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Future Developments in Insulin Pump Therapy
Progression From Continuous Subcutaneous Insulin Infusion to a Sensor-Pump System
Lynda K. Fisher, MD and
Mary Halvorson, RN, MSN, CDE
From the Center for Endocrinology, Metabolism & Diabetes, Children's
Hospital Los Angeles.
Correspondence to Lynda K. Fisher, MD, Center for Endocrinology, Metabolism,
& Diabetes, Children's Hospital, 4650 Sunset Boulevard, Mail Stop No. 61,
Los Angeles, CA 90027.
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Intensified Treatment of Type 1 Diabetes in Pediatrics Today: Achievements and Unmet Needs
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Clinicians are using more intensive insulin strategies to achieve glycemic
control. At Childrens Hospital Los Angeles, the use of multiple daily
injections (MDI) began increasing in 2001, with the introduction of the first
long-acting insulin analog, insulin glargine. Although it has been in use for
more than a decade, "intensive" insulin therapy involving the use
of insulin pumps has also increased during this time period. At Childrens
Hospital Los Angeles, we have been able to achieve lower glycosylated
hemoglobin (A1C) levels with fewer hypoglycemic episodes in regular clinical
practice using continuous subcutaneous insulin infusion when compared with MDI
(although MDI was not always defined as basal-bolus insulin). A barrier that
is often cited for MDI therapy is the burden of multiple injections each day.
This may be a greater barrier for school-aged children since they need to
leave the class-room and go someplace where injections can be monitored. Many
schools refuse to have their personnel measure insulin for their students with
diabetes. An advantage that pump users have when compared with patients using
MDI is the ability to fine-tune insulin delivery and the flexibility to start
or stop insulin delivery on demand with relative discretion. School personnel
have been more willing to monitor pump use than to check insulin dosing with
syringes. This is also less time-consuming and results in less missed class
time for younger children.
Despite the availability of new glucose-lowering agents, A1C levels have
increased (in type 2 diabetes), and as a nation, we are still above the
recommended glycemic targets. Recent data suggest that we are slipping in our
ability to continue reaching A1C
targets.1 The fear
of developing hypoglycemia is one of many barriers to aggressively lowering
A1C levels. However, studies have shown that pump therapy has the ability to
improve glycemic control and reduce the development of hypoglycemia in
pediatric patients with
diabetes.2-8
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Continuous Real-Time Glucose Monitoring for Better Control
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More frequent blood glucose monitoring increases the potential for
detecting hyperglycemic and hypoglycemic
episodes.9
Furthermore, frequent glucose monitoring is linked to improved glycemic
control and has created a demand for advances in the area of glucose
monitoring.
The Continuous Glucose Monitoring System (CGMS®) made by Medtronic
MiniMed (Northridge, Calif) was approved by the US Food and Drug
Administration in 1999 as a tool for diabetes health care professionals to
retrospectively review glucose concentrations (measured every 5 minutes) in
their patients. The rationale for this device is that frequent glucose
measurements allow for a more precise understanding of daily glucose
fluctuations without the inconvenience of frequent needle sticks. Glucose
readings from the CGMS® correlate well with blood glucose levels and with
A1C levels. The author's group has reported that the CGMS® is a useful
tool in the diagnosis of asymptomatic nocturnal
hypoglycemia10 and
in improving clinical care in children
(Figure
1).11
Other studies have also reported the effectiveness of the CGMS® in
lowering A1C levels (Figures 2
and
3),12,13
reducing hypoglycemic events (Figure
4),14
and detecting otherwise missed asymptomatic hypoglycemia
(Figure
5).14,15
Another advantage of the CGMS® is the ability to monitor blood glucose
readings using an alarm system, which will signal users when readings are low
(or high) to prevent significant hypoglycemic events (or to alert patients of
significantly elevated glucose levels).
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Figure 1. The Continuous Glucose Monitoring System (CGMS®) is a useful tool to
improve clinical care in children with diabetes. Adapted from data from
Kaufman et
al.10
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Figure 2. The effectiveness of the Continuous Glucose Monitoring System (CGMS®)
in lowering A1C levels. DCCT = Diabetes Control and Complications Trial.
Reprinted with permission from Ludvigsson et
al.13 © 2003
by the AAP.
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Figure 3. The effectiveness of the Continuous Glucose Monitoring System (CGMS®)
in lowering A1C levels. Adapted from data from Doyle et
al.12
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Figure 4. The effectiveness of the Continuous Glucose Monitoring System (CGMS®)
in reducing hypoglycemic events. From Schiaffini et
al.14 Reprinted
with permission. *The sensor was inserted subcutaneously in each patient, and
the standard 4 or 5 registrations of capillary glycemia per day were performed
(CGMS 1). Eighteen patients continued in the study, and the glucose sensor was
again inserted after a 6-week interval (CGMS 2).
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Figure 5. A significantly higher number of asymptomatic hypoglycemic events were
identified by Continuous Glucose Monitoring System (CGMS®) in comparison
with the standard 4 or 5 daily capillary glucose measurements (3.6 ±
2.3 vs 0.7 ± 0.9; P < .0001). Adapted from data from Schiaffini et
al.14
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Pump therapy has improved glycemic control and reduced hypoglycemic
episodes. Despite major improvements, therapeutic goals have not been met. The
fear of hypoglycemic events prevents aggressive lowering of A1C levels in
pediatric patients with diabetes. The CGMS® has allowed clinicians to
identify both hypoglycemia and hyperglycemia and, based on these results, make
changes in insulin dosing, which lead to improved glycemic control and to
reductions in the development of hypoglycemia. Could linking an insulin pump
with a glucose sensor that provides information on glucose levels in real time
be helpful to further improve the management of diabetes in children? Could
such a system help patients overcome the hurdles of postprandial hyperglycemia
and hypoglycemia? Will this system allow patients to better track their
glucose levels, and will it alleviate the burden of frequent finger sticks and
injections?
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Clinical Feasibility Study of the Sensor-Pump System
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We have recently participated in a clinical feasibility study with the
purpose of assessing the effect of a sensor-augmented insulin pump designed to
provide continuous glucose readings in real time. The sensor-augmented insulin
pump consists of a MiniMed Paradigm® Insulin Pump into which the monitor
function of a Guardian® RT Continuous Glucose Monitoring System is
incorporated. (The Guardian® RT was recently approved by the US Food and
Drug Administration for use in adults.) The glucose sensor is connected to a
transmitter by a short wire. Then, interstitial glucose levels are measured by
the subcutaneous sensor every 5 minutes, which are then transmitted directly
to the Paradigm® Insulin Pump. Displays of current, real-time blood
glucose readings and trend graphs are then visible on the pump screen. Alerts
for high and low blood glucose levels (set on the sensor-augmented insulin
pump) can be individualized to each user. In addition, data can also be
downloaded to a computer for retrospective review. For this study, subjects
wore their own insulin pumps and used the sensor-augmented Paradigm® pump
to view real-time sensor values.
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Study Results
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Results were presented at the ADA Scientific Meeting in 2004. The study
showed that the sensor-augmented insulin pump provided real-time sensor
glucose trends that correlated well with blood glucose readings and was useful
in managing glycemic excursions. It was helpful in educating patients through
insight and understanding and was well tolerated by patients with minor
complaints about the alarms and tape. In addition, the sensor-augmented
insulin pump improved glycemic control and reduced the development of
hypoglycemia.
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Case Studies With the Sensor-Pump System
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Two patient case studies are presented to illustrate the benefit of using
the sensor-augmented pump.
Case 1
To illustrate how the new sensor-augmented insulin pump can provide
information to adjust insulin therapy in patients, a review of 2 cases is
presented.
Case 1 is a 10-year-old female who had diabetes for 8 years. Her A1C level
was usually  7%. She had a history of nocturnal hypoglycemia, and overall
insulin dosing had been decreased at a recent health care visit. She had no
seizures or severe events. When she was started on the sensor-augmented
insulin pump, her A1C level was 7.0%. A high glucose setting of 250 mg/dL
(13.75 mmol/L) was used, and the low glucose level was set at 70 mg/dL (3.85
mmol/L). At the first follow-up visit, she complained of slight skin
irritation at the transmitter site and agreed to use Comfeel® Plus under
the transmitter. It was noted that she had high patterns of blood glucose
levels at morning snack time and at bedtime. In addition, she had a rising
glucose level between 3 am and waking. No nocturnal hypoglycemia was
observed.
The correction was made by increasing the morning insulin-to-carbohydrate
ratio to 1/15, increasing the amount of basal insulin, and starting the higher
dose of early morning basal insulin at an earlier hour to normalize waking
blood glucose values. However, postprandial glucose levels remained high.
Therefore, the insulin-to-carbohydrate ratio was increased, which resulted in
resolution of her increased postmeal glucose excursions. During the second
week, the patient was taught to improve glycemia after breakfast and to use
the sensor-augmented insulin pump to test for the "dawn"
phenomenon. She was also instructed to increase the afternoon basal insulin
dose (Figure 6). By study visit
4, after 26 days of using the sensor-augmented insulin pump, an analysis for
abnormal patterns showed lunchtime hypoglycemia despite postprandial
hyperglycemia (Figure 7). This
was corrected by changing her ratios. Subsequently, the patient was on 0.73
U/kg of insulin and achieved an A1C level of 7.3% without nocturnal
hypoglycemia.
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Figure 7. An analysis of abnormal glucose patterns showed lunchtime hypoglycemia
after 26 days of using a sensor-augmented insulin pump in case 1.
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Case 2
Case 2 is a 16-year-old female who had diabetes for 9 years. She was unable
to achieve an A1C level of less than 8% despite frequent blood glucose
monitoring (including nocturnal monitoring), appropriate carbohydrate
counting, and correcting for elevated glucose values with extra insulin. The
alarms were set the same as those described in case 1.
Figure 8 illustrates how high
her postmeal blood glucose levels were at the beginning of the study. To lower
the blood glucose level to 150 mg/dL (8.25 mmol/L), the
insulin-to-carbohydrate ratio was increased and the correction factor (insulin
sensitivity factor) was increased to consistently be 1.5 U. She was also
instructed to evaluate her readings from 10 AM to 10 PM
and to evaluate postprandial glucose values. This led to improvement in her
postprandial glucose readings (Figure
9). Her evening bolus rates were decreased by about 15%, which
still allowed her to achieve appropriate fasting blood glucose levels in the
morning but without fear of hypoglycemia. Her A1C level at the end of the
study was 7.7%. This patient told her mother that by looking at the graphs,
she finally understood the need to take insulin before eating and to check
blood glucose levels after eating to maintain good glycemic control.
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Figure 9. After being instructed to evaluate readings from 10 AM to 10
PM and to evaluate postprandial glucose values, there was an
improvement in the patient's postprandial glucose readings (case 2).
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Conclusions
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The sensor-augmented insulin pump was well tolerated by these subjects with
minor complaints about tapes and alarms. The patients' use of this new insulin
pump lowered A1C levels and reduced hypoglycemic episodes. It provided
patients and health care team members with insight into glycemic patterns,
which facilitated treatment changes.
In summary, the sensor-augmented insulin pump can offer real-time
information for "in-the-moment" diabetes management, as well as
feedback for carbohydrate counting and adjustments for physical activity.
Treatment can be optimized based on historical data from the sensor-augmented
insulin pump downloads, allowing for adjustment of pump settings, calculation
of the insulin-to-carbohydrate ratio, and calculation of insulin sensitivity
factors. Additional trials are needed to confirm long-term clinical benefits
of the sensor-augmented insulin pump system.
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References
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Late breaking poster presented at: Annual Meeting of the American Diabetes
Association; October 2004; Orlando, Fla.
The Diabetes Educator, Vol. 32, No. 1,
47S-52S (2006)
DOI: 10.1177/0145721705285644
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