Pacesetting progress in discovery and care

Joslin Legacy
Pacesetting progress
in discovery and care
Contents
2
Elliott P. Joslin, M.D.
Teamwork toward a cure
4 Differentiating diabetes
6
Patient education
8
Clinical research
10
Laboratory research
12
Expanding Joslin’s reach
14
Professional education
16
Success in pregnancy
18
Children, teens, young adults
20
Preventing complications
22
Eye research and care
On the cover
Historical image: Housed in the new special
collections library at Joslin are artifacts chronicling
the work of Elliott P. Joslin, M.D., who in 1898
launched the world’s leading effort to understand,
treat and potentially cure diabetes. Beginning with
observations recorded in patient ledgers, he and
his team explored their insights in lab settings,
from which promising findings led to treatments
to test in populations, which in turn generated
new ideas to explore in the lab—the classic model
of translational medicine that Joslin follows
today. Many of these artifacts are featured on the
timelines in this magazine.
Inset: Led by George King, M.D. (left), the 50-Year
Medalist Study is now underway at Joslin to
identify potential factors that protect people with
type 1 diabetes from developing complications.
Among hundreds of study participants who have
been complications-free for 50 years or more is
Kathryn Ham, age 83, a recipient of the 75-Year
Medal (see p. 21).
www.joslin.org
| Joslin Legacy 1
New heights of hope
The story of Joslin Diabetes Center is the story of
diabetes. In no other place in the world is there a more
concentrated effort to prevent, treat and cure diabetes.
In no other place is there more hope for a future free
from diabetes. In this publication, we celebrate the
talented and dedicated people who have brought us
to new levels of understanding today and promising
pathways to pursue tomorrow. But the milestones
presented herein represent only a select number of
highlights. After more than 115 years of highly focused
work by hundreds of diabetes scientists, clinicians and
educators, there simply is too much to recount.
We are now preparing for the ascent to the top, equipped
with the latest biotechnologies and the finest diabetes
thinkers and doers in the world. There are still many
unknowns and much work to do. But as the future
unfolds, one thing is certain—Joslin will be defining it.
John L. Brooks III
President and Chief Executive Officer
Joslin Diabetes Center
2 Joslin Legacy |
www.joslin.org
1
Elliott P. Joslin, M.D.
‘Dean of Diabetes’
Teamwork
toward a cure
1869
1922
1937–47
Born in Oxford, Mass.,
50 miles west of Boston.
After insulin’s 1921 discovery in Canada by
Drs. Frederick Banting and Charles Best,
the first dose in New England of commercial, purified insulin is administered by
Dr. Joslin’s associate Howard F. Root, M.D.
With his leadership in the study and care
of diabetes, Dr. Joslin emerges as the world’s
“Dean of Diabetes.”
Becomes world-recognized for advocating
tight control of diabetes to reduce complications (p. 20), a hotly debated issue.
1890
Graduates from Yale; remains a year to study
physiological chemistry.
1895
Graduates from Harvard Medical School as
valedictorian; wins coveted prize for diabetes
observations. Interns at Massachusetts General
Hospital, followed by residencies in Germany.
1898
Launches medical
practice in Boston’s
Back Bay. Joins HMS
faculty. Begins keeping ledgers of his diabetes patients, the first
registry of its kind.
1900
Mother is diagnosed with diabetes and follows
her son’s high-fat, low-carbohydrate diet,
living 13 more years.
1906–12
Joins metabolic investigative laboratory on
HMS campus, studying chemical balance in
health and diabetes.
1916
Publishes physician textbook The Treatment of
Diabetes Mellitus, bringing world recognition
(p. 14). Two years later, he publishes Diabetes
Manual, a practical guide for patients and
practitioners that becomes an instant success.
1952–53
At age 80, restructures his mission by organizing his group practice into Joslin Clinic. Front
row, left to right: Drs. Howard F. Root (supervises inpatients), Elliott P. Joslin, Priscilla White
(pregnancy, pediatric camping programs);
back row: Joslin’s son Allen P. Joslin, M.D.
(walk-in service), Dr. Alexander Marble (principal research investigator, editor), Robert F.
Bradley, M.D. (internal medicine, cardiac care);
not in photo is Leo P. Krall, M.D. (educator, p. 14).
Creates nonprofit Joslin Diabetes Foundation,
a forerunner to Joslin Diabetes Center.
1924
Recruits Priscilla White, M.D., to treat
children with diabetes. Over the years,
she also makes landmark contributions to
diabetes care during pregnancy (p. 16).
1922–28
Expands teaching role of nurses, including innovative “wandering nurse” program (p. 6).
1931
Creates the Achievement Medal, the first in a
series of awards celebrating people who have
lived with diabetes for extended periods of
time. Four more awards follow (p. 21).
1932
Recruits Alexander Marble, M.D., launching
formal investigative program (p. 8).
1956–57
Moves Joslin Clinic to present location.
Opens widely popular inpatient ambulatory
treatment center. Plans research lab.
1962
Dies at age 92, seeing
patients until the last
week of his life.
Dr. Joslin’s medical bag is among historical
treasures in the special collections library
at Joslin Diabetes Center (p. 12).
www.joslin.org
| Joslin Legacy 3
Momentum of confidence
B
eginning with Elliott Proctor
Joslin, M.D., the effort to combat diabetes has been driven by conviction
and optimism. Although diabetes was
observed in ancient times, physicians in the
late 1890s still did not understand this complex metabolic disorder.
Transforming diabetes care
With Dr. Joslin, the barriers began to
crumble. Fresh out of Harvard Medical School,
he dove into clinical practice, determined to
solve the problem of diabetes. Trained as a
scientist, he launched laboratory studies.
Patients began flocking to his practice.
This doctor offered something new—hope—
bolstered by unparalleled courage to face
diabetes head on.
He made patients partners in their care,
teaching them how to manage diabetes. Before
the discovery of insulin, Dr. Joslin devised
T h e
strict nutritional approaches to help patients
extend life. After insulin’s 1921 discovery, he
combined its power with glucose monitoring,
nutrition and exercise. A master of motivation, he introduced the concept for today’s
Medalist program, celebrating the years his
patients had successfully lived with diabetes.
Other people also needed to be informed.
In 1916, Dr. Joslin begin writing books for
physicians and patients.
But the challenges of diabetes were beyond
the capacity of one physician-scientisteducator. So Dr. Joslin recruited bright
energetic professionals to push the boundaries
of diabetes research and care.
Today at Joslin
Diabetes care, research and education
at Joslin Diabetes Center in Boston is now
provided by more than 700 people. Patients
see many types of experts, working together
as a team. New technologies such as insulin
pumps and continuous glucose monitors are
implemented as fast as they emerge. Ways to
communicate with patients are being transformed by the digital age (see story below).
Cultural experts reach out to ethnic populations at elevated risk for diabetes. Educators
travel worldwide to update medical professionals about new approaches. Laboratory
scientists work to unlock the secrets of cells
involved in type 1 and type 2 diabetes and its
complications.
Dr. Joslin’s prophetic words of 1928
continue to inspire: “The patient has an
excellent chance of living long and well to be
an explorer of regions in diabetes, hitherto
unknown, and thus to open up trails toward
health and the cure of diabetes, which others
can more easily follow.” {
F u t u r e
Digital diabetes care
“Dr. Elliott P. Joslin moved diabetes care out of the clinic and into the
home, where visiting nurses taught patients self-care,” says Joslin’s
Chief Medical Officer Martin Abrahamson, M.D. , F.A.C.P. (at right in
photo). “Today we’re going back into the home, this time using digital
technology to communicate with patients, 24/7/365.”
Another doctor spearheading this revolutionary approach is
Director of Quality Sanjeev Mehta, M.D., M.P.H. (at left in photo), a
pediatric endocrinologist who also is involved in the Joslin program of
“Joslin Everywhere.” Now in development, this online innovation will
enable patients to upload and download
data—blood glucose patterns, insulin doses,
nutrition, weight and exercise activity—which
then are routed to their diabetes healthcare team
for analysis and online feedback. Also on the horizon
is the “Virtual Visit,” in which patients can interact in real
time with their healthcare team via online cameras.
A secure Patient Portal will allow patients to see lab results,
make appointments and interact with their healthcare team.
Smartphone apps may subsequently support these concepts.
Masterminding this communications technology is Edward
Charbonneau, chief information officer, and Paul Penta, manager of
web-based initiatives for Joslin Everywhere. In addition to creating
digital pathways for Joslin patients, the team envisions providing
online care and educational programs to support diabetes care in
primary care practices, which provide nearly 90 percent of diabetes
care in the United States.
“Fundamental to these virtual and online capabilities is a
sophisticated but facile electronic health record (EHR), which Joslin
has customized to capture the unique aspects of diabetes care,
“says Dr. Mehta. The Joslin EHR has recently been upgraded to
expand its use as a repository of health information for clinicians and
researches to explore new ways to prevent and treat diabetes. {
4 Joslin Legacy |
www.joslin.org
2
Type 1 and
type 2 diabetes
Differentiating diabetes
Today when patients are diagnosed with diabetes, many learn that
their diabetes is type 1 or type 2, a differentiation key to shaping
effective treatment strategies. This distinction often drives different
research pathways, but scientists at Joslin who study genes,
molecules and cellular signals at the very basic level also find areas
of common ground.
1898–1921
1979
Before insulin’s discovery, the treatment
advocated by Elliott P. Joslin, M.D., for all
patients with diabetes emphasizes marked
dietary restriction (fasting) to prevent
ketoacidosis. This potentially fatal condition
occurs when insulin levels are very low and
the body produces large amounts of ketones
via metabolism of fatty acids, causing blood
acidity to increase. This is usually accompanied by high glucose levels (hyperglycemia).
In healthy individuals this normally does not
occur because the pancreas responds to rising
glucose levels by producing insulin.
The National Diabetes Data Group publishes
new terminology to classify diabetes,
distinguishing type 1 and type 2 diabetes.
1922–70s
With the discovery
of insulin, the starvation diet is laid to rest.
Physicians work to
help diabetes patients
achieve a balance
between diet, exercise
and insulin, the
new “miracle drug.” Receiving the first dose
from Dr. Joslin’s team is a 41-year old nurse,
Elizabeth Mudge, a near-death patient who
had survived for five years on diet alone.
Within six weeks, she gains 31 pounds and
goes on to live another 25 years.
Insulin’s discovery launches a new field of
endocrinology research. Over the decades,
medical science would begin to discern differences between type 1 and type 2 diabetes.
1980
Among talented clinicians joining Dr. Joslin’s
research efforts is Howard F. Root, M.D.,
renowned for increasing the understanding
neuropathy and the loss of sensitivity that
potentially occurs with diabetes; also for
his combined medical and surgical approach
to salvage the foot, as depicted in this wall
mural at Joslin.
Until now, insulin has been extracted from
animal pancreases. In a nationwide race to
produce human insulin, William Chick, M.D.,
and colleagues at Joslin and Harvard are
among the first to successfully insert the
human insulin gene into bacteria, forming
the basis of recombinant DNA production of
human insulin available later.
1980s–present
1965–70s
Various research studies
suggest that type 1
diabetes is an autoimmune
disease in which the
body’s immune system
mistakenly attacks
the insulin-producing
beta cells of the pancreas. To survive, patients
must get insulin from injections.
1976
C. Ronald Kahn, M.D., who later joins Joslin
Diabetes Center, uncovers evidence of altered
insulin receptors in obesity and diabetes—key
information about insulin resistance associated with type 2 diabetes, in which the body
still can produce insulin but resists its effect.
As findings explode from Joslin’s research
labs, each discovery informs the next.
Today at Joslin, scientists are continuously
learning more about human metabolism and
what goes wrong in both type 1 and type 2
diabetes, using the latest techniques to map
genes, assess protein signals and monitor
changes in the pancreas, including state-ofthe-art imaging technologies (in photo above,
the magnetic resonance image on the right
shows pancreatic inflammation in type 1 diabetes, as compared with the control on the left).
www.joslin.org
P a c e s e tt i n g
| Joslin Legacy 5
r e s e a r c h
Targeting type 1 diabetes
Pursuing type 2 diabetes
In type 1 diabetes, the immune system mistakenly attacks the
pancreas. Many research teams at Joslin are working to better
understand this complex autoimmune process, including scientists
in the Human Immunology Program Project (HIPP).
Novel studies of type 2 diabetes also are underway at Joslin, such as
those highlighted below. Together, this body of work is shedding light
on how cells work, what goes wrong in type 2 diabetes, and potential
ways to treat and prevent it.
Photo above, left to right:
Stephan Kissler, Ph.D., studies the genes involved in type 1
diabetes, which are spread over more than 50 genomic regions.
But little is known about specific gene variants and how they impact
the immune system. His goal is to uncover key defects in immune
regulation that could be targeted to treat or cure type 1 diabetes.
Photo above, left to right:
Aaron Cypess, M.D., Ph.D., M.M.Sc., studies two types of fat: white,
which stores energy, and brown, which generates heat and is quite active
in infants. But adults also have brown fat, and he is developing strategies
to activate it, potentially boosting metabolism and reducing weight.
Myra Lipes, M.D., recently discovered that when people with
type 1 diabetes suffer a heart attack, they have a greater chance of
developing further heart damage, caused by factors triggering an
autoimmune response against cardiac muscle tissue. Her research is
focusing on how to selectively stop this detrimental response.
Jason Gaglia, M.D., M.M.Sc., is harnessing the power of magnetic
nanoparticle-enhanced magnetic resonance imaging (MNP-MRI)
to visualize changes in the pancreas (see image on opposite page).
This technique holds tremendous promise for studying the disease
process and the effect of new diabetes treatments.
Thomas Serwold, Ph.D., focuses on how immune cells called T cells
develop in the thymus, where they learn to tolerate the body’s own
cells. But if this process is imperfect, “bad” T cells may survive. His lab
is investigating how to detect and trap destructive T cells before they
can attack pancreatic beta cells.
Aldo Rossini, M.D., is the senior advisor of HIPP. During his
research career, he has studied the mechanisms involved in loss of
immune tolerance that occurs in type 1 diabetes and strategies to
reestablish immune tolerance to prevent the disease. {
C. Ronald Kahn, M.D., who discovered the insulin receptor, focuses
on complex signals that govern multiple actions of insulin inside the
cell, including proteins that regulate insulin activity in tissues such as
the liver, fat and brain and other signals involved in insulin resistance.
Steven Shoelson, M.D., Ph.D., studies how obesity promotes
inflammation in adipose tissue and systemically, including roles of
various white blood cells that may either protect or confer added risk.
He has translated this into safe anti-inflammatory approaches that
lower blood glucose in patients with type 2 diabetes.
Photo at right, left to right:
Yu-Hua Tseng, Ph.D., has found
a way to induce precursor cells
found in white fat to differentiate
into brown fat, leading to
increased energy expenditure.
She also is exploring how mature
brown fat cells can be stimulated
to boost metabolism.
Mary-Elizabeth Patti, M.D., is studying genes that raise the risk
of type 2 diabetes, working to identify factors found in prediabetes.
She also looking for early-life factors that promote increased risk of
obesity and diabetes later in life. {
6 Joslin Legacy |
www.joslin.org
3
Patient
education
Skills for life
Patient education is at the heart of the JoslinCare™ model of
diabetes care, with a team of experts guiding patients every
step of the way and empowering them with individualized
pathways to manage the day-to-day care of diabetes.
1915
1937
1981
Patient education becomes the hallmark of
Dr. Joslin’s care model, with patients instructed
on diet and general diabetes care. Ferric
chloride is used to measure blood glucose,
performed in hospital. Vegetables are cooked
three times to remove as many carbohydrates
as possible. Diets are high in fat to give energy
without rapidly increasing blood glucose: 70%
fat, 18% protein, 12% carbohydrate. Patients
are advised to be ultra thin.
When long-acting insulin is developed in Denmark, Joslin researchers help fine-tune its use.
Home glucose monitors are now available.
Also disposable sterile syringes and needles.
Diets become lower in fat—30% of intake—
to help prevent heart disease. Aspartame is
introduced as an artificial sweetener.
1918
Dr. Joslin publishes the first-of-its-kind
diabetes care guide for patients.
1922
Insulin is discovered, but
only short-acting insulin is
available. Glass syringes
are sterilized with each use;
large steel needles are sharpened on pumice
stone. Diets are still high in fat (70%), low in
carbohydrates (20%). Patients weigh food on
scales to align with insulin action.
1927
Harriet McKay is the first diabetes “wandering
nurse,” visiting patients in homes, hospitals and
diabetes camps to ensure quality care—a precursor
to today’s Certified Diabetes Educators.
1948
Intermediate-acting insulin becomes available.
Dietary recommendations are now 40% fat,
equal to carbohydrate intake.
1956
Dr. Joslin opens an inpatient
teaching unit, where patients are
immersed in experiential learning.
They eat together and monitor
urine sugars in the “Rainbow Room,” named
for the range of colors that precipitate from
Benedict’s solution with various sugar levels.
Late 1950s
Joslin participates in testing oral medications
to control type 2 diabetes. Over the years,
various “diabetes pills” emerge, improving
insulin’s ability to move glucose into cells,
slowing the rise of blood glucose or stimulating
the pancreas to release more insulin.
Early 1970s
With MIT, Joslin researcher Stuart Soeldner,
M.D., creates a device that measures blood
glucose levels and dispenses insulin into the
bloodstream every few minutes—an early
prototype for the artificial pancreas that
industry is striving to develop today.
1978
When revolutionary insulin pumps emerge, Joslin
organizes a weekly teaching clinic. Today, Joslin’s
insulin pump program continues to have the
largest number of patients anywhere in the world.
1990
Joslin begins to address Asian Americans’
higher risk of diabetes with research, clinical
and teaching programs, later emulated by
other diabetes centers nationwide. In 2000,
Joslin formally launches the Asian American
Diabetes Initiative.
2002
The Latino Diabetes Initiative begins,
providing this population at higher risk for
type 2 diabetes a Spanish-speaking clinic and
online and published learning tools.
2003
Joslin launches the Center for Innovation in
Diabetes Education (next page).
2011
Joslin introduces the
USDA’s Healthy Plate,
a visual meal-planning
method in which half
the meal is reserved for
vegetables and fruits.
2012
Joslin announces plans for the Black Diabetes
Initiative to reach out to the black population
about increased risk of type 2 diabetes.
www.joslin.org
| Joslin Legacy 7
‘A better state of being’
A
t Joslin, patients become key
partners in their diabetes care, with
Certified Diabetes Educators helping
them develop key skills important to
successful management of diabetes:
• Nurse educators teach patients how to inject
insulin, take medications, and use insulin
pumps and glucose monitors
• Registered Dietitians give guidance on types
of nutrients, food choices and meal planning
• Mental health counselors help patients with
emotional challenges and taking more positive
approaches to coping with diabetes
• Exercise physiologists teach how physical
activity benefits diabetes control and overall
well-being
“Dr. Joslin was the
first diabetes educator,
believing an engaged
patient is vital to the
person’s ability to
manage diabetes,”
says Katie Weinger,
Ed.D., R.N. (at left),
who directs Joslin’s
Center for Innovation
in Diabetes Education
(CIDE). “Today, we continue to be very patientcentered, taking patients from where they are to a
better state of being.”
Among early heroines is Harriet McKay,
R.N., who worked with Dr. Joslin as the first
“wandering nurse.” McKay traveled to patients’
homes, sometimes staying a few weeks until the
patient and their family had learned the many
skills involved in diabetes self-care. She also
trained other nurses, who encouraged patients
to build care skills into their personal lifestyle.
The CIDE is continuously developing new
ways to transform diabetes teaching models.
Using educational and behavioral research, it
develops programs that aim to improve patients’
understanding of diabetes, self-care and successful
long-term diabetes management.
Among popular offerings are interactive
learning games such as the CarbChallenge,
FatChallenge and Discovering the Food Label.
Web-based and web-streamed programs are
expanding the teaching repertoire, sharing Joslin’s
expertise with educators and patients worldwide. {
T ECHNICA L
G O A L
Is ‘artificial
pancreas’ next?
Sometimes the patient ends up
teaching the teacher. Patient
Stephanie Edwards (left) recently
demonstrated her brand-new
continuous glucose monitor
(CGM) to Director of Educational
Services Jo-Anne Rizzotto, M.Ed.,
R.D., C.D.E. (right), seeing that
model for the first time.
Edwards is among people
with type 1 diabetes who embrace
advances in diabetes care as
fast as they emerge. The CGM
provides a continuous record of
the patient’s glucose, reported
on a digital device worn close to
the body. Its sensor, inserted just
under the skin, measures glucose
in subcutaneous tissue.
“It takes longer for glucose to show up in subcutaneous tissue,” says Howard
Wolpert, M.D. (below), who oversees Joslin’s programs centered on incorporating
the CGM and the insulin pump into patient care. “So we’ve computed new formulas
for people reading their glucose levels on the CGM, verifying and fine-tuning these
algorithms in clinical trials.”
The CGM often is used with an insulin pump, which sends out a steady stream of
insulin to maintain a basal level, calculated for the person’s individual needs. When more
insulin is needed, such as after meals, the patient prompts the pump to deliver more.
In combination, the pump and CGM take the
place of the pancreas. Normally, the pancreas
detects rising and falling glucose levels and
automatically responds. But in type 1 diabetes,
those functions have been lost. The patient must
become “the brains of the pancreas,” learning
these skills from their diabetes education team.
To date, no single device can do both functions.
“Research efforts are focused on developing a
single closed-loop device, or ‘artificial pancreas,’
that can sense glucose levels and automatically
deliver insulin like a normal pancreas,” says
Dr. Wolpert. “We’re getting closer to that ideal.” {
8 Joslin Legacy |
www.joslin.org
4
Clinical
research
The power of place
Joslin patients have an extraordinary advantage. In addition to
receiving the latest in diabetes care, they have opportunities
to shape new treatments. Today, more than 260 clinical studies
are underway with over 160 involving active patient visits—
the largest single-site clinical research program in the world
focused specifically on diabetes and related conditions.
1894
1970s
2008
As a medical student, Elliott P. Joslin is
assigned a patient with diabetes, but
no effective treatments are available.
He begins his lifelong pursuit for answers.
Home blood glucose monitoring (using
reagent strips) and insulin pumps help
improve patients’ control of diabetes,
accelerating clinical studies.
1922
1980s
Allison Goldfine, M.D., and
Steven Shoelson, M.D., Ph.D.,
show that salsalate, an antiinflammatory drug similar to
aspirin, may prevent and help
treat type 2 diabetes; now in clinical trials.
Future Nobel Laureate George Minot, M.D.,
becomes Patient No. 2383, first surviving on
Dr. Joslin’s restricted diet, then benefiting
from insulin.
Joslin researchers find people with early signs
of insulin resistance are likely to develop type 2
diabetes unless they lose weight.
Late 1920s
Joslin researchers publish new ways to treat
diabetic coma; also to save feet and legs from
amputation due to diabetic complications.
Using blood samples collected by Dr. Soeldner
(see above), George Eisenbarth, M.D., and
colleagues discover the pre-diabetes stage in
which islet-cell autoantibody can be detected
and insulin secretion begins to decline.
1931
1992
To manage his diabetes,
inventor Thomas Alva
Edison, age 84, consults
with Dr. Joslin.
1947
U.S. Public Health Service conducts the
first-ever epidemiology survey of its kind in
Dr. Joslin’s hometown of Oxford, Mass.
Late 1950s
Joslin physicians participate in testing oral
medications to control type 2 diabetes.
1960­–80
Joslin researcher Stuart Soeldner, M.D.,
collects blood samples from twins and triplets
with diabetes, anticipating the powerful
potential of this biobank for future studies.
With insurance coverage declining for
diabetes care in hospital beds, Joslin creates
outpatient clinics where patients can receive
care and benefit from research findings,
evolving into the Clinical Research Center.
2002
The multicenter Diabetes
Prevention Program study,
led at Joslin by Edward
Horton, M.D., shows
people with elevated
risk for type 2 diabetes
can reduce their risk by
58% through sustained
moderate weight loss and increased exercise.
2005
Joslin launches the Medalist Study to
better understand prevention of diabetes
complications (p. 21).
2009
Aaron Cypess, M.D., Ph.D., and colleagues
demonstrate adults still have energy-burning
brown fat as adults, paving the way for new
treatments for obesity and type 2 diabetes.
2010
Measuring brain activity “in action,” Gail
Musen, Ph.D., launches a study to determine
if people with type 2 diabetes are at higher
risk for Alzheimer’s disease.
2012
Joslin receives a $9.5 million, multiyear
Diabetes Research Center (DRC) grant
from the National Institute of Diabetes and
Digestive and Kidney Disorders (NIDDK).
Joslin also receives a Massachusetts Life
Sciences Center capital grant of $5 million,
matched by private donors, for a new
Translational
Center for the
Cure of Diabetes,
celebrated by
Governor Deval
Patrick and a
Joslin patient
at the symbolic
groundbreaking.
www.joslin.org
| Joslin Legacy 9
Finding answers, one patient at time
A
fter struggling with type 2 diabetes for four years,
James Dugan jumped at the chance to enroll in a clinical weight-management study.
Shown in photo at right with Joslin exercise physiologist Jacqueline Shahar, M.Ed.,
R.C.E.P, C.D.E., he has emerged a winner. Within half a year, he lost nearly 50 pounds.
His blood glucose level and blood pressure have dropped to normal ranges. He no longer needs
cholesterol or blood-pressure medications, and his diabetes medications have dropped from
three to one.
Aiming to help overweight diabetes patients lower their blood glucose levels by slimming down,
among principal investigators of the “SLIMM-T2D” study are Joslin diabetologists Allison Goldfine,
M.D. (photo below at right), director of clinic research, and Osama Hamdy, M.D., Ph.D. (center),
director of the obesity clinical program.
Patients are randomly assigned to one of two study groups. Some have bariatric surgery. Others
are enrolled in Joslin’s multidisciplinary weight-management program called “Why WAIT,”
for Weight Achievement and Intensive Management, created by
Dr. Hamdy. The comparison will illuminate the best option.
Dugan was assigned to Why WAIT, in which exercise is integrated
with medication adjustments, nutrition plans and behavioral
support. “To date, 530 participants in various Why WAIT studies
have lost an average of 10.3 percent of their weight during the initial
12 weeks, then maintained an average loss of 6.3 percent on their own
for four years afterwards, aided by a case manager,” says Dr. Hamdy.
“By continuing to do what they’ve learned, they’ll stay winners.”{
T RANS L A T I O NA L
RESEARCH
Speeding new treatments
It started with a doctor and a ledger book. Early in his career, Elliott P.
Joslin, M.D., observed and recorded the progress of each of his diabetes
patients, gaining insights of promising pathways to pursue in the lab,
which in turn could be studied in clinical settings, then across patient
populations. Embodied in one physician, the cycle of translational
diabetes research had begun.
Major progress has been made, but key questions remain: Why do some
people get diabetes and others do not? Why do complications emerge, and how
can we prevent them? How can we better tailor treatments to unique populations?
How can we reach more people? Can we prevent diabetes altogether?
Adding to these challenges, a pandemic of diabetes is now afflicting
nearly 26 million people in the United States and 366 million worldwide.
Prevalence rates are expected to double by the year 2030.
Lab
Clinic
Population
New tools
and new
Applications
Joslin is addressing this challenge by creating the Translational Center
for the Cure of Diabetes, launched in 2012 by a $5 million gift from the
Massachusetts Life Sciences Center, matched by $5.8 million from private
donors—the largest capital infusion in Joslin’s history. The Translational
Center will focus on five pivotal areas:
• Nutrition’s remarkable power: In a new research and demonstration
kitchen, Joslin will investigate nutrition’s key role in controlling
diabetes and advancing wellness.
• Why exercise matters: In a state-of-the art exercise facility, Joslin will
develop a premier exercise physiology program, exploring the key role
of exercise in managing and preventing diabetes.
• Molecular mysteries of life: Using the power of next-generation
sequencing, Joslin will apply this sophisticated laboratory tool to
studies of genes and their functions.
• Expanding the biobank: Increasing Joslin’s collection of biological
specimens is essential to identifying diabetes survival factors and
developing new targets for diagnostic tests and treatments.
• Speeding therapies to patients: By expanding clinical research
capacity, Joslin will accelerate the translation of discoveries into
improved therapies and possible cures.
10 Joslin Legacy |
www.joslin.org
5
Laboratory
research
Below is a sampling of research at Joslin.
Other advances are highlighted throughout
this publication and at www.joslin.org.
1906–12
Harvard scientist Frederick Allen, M.D.,
conducts metabolism studies leading to
the “starvation diet” to prolong survival of
people with diabetes. Elliott P. Joslin, M.D.,
conducts similar studies at Carnegie Nutrition
Laboratory in Boston.
1932–59
Alexander Marble, M.D.,
is recruited as research
director, launching
Joslin’s formal research
program. He also serves
as chief editor of several editions of
Dr. Joslin’s textbook. In 1986, Joslin
establishes an annual lectureship in his honor.
1959
Albert Renold, M.D., is named research
director, bringing more basic research into
the Joslin portfolio.
1962
George Cahill Jr., M.D., is
appointed research director.
He becomes the international
leader in studying how the body
uses, stores and makes energy from glucose.
1981
C. Ronald Kahn, M.D., becomes research
director. His laboratory publishes the first
work showing how the insulin receptor sends
signals inside cells.
Unlocking cellular secrets
To find a cure for diabetes, scientists must look deep inside cells.
At Joslin, major initiatives are underway to understand the
molecular, genetic and cellular signals involved in type 1 and
type 2 diabetes. By identifying pathways in the lab with potential
to protect or restore normal cellular function—then testing those
findings in clinical settings—new treatments will emerge.
1985
2006
George King, M.D.,
who pioneers the use
of cell-culture models
to study diabetes
complications, shows
insulin is critical for
maintaining bloodvessel integrity (see
complications and eye research, pp. 20 and 22).
Laurie Goodyear, Ph.D., discovers a novel
signaling mechanism for regulating glucose
uptake in skeletal muscle, key to understanding
the role of exercise in diabetes control.
1996
Steven Shoelson, M.D., Ph.D., and colleagues
discover a “master switch” activated by
obesity and a fatty diet, causing insulin
resistance leading to type 2 diabetes.
They subsequently show aspirin-like drugs
can turn off this inflammatory response.
2000
George King, M.D., is named research director.
Susan BonnerWeir, Ph.D.,
and Gordon
Weir, M.D.,
discover a way
to encourage
pancreatic cells that normally do not produce
insulin to become insulin-producing islet cells.
2003
Andrzej Krolewski, M.D., Ph.D., and
colleagues discover that early kidney disease
in type 1 diabetes patients can be stabilized or
even reversed with proper medical screening
and diabetes control.
2007
Alessandro Doria, M.D., Ph.D., identifies genes
that contribute to type 2 diabetes and its
complications. A year later, his lab identifies
a relationship between poor blood glucose
control and a specific chromosome locus,
possibly affecting risk of coronary artery
disease in patients with type 2 diabetes.
2009
Rohit Kulkarni, M.D., Ph.D., identifies a
mechanism by which insulin-producing cells
are killed, occurring when the cells themselves
cannot import insulin properly.
Robert Stanton, M.D., and colleagues show
that high blood glucose can lower the activity
of a key enzyme that normally protects beta
cells from oxidative stress.
2010
Yu-Hua Tseng, Ph.D.,
and colleagues identify
adult stem cells in skeletal muscle and
white fat (large cells in image) that can be
transformed into “good” energy-burning
brown fat (smaller polyhedrons).
2012
T. Keith Blackwell, M.D., Ph.D., identifies a
mechanism for a cell-growth regulator that
plays a role in aging and diabetes (see next page).
www.joslin.org
T O W AR D
A
| Joslin Legacy 11
CURE
The promise of purpose
Joslin has the largest collection of diabetes
researchers under one roof—endocrinologists,
clinical researchers, geneticists, molecular
biologists, bioinformatics specialists and more.
Facing a disease that is rapidly becoming a
pandemic, Joslin is amplifying its laboratory
studies, organized into six basic science sections
that feed into a large clinical research section
and translational medicine program (p. 9).
Primary research faculty now number
more than 35, a sixfold increase since 1981.
These experts guide 120 fellows, talented
young investigators with M.D. and/or Ph.D.
degrees drawn to Joslin from all corners of the
globe to explore innovative ideas. Joslin also
is an affiliate of Harvard Medical School, with
nearly 12,000 faculty, the most prolific biomedical research community in the world.
At Joslin, Chief Scientific Officer George
King, M.D., and department leaders have charted the following course for laboratory research:
Amy Wagers, Ph.D., studies mechanisms of
tissue maintenance and regeneration, focusing
primarily on the role of two types of adult stem
cells, one that makes blood and another that
makes skeletal muscle, with the goal of finding
ways to promote the repair of tissues damaged
by diabetes.
• Prevent and cure type 1 diabetes: Study the
immune system and all phases of autoimmunity, how to prevent destruction of pancreatic
beta cells, and new ways to regenerate or replace them. Link this lab research with clinical
strategies to quiet the autoimmune response,
transplant insulin-producing cells and develop
a closed-loop system, or artificial pancreas.
• Prevent and reverse type 2 diabetes:
Launch studies of microbes found in the gut
and their gene expression. Increase research
in exercise physiology. Continue Joslin’s
groundbreaking research in insulin resistance
and biology of brown fat; elucidate the interconnected complexities of type 2 diabetes.
• Prevent diabetes complications: In vascular
tissues such as the heart, kidney and eye,
explore cell-based pathways of oxidative
stress and vascular change, seeking to identify factors that have protected people with
type 1 diabetes for 50 years or longer without
developing complications (pp. 21 and 23).
Rohit Kulkarni, M.D., Ph.D., focuses on growth
factors and signaling pathways that regulate
islet-cell regeneration and survival, coaxing
induced pluripotent stem (iPS) cells from skin to
differentiate into insulin-producing beta cells, and
investigating a genetic signaling protein associated
with islet growth in obesity and insulin resistance.
Computer-generated image of insulin molecule
• New technologies: Expand the biobank, a
valuable depository of biospecimens collected
from patients. Also increase capabilities in
genomics, the analysis of the complete set of
DNA within an organism; proteomics, largescale studies of protein structure and function;
and metabolomics, studies of end products of
metabolism. Enhance bioinformatics, imaging
systems and core facilities that provide highly
sophisticated, shared lab technologies.
T. Keith Blackwell, M.D., Ph.D., studies the tiny
roundworm C. elegans, a simple animal model
with a three-week lifespan. His research holds
promise for elucidating cellular and metabolic
stress involved in diabetes complications,
reducing inflammation, slowing aging and
promoting regeneration or repair of beta cells.
12 Joslin Legacy |
www.joslin.org
6
Expanding
Joslin’s reach
From Boston
to the world
1906
The first location
81 Bay State Road
In the early 20th century, doctors
often practice from their homes.
Elliott P. Joslin, M.D., and his wife,
Elizabeth, build this five-story
townhouse in Boston’s Back Bay, a
popular neighborhood for medical
practices. On the second floor is
Dr. Joslin’s office, where he sees
patients. A large dining room
evolves into a multipurpose
area for nurses to teach patients
about diabetes care, compile
publications including Dr. Joslin’s
textbooks and handwritten
patient ledgers, and host
professional colleagues from
around the world.
Joslin Diabetes Center today houses a special library, a replica of
the dining room in Dr. Joslin’s original townhouse in Boston.
This library is the headquarters of Joslin’s special collections, curated
by diabetologist Donald M. Barnett, M.D. (in photo), who early
in his career served with Dr. Joslin. Artifacts and books abound,
many made possible by the generosity of Dr. Joslin’s descendants.
The collection is the repository for the Joslin achievement medals
awarded over the past 80 years. Rows of bookshelves display the
original accounting ledgers that
Dr. Joslin began as the world’s
first diabetes registry to study
clinical outcomes. During his life,
the Joslin Clinic group cared for
nearly 60,000 patients.
Today, Joslin’s computerized
database system contains five
times as many cases, a “gold mine”
of data to track patients’ progress
and assess new yardstick indicators
in the treatment of diabetes.
1934
The second location
The Baker Clinic, Deaconess Road
The second major Joslin location, located near Harvard Medical
School, is made possible by George F. Baker, a philanthropist from
New York City and diabetes patient of Dr. Joslin. His pivotal gift
results in a modern diabetes center, designed by Dr. Joslin to fully
embody his principles of care. The first floor contains a foot clinic,
dental clinic and classrooms. The second floor houses research
laboratories. The third, fourth and fifth floors contain spaces for
pediatric patients, adult inpatients and suites for eye surgery.
The sixth floor houses an elaborate recreation facility, reflecting
Dr. Joslin’s viewpoint that exercise is a key element of diabetes care.
www.joslin.org
| Joslin Legacy 13
J
oslin Diabetes Center started with one man’s passion. Unwilling
to accept status-quo thinking about diabetes, Elliott P. Joslin,
M.D., began his quest to defeat it. More than a century later,
the diabetes center named in his honor is respected the world over,
and the expertise flowing from Joslin’s clinics and labs is available at
an ever-growing number of affiliates located around the globe.
1957–today
The third location
170 Pilgrim Road,
15 Joslin Road,
One Joslin Place
Now nearly 90 years old,
Dr. Joslin keeps planning
for the future, breaking
ground for a four-story
building on Pilgrim
Road. Over the next four
decades, this address
undergoes several
building expansions,
evolving into the
structure that today
carries the address One
Joslin Place. Across the
street is the beautifully
landscaped Joslin
Park. Each year, more
than 22,000 adult and
pediatric patients come
to receive state-of-the-art diabetes care at Joslin Diabetes Center in
Boston, staffed by more than 700 people, including 300 scientists
working to understand the biological mysteries of diabetes.
1980s–future
Around the world
National and global partners
With the world facing a diabetes
epidemic of enormous proportions,
what does the leading diabetes center
do? It grows to reach more people. In
recent years, Joslin has developed a
National Affiliates program, a network
of more than 46 hospitals, medical
centers and physician practices
where Joslin provides on-site training,
new guidelines to measure data and
expert feedback to improve patient
outcomes. Joslin programs also are underway in skilled nursing
and long-term care facilities. And a vibrant certification program is
available to help primary care doctors effectively manage diabetes
and its complexities. Joslin also is expanding into the world arena,
today developing partnerships in countries around the globe.
In addition, Joslin’s Healthcare Services Program offers a wide array
of educational programs—printed, online and mobile tools as well
as live instruction in primary care offices and other professional
settings. It also shapes innovative corporate alliances that benefit
people with diabetes, consumers and healthcare professionals.
14 Joslin Legacy |
www.joslin.org
7
Professional
education
1898–1962
Updating the team
In an acclaimed Professional Education program launched a century
ago, Joslin Diabetes Center imparts the latest knowledge about
diabetes to all members of the healthcare team. Offered in a wide
range of formats—from live symposia to web-based learning—
Joslin’s educational programs reach all corners of the world, shaping
the future well-being of diabetes patients everywhere.
1935–85
2009
Joslin’s scholarly research director,
Alexander Marble, M.D., serves as editor of
eight editions of Joslin’s physician textbook,
often the primary source for clinical and research findings published for the first time.
The online Joslin Professional Education Continuum (JPEC) is launched, providing nationwide, accredited, curriculum-style, sequential
continuing education activities for healthcare
professionals. JPEC expands knowledge, builds
clinical skills, and provides analytical tools to
improve practice care systems, patient support
and performance in diabetes care.
1947–2002
Elliott P. Joslin, M.D., serves 64 years on the
faculty of Harvard Medical School (HMS),
teaching medical students, training residents,
and providing educational opportunities for
physicians to stay abreast of new developments in diabetes research and care.
1916
To widely
inform the
profession,
Dr. Joslin
publishes a
400-page
physician
textbook
titled The Treatment of Diabetes Mellitus, the
first edition of its kind in the English language.
1925
When the libraries of HMS and Harvard
School of Public Health are combined,
Dr. Joslin chairs the Committee on Library,
giving direction to this professional resource,
which evolves into the renowned Countway
Library of Medicine.
Leo P. Krall, M.D., joins
Joslin as a fellow, rising
over the next 50 years to
international prominence
in professional diabetes
education. He directs
Joslin’s Education Division, chairs the annual
Harvard-Joslin course and travels extensively
worldwide, with particular interest in teaching
about diabetes in developing countries. He
also founds the Joslin International Fellows
Program, which provides training and educational opportunities for diabetes clinicians
from around the world.
1985
Dr. Krall is elected president of the
International Diabetes Federation, an umbrella
organization for diabetes professionals, today
active in more than 160 countries.
2001
Edited by Richard S. Beaser, M.D., Joslin
publishes the first edition of Joslin’s Diabetes
Deskbook, a comprehensive guide for
primary care providers for treating diabetes
and its complications. A third edition is
now underway.
2011
Joslin launches landmark projects combining
Continuing Medical Education (CME) with
research to establish the accuracy and predictive value of educational assessments in gauging the efficacy of certified CME programs.
2012
Joslin holds its first annual Diabetes Innovation
conference, a catalyst for innovative ideas,
collaboration and action to address the cost,
productivity, and quality-of-life impact of diabetes, obesity and related conditions on society.
For the second consecutive time, the
Accreditation Council for Continuing Medical
Education awards Joslin a six-year “Accreditation
with Commendation,” the highest rating
achievable. Contributing to this success is
Joslin’s exemplary performance in program
planning, needs assessment, evidencebased educational activity and innovative
educational outcomes
measurements.
The 14th edition of
Dr. Joslin’s textbook is
published, continuing
as the world’s leading
resource on diabetes.
www.joslin.org
H O RI Z O NS
O F
| Joslin Legacy 15
CARE
New insights at their fingertips
“By learning new evidence-based
advances in diabetes care, all
members of the diabetes team—
physicians, physician assistants,
nurse practitioners, nurses,
dietitians, pharmacists and other
healthcare professionals—are
better equipped to improve
patient outcomes in the future,”
says diabetologist Richard S.
Beaser, M.D., Joslin’s medical
executive director of Professional
Education (photo at right).
At Joslin, lunchtime lectures
are held twice a week in which
internal and external experts share
diabetes advances in the clinic and
laboratory. Radiating outward are
regional, national and international
learning programs.
Led by Joslin experts as well as nationally known guest faculty, accredited courses
provide knowledge and build skills of physicians and other health professionals
as they fulfill their continuing medical education (CME) requirements. Among
prominent events held in Boston are the annual Harvard-Joslin Diabetes Course and
new Cardiometabolic Congress, attracting professionals from around the world.
Much of this education is available online through the Joslin Professional Education
Continuum (JPEC) portal.
Continuing education is also available for nurses, nutritionists and behaviorists
who need updated information about diabetes detection, treatment improvements
and prevention strategies.
A new symposium for all stakeholders is the Diabetes Innovation conference, held
in Washington, D.C. Presentations are designed to provoke innovation and action
to address the cost, productivity and quality-of-life impact of diabetes, obesity and
related conditions on society.
Diabetes education begins early for students at Harvard Medical School, of
which Joslin is a teaching affiliate. Among physician-scientists who move fluidly
between seeing patients at
Joslin Clinic and teaching
HMS students is kidney
specialist Robert Stanton,
M.D., in photo at left with
medical students Vadim
Shteyler and Simin Gharib
Lee, who throughout their
future careers will have
ongoing access to Joslin’s
leaders in diabetes care. {
Voices of revered educators
In a 2012 symposium commemorating the 90th
year of insulin use, a videotape was presented of
two prominent diabetes clinicians of the past:
Leo P. Krall, M.D. (1915–2002), who directed
Joslin’s diabetes education program (see timeline),
and Samuel B. Beaser, M.D. (1910–2005), whose
son, Richard, now directs Joslin’s Professional
Education program. Excerpts follow:
DIABETES PRACTICE IN 1938
Dr. S. Beaser:
The practice of diabetes was entirely different from the
diabetes today.…We didn’t have blood sugars outside [the
hospital]; all we had was urine tests, which the patient did…
with a Bunsen burner, the old-fashioned way as we did in
the hospital.
INSULIN AND TIGHT CONTROL
Dr. Krall:
Everyone thought that with the discovery of insulin,
everyone would be cured. If you lacked thyroid, you would
take it. If you missed adrenal, you would take cortisol.
You were essentially cured. But, [diabetes patients] took
insulin and they still had complications….eye problems,
kidney problems, heart problems…Some physicians said
it made no difference what you did as long as you gave
insulin....Dr. Joslin and his group never deviated for a
moment from the belief that tight control was important.
DIABETES PILLS
Dr. S. Beaser:
As a result of the use of oral pills, we learned a good deal
about the action of insulin or insulin-like substances.
We learned that it wasn’t only in the pancreas that the
pills worked, but also…in the liver, the fat, the muscle, as
well as the pancreas. So the age of the oral pills opened up
a new era in medicine.
PROFESSIONAL COLLEGIALITY
Dr. Krall:
Dr. Joslin would visit every person [attending physicians
and residents] once a year, in their home…no longer than
24 hours or so after he visited you, you’d get a thank-you
note. Extremely thoughtful. Very bright, very alert.
A wonderful manager.…On top of everything.
16 Joslin Legacy |
www.joslin.org
8
Success in
pregnancy
‘She made it possible’
In the early 20th century, women with diabetes were advised to
avoid pregnancy. But Priscilla White, M.D., a courageous doctor
at Joslin, stepped forward, developing medical pathways to help
diabetes patients give birth to healthy babies, then sharing
these critically important guidelines with physicians worldwide.
At Joslin, her remarkable legacy of leadership continues today.
1924
1949
1981
Priscilla White, M.D., is
recruited to Dr. Joslin’s
team. Over the next
50 years, she develops
strategies that dramatically
improve the care of pregnant mothers with
diabetes and their babies’ survival.
Dr. White introduces the White Classification
of Diabetic Pregnancies, which categorizes
patients according to their risk, tailoring treatment accordingly. Risk levels are determined
by age at onset, duration, and presence of
vascular disease and renal complications.
This classification is widely adopted.
Dr. Hare and colleagues find an association
between elevated maternal hemoglobin A1C
in early pregnancy and major congenital
anomalies in infants of diabetic mothers.
1930s
1961
While most women with type 1 diabetes are
being advised to avoid pregnancy, Dr. White
staunchly defends allowing them to have children. Her approach centers on weekly monitoring the patient’s blood glucose and obstetric
status. She attends her patients’ deliveries.
M. Donna Younger, M.D.,
joins the Joslin staff, working
with Dr. White.
In caring for children with
diabetes, Dr. White brings
her dog Heidi to the office
to help them look forward
to their appointments.
She contributes to the
success of summer camps
for children with diabetes.
1945
After Dr. White drives a patient to the hospital,
the patient later writes: “She made it possible
to fulfill our lives as women and mothers.”
1968
Dr. White adds proliferative retinopathy
to risk factors in her classification of
diabetic pregnancies.
1974
Dr. White retires. Over her career at Joslin, the
fetal success rate has risen from 54% to more
than 90%. She has managed the deliveries of
over 2,200 women with diabetes and supervised some 10,000 cases of type 1 diabetes.
She later becomes the first woman to receive
the Banting Medal, the highest scientific
award of the American Diabetes Association.
1977
Dr. White and John Hare, M.D., publish a
paper reviewing 50 years of experience
with pregnancy in women with diabetes,
contributing the significant increase in
fetal survival to factors such as improved
insulins, antimicrobial agents and specific
tests applicable to pregnancy in diabetes for
assessment of fetal health.
1984
Joslin and Brigham and Women’s Hospital
launch the annual Priscilla White Lectureship
on Metabolism, presented by distinguished
scientists.
1989
Dr. White dies at age 89.
1997
Mary Loeken, Ph.D., discovers that genes
in the embryo that control organ formation
may not function properly when a mother is
diabetic, and this can cause birth defects.
2005
Mary-Elizabeth Patti, M.D., and colleagues
show that poor prenatal nutrition permanently damages the function of insulin-producing
cells in the embryo’s pancreas, raising the risk
the child will later develop type 2 diabetes.
2011
The Loeken lab uncovers the mechanism by
which a protein, whose production is reduced
in embryos of diabetic mothers, stops the
activity of the cell-death protein p53,
a significant advance toward understanding the elevated risk of birth defects among
babies born to mothers with diabetes.
www.joslin.org
L e a d i n g
| Joslin Legacy 17
pat h way s
Champions of mothers-to-be
P
riscilla White, M.D., had a unique
destiny. “Dr. Joslin hired her in an era
when women were even having trouble getting into medical school,” says
Donald Barnett, M.D., a retired Joslin diabetologist and historian. “Thanks to her perseverance, today women with diabetes are able to
achieve successful pregnancies at a rate nearly
matching mothers without diabetes.”
Over Dr. White’s long career, which began
at Joslin in 1924, the fetal success rate rose from
54 percent to more than 90 percent, approaching where it stands today—approximately
95 percent. With extraordinary devotion to
her patients, she was with them during childbirth. When she retired, the hallways of Joslin
were flooded with thankful mothers and offspring celebrating her professional expertise
and courage, which had resulted in life itself.
Nearly singlehandedly, Dr. White fought
the prevailing opinion that women with
diabetes should avoid pregnancy. Instead,
she championed Dr. Joslin’s stance that
tight control of diabetes was the best way to
stave off complications. She added another
dimension, based on adjusting medications
and diet to align with hormonal changes
that occur during pregnancy. The White
Classification of Diabetic Pregnancies is
still used today. Refined over the years, it
categorizes patients according to their risk
as determined by age of diabetes onset, duration, and
presence of heart, kidney
and eye complications.
Today, the Pregnancy Program at Joslin continues to
thrive under the direction of
Florence Brown, M.D., shown
in photo with Joyce Leung, a
patient with type 1 diabetes
who has gone through two
successful pregnancies. Each
year, the program attracts
more than 200 mothers-to-be
from around New England.
Patients have type 1 or 2 diabetes or gestational diabetes. Their diabetes
is monitored closely in concert with their
obstetric team.
In pregnancy, the placenta makes hormones that increase the body’s resistance
to insulin, causing the mother’s blood
glucose to rise. This can cause preeclampsia, a potentially life-threatening condition
characterized by high blood pressure and
excessive protein in the urine. High blood
glucose levels around the time of conception
increase the risk of birth defects in the baby.
Moreover, excess glucose from the mother
may cross the placenta and be stored as fat,
causing a high-birth-weight infant with in-
creased risk for obesity and diabetes later in
life. The strategy is to keep blood glucose as
close to normal as possible during the ninemonth gestation period.
Lab research at Joslin also is underway.
Mary Loeken, Ph.D., has discovered crucial
clues about the causes of birth defects that
may occur in pregnancies of women with
diabetes. And Mary-Elizabeth Patti, M.D., is
exploring how the risk of developing type 2
diabetes can be handed down to the following generations in ways not based on parental
DNA, but possibly on factors such as poor
nutrition or reduced muscle mass. {
Thank you for 50 years
M. Donna Younger, M.D., (center front), a protégé of
Dr. White, recently was honored for more than 50 years of service
at Joslin, surrounded by staff and well-wishers. At the event, a fund
was established in her name to support clinical excellence in teaching
and patient care. Dr. Younger’s portrait also was unveiled. “Future
generations will always be inspired by her smile,” said Joslin President
and CEO John L. Brooks III. “She is exemplary of the Joslin spirit of
patient-centered care.”
Dr. Younger joined the staff in 1961, when many of Joslin’s early
luminaries were still practicing—Drs. Elliott P. Joslin, Howard Root
and Priscilla White, of whom she was a protégé. “With Dr. White, the
fetal success rate skyrocketed” says Dr. Younger. “Today with proper
prenatal care, the majority of women with diabetes can carry to full
term and give birth to a healthy baby.” {
18 Joslin Legacy |
www.joslin.org
9
Children, teens,
young adults
The new normal
Serving more than 2,000 patients each year, Joslin’s Pediatric,
Adolescent and Young Adult Program offers the widest range
of diabetes care and support available anywhere for young
people and their families. Here, kids go about the business of
being kids, with a team of experts helping each child achieve
optimal health and well-being into early adulthood.
1898
1931
1980s–90s
Elliott P. Joslin, M.D., records his first pediatric
patient as Patient No. 4 in his ledger.
Although life expectancy for type 1 diabetes is
around 18 months, this boy lives another four
years. Children with diabetes are won over by
Dr. Joslin’s gentle yet firm coaching manner.
Dr. Joslin receives a $1 donation from a
shoeshine boy with diabetes (p. 24).
Joslin introduces and expands
usage of insulin pumps among
pediatric patients. Today more
than 60% receive insulinpump therapy.
1922
After insulin becomes available, Dr. Joslin
is overjoyed: “Who wants a vacation when
he can watch mere ghosts of children start
to grow, play and make noise?”
1932
Modeled after a summer camp program
started by Dr. Joslin seven years earlier,
the Clara Barton Camp for Girls with
Diabetes opens in North Oxford, Mass.,
with Dr. Joslin as the first medical director.
1948
2002
Ann Goebel-Fabbri, Ph.D., publishes a paper
on understanding eating disorders and ways
to prevent them, launching a major program at
Joslin in this area.
2003
1923
Online discussion boards are started for
teens and their families to learn more about
living with diabetes.
When the president of Eli Lilly and Co., the
first U.S. company to commercially make
insulin, receives a thank-you letter from
children in Dr. Joslin’s care, he sends each
child a new doll and insulin kit. The little girls
name their dolls “Lilly” (image below).
2007
The Elliott P. Joslin Camp for Boys is founded
in Charleton, Mass. Operated by a nonprofit
organization, both camps are still active today.
1970s
Home blood glucose monitoring, smaller
insulin needles and disposable syringes are
now available, making it easier to accept
therapies requiring multiple insulin doses.
1970s
Joslin formally establishes the Pediatric Clinic,
with Joseph Wolfsdorf, M.D., among early
pediatric endocrinologists. Today Lori Laffel,
M.D., M.P.H., directs this expert team of
diabetes and child-development specialists—
international leaders in family-centered care.
Research by Dr. Laffel and
colleagues shows teens
with type 1 diabetes have
improved blood glucose
control, thanks in part to
rapid introduction of innovative technologies
into pediatric diabetes care, including pumps,
sensors and text messaging.
2010
Joslin begins the New Onset Program for
children with type 1 diabetes whose condition
at onset allows for outpatient care rather
than hospitalization.
2012
Joslin launches Young Adult Support Program,
addressing specific challenges of the teen years
and easing the transition to adult diabetes care.
www.joslin.org
‘Grow, play and make noise’
| Joslin Legacy 19
P e d i at r i c
pat h way s
Use CGM to best advantage
Joslin investigators are looking to increase
pediatric use of the continuous glucose
monitor (CGM), a device that continuously
reports glucose levels (p. 7). Studies focus
on problem-solving skills and behaviors
that will lead to using the CGM to the
same advantage as adult patients.
Eat carbs smartly
J
oslin’s pediatric program offers
exceptional expertise to young patients
of all ages, from infants to teenagers
and into early adulthood. Family teamwork is vital, and Joslin’s family-centered
approaches—validated by research findings—are among the most comprehensive
in the world.
Joslin also is a key player in setting
pediatric care standards. Approximately 90
percent of pediatric patients at Joslin have
type 1 diabetes. Until recently, many were
hospitalized during the first week after onset.
“With our New Onset Program, we often can
teach diabetes management skills to families
on an outpatient basis, saving the child the
distress of being in the hospital,” says Lori
Laffel, M.D., M.P.H., who heads the Pediatric,
Adolescent and Young Adult Section.
Families learn how to incorporate the
child’s care into everyday life. “The greatest
way to normalize the life of a child with
diabetes is by frequently monitoring blood
glucose,” says Dr. Laffel. “Diabetes is not a doit-yourself condition. Persons of all ages do
best with support and avoidance of isolation.
We know from research that children whose
care is managed with family teamwork do the
best, with respect both to glycemic control
and quality of life.”
Today at Joslin, child-life specialists
use coaching methods such as therapeutic
art and medical play. The Zubricki family,
whose two children have type 1 diabetes
(photo above), enjoy a Joslin diabetes card
game, a fun format to learn about their care,
guided by Jennifer Griffin, M.S., C.C.L.S.
“We explain how taking good care of
their diabetes today will also help them be
strong and healthy tomorrow,” says Cynthia
Pasquarello, B.S.N., R.N., C.D.E., nurse
manager and educator, in photo below with
Tom Zubricki (left), who has type 1 diabetes
and once was her patient. In family sessions,
she now coaches his 7-year-old son, Matthew.
Each family has a “care ambassador,” who
provides personalized support during and
between visits. Joslin’s research shows this type
of follow-up care results in better blood glucose
control and fewer hypoglycemic episodes,
emergency room visits and hospitalizations.
Joslin’s insulin-pump program for
pediatric patients is the largest in the world,
with more than half using a pump, some as
young as six months old. The Young Adult
Support Program addresses the social and
psychological challenges that can derail
diabetes routines in the older teen and
young adult years. It also helps young adults
transition to adult care.
About 10 percent of Joslin’s pediatric
patients have type 2 diabetes, largely
associated with excess weight. Joslin’s new
Childhood Weight Management Program
aims to identify children at risk and
intervene early on. {
Pediatric research is also underway to
promote good nutrition in children with
type 1 diabetes, who today are often
overweight. It is important for all children
and adults, with or without diabetes, to
eat more fruits, vegetables and whole
grains to manage weight. For people with
diabetes, these dietary changes can help
improve diabetes control.
Transition well
Pediatric patients with diabetes generally
receive their care from diabetes specialists.
But adult care often is managed by primary
care physicians. Joslin is developing
standards of care to determine the best
approach for successfully transitioning
diabetes care into adulthood.
Who’s at risk?
Joslin is among diabetes centers
nationwide participating in the TrialNet
study, which is screening family
members of people with type 1 diabetes
to determine risk, with the goal of
identifying ways to preserve pancreatic
beta-call function and preventing
progression to type 1 diabetes.
Handprints of pediatric patients cover the clinic's ceiling
20 Joslin Legacy |
www.joslin.org
10
Preventing
complications
Defying the odds
Significant numbers of type 1 diabetes patients who have
had diabetes for 50 years or longer are able to remain free
of complications. Some even retain some insulin production.
In a wide array of laboratory and clinical research studies,
Joslin is exploring why.
1931
1989
2008
With insulin available for nearly 10 years,
new health problems begin to arise—
complications involving blood vessels,
nerves, eyes and kidneys. Physicians
intensely debate if tight control of diabetes
is worth the effort. Elliott P. Joslin, M.D.,
and his team say yes, “The best control
prevents complications.” Research begins on
preventing complications, in collaboration
with other medical specialties.
Dr. King and colleagues demonstrate that high
blood glucose levels activate protein kinase C,
part of a major signaling pathway that causes
cellular changes in the eye, kidney and arteries,
leading to diabetic complications.
C. Ronald Kahn, M.D., identifies insulin
resistance in the liver as a key factor in
the cause of metabolic syndrome and
associated atherosclerosis.
Dr. Joslin awards the first Medal to patients
who have lived with diabetes
for 10 years. In the years
ahead, the Medalist
Program would celebrate
patients who live much
longer (see opposite page).
1950s–70s
Joslin physicians devise revolutionary surgical
and medical approaches for saving feet and
limbs damaged by diabetes, a success record
unsurpassed anywhere in the world.
1983
Joslin publishes the Cohort Study, centered
on patients with onset of type 1 diabetes 20,
30 or 40 years beforehand, revealing key data
on diabetes progression and complications.
1985
George King, M.D., who pioneers the use
of cell-culture models to study diabetes
complications, shows insulin is protective
of blood vessels.
1991
When the microalbuminuria test becomes
available for early detection of kidney disease,
Joslin begins investigations to uncover genetic
factors underlying susceptibility to kidney
damage from diabetes.
1993
The landmark
Diabetes Control
and Complications
Trial (DCCT) confirms
Dr. Joslin’s long-held
belief that good blood glucose control helps
prevent diabetes-related complications.
1994
Dr. King and Lloyd P. Aiello, M.D., Ph.D.,
discover increased levels of vascular
endothelial growth factor (VEGF) in eye fluid
in diabetic retinopathy patients, setting the
stage to block this damaging growth factor.
1995
Joslin clinical researchers identify blood
glucose levels that limit kidney disease. 2005
Joslin formally launches the 50-Year Medalist
Study to learn how people survive diabetes
50 years or longer with surprisingly few
complications (see opposite page).
2009
Edward Feener, Ph.D., discovers a potent
inflammatory system involved in diabetic
macular edema, high blood pressure, kidney
disease and stroke, suggesting new drug
targets for treating diabetes complications.
2010
Hillary Keenan, Ph.D., and
Dr. King demonstrate a high
percentage of people with
type 1 diabetes for 50 years
or longer may still have insulin-producing islet
cells (see image). The King lab also shows that
insulin guards against artery damage and
atherosclerosis, major causes of death in
type 1 and 2 diabetic patients.
2011
Andrzej Krolewski, M.D., Ph.D., and Monika
Anna Niewczas, M.D., Ph.D., identify two novel
markers that, when elevated in the bloodstream,
can accurately predict the risk of kidney failure in
patients with type 1 and type 2 diabetes. These
findings are confirmed by the DCCT in 2013.
2012
Amy Wagers, Ph.D., and colleagues discover
age-related impairment of the body’s ability
to replace the protective myelin sheaths that
surround nerve fibers may be reversible,
offering hope for strategies to restore
damaged nerve tissue in diabetes.
www.joslin.org
5 0 - YEAR
M E D A L IS T
| Joslin Legacy 21
S T U D Y
Seeking protective factors
Complications to diabetes are just that—biologically complicated. Blood
travels to every tissue in the body, so if it contains higher than normal
glucose levels, over time this long-term exposure can damage delicate
heart, kidney, eye and nerve tissue. Although diabetes complications
often occur within 30 years, a significant number of people with type 1
diabetes are free of complications after 50 years or more.
To understand why, in 2005 Joslin launched the 50-Year Medalist
Study, the first of its kind. To date, more than 900 patients from 49
states across the country have enrolled. If potential protective factors
can be identified, perhaps these findings can lead to novel treatments
benefitting all patients with diabetes.
Extraordinary
milestones
J
oslin Diabetes Center regularly
celebrates patients who have lived successfully
with diabetes. Numbers are getting so large,
the event is now scheduled in an off-site
function hall. To date, Joslin has awarded more
than 3,900 medals for the 50-year mark and
64 medals celebrating 75 years. In 2013, two patients
are receiving the new 80-year medal. {
Some patients have lived successfully with diabetes for more than 75
years. “In 1937 at age 8, I was diagnosed with diabetes,” says Kathryn Ham
(at center in photo). “In my early years, I knew both Dr. Joslin and
Dr. Priscilla White, who helped me through pregnancy.” She is now in the
Medalist Study, headed by Joslin’s Chief Scientific Officer George King,
M.D. (left), and Hillary Keenan, Ph.D. (right). The study is supported by
the Juvenile Diabetes Research Foundation (JDRF), the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK), and donations
from Medalists themselves.
Medalists first complete an extensive medical history questionnaire
and provide lab data. Findings show as a group they have controlled
their blood glucose levels well for many years, with nearly 35 percent
escaping serious complications.
Medalists also travel to Joslin, where researchers assess eye, kidney,
nerve and heart function; also metabolic changes in blood and the
ability to produce insulin. Genetic studies are seeking to understand if
there are factors differentiating Medalists from other type 1 diabetes
patients. Among exciting discoveries is that most are consistent
with typical type 1 diabetes, including genetic factors and clinical
characteristics such as high-density “good” cholesterol (HDL) and
relatively low body weight.
Approximately 90 percent of Medalists do not have kidney problems.
About 40 percent do not have serious eye disease—even after 50 to 80
years. Moreover, 35 percent have factors or genes protecting them from
developing diabetic eye disease (see eye research p. 23).
Surprisingly, more than 66 percent appear to still produce some
insulin. This raises the possibility that many type 1 diabetes patients
have protection from beta-cell destruction. A new study of 40 patients
is now underway to see if beta cells can be revitalized. {
1931
1948
1970
Joslin Life Expectancy
10-Year Medal
Joslin Quarter-Century
Victory Medal
Joslin
50-Year Medal
1995
2013
Joslin Victory Award
75-Year Medal
Joslin
80-Year Medal
22 Joslin Legacy |
www.joslin.org
Vascular victories
11
Eye research
and care
Called the windows to the soul, the eyes also offer a remarkable
vista for observing the impact of diabetes. Covered by blood
vessels, the delicate tissues of the retina and macula can be
damaged by high blood glucose. To prevent vision loss in people
with diabetes, Joslin researchers are generating one breakthrough
after the next, elevating diabetes eye care to new heights.
1931
1966
1994
Insulin has been available for nearly a decade.
But complications now begin to arise, including
vision loss caused by the damage high blood
glucose can inflict on blood vessels in the
eye. Damage occurs in two primary ways.
In proliferative (advanced) diabetic
retinopathy, blood vessels grow where they
don’t belong. In diabetic macular edema,
the blood vessels leak, causing swelling in
the macula, the retinal area responsible for
sharpest vision.
The Massachusetts Lions Eye Research Fund
begins its support of the Beetham Eye Institute,
over the years providing more than $5.8 million
for cutting-edge research on early-stage,
diabetes-related eye conditions, leading to novel
treatment advances, imaging techniques and
cellular evaluation of innovative therapies.
Lloyd P. Aiello, M.D., Ph.D., and George King,
M.D., demonstrate vascular endothelial
growth factor (VEGF) causes damage to
blood vessels and bleeding into the eye.
They subsequently show a VEGF inhibitor
stops this vascular damage associated with
macular edema, or swelling of the retina.
1968
1998
1932
William P. Beetham, M.D.,
who had worked with Elliott
P. Joslin, M.D., since 1925,
officially joins the Joslin
team, rising to international
stature in diabetic eye
disease. By 1950, many
patients have severe
diabetes complications,
including blindness, and
it is not uncommon for
seeing-eye dogs to outlive
their owners. Thanks to
advances forged under Dr.
Beetham’s leadership, such
service dogs are now a rare
occurrence at Joslin, where
the Beetham Eye Institute
is named in his honor.
Dr. Beetham (left)
and Lloyd M.
Aiello, M.D. (right),
pioneer panretinal
laser treatment
for diabetic eye disease, using ruby laser to
revolutionize treatment of this devastating
complication.
1971
Joslin physicians play a leadership role in the
Diabetes Retinopathy Study, a randomized
clinical trial that proves the benefit of ruby
laser treatment. Refined over the years, this
remains the primary treatment for diabetic
retinopathy today.
1979
With Dr. L.M. Aiello serving as co-chair, the
landmark 10-year multicenter Early Treatment
of Diabetic Retinopathy Study is launched to
set standards of when to use laser to prevent
vision loss from diabetic eye disease.
1993
The landmark Diabetes Control and
Complications Trial confirms that good blood
glucose control can stave off diabetes-related
complications, including blindness.
Dr. L.M. Aiello, with Sven-Erik Bursell, Ph.D.,
launches the Joslin Vision Network, in which
a retina camera takes detailed pictures of the
back of the eye. Coupled with telemedicine
and online transmission capabilities, these
cameras can be installed in nearly any clinical
setting worldwide, with images transmitted
back to Joslin’s eye experts for evaluation.
2010
Based on research by
Drs. L.P. Aiello and King,
a national clinical trial
confirms the effectiveness
of injecting the eye with
the drug ranibizumab, a
VEGF inhibitor, as a standard treatment for
diabetic macular edema (in image, before and
after treatment). This study also accelerates the
way drugs go through clinical trials.
2012
Edward Feener, Ph.D., expands on his earlier
Joslin discovery showing that macular edema
caused by a non-VEGF pathway is associated
with a protein called plasma kallikrein, for
which he identifies an inhibitor. Clinical trials
are now underway to test its potential as a
new eye treatment.
www.joslin.org
| Joslin Legacy 23
Carrying the torch
T
o be a pioneer in medicine
is a rare distinction. To have a
family with three generations
of pioneers— each making
quantum leaps in eye research and care—is
even more extraordinary.
Joslin has such a family. Beginning with
William P. Beetham, M.D. (in portrait),
the torch of diabetes eye research and care
has been carried by his son-in-law Lloyd
M. Aiello, M.D. (left), and grandson Lloyd
Paul Aiello, M.D., Ph.D. (right). Collectively,
they are responsible for pioneering novel
techniques that have dramatically reduced
vision loss from diabetes. Today, the average
vision for Joslin patients is 20/20.
In the past, blindness was common. “With
the discovery of insulin, diabetes became a
disease you could live with,” says Dr. L.M.
Aiello. “But over time, high glucose levels can
damage blood vessels in the eye, heart and
kidneys. In 1952, if patients had proliferative
diabetic retinopathy, they often had other
widespread vascular damage. Their chance of
dying within five years was 73 percent.”
With the advent of the ruby laser,
Dr. Beetham had a revolutionary idea.
In proliferative (advanced) diabetic
retinopathy, blood vessels grow where they
don’t belong. Perhaps this invasive growth
could be stopped by making thousands of
E y e
pinpoint “burns” in the back of
the eye on the retina. Assisted
by Dr. L.M. Aiello, the first
panretinal laser procedure was
performed in 1967 (see photo in
timeline). It worked. Basically,
the eye continues to see by
“summating” vision across the
tiny cauterized areas.
Patients flocked to Joslin in
droves. Dr. L.M. Aiello recalls
caring for 90 patients per day, from
6 a.m. to 11:30 p.m. The procedure
soon was tested in a nationwide
clinical study, and for more than
40 years has been the treatment
standard for proliferative diabetic
retinopathy. Recognizing diabetes
patients in other parts of the world
also need proper eye screenings and care,
in 1998 he was instrumental in creating the
cutting-edge Joslin Vision Network. In this
high-tech approach, detailed retinal images
are taken elsewhere, such as Venezuela, then
transmitted to Joslin, where eye experts
evaluate them and send back a treatment plan.
Another eye problem can occur with
diabetes—macular edema. In this condition,
blood vessels leak, causing swelling in
the macula, the retinal area responsible
for sharpest vision. Dr. L.P. Aiello, who
heads the world-renowned Beetham Eye
Institute named for his grandfather, recently
pioneered a way to stop this swelling, using
a drug injected into the vitreous of the eye
to stop a growth factor that commonly
causes this problem (see image in timeline).
Today this therapy is the international
treatment standard. On the horizon, he is
developing noninvasive technologies to detect
and study real-time functional and structural
changes in the diabetic eye, perhaps allowing
even earlier intervention. {
c l u e s
How do Medalists do it?
Remarkably, some Joslin 50-Year Medalists have survived with diabetes for more than five decades
with little or no diabetic retinopathy or other complications (see story on p. 21). “A large majority
maintain perfect or excellent vision,” says Jennifer K. Sun, M.D., M.P.H. (right). She and proteomics
researcher Edward Feener, Ph.D. (left), are working to identify key molecules and pathways that
protect these unique patients and understand how they prevent diabetic eye disease. The goal
is to create novel treatments that benefit all patients with diabetes, including those who are
naturally more susceptible to eye complications.
Other studies focus on developing ways to predict which diabetes patients will develop eye
problems. For example, Joslin’s scientists are correlating the presence of eye complications with
biological markers, substances or findings that indicate a problem exists or will develop. They also
are measuring retinal blood flow and thickness, using ultra-high-resolution images to study various
layers of the retina. {
24 Joslin Legacy |
www.joslin.org
Letter from a shoeshine boy
Over the years, patients from all walks of life have expressed their
gratitude for the lifesaving care provided by experts at Joslin Diabetes
Center. This letter from a 15-year-old diabetes patient, penned more
than 80 years ago,
demonstrates how trust
and hope for the future
can build momentum
in the fight against
diabetes—one gift at a
time, one person at a time.
joslin.org/highhopes
Writing the next chapter
Joslin’s legacy of global leadership is still unfolding. Much work lies ahead as our dedicated
scientists and clinicians continue searching for promising ways to prevent, treat and cure
diabetes and its complications.
To learn how you can make a difference in the lives of patients everywhere, please contact
the Development Office, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215;
phone (617) 309-2412 or (888) JOSLIN-2.
www.joslin.org
Joslin Diabetes Center is the world's preeminent diabetes
research and clinical care organization. Joslin is dedicated
to ensuring that people with diabetes live long, healthy
lives and offers real hope and progress toward diabetes
prevention and a cure. Founded in 1898 by Elliott P. Joslin,
M.D., Joslin is an independent, nonprofit institution
affiliated with Harvard Medical School.
www.joslin.org
| Joslin Legacy 25
Joslin Legacy is produced by the Communications Department at
Joslin Diabetes Center.
director
Jeffrey Bright
design
Richard Chiarella, Innovative Resource Group
writer & editor
Christine Paul
photography
John Soares
Stephanie M. McPherson
Historical consultant
Donald M. Barnett, M.D.
Computer-generated image of insulin molecule
One Joslin Place, Boston, MA 02215
www.joslin.org
(617) 309-2400