4276 Inpatient Skills

Journal Club Two

Lincy Varughese

Outpatient Glycemic Control with a Bionic Pancreas in Type 1 Diabetes

Steven JR, Firas HE, Manasi S, et al. NEJM. 2014;371(4):313-25.
Background: The safety and effectiveness of automated glycemic management have not been tested in
multiday studies under unrestricted outpatient conditions. The bionic pancreas is deemed to offer several
benefits when compared to the current standard of care with insulin pump therapy. There is a disconnect in
that, replacement insulin is dosed as a best compromise to lower post-prandial glucose levels while avoiding
hypoglycemia whereas pancreatic function, releases insulin aggressively and later includes automatic
release of glucagon to manage the blood sugar level. 1 Various studies demonstrate that systems being
developed for closed loop control with portable devices for patients with T1DM in outpatient settings are
feasible; and that improved and stable near-normal glycemic control can be achieved without increasing the
risk of hypoglycemia.2
Methods:
1.
2.

Objective:
a. To evaluate the effect of an automated glycemic control device in the management of blood
glucose in type 1 diabetes mellitus.
Study Design:
a. Table 1 [page 316]: Patient Characteristics
b. Supplementary Appendix:
i. Figure S1: Beacon Hill Study Consort Flow Diagram
ii. Figure S2: Summer Camp Study Consort Flow Diagram
c. Random order, unblended, cross-over design
d. Single 10 day study with a 5 day cross over consisting of adolescent and adult populations 52 total participants
e. Intervention:
i. Adults population was asked to spend 5 days using their insulin pumps at home,
monitor their blood glucoses, and note any interventions they made for
hypoglycemia. Upon completion of the 5 days, they were assigned to the Beacon
Hill community and placed on the bionic pancreas for analysis of blood glucose
regulation.
ii. Adolescent population was pulled from a summer camp and were also required to
complete 5 days of their control therapy and then 5 days of therapy with the bionic
pancreas. They were closely monitored and any interventions made were noticed.
iii. The bionic pancreas consisted of a Dexcom G4 Platinum CGM and iPhone for
control and data collection. It provides insulin therapy only on the basis of weight
and dietary announcements and also provides glucagon when blood glucose levels
are low.

Inclusion
All patients had at least a 1-year history of type 1
diabetes mellitus and were receiving IPT therapy.
Adults over the age of 21: participating in Beacon
Hill study
Adolescents 12-21: participating in a diabetes
summer camp.

3.

4.

Exclusion in Both Populations

Pregnancy or Unprotected Sexual Activity
Cystic Fibrosis
Pancreatitis or any other Pancreatic disease

Hypoglycemic Unawareness
End Stage Renal Disease
f.
Supplementary Appendix: Extended Exclusion Criteria
Outcomes:
a. Primary:
i. The mean plasma glucose level [obtained every 2 hours]
ii. The mean percentage of time that the patient had a low glucose level [<70 mg/dL]
b. Secondary:
i. Number of carbohydrate interventions for hypoglycemic episodes
ii. The mean glucose level measured by the continuous monitoring system
iii. Time spent in clinically relevant glucose ranges
iv. The fraction of patients with a mean glucose level that was consistent with their
therapeutic goals
Statistical Analysis:
a. 10 day comparative study of two study populations
b. Random-order, unblinded, crossover design
c. Data reported consisted of blood glucose measurements provided by glucometers.

4276 Inpatient Skills

d.

Journal Club Two

Lincy Varughese

Data analysis of comparisons were performed with the paired-sample, heteroscedastic

students t-test
i. Mean daily differences were calculated

Results:
1.
2.
3.

Table 2: [page 317] Summary Results of All 5-day Experiments Among Adults and Adolescents
Supplementary Appendix : Adverse Events
Review of groups after intervention:

Primary Outcome

Adults IPT

Adults BP

P-value

159 mg/dL

133 mg/dL

P<0.001

7.3%

4.1%

P=0.01

3.4

2.2

P=0.15

Adolescents IPT

Adolescents BP

P-value

157 mg/dL

138 mg/dL

P=0.004

7.6%

6.1%

P=0.23

6.6

3.0

P<0.001

Mean Plasma
Glucose
Mean % Time with
Glucose <70mg/dL
Hypoglycemic
Intervention
Primary Outcome
Mean Plasma
Glucose
Mean % Time with
Glucose <70mg/dL
Hypoglycemic
Intervention
5.

4.

Fi
gu

re 1 : [page 318] Variation in the Mean Glucose Level among Adults and Adolescents
Figure 4 : [page 321] Histogram Distribution of Mean Glucose Levels and Insulin Doses among
Adults and Adolescents

Authors Conclusions: Despite these challenges associated with currently available technologies, the use
of the bi-hormonal bionic pancreas in our two short-term studies resulted in better glycemic control than is
possible with the current standard of care.
Strengths
Distribution in population demographics

Cross-over design

Accessibility of technology and the applicability of

this to everyday life
Monitoring of adolescent populations and adult BP
population
Insulin administration without the use of carb
counting or correction factors.
Automatic awareness of hypoglycemia and Glucagon
administration to prevent adverse events

Limitations
Patients were limited in alcohol intake, however
higher amounts may compromise glucagon efficacy.
Interventions for hypoglycemia were possibly made
more actively due to the monitoring by study staff
than what might occur in real life.
Wireless connectivity problems caused isolated
missed doses of insulin and glucagon which may
have led to hypoglycemia that could otherwise have
been prevented
Acetaminophen use with the BP leads glucose
overestimation.
Increased insulin administration for those who are
poorly managed.
The long-term safety of peripheral micro dose
glucagon administration has not been established

Personal Conclusions: This study shows that the BP promises a better ability to control blood glucose
levels and maintain a therapeutic range for individuals than current standards of care. However, due to the
lack of true life experiences, small population size, short study duration, and other previously mentioned
limitations, this concept will require more extended research before it is appropriate for the general
population.

4276 Inpatient Skills

Journal Club Two

BP = Bionic Pancreas

Lincy Varughese

IPT = Insulin Pump Therapy

References:
1.

2.

Peyser T, Dassau E, Breton M, Skyler JS. The artificial pancreas: current status and future prospects in
the management of diabetes. Ann NY Acad Sci. 2014;1311(1):102-123. doi:10.1111/nyas.12431.
Skyler JS. T1DM in 2014: Progress towards a bionic pancreas. Nat Rev Endocrinol. 2015;11(2):75-76.
doi:10.1038/nrendo.2014.228.