric populations. Further-
more, the patients enrolled in these studies were in general
highly motivated and had access to well-trained study teams
who were specifically funded to take the time and make the
effort to optimize the utility of the technology. The patients in
one study,14 for example, had scheduled follow-up visits at
weeks 1, 4, 8, 13, 19, and 26 plus an additional phone call in
between each visit to review blood glucose values. How CGM
will translate into real-world practice in which this degree of
intensive intervention cannot generally be provided is thus
unclear. Extensive exclusion criteria, in many studies includ-
ing severe hypoglycemia or hypoglycemic unawareness, of-
ten limit applicability to patients who would theoretically
stand to gain significant benefit from sensor use. Finally,
studies are generally short term (3 months or less). As with
any intervention requiring consistent patient action, it is
possible that RT-CGM could lose effectiveness if patients be-
come complacent over time.
Effect on A1c
Several controlled trials have suggested moderate effects
on A1c in adults with consistent use.
A recent randomized controlled trial stratified 322 subjects
with T1DM by age group and assigned them to RT-CGM
(device varied according to patient preference) or SMBG for
26 weeks.14 Eighty-three percent of the 52 adult subjects over
the age of 25 years had a baseline A1c between 7% and 8%.
Subjects in this subgroup who were randomized to RT-CGM
achieved a statistically significant 0.5% greater reduction in
A1c at 26 weeks relative to the control group. In contrast,
subjects between 15 and 24 years of age did not benefit. The
difference in outcomes may be attributable to frequency of
sensor use: 83% of those over 25 years wore the sensor at least
6 days per week compared to only 30% of subjects 1524 years
old. This suggests that the technology is only useful with high-
intensity use, probably through RT modification of diet,
medication, and lifestyle patterns. Indeed, patients >25 years
of age had lower baseline A1cs than the younger patients, also
suggesting that other factors, such as differences in knowl-
edge base, awareness and=or concern over prevention of
complications, or frequency of SMBG may have affected
outcomes. This study is unique in that it provides details of
specific standardized instructions for adjustment of therapy
in response to RT-CGM.15
Another controlled study found that a combination of pe-
diatric and adult patients with poorly controlled T1DM
(baseline A1c >9.5%) had a 0.6% greater reduction in A1c at 3
months relative to controls using RT-CGM.16 Once again,
continuous use was paramount, as those patients who un-
derwent intermittent RT-CGM use (3 day periods every 2
weeks) did not achieve benefit. Ninety-five percent of the
patients in the continuous arm reported making changes to
their insulin dose, diet, or lifestyle based on the results of the
RT-CGM, suggesting that even patients with poor control
(and possibly less meticulous self-care habits) can be moti-
vated to succeed. This is also supported by less rigorous, non-
randomized data.17
FABIATO ET AL.
Advanced insulin dosing features of sensor-augmented in-
sulin pumps may provide a more straightforward means of
applying RT-CGM information to short-term modifications
in insulin therapy. In a recent 6-month trial of 146 patients with
T1DM, patients were assigned to sensor-augmented pump
therapy versus pump therapy alone.18 The sensor group
achieved an A1c reduction similar to that of the control group.
However, the sensor group was able to achieve the reduction
in A1c without an increase in the rates of hypoglycemia,
whereas the control group had an increased frequency of
hypoglycemia. Furthermore, subgroup analysis demonstrated
that patients who maintained >60% sensor utilization achieved
a significant reduction in A1c relative to the control group. This
once again emphasizes the importance of adherence.
Finally, a randomized controlled trial enrolled 65 patients
with poorly controlled (A1c 810%) type 2 diabetes mellitus
(T2DM), treated with oral hypoglycemics, insulin, or a com-
bination of the two.19 No changes were made to insulin doses
or oral hypoglycemic agents in patients assigned to either
group unless hypoglycemia occurred. Patients in the RT-CGM
group only wore the device for 3 days at a time each month for
the 3-month study. Each group received lifestyle counseling
monthly based on SMBG or RT-CGM readings. However, the
group assigned to RT-CGM was also instructed to increase
their activity levels and eat less in response to hyperglycemia
alarms and to confirm hypoglycemic alarms with SMBG be-
fore treating. The results demonstrated a significantly greater
reduction in A1c in patients randomized to RT-CGM com-
pared to controls (1.1% vs. 0.4% respectively, P 0.004). The
findings were associated with significant reductions in caloric
intake, body mass index, and a significant increase in exercise
time over the 3-month study. The results are contrary to those
of studies involving patients with T1DM in which continuous
intensive use is necessary. It is not entirely unexpected, how-
ever, because many patients with T2DM still have endogenous
insulin production and consequently would be more likely to
respond to diet and lifestyle modification. Nevertheless, over
half of the patients were receiving insulin, and the duration of
diabetes was over 10 years in both groups, suggesting that
endogenous insulin production was poor. It is unclear whe-
ther patients who performed SMBG measurements only
would have achieved similar reductions in A1c if they were
also instructed to respond in similar ways to their SMBG
readings as those with RT-CGM. Further study is needed to
determine whether reduction in A1c is dependent upon in-
sulin use. Cost-benefit analysis and an assessment of the du-
rability of the effect over time are necessary to determine
whether RT-CGM may be feasible for the millions of patients
with poorly controlled T2DM in the United States alone.
Hypoglycemia
Hypoglycemia is regarded by many patients and providers
as the primary barrier to reaching treatment goals.20 Fear of
hypoglycemia causes many patients to target higher glucose
levels than currently recommended and makes them reluctant
to implement adjustments in therapy (see Scenario 4 below).
Furthermore, hypoglycemia unawareness and serious hypo-
glycemia can be associated with death and disability.21
CGMS has been utilized as a way to better characterize
hypoglycemia as well as to limit its occurrence.12 However,
CGMS may overestimate the frequency of hypoglycemia
CLINICAL EXPERIENCE WITH CGM IN ADULTS
when compared to concomitant SMBG values,22 and it has
reported hypoglycemia in normal subjects at a similar rate as
in patients with T1DM.23 Nevertheless, interstitial glucose
may reflect physiologic glucose levels in tissues such as the
brain better than blood glucose and may thus be the more
relevant measure. For example, interstitial glucose more clo-
sely follows recovery of cognitive function after a hypogly-
cemic event than blood glucose.24
Although there may be greater accuracy with newer gen-
eration RT-CGM devices, it is still unclear whether all hypo-
glycemic events detected by sensors are clinically relevant.
Controlled trials have achieved moderate reductions in A1c in
specific populations without a concomitant increase in hy-
poglycemia.16,18 This is a substantial achievement given that
intensive insulin regimens targeting improvements in glycemic
control almost always increase the risk of hypoglycemia, a
phenomenon that was most comprehensively documented in
the Diabetes Control and Complication Trail and the United
Kingdom Prospective Diabetes Study. A short-term controlled
study did demonstrate that patients using RT-CGM spent 21%
less time with glucose values <55 mg=dL than controls.25
However, no study has demonstrated a reduction in severe
hypoglycemic events or hypoglycemia unawareness, outcomes
for which these studies were not designed, given that patients
at high risk were not generally recruited.
Glycemic variability
It has been hypothesized that glycemic variability may
carry a risk for complications independent of A1c.26 Glycemic
excursions in patients whose A1c is at goal, for example, have
been linked to macrovascular and possibly microvascular
complications.27,28 Glycemic variability also predicts the risk
of severe hypoglycemia.29,30
RT-CGM has also been investigated as a tool for modifying
glycemic excursions. In one controlled study of RT-CGM,
insulin-treated patients with T1DM and T2DM experienced a
23% reduction in postprandial hyperglycemia and spent 26%
more time in the euglycemic range as compared to patients in
the control group.25 Improvements in measures of glycemic
variability were reported elsewhere.31,32 Reduction in gly-
cemic variability using RT-CGM, therefore, may foretell
benefits on complications, but this will need to be examined
more specifically.
CGM Use
Patient selection
As the technology improves, a larger percentage of patients
stand to benefit from CGM.
Until then, the cost of RT-CGM, as well as its modest effi-
cacy in selected patients managed in highly experienced well-
funded centers, warrants judicious patient selection. The most
ideal candidates appear to be those who are well educated
about their diabetes and highly motivated and yet still unable
to achieve an A1c target of <7%.
Other candidates for whom limited data are available who
may benefit include:
1. Patients with severe hypoglycemia, hypoglycemic un-
awareness, or fear of hypoglycemia that impedes ad-
justment of therapy
2. Patients with significant glycemic lability
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3. Patients contemplating pregnancy or who are currently
pregnant33,34 (discussed by Chitayat et al.35 in this
supplement)
4. Intermittent RT-CGM in patients with T2DM19
More data are needed to recommend for or against the use
of RT-CGM for other settings, such as in patients with gas-
troparesis, athletes, or hospitalized patients. In contrast, pa-
tients who are unwilling to engage in scrupulous self-care
behaviors would not be expected to benefit. That is not to say
that RT-CGM will not one day be capable of supplanting
SMBG, just as SMBG has replaced urinary glucose assess-
ments, but further refinements in the technology are needed.
Implementation
Improvements in glycemic control have been most pro-
nounced when RT-CGM is implemented in conjunction with
comprehensive education and close follow-up. Patients, and
even providers, may become overwhelmed when confronted
by the stream of information that RT-CGM imparts. There-
fore, RT-CGM instruction lends itself to a similar model as
that used for insulin pumps, using well-trained diabetes ed-
ucators to guide patients through a gradual, stepwise im-
plementation process. This type of education may be more
difficult for those physicians outside of a research or large
academic setting or without access to diabetes educators, but
should not preclude sensor use altogether.
Expectations
Patients may have misconceptions regarding the capability
of RT-CGM.36 In a study of patients with T1DM and T2DM,
most agreed that the device was easy to use and understand,
but patients were least satisfied with regards to the calibration
interval and the tendency toward error.37 Patients must un-
derstand that the current technology is only capable of pro-
viding adjunctive assistance. In our center, we have had
several patients who, despite meticulous education, have
made serious errors resulting in extreme glycemic excursions
as a result of not confirming RT-CGM with SMBG results
prior to making corrections. As with SMBG, RT-CGM is only
useful if patients actually view the data and implement
changes in insulin therapy, diet, and other lifestyle elements.
As such, patients must shift to making decisions based upon a
constant flow of glucose trends, rather than upon sporadic
glucose points in time. This may be especially challenging for
seasoned patients, who may have difficulty accepting this
paradigm shift in diabetes self-management (see Scenario 5
below). It may be helpful for patients to attend introductory
RT-CGM education sessions or investigate products on-line
before they commit to the technology. Likewise, it has been
our experience that it can take 36 months or more for patients
to become self-empowered, that is, to understand the infor-
mation well enough to make changes to their regimens on
their own.
Baseline knowledge
We recommend that patients undergo individual or group
training covering intensive diabetes self-management prior to
embarking on training for RT-CGM. Because of the com-
plexity of new decisions that will be required, even patients
who have received such education in the past would benefit at
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least from condensed refresher instruction. Some risk be-
coming overwhelmed by the plethora of glucose values and
even ignoring the alarms. Other patients may be tempted
to repeatedly bolus in response to hyperglycemia, placing
themselves at risk of hypoglycemia, or, conversely, to over-
compensate for hypoglycemia with excessive carbohydrate
intake. Therefore, patients should understand the timeaction
profile of insulin prior to starting RT-CGM. For pump pa-
tients, this includes the time of active insulin set on their
pump, although lockout features can provide protection from
insulin stacking. Patients must receive explicit instructions
regarding when to re-bolus and how to reduce the insulin
dose to avoid insulin stacking (see RT use section below).
Conversely, patients must understand how to appropriately
manage hypoglycemia. In one study, insulin stacking was
uncommon in patients using RT-CGM, but overzealous
treatment of hypoglycemia was frequent enough to partially
obscure the gains in glycemic control.38
Selection of the device
A comparison of the four devices currently approved by
the FDA is beyond the scope of this article. However, features
such as size, duration of initial calibration, ease of subsequent
calibrations, sensor and battery life, water resistance, accuracy
and density of data, and display features such as trend arrows
and graphs, as well as software programs for data review, are
all considerations in choosing a sensor. Compatibility with
insulin pumps and blood glucose monitors also differs. Fi-
nally, devices differ by cost. The selection should depend
upon patient preference, but educators and=or providers
comfort level may also play a role.
As stated above, the FDA-approved sensor life varies from
as little as 3 days with the Medtronic (Northridge, CA) device
to as many as 7 days with the DexCom (San Diego, CA)
sensor. With the significant expense of sensors and the often
poor reimbursement, many patients have been forced to ex-
tend the duration of use of each sensor through recalibration.
An article by Garg et al.39 supports 10-day use of the DexCom
sensor, but the safety and accuracy of such off-label use re-
quire further study.
It may also be possible that sensors could suit individual
patients differently. In our experience, if a patient does not
respond to one sensor, a different sensor could be tried. In
practice, however, this may not generally be feasible once a
sensor has already been purchased.
Although an extensive discussion of reimbursement is be-
yond the scope of this article, it is important to note here that
several major insurance carriers have recently approved CGM
use. As more cost-benefit data become available, reimburse-
ment for CGM use may become more widespread.
Technical considerations
Based on comparisons with blood glucose meters, patients
may become frustrated and get the impression that RT-CGM
is simply an inaccurate tool.37 However, as discussed by
Cengiz and Tamborlane40 in this supplement, interstitial
glucose imparts fundamentally different information than
blood glucose. Patients and providers must understand that
interstitial glucose measurements tend to lag behind blood
glucose, particularly during rapid swings. Thus, hyperglyce-
mia and hypoglycemia trends and alarms must be confirmed
FABIATO ET AL.
with SMBG before action is taken to correct the finding. As the
technology improves, requirements for reliance upon SMBG
to confirm RT-CGM values may lessen.
The capability of RT-CGM to reflect blood glucose is in part
reliant upon appropriate calibration with SMBG. It is crucial
that patients perform SMBG testing correctly, and only on the
fingertips for calibration purposes. Calibration must be per-
formed during steady state, when patients are fasting, or at
least pre-meal, when glucose levels are changing the least. In
particular, it has been shown that a few calibrations during
steady state are more important for determining RT-CGM
accuracy than many calibrations during times of fluctuating
blood sugars (i.e., during hypoglycemia, exercise, or post-
meal).13,41 Trend arrows on some devices as well as automatic
calibration lockouts can assist the patient in identifying ap-
propriate times for calibration. With that said, there are oc-
casional patients who despite exhaustive education, close
follow-up, and repeated calls to company hotlines, can never
achieve acceptable RT-CGM performance with one or more
devices. Whether this is related to patient factors that are as
yet unrecognized or technical issues is unclear but disturbing
to patients and practitioners alike.
Targets
Targets appear on line graphs of the receiver and on soft-
ware readouts for patient reference. Targets should be pro-
grammed based on a patients particular needs, depending on
the patients control and comfort level. Targets should gen-
erally be set higher for patients with severe hypoglycemia. An
expert consensus suggests either setting standard pre-meal
and post-meal targets of 80130 mg=dL and 140180 mg=dL,
respectively, or setting wider targets based on the patients
baseline SMBG profile.42 Setting a wide target initially may
help to improve patient compliance because patients whose
readouts continually appear outside of the target range may
become easily frustrated not only by a sense of failure but by
frequent and disruptive alarms. Targets can then be gradually
tightened as the patient becomes accustomed to the device.
Patients should be warned that early in the process it is not
unreasonable to expect as many as 50% of the readings to be
outside the target range.
Alarms
Alarm thresholds may or may not be set at the actual target
values, depending upon the desired sensitivity and specific-
ity. One study demonstrated that a hypoglycemia alert was
able to distinguish a blood sugar of 70 mg=dL or less with 67%
sensitivity and 90% specificity; however, the false alert per-
centage was high at 47%.38 For hyperglycemia defined as
>250 mg=dL, the sensitivity was 63% with a specificity of 97%
and a false alert percentage of 19%.
Alarms may be programmed for hypoglycemia and hy-
perglycemia, but also for projected hypoglycemia or hyper-
glycemia on some devices. Projected alarms activate when the
CGM glucose value and the rate of change predict that the
glucose value will cross the actual hyperglycemia or hypo-
glycemia alarm threshold at a preset time, such as 1030 min.
In general, fewer false readings occur at longer intervals.38
According to the consensus panel, alarms should be in-
troduced one at a time so that patients can become familiar-
ized with the appropriate responses required for each without
CLINICAL EXPERIENCE WITH CGM IN ADULTS
becoming overwhelmed.42 An alarm set at
70 mg=dL may
be appropriate in most patients except those with hypogly-
cemia unawareness, where
80 mg=dL or higher may be
more desirable. However, the current sensor technology is not
as accurate at 70 mg=dL, so the false-positive percentage will
likely be higher at this setting. The consensus panel recom-
mends an initial hyperglycemia alarm to be set at 250 mg=dL
and be reset to 180200 mg=dL over time.42 This process ne-
cessitates an individualized approach because frequent
alarms in the less motivated patient could spur frustration
and complacency, but may not be sensitive enough in patients
with hypoglycemia unawareness. Alarms may also be dis-
abled or set to vibrate in order to minimize patient attrition,
but this may defeat the purpose of the device.
Interpretation of data and adjustment in therapy
Data may be interpreted based on instantaneous readouts
(in response to glucose trends or alarms) or retrospective use
(in response to cumulative patterns over several days or
weeks). The expert panel recommended no action in the first
37 days to allow a patient to simply acclimate to the device.42
RT use
The RT goal for the patient is to be able to identify short-
term trends in the data and to make changes in nutrition or
insulin regimen concurrently in order to prevent or treat
glucose values that are out of the target range. For example,
a blood glucose of 70 mg=dL may be treated presumptively
in a patient whose interstitial glucose is dropping rapidly,
whereas the same number in a patient whose glucose is
climbing could simply be observed. Subjects must also be
cautioned that the display on the current sensors is such that
despite a flat trend arrow, a patients blood sugar could be
changing by as much as 59 mg=dL=h, depending on the par-
ticular device.42
One limitation of the current literature is that many studies
generally have not described validated or even standardized
algorithms for implementing changes in therapy, despite the
fact that they may have been used. Two exceptions are the
DirecNET and the Juvenile Diabetes Research Foundation
studies, which used very similar algorithms (Fig. 1).15,43 In the
Juvenile Diabetes Research Foundation study, patients took
action within two main scenarios:
1. Upward or downward adjustment of bolus insulin based
upon the rate of change in sensor glucose. For example,
patients are instructed to increase their pre-meal bolus
by 10% for a 2040 mg=dL=h increase (indicated as one
up arrow on the Medtronic sensor) and increase pre-
meal bolus by 20% for an upward trend of >40 mg=
dL=h (indicated as 2 up arrows on the Medtronic sen-
sor). Downward arrows were treated in an opposite
manner. No change in bolus dose required if the change
was <20 mg=dL=h.
2. Therapy to prevent or treat hypoglycemia or hyperglycemia
based upon projected or actual alarms. For high alerts,
patients are instructed to wait at least 2 h before using
repeated correction dosing. They consumed 15 g of
carbohydrates for low alerts and 10 g for projected low
alerts. In addition, a consensus panel advised good
hypoglycemia management skills, including repeating
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Perform SMBG
Before Meals Between Meals
Calculate insulin dose Calculate insulin dose
(I:CHO plus correction) (Correction dose only)
RT-CGM Adjustment of Insulin Bolus
Change in Prandial Insulin
Glucose Trend Trend Arrows
Dose
Rising > 40 mg/dl ( ) Increase 20%
Rising 20-40 mg/dl ( ) Increase 10%
Rising or falling by <20 mg/dl No arrows No change
Glucose falling 20-40 mg/dl ( ) Decrease 10%
Glucose falling by > 40 mg/dl ( ) Decrease 20%
FIG. 1. Algorithm for RT-CGM adjustment of insulin.
I:CHO, insulin:carbohydrate.
SMBG measurement in 15 min and discouraging the
practice of interrupting the basal rate on pumps, which
can set a patient up for wide swings in glucose.42
While limited data are available in adults, pediatric patients
and parents using this algorithm conveyed good under-
standing and initial acceptance, but by 13 weeks, only 59%
reported using it at least 50% of the time. This may reflect the
development of complacency with the device or algorithm,
but the trends seen toward progressively more insulin ad-
justments over time suggests that use of the sensor was
helpful in helping patients recognize subtle intricacies in
glucose patterns and subsequently individualize their treat-
ment plans.
Retrospective use
Randomized trials have clearly shown that patients achieve
benefit largely from intensive, daily use of the device, sug-
gesting that retrospective analysis may only provide mar-
ginal, if any, benefit.1013 However, optimal use of RT-CGM
may also involve more in-depth study of the graphs acces-
sible on the CGM software or website provided by each
manufacturer. Patients should be instructed not to become
preoccupied with the day-to-day variability in glucose mea-
surements on these readouts, but to make adjustments in
basal or bolus insulin based upon patterns seen on at least 2
out of 3 days.15,43 Patients and providers may also gain insight
into the appropriate timing and distribution of insulin boluses
in response to variable meal composition, as well as the re-
sponse to exercise or medications, such as pramlintide (Fig. 2)
and prednisone (Fig. 3). Finally, as demonstrated with tradi-
tional CGMS, RT-CGM may be useful for identifying recur-
rent trends, such as the dawn phenomenon, and guiding
adjustments in basal rates.44,45
The published algorithms for RT-CGM provide detailed
instructions for self-adjustment of insulin with retrospective
use.15,43 Although these algorithms are complex, they have
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FIG. 2. RT-CGM use to evaluate the effect of pramlintide on glucose excursions.
been shown to be feasible in study populations. However, less
sophisticated patients are likely to require simplification or
individualized guidance. A consensus statement has recom-
mended that patients review and download their data prior to
each appointment to identify problem areas on which to focus
prior to each appointment.42 This could reduce the amount of
time spent in each encounter. Providers, in turn, may find it
useful to customize the devices software analysis by identi-
fying only a few graphs on which they wish to focus during a
visit. Graphs of the weekly blood glucose trend in addition to
breakdown by meals and daily blood glucose in instances of
severe highs or lows may be particularly useful.
Clinical Scenarios
A few clinical scenarios will be presented in this section to
illustrate several of the points discussed thus far in this review
article.
Ideal candidates
Scenario 1. This is a 40-year-old patient with T1DM for
approximately 20 years, complicated by proliferative reti-
nopathy. Despite initiation of an insulin pump and frequent
SMBG (at least four times daily), the patient was unable to
obtain an A1c <7%. The patient received training from a
skilled diabetes educator and purchased the RT-CGM device
that paired with his insulin pump. The patients pre-RT-CGM
A1c was 7.9%. By identifying trends towards hypo- and
FABIATO ET AL.
hyperglycemia and making adjustments in both his basal
settings and his insulin to carbohydrate ratio, the patient
was able to obtain an A1c of 6.5%. While attenuating
his glycemic excursions and tightening his overall control,
the sensor alarms helped prevent the increase in hypoglyce-
mic episodes possible with tightened control. Unfortunately,
the patients insurance company elected not to cover the
sensor so the patient had to discontinue its use. The patients
A1c rose to 7.7% off of the sensor despite continued frequent
SMBG.
Scenario 2. This is a 39-year-old patient with T1DM for
18 years. The patients A1c had been averaging 6.5% for
several years with use of an insulin pump and SBMG at least
four to six times daily. When sensors became available, the
patient purchased one and paid for it out-of-pocket. Analysis
of sensor data has taught him how various foods affect his
blood sugars. He now administers his pre-meal bolus earlier
and has had an attenuation of postprandial hyperglycemia.
The patients A1c has improved slightly to 6.2% without an
increase in hypoglycemia. In fact, the patient has actually re-
gained hypoglycemia awareness and now feels safer even
when not wearing the sensor.
These two scenarios reiterate several key points, in partic-
ular that consistent sensor use with RT adjustments in diet,
lifestyle, and therapy leads to the most significant results.
Patients who receive adequate education and guidance and
CLINICAL EXPERIENCE WITH CGM IN ADULTS S-99

FIG. 3. A 42-year-old woman with T1DM and multiple sclerosis was treated with a prednisone taper to prevent a multiple
sclerosis flare. With the use of CGM, the patient and her healthcare providers were able to identify a significant increase in
fasting and postprandial glucose: (a) before prednisone and (b) after prednisone. This led to a 50% increase in her basal rate
and an increase in her insulin to carbohydrate ratio from 1:8 to 1:5, which resulted in more stable blood glucose (BG) levels.

feel comfortable making these adjustments will likely
experience the most benefit. The issue of insurance coverage
remains a significant limiting factor, and cost-benefit analyses
are needed to help determine which patients qualify. Lastly,
the ability of RT-CGM to help patients regain hypoglycemia
awareness is one of the key potential benefits of sensor tech-
nology; however, assessment of the true effect has been lim-
ited by frequent exclusion of these patients from controlled
trials and the inaccuracy of current sensor technology in the
hypoglycemic range.
Pitfalls
Scenario 3. This is a 42-year-old woman with T1DM for
28 years. The patient was deemed a good candidate for the
sensor because of an A1c of 7.9% despite SMBG four to six
times daily (Fig. 4a). The patient received similar training as
the patient in Scenario 1, and with adjustment of her insulin
regimen, the patient was able to obtain an A1c of 6.3% (Fig.
4b). However, the patient had two episodes of severe hypo-
glycemia overnight requiring assistance from a family mem-
ber (Fig. 4c). In both instances, the alarms on the insulin pump
sounded for several hours before the patient received assis-
tance. During the first incident, the patient slept through the
alarm. This problem was reported previously with the use of
sensor-augmented pumps. Because the sensor alarm is part of
the pump, which remains attached to the body during sleep,
thick bedding may muffle the alarms.46 The patient did not
respond to the alarms during the second incident. After the
medical staff was made aware of the hypoglycemic episodes,
the patients glycemic goals were briefly loosened, and the
patients total daily insulin dose was decreased by 25%. Over
time, with more education and slow titration, the patients
control has again been tightened without an increase in hy-
poglycemia. This is an example of the utility of sensors for
permitting tightening of glycemic control without increasing
hypoglycemia. However, the lag time between interstitial
glucose and capillary glucose may limit the ability to prevent
hypoglycemia if rapid changes in capillary glucose occur.
Further, the relative inaccuracy of current sensor technology
in the hypoglycemic range and associated frequent false
alarms may contribute to patient disregard and even discon-
tinuation of use.
Scenario 4. This is a 31-year-old man with T1DM for
approximately 8 years who had a severe hypoglycemic epi-
sode requiring medical assistance soon after his diagnosis. As
a result, the patient and his wife have developed a magnified
fear of hypoglycemia and attempt to maintain his blood
sugars consistently in the mid-200 mg=dL range (Fig. 5a). The
patient was considered to be a good candidate for use of the
sensor as the alarms could be set to detect hypoglycemia,
allowing the patient to tighten his overall control. However,
despite approximately 25 patient-hours with medical staff
including significant education and multiple adjustments to
S-100 FABIATO ET AL.

FIG. 4. A patient with severe hypoglycemia, a 42-year-old woman with diabetes for 28 years who was able to obtain
improvement in A1c with the sensor. However, the patient experienced an increase in hypoglycemia with the decrease in
A1c: (a) CGM data before initiation of sensor, (b) CGM data after glucose control was briefly loosened and then re-tightened,
and (c) CGM daily data during one of two episodes of severe hypoglycemia requiring assistance (alarm bells) that the patient
did not hear. BG, blood glucose.

his insulin regimen in addition to behavioral counseling, the
patients A1c remains above 9% despite use of the sensor for
more than 1 year (Fig. 5b). He maintains that the sensor is
inaccurate because he reports feeling low frequently despite
sensor readings in the 200 mg=dL range. Unfortunately,
the patients fear of hypoglycemia has been so intense that
he overrides the bolus system and occasionally shuts off
the pump completely when he sees downward trends.
This example illustrates the limitations of RT-CGM in
overcoming certain psychological barriers in patients with
diabetes.
Scenario 5. This is a 67-year-old man with a 20-year
history of late-onset T1DM. The patient was also thought to
be a good candidate for the sensor given an A1c of 7.6%
despite frequent SMBG. The patient received adequate ed-
ucation about use of the sensor and has become extremely
comfortable with making changes to the settings. Over
several visits, providers have recommended raising the hy-
poglycemia target and shortening the alarm snooze time in
order to increase the sensitivity of hypoglycemia warnings.
Recommendations were also made to lower the hypergly-
cemia target and shorten the alarm snooze time from 2 h to
1 h to limit hyperglycemia and, therefore, decrease the risk of
diabetic ketoacidosis. The patient, however, maintains his
independence in the management of his diabetes and rou-
tinely changes the alarms back to their previsit settings.
After over a year of continuous use, the patient has been able
to obtain a 0.6% decrease in A1c with sensor use, bringing
him almost to goal. Making the additional changes to the
low and high targets, however, could lead to a further im-
provement in glycemic control. This scenario illustrates that
some seasoned patients may have difficulty accepting pro-
vider input and marked changes in the approach to therapy,
limiting their ability to achieve maximal benefit. A patients
willingness to make both self-directed and provider-initiated
CLINICAL EXPERIENCE WITH CGM IN ADULTS S-101

FIG. 5. Psychological barriers to optimal RT-CGM use. The example patient is a 31-year-old man with a severe hypogly-
cemic episode soon after his diagnosis of T1DM with a subsequent magnified fear of hypoglycemia. This severely limited his
willingness to implement changes suggested by medical staff and contributed to lack of improvement in glycemic control
with use of the sensor for 13 months: (a) CGM data before initiation of sensor and (b) CGM data after 13 months of sensor
use. BG, blood glucose.

changes should be assessed in determining appropriate
candidates.
Conclusions
Limitations exist in evaluating the current randomized
trial data for the effect of RT-CGM on glycemic control. The
technology is rapidly evolving, but substantial barriers exist
to widespread implementation. Longer-term studies in more
diverse practices and populations are needed, and neither
cost-effectiveness nor impact on quality of life has been ade-
quately studied. Steps, such as simplified treatment algo-
rithms, are needed to make implementation of the sensor
more conducive to an office setting with busy practitioners.
However, it appears that with appropriate patient selection,
comprehensive education, and careful follow-up by expert
practitioners, adult patients who consistently use RT-CGM
can make changes in their treatment based on RT and retro-
spective trends, improve self-efficacy, and experience signif-
icant benefit.
Author Disclosure Statement
No competing financial interests exist for K.F., M.D., C.I.,
and J.S. J.L. reports receiving grants or research support from
Amylin, Hoffman-LaRoche, Intekrin, Lilly, Medtronic, Novo
Nordisk, Novartis, Osiris, Pfizer, National Institutes of
Health=National Heart Lung and Blood Institute, Tolerx,
and Transition Therapeutics, honoraria fees from American
Academy of Phyiscan Assistants, Amylin, Novo Nordisk,
Pfizer, Sanofi-Aventis, and Smiths Medical, consulting fees
from Amylin, Astra-Zeneca, BMS, and Sanofi-Aventis, and
lecture fees from Amylin, Novo Nordisk, and Smiths Medi-
cal. T.O. reports receiving lecturing fees from Amylin, Pfizer,
Sanofi-Aventis, Takeda, Medtronic, and DexCom. J.B. is a
shareholder of Insulet and under contract with the University
of North Carolina; he is an investigator for Amylin and
Medtronic and consultant to Abbott, Amylin, and Johnson
and Johnson. K.D. reports receiving grant support from Novo
Nordisk, Diramed, and Tolerx and consulting fees from Eli
Lilly and Diramed and serves on the advisory board of Gly-
comark.
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The University of North Carolina Chapel Hill
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E-mail: jbuse@med.unc.edu