Self-monitoring of blood glucose (SMBG) has become a major tool
in the management of diabetes ().
The major inconvenience of SMBG is due to the fact that blood glucose
is only intermittently measured by fingerstick capillary blood sampling,
from which only a partial and therefore incomplete picture of blood
glucose fluctuations can be made ().
Because of many factors, including pain and inconvenience, many
children with diabetes do not accept frequent fingersticks for SMBG.
One parent of a child with diabetes compared his daughter's daily
four SMBG values to hearing four notes of a symphony ().
The availability of the continuous glucose monitoring system (CGMS)
(Medtronic; Northridge, CA, USA) offers the opportunity for pediatric
type 1 diabetic patients to match the demands of intensive therapy
with the intensive monitoring of blood glucose levels ().
The diabetes control and complications trial DCCT established that
intensive and multidisciplinary treatment of type 1 diabetes mellitus
(DM1) improves metabolic control and reduces the complications of
the disease ().
Estimates showed that a significant damage to quality of life is
frequently due to DM1 in children and adolescents, including functional
limitations, social and economic stress, even major depression ().
Psychological aspects and children's acceptance of DM1 may exercise
some influence over their glucose control ().
Despite excellent A1c levels and target preprandial glucose levels,
pediatric diabetic patients often experience nocturnal hypoglycemia
and postprandial hyperglycemia that are not evident with routine
In addition, families frequently do not measure blood glucose levels
during the night and 55% of severe hypoglycemic events in the DCCT
occurred during sleep ().
Several studies demonstrated the utility of the CGMS in improving
metabolic control, detecting more glucose excursions (hypoglycemia
and hyperglycemia) and in detecting more postprandial hyperglycemia
than SMBG ().
The efficacy of the CGMS in detecting hypoglycemia is not well established
in the medical literature ().
There was no information in Brazil about the effects of CGMS in
pediatric type 1 diabetic patients. This study aimed to determine
the impact of CGMS upon the detection of glucose excursions, unrecognized
hypoglycemia and upon improving metabolic control in DM1 pediatric
patients. The accuracy and complications of CGMS in children and
adolescents are discussed.
Subjects and methods
This retrospective study assessed 16 diabetic patients (16.12±4.41
years), whose duration of DM1 was 2-18 years, with a mean duration
of 7.81±4.83 years, submitted to CGMS for 72 hours (Medtronic;
Northridge, CA, USA). Each child had a mean HbA1c level > 7%
(range, 7-10.9%) 3 months before participating in the study. All
participants were on intensive insulin treatment, 20% receiving
continuous subcutaneous insulin infusion (insulin pump therapy)
and 80% receiving multiple daily injections (MDIs). There were 62.5%
of females and 37.5% of males. The selection of these patients was
based on the presence of DM1, HbA1c > 7% 3 months before the
exam and ability to operate the CGMS monitor. There were no restrictions
regarding sex, race, education, social or economic status.
The Medtronic MiniMed (Northridge, CA, USA) CGMS, the first model
approved by the FDA (Food and Drug Administration, USA) was used
for subcutaneous glucose monitoring. Glucose is measured by an electrochemical
assay of glucose oxidase, in which values from 40 to 400 mg/dl are
detected. The system consists of a subcutaneous sensor connected
by a cable to a pager-sized glucose monitor. Glucose readings are
made by the monitor every 10 seconds and an average glucose value
is stored in the monitor's memory every 5 minutes (up to 288 measurements
per day and 864 in all exams). Each glucose sensor provides glucose
information for up to 72 hours. After the initial 60 minutes, the
electrical current in nanoampere is converted into glucose value
after this information is measured by the monitor. The values stored
in the monitor are downloaded by the MiniMed Com-Station and presented
in graphical and statistical form via a computer program and the
sensor is eliminated. The original Medtronic MiniMed glucose sensor
was modified in November, 2002. This modification resulted in improved
accuracy. In this study, the new modified sensors were utilized.
All patients received basic instructions about the CGMS operation
and about the registry of all events in the "patient's diary",
by one of the authors (F.F.R.M). During the CGMS, all participants
had to perform at least four capillary blood glucose (CBG) tests
a day and enter these values into the CGMS monitor to obtain correlation
coefficients between the SBGM and the CGMS values. All SBGM tests
were performed using a digital glucometer (Accu-Chek Active; Roche
Diagnosis). The first CBG value was entered after 60 minutes of
CGMS. Families were asked not to change their dietary practices
during the study.
The following parameters were analyzed: correlation coefficient
(%); mean absolute difference (MAD); number of sensor readings;
duration of the exam (h); mean CBG and mean glucose value measured
by the CGMS; glucose excursions (CGMS vs. CBG); postprandial hyperglycemia
(normal range; NR < 140 mg/dl); nocturnal hypoglycemia; A1c levels
at the beginning and after 3 months; complications (trauma, local
infection, disconnection), noncompliance, and therapeutic management
The correlation coefficient and MAD were calculated by the Medtronic
software and defined as > 0.79% and < 28%, respectively, to
meet the optimal accuracy criteria. The MAD was determined by the
average difference between the glucose values obtained by the sensor
and blood glucose values in percentage (%) for a given day. The
number of measurements by the CGMS was considered significant if
higher than 80% (> 640 readings/72h). The accuracy of the CGMS
sensor was based on the comparison of capillary blood glucose values
and the values obtained by the sensor using Pearson's correlation
during hypoglycemia, normoglycemia and hyperglycemia, with a p value
Symptomatic glucose excursions were based on patients' information
and compared to the CGMS values. Hypoglycemia and hyperglycemia
were defined as blood glucose < 70 mg/dl and > 180 mg/dl,
respectively. The duration of hypoglycemia, hyperglycemia and normoglycemia
were recorded in percent for the sake of comparison. Postprandial
hyperglycemia was considered when blood glucose values were over
140 mg/dl 2 hours after lunch. Nocturnal hypoglycemia was detected
by glucose < 70 mg/dl between 11 p.m. and 7 a.m.
A1c values were determined at the beginning and 3 months after
the CGMS in 13 patients. A1c values were determined by using high
performance liquid chromatography (HPLC), with a normal range of
4.3 to 6.9%.
The complications during the CGMS were based on medical observation
and patients' information. Complications were analyzed during the
implantation of the sensor (bleeding and pain) and during the exam
(trauma, local infection, disconnection, psychological aversion,
technical deficiency, other "warnings"), noncompliance
and therapeutic management after CGMS.
The data were collected and analyzed by the Minitab software, by
the t test, chi-square test and regression test. A p value <
0.05 was regarded as significant. In cases of continuous variables
without normal distribution, the data were expressed as median (M)
and IQ25-75% and compared by the Mann Whitney test. The variables
expressed by percentage were analyzed by median and IQ25-75%.
The number of glucose readings during CGMS showed a median of 780,
Q1 = 715.2 and Q3 = 840.7 (NR > 680), with a significant value
in 87.5% of patients. The average number of hours per sensor was
71.4 hours/median of 70.25 hours. The correlation coefficient between
SBGM and CGMS values was 0.86±0.21 (NR > 0.79), with ideal values
in 93.75% of the studied patients. With regard to the MAD, the median
value was 12.6%, with Q1= 11.1 and Q3 = 16.5 (NR < 28%), which
was significant in 87.5% of patients. The main reason for the higher
numbers of usable CGMS data were patient compliance, due to inclusion
of minimum four capillary glycemia each day.
The mean capillary glucose values obtained by the CGMS sensor were
214.3±66.5 mg/dl vs. 207.6±54.6 mg/dl, with statistical significance
detected by Pearson's correlation (p = 0.001) (Figure 1) and Mann-Whitney
test (W = 151, significant at 0.97).
Figure 1 -
Correlation of glucose values detected by the continuous glucose
monitoring system (CGMS) sensor vs. fingerstick sampling values
in pediatric type 1 diabetic patients (r2 = 0.77; p =
As to glucose excursions, CGMS was more efficient compared to
fingerstick CBG sampling, according to the Mann-Whitney test (W
= 74, significant at 0.53). Postprandial hyperglycemia was identified
in 60% of pediatric type 1 diabetic patients with a median of 157
mg/dl; Q1= 104 mg/dl and Q3 = 246 mg/dl (NR < 140 mg/dl). Nocturnal
hypoglycemia was detected in 46.7% of these patients. During the
CGMS (72 hours), the patients were in a state of hyperglycemia,
hypoglycemia and normoglycemia during M = 59% (Q1: 22.5, Q3: 82.5);
M = 5% (Q1: 1, Q3: 8) and M = 40% (Q1: 14.5, Q3: 69.5), respectively.
The evaluation of A1c levels in eight (50%) patients before CGMS
and after 3 months showed statistical significance with decreased
level of A1c in this population (8.18±1.5 vs. 7.28±1.3; p = 0.034).
No complications were observed in 93.7% of patients. Disconnection
was the most common sign in this case (12.5%). No trauma, local
infection, allergy, bleeding or other symptoms were detected during
CGMS in this study. Psychological aversion and technical deficiency
were not observed in this population. All patients (100%) fully
completed the CGMS.
The therapeutic management of pediatric type 1 diabetic patients
was changed in 100% of patients, including insulin dose adjust,
change of insulin type, introduction of nutritional and psychological
support and physical activity.
This study is the first one that assesses the accuracy, utility
and complications of CGMS in pediatric patients in Brazil. In the
present study, all patients who used the CGMS showed some decline
in HbA1c levels after 3 months, as also described by Ludvigsson
et al. ().
According to these data, only 50% of control children (who had the
same care and SBGM testing, but not the CGMS) showed a reduction
in HbA1c levels. After 3 months, the decrease in mean HbA1c levels
for the CGMS group ranged from 8.18 to 7.28%, similar to the findings
of Ludvigsson et al. ().
The CGMS involves the insertion of a subcutaneous sensor, which
is easier for some patients compared with others. Three of the 12
adults chosen by Bode et al. did not participate, and one of the
12 children who initially volunteered to participate in this trial
did not complete any sensors. These data show total adherence to
the CGMS, with no interruption during the procedure.
These data showed that the CGMS was highly accurate compared to
CBG, a finding that is consistent with the medical literature ().
Sachedina & Pickup demonstrated the correlation between sensor
and fingerstick values in 18 DM1 patients submitted to CGMS for
72 hours. The CGMS proved to be better than intensive CBG (eight
times a day) at the detection of asymptomatic hypoglycemia and postprandial
hyperglycemia, which is in agreement with our data ().
We verified a correlation coefficient of 0.86, with a significant
value in more than 90% of patients, corroborated by Djakoure-Platonoff
et al. ().
They obtained a correlation coefficient of 0.92, with a significant
value in 93% of cases and a MAD of 25%. This group considered CGMS
for 72 hours as highly accurate and as the gold standard for the
determination of the glucose profile in diabetic individuals. Guerci
et al. reported the accuracy, performance, and reproducibility of
the CGMS in 18 type 1 diabetic patients submitted to CGMS for 72
hours, with mean duration of CGMS recording of 63±12 hours,
692 pairs of data for glucose meter readings and CGMS, correlation
coefficient ranging from 0.87 to 0.92 (NR > 0.79) and the mean
absolute error ranging from 12.8 to 15.7% (NR < 28%) as the most
frequent observations ().
In pediatric patients, the CGMS showed to be a very safe method
and an important alternative to promoting the reduction of A1c levels,
therapeutic adjustment, education and motivation of patients ().
In the USA, 12 diabetic adolescents (A1c > 8%) were submitted
to CGMS for 72 hours. The CGMS promoted detection of glucose excursions
in all patients, postprandial hyperglycemia in 10/12 cases and nocturnal
hypoglycemia in 30% of patients. After 2 months, they observed a
significant decrease in A1c levels ().
These data were very similar to our findings in Brazilian children
and adolescents with DM1.
About the efficacy of the CGMS sensor in detecting glucose excursions,
our results corroborated those obtained in many other studies ().
These data showed that the CGMS is very useful to detect postprandial
hyperglycemia. Recent data of 91 DM1 patients estimate that the
accuracy of the CGMS sensor is more effective in elevated glucose
levels than in hypoglycemic state ().
The efficacy of the CGMS in detecting hypoglycemia is not well
established in the medical literature ().
Boland et al. detected nocturnal hypoglycemia in 70% of 56 type
1 diabetic children submitted to CGMS for 72 hours and considered
this method a gold standard for the management of hypoglycemia in
the pediatric population submitted only to SMBG ().
Guerci et al. observed low sensitivity of the CGMS sensor in detecting
hypoglycemic levels (33%) in diabetic patients ().
According to Mcgowan et al., the CGMS sensor presented low efficacy
in detecting hypoglycemia in adolescents with DM1. The correlation
coefficient during hypoglycemic episodes showed only 0.76 (NR >
0.79) of concordance and has to be analyzed with caution ().
Chico et al. ()
reported that the CGMS was useful in detecting unrecognized hypoglycemia
and in improving metabolic control in 70 diabetic patients submitted
to CGMS for 72 hours. The CGMS detected unrecognized hypoglycemia
in 62.5% of type 1 diabetic patients and in 46.6% of type 2 diabetic
patients, and a remarkable decrease in A1c levels was observed after
3 months in both types of patients, similarly to these data. These
findings suggest that the CGMS is useful in detecting unrecognized
hypoglycemia in diabetic patients and in improving metabolic control.
However, Kovatchev et al. revealed that the accuracy of sensor readings
was lower in hypoglycemia (73.5%) versus euglycemia (99%) and hyperglycemia
(95.4%), and failure to detect hypoglycemia was the most common
error during the test ().
In a recent study of nocturnal hypoglycemia with 50 children with
diabetes who were hospitalized overnight, 47% had a blood glucose
level below 60 mg/dl (< 3.3 mmol/l) during the night (using hourly
blood glucose determinations) ().
The authors found that 49% of the cases were asymptomatic. The data
obtained by Ludvigsson et al. suggest that the incidence of asymptomatic
episodes amounts to approximately 85% (17 of 20).
No complications were observed in 96.7% of patients. No trauma,
local infection or bleeding was detected. The insulin regimen was
adjusted in 100% of patients. In Guerci et al., disconnection was
the most common problem detected during the CGMS, without any side
effects reported at the site of sensor implantation ().
In this study, disconnection was the most common problem detected
during the CGMS, in agreement with Guerci et al. Ludvigsson et al.
observed some failure to enter at least four SBGM values during
the day and that usable data were not obtained ().
According to these data, all the children had at least four fingerstick
values entered, resulting in high accuracy of CGMS values.
This study suggests that the CGMS is a very good method for the
detection of glucose excursion, postprandial hyperglycemia, and
for the improvement of metabolic changes in therapeutics with significant
impact on A1c levels of pediatric type 1 diabetic patients. The
CGMS is a very safe, well-tolerated and highly accurate method,
with a low complication rate. The use of this method should be actively
encouraged by physicians and patients. The efficacy of the CGMS
in detecting hypoglycemia is still unclear in the medical literature.