An Artificial Pancreas by MikeJenny


									            reprinted from the Winter 2006 issue

          An Artificial Pancreas

          How Close
          Are We To
          The Loop?
         The 40-year old idea of using a machine to replace the
        lost endocrine pancreas function in people with diabetes
         is approaching reality. Technology has finally caught up
          with the work of people like Dr. Arnold Kadish, who is
        credited with devising the first experimental closed-loop
        artificial pancreas in 1964. The idea evolved by 1977 into
                 a machine still in use today, the Biostator.
by WAyne L. CLArk
ILLusTrATIon by DAvID CuTLer

         he problem is, the Biostator is      abolic Monitoring (TMM). The unique            technologies that will allow them to take
         roughly the size of a dormitory      partnership combines JDRF’s interests          better care of themselves, and to make
         refrigerator, and requires two       in glucose monitoring with that of the         that easier. We want to make this hap-
         catheters inserted in the patient.   military in being able to remotely moni-       pen sooner.”
One draws out blood and measures the          tor the condition of soldiers in the field.       “It won’t be just research funding,”
glucose level, and the other infuses the         JDRF’s contribution to the metabolic        says Lawrence Soler, JDRF vice presi-
appropriate amount of insulin. Obvi-          monitoring project has been to help the        dent for government relations. “This
ously not suitable for daily consumer         Defense Department identify research           effort will require both research and
use, it has found a home in clinical labo-    priorities and attract top researchers,        advocacy. For these new technologies to
ratories, where the ability to manipulate     and to lobby Congress for continued            reach people with diabetes, we need to
blood glucose levels is an important part     funding of the project.                        work in Washington, D.C. to help them
of diabetes research.
    The old idea of an artificial pancreas
is new again. JDRF has made the devel-
opment of a closed loop artificial pan-
                                                           A system that could be used
creas one of its six research goals to be
achieved within five years.
                                                           for overnight hypoglycemia
    Over the past few years, JDRF has
partnered with the U.S. Army and the                        prevention would be a vast
National Institutes of Health (NIH) to
further development and clinical applica-
tions of glucose sensing technologies, says
                                                               improvement for people
Aaron J. Kowalski, Ph.D., scientific pro-
gram manager for JDRF. “Private com-
                                                                         with diabetes.
panies have been investing heavily in this
area as well, and we have channeled our           JDRF is also involved in securing fed-     get approved by the federal government
resources into complementary areas. We        eral funds for and providing input to the      and covered by government and private
now plan to actively pursue opportunities     Diabetes Research in Children Network,         health insurance. We want a thriving
in both research and advocacy that will       or DirecNet. This national network of          marketplace that will encourage compa-
speed progress towards closing the loop.”     clinical centers is dedicated to researching   nies to develop an artificial pancreas and
    “The need is urgent,” Dr. Kowalski        the use of glucose monitoring technology       its components, bring them to market,
says. “The 1993 Diabetes Control and          and its impact on the management of type       and make them available to all people
Complications Trial (DCCT) and other          1 diabetes in children. It is sponsored by     with diabetes.”
research since then has shown that            the NIH, and its work includes assessing           The renewed emphasis on the artifi-
tight blood sugar control significantly       the optimal use of continuous glucose          cial pancreas is welcomed by clinicians.
reduces the risk of diabetes-related          sensors, their accuracy, and their impact          “This is particularly important for
complications. However, tight control         on quality of life.                            children and adolescents,” says William
is extremely difficult to achieve and the         “With the recent approval of a con-        V. Tamborlane, M.D., professor and
majority of patients are not reaching         tinuous glucose sensor and other excit-        section chief of pediatric endocrinology
recommended Hemoglobin A1C levels             ing technologies in the pipeline, JDRF         at Yale University, “because until there’s
[HbA1c, a measurement used to reflect         has carefully assessed the field to find       a breakthrough in transplantation that
glucose levels over 8 to 12 weeks]. This      opportunities to speed progress,” Kow-         doesn’t require immunosuppression,
must change.”                                 alski says. “A comprehensive plan was          you’re not going to want to expose young
    Since 2001, JDRF has worked with          recently presented to the JDRF Board           people to immunosuppressive therapy.”
the U.S. Department of Defense, along         of Directors and we have already begun             Dr. Tamborlane also chairs the
with the NIH and the National Aeronau-        its implementation. With this plan, we         DirecNet Steering Committee, and has a
tic and Space Administration (NASA),          want to ensure that people with diabe-         long-standing interest in insulin pumps
in a project called Technologies for Met-     tes will have access to safe and effective     for children.

    Immunosuppression is a concern be-                  with glucose. That same reaction forms       downloaded in the physician’s office at
cause it carries long-term risks that can be            the basis of the Medtronic MiniMed           the end of the three days. The concept
as significant as those associated with a               Continuous Glucose Monitoring System         is similar to that of the Holter Moni-
similar length of time on insulin therapy.              (CGMS), approved by the FDA in 1999.         tor used to record heart activity over a
Young children, who could benefit most                  It continuously records glucose levels in    period of time.
from early islet transplantation, might be              the interstitial fluid—which lies between       The CGMS has been used to help
trading one disease for another.                        blood vessels and the cells, under the       patients and physicians get a better pic-
    Another reason for the uptick in inter-             skin—by means of a glucose oxidase-          ture of how blood glucose levels vary
est in the artificial pancreas is the discov-           plated platinum electrode. The sensor        throughout the day and night, especially
ery that blood glucose control is impor-                is worn for three days, and calibrated       those “excursions” above or below the
tant in surgical patients and intensive                 once a day with a standard blood glu-        target range that may not be picked up
care patients, even those who do not have               cose meter. The system doesn’t display       by routine testing. It also has been valu-
diabetes. Strong evidence indicates that                the information for the patient, but it is   able for clinical research, showing how
high blood glucose, which can occur even
in non-diabetic patients who are critically
ill or have had major surgery, contributes
to a higher incidence of infections. It also
has a negative influence on blood pres-
sure and increases clotting.
    In light of these findings, biotechnol-
ogy companies can consider a larger
market for the artificial pancreas or its
components, such as a continuous glu-
cose sensor.
    Add to this the increasing ability to
miniaturize components, the improve-
ment of short-distance wireless commu-
nications, and new fast-acting insulin
analogs—as well as a renewed major
infusion of support from JDRF—and
the stage is set for a leap forward in the
development of an artificial pancreas.

ThE machINE
The artificial pancreas must have three
components: a sensor that continuously
monitors glucose levels, an insulin delivery
system, and computer program algorithms
that calculate the correct insulin dose
based on the sensor readings. The sen-
sor has until recently been the most sig-
nificant barrier to achieving a closed-loop
system, but there is recent progress on
several fronts.
    The standard glucose meters used                           William V. Tamborlane, m.D.,
to check blood drawn with fingersticks                         professor of peDiaTric
                                                               enDocrinology, yale UniVersi T y
make use of a chemical reaction in
which the enzyme glucose oxidase reacts

PHOTOGRAP H B Y GA l E ZU CkE R P H O T O G R A P H Y                                                       t o s u b s c r i b e , v i s i t w w w. j d r f . o rg   

blood glucose levels can be affected by       ing a “Pre-Market Approval” applica-             cutaneous fatty layer under the skin. A
medications, surgery, different insulin       tion for the product.                            perfusion fluid inside the catheter is in
formulations, and other factors.                  San Diego-based DexCom is develop-           continuous contact with the interstitial
    The lifetime of the glucose oxidase       ing the STS Sensor, which also consists          fluid, and pulls glucose into the catheter.
sensor is limited. As a foreign substance,    of a sensor inserted under the skin, a           The perfusion fluid is then pumped out
it triggers the body’s protective measures    wireless transmitter, and a receiver that        into a measuring device.
which slowly erode the sensor’s accu-         displays continuous glucose readings                 Light—or more accurately, infrared
racy. Like most subcutaneous catheters,       and trend information. It also has high          or near-infrared light—may prove use-
such as an insulin pump catheter, it must     and low alerts. The sensor will need to          ful as a noninvasive way to measure glu-
be changed every few days in any event        be replaced every three days. The system         cose. In theory, glucose either absorbs
in order to avoid infection.                  is currently under FDA review.                   or scatters light differently than other
    Medtronic MiniMed has developed a             DexCom is also working on a long-            constituents of the skin and subcutane-
new continuous sensor based on the glu-       term sensor that would be implanted in           ous tissue, and measuring the effect of a
cose oxidase reaction. The Guardian RT        a surgical procedure under local anes-           beam of light could provide the informa-
(“Real Time”) received FDA approval           thetic and would last for a year.                tion to calculate glucose levels.
in August 2005. The system records as             There are other approaches under                 Among the companies working with
many as 864 glucose readings during a         investigation in at least two dozen labo-        near-infrared light is Sensys Medical.
three-day period, after which the sensor      ratories. Some are noninvasive or mini-          Their technology uses diffuse reflectance
is replaced. The sensor wirelessly trans-     mally invasive and measure the glucose           spectroscopy to detect how much light
mits readings to a monitor every 5 min-       in interstitial fluid. Others are intended       is absorbed by various molecules. Each
utes. The patient reads the glucose value     to be implanted deep in the body, inside         type of molecule has its own absorp-
on the monitor’s screen and decides on        veins where they can measure blood glu-          tion profile, so the idea is to measure the
an insulin dose. Patients can set alarms      cose levels.                                     proportion of light absorption that cor-
to warn them of dangerously high or               One minimally invasive method actu-          responds to glucose.
low levels, and all the information can       ally brings the interstitial fluids out of the       A different kind of light, fluorescense,
be downloaded to a computer and dis-          tissue so they can be tested. A technique        may eventually provide a means of glucose
played as reports and charts. The system      called reverse iontophoresis applies a           detection and measurement. GluMetrics
needs to be calibrated twice a day using      weak electrical current to the skin, and         is a California company that has devel-
a standard blood glucose meter.               pulls interstitial fluids out through the        oped a glucose sensing technology called
    The company is currently testing a        skin and into a measuring device. The            GluGlow. This boronic-acid based sub-
system that would tie the Guardian RT         Cygnus GlucoWatch G2 Biographer,                 stance glows in the presence of glucose.
to an insulin pump. The pump would            introduced in 2001, uses this method.            The company’s first application will be a
calculate a recommended dose, and the         The device must be calibrated with a             catheter tipped with GluGlow, that can be
wearer would decide if it was appropri-       standard blood glucose meter when the            used to monitor hospitalized patients.
ate. This is sometimes referred to as an      sensor is changed, every 13 hours.                   Animas is one of the companies
“advise you” open loop system.                    SpectRx, a Georgia-based company,            “going deep” with glucose sensor tech-
    Abbott Laboratories, which acquired       is developing a technology that uses a           nology. Their product is intended to be
TheraSense and its FreeStyle product          laser to create microscopic holes through        surgically implanted in the abdomen
line in 2004, is developing the “FreeStyle    the outer layer of dead skin. The intersti-      and will measure blood glucose lev-
Navigator.” This system consists of a         tial fluid then flows out of the holes into      els by passing a light beam through a
biochemical sensor that is inserted under     a patch that contains a standard glucose         blood vessel.
the skin, a transmitter that snaps onto the   sensor. The results are displayed on a
sensor, and a pager-sized receiver. Infor-    wireless meter.                                  INsulIN PumPs
mation is transmitted wirelessly once             A new generation of sensors also             Insulin delivery is the furthest along of
every minute. The display shows glucose       measures glucose levels in the intersti-         the three artificial pancreas components.
readings, arrows indicating the trend in      tial fluids, but uses a different minimally      A true artificial pancreas clearly cannot
the readings, and the rate of change in       invasive technology called microdialysis.        rely on manual injections of insulin, so
the trend. The FDA is currently review-       A thin catheter is inserted into the sub-        the advent of the insulin pump was a

critical step. The first prototype insulin   eter. The Insulet OmniPod consists of a           any testing and insulin delivery system.
pump was the size of a backpack and          small insulin-containing “pod” pump               In fact, control of blood glucose by any
was worn as one. Since the first com-        that sticks to the skin, and a unit that is       means other than the native pancreatic
mercially available insulin pump was         both a glucose meter and a wireless con-          beta cell is complicated by food intake,
introduced in 1983, the machines have        troller for the pump. The device received         physical activity level, stress, illness,
steadily become smaller, more accurate,      initial FDA clearance earlier this year,          and sleep. An artificial pancreas has to
and more user-friendly.                      and the company hopes to have it avail-           account for all these variables with a
    The pump created a revolutionary         able in late 2005.                                computer program.
change in how people with type 1 dia-                                                             “Even with current open-loop ther-
betes receive their insulin. Instead of      PuTTINg IT all TogEThER                           apy, the transition from conventional
subcutaneous injections several times        Once the loop is closed, the system must          fingerstick blood monitoring to continu-
a day, the pump continuously infuses a       be flexible and “smart.” The ability to           ous glucose monitoring will be difficult
“basal” dose of insulin through a very       control blood glucose with an artificial          enough,” Dr. Tamborlane says. “When
thin catheter inserted under the skin.       pancreas is subject to the same issues as         you’re deciding your pump dosage, you
The continuous infusion mimics a real
pancreas. The pump wearer can give
“bolus” doses to compensate for the car-
bohydrates they take in at meals, or sus-       DirecNet
pend the basal rate if their blood glucose      The mission of the Diabetes Research in Children Network (DirecNet) is to investigate

level is running too low. The user must         the potential use of glucose monitoring technology and its impact on the management
                                                of type 1 diabetes in children. It is co-funded by the National Institute of Diabetes and
still check blood glucose levels with a
                                                Digestive and Kidney Diseases (NIDDK) and the National Institute of Child Health and
conventional meter, usually four to five
                                                Human Development (NICHD) and is made up of five clinical centers and one data co-
times a day.
                                                ordinating center. JDRF is represented on the DirecNet Steering Committee and actively
    In July 2003, the FDA approved an
                                                seeks continued federal funding for the network.
integrated blood glucose meter and
                                                Current studies include:
insulin pump from Medtronic MiniMed
                                                •   A Pilot Study to Evaluate the Navigator Continuous Glucose Sensor in the
and Becton, Dickinson and Company. It
                                                    Management of Type 1 Diabetes in Children
combines the Paradigm 512 pump with
                                                •   The Effect of Basal Insulin During Exercise on the Development of Hypoglycemia
the Paradigm Link Blood Glucose Moni-               in Children with Type 1 Diabetes
tor, which includes a dose calculator.          •   Nocturnal Hypoglycemia Prevention Study
This is an “open loop” system that still        Previous studies:
requires the user to test his or her blood      •   The Accuracy of Continuous Glucose Monitors in Children with Type 1 Diabetes
with finger sticks, but the meter sends         •   A Pilot Study to Evaluate the GlucoWatch 2 Biographer in the Management of
the data to the pump, which performs                Type 1 Diabetes in Children
a calculation and recommends a dose.            •   The Effect of Exercise on the Development of Hypoglycemia in Children with
The user decides if the recommendation              Type 1 Diabetes
is correct, then pushes a button to tell
the pump to deliver it.                         DirecNet CeNters
    In mid-2005, Deltec released a com-         •   Barbara Davis Center for Childhood Diabetes, Denver, CO
bination pump and monitor in a single           •   Nemours Children’s Clinic, Jacksonville, FL
unit. The catheter-based system consists        •   University of Iowa Carver College of Medicine, Department of Pediatrics,
of a blood glucose module that snaps                Iowa City, Iowa
onto an insulin pump and communicates           •   Yale University School of Medicine, Department of Pediatrics, New Haven, CT

with it wirelessly.                             •   Stanford University, Division of Pediatric Endocrinology and Diabetes, Stanford, CA
                                                •   Data Coordinating Center: Jaeb Center for Health Research, Tampa, FL
    The latest variation is an “unte-
thered” pump that eliminates the need           For more information, visit and search
for a physical connection between the           for ‘DirecNet’
pump and the insertion point of the cath-

                                                                                                       t o s u b s c r i b e , v i s i t w w w. j d r f . o rg   

won’t be locked in to four, five, or six              the various scenarios,” says Darrell M.      Dr. Wilson says. “Then you would be
tests a day. You can actually see what                Wilson, M.D., professor and chief of         dealing with one or two algorithms. One
your blood sugar is doing every five min-             pediatric endocrinology at Stanford Uni-     of the advantages of closing the loop is
utes. That’s going to be challenging for              versity. “If they were on insulin glargine   that it ‘steps over’ the need to understand
doctors as well as patients because when              and lispro four times a day, how would       how best to use the information.
you get all this information, you have to             they use the information? What would             “Linking these pieces together is not
know how to deal with it.”                            you tell somebody if it was an hour and      trivial. If you consider that it’s auto-
    Some believe that closing the loop                a half after a meal and they had taken       pilot at that point, you have to be very
might be simpler in many ways.                        their humalog? Did you forget to give        sure that you’re not going to risk a cata-
    “When we asked ourselves how a                    your shot? Did you underestimate your        strophic failure. Even with an ‘advise
patient would use all the information                 carbohydrates? Is this just a bad day?       you’ system, people will put a lot of faith
a continuous monitor could provide,                      “That’s why we wonder if it might be      in the system’s advice, so you want to
it became difficult to come up with all               better to go ahead and close the loop,”      make sure it’s good advice.”
                                                                                                       The problem with the accuracy of
                                                                                                   today’s sensors, and the way they might
                                                                                                   be used to operate an insulin pump, is
                                                                                                   largely a matter of kinetics. Put another
                                                                                                   way, there are delays in the system in
                                                                                                   both measurement and insulin delivery
                                                                                                   for which an algorithm has to account.
                                                                                                       “There is about a 10 to 15 minute
                                                                                                   delay before subcutaneously delivered
                                                                                                   insulin becomes effective,” says Bruce
                                                                                                   Buckingham, M.D., associate professor
                                                                                                   of medicine at Stanford University. “But
                                                                                                   when you eat, your blood sugar goes up
                                                                                                   quickly, so you get a mismatch between
                                                                                                   the insulin you need and the insulin you
                                                                                                   get. Also, insulin delivered subcutane-
                                                                                                   ously lasts about four to six hours, so if
                                                                                                   you deliver a lot of insulin to try to keep
                                                                                                   your blood sugar from going too high
                                                                                                   after a meal, then you may be at risk
                                                                                                   from the residual insulin causing a low
                                                                                                   blood sugar four to six hours later.
                                                                                                       “There also is a delay for the sensor
                                                                                                   itself. Most of the sensors we have at
                                                                                                   present are subcutaneous, so there is a
                                                                                                   delay of anywhere from five or six min-
                                                                                                   utes to 15 minutes as the glucose moves
                                                                                                   from the blood to the interstitial space.”
                                                                                                       What’s more, the sensors are coated
( L ) D a r r e l l m. W i l s on, m .D.,                                                          with a biocompatible membrane to stall
p r o f e s s o r a nD c h i ef of pe DiaT ric
e nD o c r i n o l o g y, s Ta nfor D Uni Versi T y                                                the body’s attempt to cover over the for-
( R ) b rU c e b U c k i n g h am, m .D.,
                                                                                                   eign body, and the membrane creates a
a s s o c i aT e p r o f e s s o r of me Dicine,                                                   ‘sensor lag’ of several minutes.
s Ta n f o rD U n i V e r s iT y
                                                                                                       “If you’re in a ‘steady state’, where
                                                                                                   you’re not inducing a lot of changes,”

6   from the WINTER 006 JDRF COUNTDOWN MAGAZINE                                                                       PHOTOGRAPH BY JAC k HUTCHESON
Dr. Buckingham says, “the sensor does          majority are well outside that degree of       face. A small, waterproof system would
very well in closing the loop. It is the       variability.”                                  allow full daily activities, participation
meal-related issues that are going to              Even a system that could be used           in sports, and could be used by young
pose the challenge.”                           for overnight hypoglycemia prevention          children as well as adults. Not many
    On the other hand, despite the lag         would make for a vast improvement in           patients would wear a backpack all
time, measuring interstitial glucose lev-      the quality of life of people with diabetes,   day to deliver insulin, but thousands—
els may be more relevant to what the           especially children and their parents.         including infants and toddlers—use the
body needs.                                        “If we can get results that are much       small insulin pumps of today.”
    “For 25 years we have been using           better with the same effort or less effort,       The ultimate artificial pancreas, many
blood glucose measurements, and every-         I think most of our patients and families      believe, would be a system that could be
one’s used to them,” Dr. Buckingham            would be happy with that,” Dr. Tambo-
says, “but the more important level may
be the brain glucose. The interstitial fluid
                                               rlane says. “If a parent could know that
                                               they just have to turn a switch a night,             We’re much
                                                                                                     closer than
is in between the blood and the cells, so      and that the likelihood of getting low is
it has been suggested that the interstitial    minimal, they could sleep through the
fluid more closely reflects what’s going       night. You could adjust for some inac-
on in the brain. It required a paradigm
shift in our thinking when we made the
                                               curacies in the sensors just by shooting
                                               for a higher target.”
                                                                                                   people think.
transition from using urine glucose mea-           To illustrate the point, Dr. Tambor-
surement and changed to blood glucose          lane poses the example of a closed loop        implanted within the body. That would
measurements to manage diabetes. It may        system with a sensor that is much less         remove not only the need for a person
be time to make another paradigm shift         accurate than the ones currently avail-        to actively manage it, but also would
in how we think about glucose levels.”         able, that reads 50 percent higher than        remove the external pump, meter, and
                                               the actual value. If the sensor was set        sensor and the associated inconvenience
hoW gooD Is gooD ENough?                       to a target of 120 mg/dl, the lowest           of having them appended to the body.
When will the technology be far enough         the actual blood glucose level could get       Other observers are skeptical.
along to allow “closing the loop?”             would be 80 mg/dl before the pump                  “I’m not so sure about a fully
   “There are two schools of thought,”         stopped delivering insulin.                    implantable system,” Dr. Tamborlane
Dr. Wilson says. “One is that it has to be         “I think most of my patients would         says. “There are technical problems with
perfect, and produce results that reflect      be happy if they could wake up at 120          it. The refill process, for instance, is like
nondiabetic physiology almost exactly.         and know they’d go no lower than 80,”          a mini-surgical procedure, because it
The other is that we need a technology         Dr. Tamborlane says. “Even if it was off       has to be done under sterile conditions.
that is better than what we have now,          by 50 percent, you’d still be safe. The        I think the external route might be fine
that it doesn’t have to be perfect. I’m in     more accurate the better, of course, but       for most people.”
the latter camp. If we can show a signifi-     you have a margin of error.”                       That hasn’t stopped some investiga-
cant improvement in control, we would              The artificial pancreas will almost        tors from pursuing an implanted closed
go a long way down the road to helping         certainly evolve over time, with the           loop system. In fact, the first clinical
people with diabetes. Waiting for perfec-      units becoming less of an intrusion for        trial of a fully-implanted artificial pan-
tion ignores the difficulties that all our     patients.                                      creas is underway in France. The trial is
patients and families have with the cur-           “It’s important to remember that           under the direction of Eric Renard, M.
rent technology.                               we are in the first generations of these       D., Ph.D., professor of endocrinology,
   “If you had a reasonably reliable sen-      devices,” says Dr. Buckingham. “Cur-           diabetes, and metabolism at Montpellier
sor that controlled a pump in a reason-        rent sensors and transmitting devices          Medical School in Montpellier, France.
able fashion, and you could stay within        will become smaller. It may be possible        The system consists of a sensor that is
25 points of target, you could set it at       to combine the insulin infusion set and        implanted in a neck vein, and an implant-
125 and run between 100 and 150,”              the glucose sensor into a single, subcuta-     able insulin pump connected to the sen-
Dr. Wilson says. “There may be a few           neously-inserted device, with the entire       sor by a wire under the skin. Both devices
people managing that now, but the vast         unit the size of a quarter on the skin sur-    are from Medtronic MiniMed.

                                                                                                     t o s u b s c r i b e , v i s i t w w w. j d r f . o rg   

   The first five patients who used the            Longevity of the full-implant equip-       tem,” he says. “Just do what our patients
device for six months did well: the sen-        ment is an issue that must be addressed,      are doing now: give something of a bolus
sor was 95 percent accurate compared            since the sensors last only nine months       before eating, which wouldn’t have to be
against finger-stick readings with con-         and the pump must be replaced roughly         the whole amount you would normally
ventional meters. Trial participants            every eight years.                            take, and then let the sensor take over to
delivered their own insulin during most                                                       do the fine-tuning.
of the trial, based on the sensor read-         WhaT’s NExT?                                      “You don’t have to go from not very
ings. The researchers “closed the loop”         The progress toward an artificial pan-        good to perfect,” Dr. Tamborlane says.
for a two-day period, and found that the        creas didn’t follow the course many sci-      “It’s a big step to go from not very good
patients’ blood glucose levels stayed in        entists thought it might.                     to very good. I think we’re much closer
the desired range 42 percent of the time,           “I think people have had a mindset        than people think. In the work we’re
compared to only 21 percent of the time         that development of a new sensor would        doing with children, that JDRF supports,
in patients using conventional meters to        follow a particular pathway,” Dr. Wilson      we’ve already had five or six children go
adjust insulin delivery.                        says. “First it would be available experi-    for over 36 hours on automatic control.”
   The researchers then tested the closed-      mentally, then you’d use it retrospectively       JDRF has swung its support to the
loop system using not only an algorithm to      like the CGMS from MiniMed, and then          artificial pancreas, and not just for the
control the pump’s insulin delivery based       you might use it as a nocturnal hypogly-      sake of an artificial pancreas itself.
on the sensor readings, but also a pre-meal     cemia detector or a meter replacement.            “The development of an artificial
bolus of insulin from the pump to address       Then, you would get to the point where        pancreas could actually contribute to
the problem of higher post-meal blood           you’d have an ‘advise you’ system, and        our biological cure goals,” Dr. Kowalski
glucose levels. The protocol produced           finally you could close the loop.             says. “For instance, when you transplant
lower post-meal glucose levels and did not          “One thing that’s become clearer is       islet cells, many of them die. There are
increase hypoglycemic episodes, which           that the idea of a hypoglycemia detector      a number of suspected reasons, but one
often occur when a person “overtreats” a        doesn’t play to the strengths of the cur-     of them could be the toxicity of hyper-
high blood glucose level with extra insulin.    rent sensors,” he says. “They have less       glycemia. If you could use an artificial
Trial participants also stayed within the       accuracy in the low ranges, so there’s a      pancreas to get a patient to euglycemia
target range of 70 and 120 mg/dl nearly         dilemma: the risk of too many false pos-      prior to the transplant, the patient might
50 percent more of the time.                    itive alarms. As a pump controller, how-      do better.”
                                                ever, if you set it to keep you at 150 and        There is already evidence that an
                                                you’re off by 70 points, you’re still okay.   artificial pancreas might extend the
                                                With the current sensors, it makes sense      “honeymoon” period in new-onset dia-
                                                to move more quickly to an application        betes. Research using the Biostator dem-
                                                where you’re closing the loop, because        onstrated some preservation of beta cell
                                                you’re in the range where the sensors         function. Beta cell regeneration is one
                                                work better.”                                 of many avenues to euglycemia, and an
                                                    A closed-loop system might not            artificial pancreas might help the regen-
                                                have to be “all or nothing,” either. For      eration process.
                                                instance, there might be concern that the          “I call the artificial pancreas the
                                                system would not react quickly enough         bridge to the biological cure,” Dr. Kow-
                                                to cover the rapid postprandial rise in       alski says. “It will have a major impact
                                                blood glucose, because of the delays          on people with diabetes while we get to
                                                inherent in measuring the rise in intersti-   solutions for beta cell regeneration, islet
                                                tial glucose levels. No problem, says Dr.     cell transplantation, or an islet supply.
                                                Tamborlane.                                   It will help forestall complications, help
                                                    “You can adjust for postprandial          with the problem of hypoglycemia, and
aa r o n J . k oWa l s k i , ph.D.,
J Dr f s c i e nT i f i c p r o gram m anager   highs by making it a semi-automatic sys-      generally improve quality of life.” l

   from the WINTER 006 JDRF COUNTDOWN MAGAZINE                                                                  Part #9197801-011

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