Joslin Legacy - Joslin Diabetes Center · | joslin legacy 1 ... concentrated effort to prevent, treat and cure diabetes. ... new “miracle drug.”

Joslin LegacyPacesetting progress in discovery and care

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 coverHistorical 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).

Contents

www.joslin.org | joslin legacy 1

New heights of hopeThe 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 IIIPresident and Chief Executive OfficerJoslin Diabetes Center

2 joslin legacy | www.joslin.org

Elliott P. Joslin, M.D.‘Dean of Diabetes’

Teamwork toward a cure

1869Born in Oxford, Mass., 50 miles west of Boston.

1890Graduates from Yale; remains a year to study physiological chemistry.

1895Graduates from Harvard Medical School as valedictorian; wins coveted prize for diabetes observations. Interns at Massachusetts General Hospital, followed by residencies in Germany.

1898Launches medical practice in Boston’s Back Bay. Joins HMS faculty. Begins keep-ing ledgers of his diabetes patients, the first registry of its kind.

1900Mother is diagnosed with diabetes and follows her son’s high-fat, low-carbohydrate diet, living 13 more years.

1906–12Joins metabolic investigative laboratory on HMS campus, studying chemical balance in health and diabetes.

1916Publishes 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.

1922After insulin’s 1921 discovery in Canada by Drs. Frederick Banting and Charles Best, the first dose in New England of commer- cial, 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.”

1924Recruits Priscilla White, M.D., to treat children with diabetes. Over the years, she also makes landmark contributions to diabetes care during pregnancy (p. 16).

1922–28Expands teaching role of nurses, including in-novative “wandering nurse” program (p. 6).

1931Creates 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).

1932Recruits Alexander Marble, M.D., launching formal investigative program (p. 8).

1937–47Becomes world-recognized for advocating tight control of diabetes to reduce complica-tions (p. 20), a hotly debated issue.

1952–53At age 80, restructures his mission by organiz-ing his group practice into Joslin Clinic. Front row, left to right: Drs. Howard F. Root (super-vises 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 (prin-cipal 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.

1956–57Moves Joslin Clinic to present location. Opens widely popular inpatient ambulatory treatment center. Plans research lab.

1962Dies 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).

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Momentum of confidence

“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. {

Beginning with Elliott Proctor Joslin, M.D., the effort to combat dia-betes has been driven by conviction and optimism. Although diabetes was

observed in ancient times, physicians in the late 1890s still did not understand this com-plex metabolic disorder.

Transforming diabetes careWith 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

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 motiva-tion, 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-scientist-educator. So Dr. Joslin recruited bright energetic professionals to push the boundaries of diabetes research and care.

Today at JoslinDiabetes 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 trans-formed by the digital age (see story below).

Cultural experts reach out to ethnic popu-lations at elevated risk for diabetes. Educators travel worldwide to update medical profes-sionals 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.” {

T h e F u T u r e

Digital diabetes care


Type 1 and type 2 diabetes

Differentiating diabetesToday 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.

1898–1921Before 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 accompa-nied by high glucose levels (hyperglycemia). In healthy individuals this normally does not occur because the pancreas responds to rising glucose levels by producing insulin.

1922–70sWith the discovery of insulin, the starva-tion 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 differ-ences between type 1 and type 2 diabetes.

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.

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.

1976C. 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 associ-ated with type 2 diabetes, in which the body still can produce insulin but resists its effect.

1979The National Diabetes Data Group publishes new terminology to classify diabetes, distinguishing type 1 and type 2 diabetes.

1980Until 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

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-of-the-art imaging technologies (in photo above, the magnetic resonance image on the right shows pancreatic inflammation in type 1 diabe-tes, as compared with the control on the left).

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P a c e s e T T i n g r e s e a r c h

Targeting type 1 diabetesIn 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).

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.

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. {

Pursuing type 2 diabetesNovel 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: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.

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. {


Patient education

Skills for lifePatient 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.

31915Patient 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.

1918Dr. Joslin publishes the first-of-its-kind diabetes care guide for patients.

1922Insulin 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.

1927Harriet 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.

1937When long-acting insulin is developed in Den-mark, Joslin researchers help fine-tune its use.

1948Intermediate-acting insulin becomes available. Dietary recommendations are now 40% fat, equal to carbohydrate intake.

1956Dr. 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 1950sJoslin 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 1970sWith 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.

1978When 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.

1981Home 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.

1990Joslin 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.

2002The Latino Diabetes Initiative begins, providing this population at higher risk for type 2 diabetes a Spanish-speaking clinic and online and published learning tools.

2003Joslin launches the Center for Innovation in Diabetes Education (next page).

2011Joslin introduces the USDA’s Healthy Plate, a visual meal-planning method in which half the meal is reserved for vegetables and fruits.

2012Joslin announces plans for the Black Diabetes Initiative to reach out to the black population about increased risk of type 2 diabetes.


‘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 patient-centered, 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 e c h n i c a 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.” {


Clinical research

The power of placeJoslin 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.

1894As 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.

1922Future Nobel Laureate George Minot, M.D., becomes Patient No. 2383, first surviving on Dr. Joslin’s restricted diet, then benefiting from insulin.

Late 1920sJoslin researchers publish new ways to treat diabetic coma; also to save feet and legs from amputation due to diabetic complications.

1931To manage his diabetes, inventor Thomas Alva Edison, age 84, consults with Dr. Joslin.

1947U.S. Public Health Service conducts the first-ever epidemiology survey of its kind in Dr. Joslin’s hometown of Oxford, Mass.

Late 1950sJoslin physicians participate in testing oral medications to control type 2 diabetes.

1960 –80Joslin researcher Stuart Soeldner, M.D., collects blood samples from twins and triplets with diabetes, anticipating the powerful potential of this biobank for future studies.

1970s Home blood glucose monitoring (using reagent strips) and insulin pumps help improve patients’ control of diabetes, accelerating clinical studies.

1980sJoslin researchers find people with early signs of insulin resistance are likely to develop type 2 diabetes unless they lose weight.

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.

1992With 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.

2002The 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.

2005Joslin launches the Medalist Study to better understand prevention of diabetes complications (p. 21).

2008Allison Goldfine, M.D., and Steven Shoelson, M.D., Ph.D., show that salsalate, an anti-inflammatory drug similar to aspirin, may prevent and help treat type 2 diabetes; now in clinical trials.

2009Aaron 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.

2010Measuring 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.

2012Joslin 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.

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Finding answers, one patient at timeA

f t e r s t r u g g l i n g w i t h t y p e 2 d i a b e t e s f o r f o u r y e a r s , 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 r a n s L a T i O n a L r e s e a r c h

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.

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.

PoPulationCliniC

lab

new tools and new

aPPliCations


laboratory research

Unlocking cellular secretsTo 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.

Below is a sampling of research at Joslin.Other advances are highlighted throughout this publication and at www.joslin.org. 1906–12Harvard 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.

1932–59Alexander 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.

1959Albert Renold, M.D., is named research director, bringing more basic research into the Joslin portfolio.

1962George 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.

1981C. Ronald Kahn, M.D., becomes research director. His laboratory publishes the first work showing how the insulin receptor sends signals inside cells.

1985George King, M.D., who pioneers the use of cell-culture models to study diabetes complications, shows insulin is critical for maintaining blood-vessel integrity (see complications and eye research, pp. 20 and 22).

1996Steven 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.

2000George King, M.D., is named research director.

Susan Bonner-Weir, 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.

2003Andrzej 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.

2006Laurie 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.

2007Alessandro 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.

2009Rohit 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.

2010Yu-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).

2012T. 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).

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T O W a r D a c u r e

The promise of purposeJoslin 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 biomedi-cal research community in the world.

At Joslin, Chief Scientific Officer George King, M.D., and department leaders have chart-ed the following course for laboratory research:

• Prevent and cure type 1 diabetes: Study the immune system and all phases of autoimmu-nity, how to prevent destruction of pancreatic beta cells, and new ways to regenerate or re-place 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 inter-connected 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 iden-tify factors that have protected people with type 1 diabetes for 50 years or longer without developing complications (pp. 21 and 23).

• 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, large-scale 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.

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.

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.

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.

Computer-generated image of insulin molecule

1906The first location81 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.

1934The second locationThe 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.


Expandingjoslin’s reach

From Boston to the world6

1957–todayThe third location170 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–futurearound the worldNational 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.


Joslin 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.


Professional education

Updating the teamIn 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.

1898–1962

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 develop-ments in diabetes research and care.

1916To 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.

1925When 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.

1935–85Joslin’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 re-search findings published for the first time.

1947–2002Leo 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 edu-cational opportunities for diabetes clinicians from around the world.

1985Dr. Krall is elected president of the International Diabetes Federation, an umbrella organization for diabetes professionals, today active in more than 160 countries.

2001Edited 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.

2009The online Joslin Professional Education Con-tinuum (JPEC) is launched, providing nation-wide, 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.

2011Joslin launches landmark projects combining Continuing Medical Education (CME) with research to establish the accuracy and predic-tive value of educational assessments in gaug-ing the efficacy of certified CME programs.

2012Joslin 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 diabe-tes, 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, evidence-based 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.

7


h O r i Z O n s O F c a r e

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 educatorsIn 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 1938Dr. 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 CONTROLDr. 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 PILLSDr. 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 COLLEGIALITYDr. 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.


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.

1924Priscilla 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.

1930sWhile most women with type 1 diabetes are being advised to avoid pregnancy, Dr. White staunchly defends allowing them to have chil-dren. Her approach centers on weekly monitor-ing the patient’s blood glucose and obstetric status. She attends her patients’ deliveries.

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.

1945After Dr. White drives a patient to the hospital, the patient later writes: “She made it possible to fulfill our lives as women and mothers.”

1949Dr. White introduces the White Classification of Diabetic Pregnancies, which categorizes patients according to their risk, tailoring treat-ment accordingly. Risk levels are determined by age at onset, duration, and presence of vascular disease and renal complications. This classification is widely adopted.

1961M. Donna Younger, M.D., joins the Joslin staff, working with Dr. White.

1968Dr. White adds proliferative retinopathy to risk factors in her classification of diabetic pregnancies.

1974Dr. 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 super-vised 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.

1977Dr. 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.

1981Dr. Hare and colleagues find an association between elevated maternal hemoglobin A1C in early pregnancy and major congenital anomalies in infants of diabetic mothers.

1984Joslin and Brigham and Women’s Hospital launch the annual Priscilla White Lectureship on Metabolism, presented by distinguished scientists.

1989Dr. White dies at age 89.

1997Mary 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.

2005Mary-Elizabeth Patti, M.D., and colleagues show that poor prenatal nutrition permanent-ly damages the function of insulin-producing cells in the embryo’s pancreas, raising the risk the child will later develop type 2 diabetes.

2011The 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 understand-ing the elevated risk of birth defects among babies born to mothers with diabetes.

8


Champions of mothers-to-beP

riscilla White, M.D., had a unique destiny. “Dr. Joslin hired her in an era when women were even having trou-ble getting into medical school,” says

Donald Barnett, M.D., a retired Joslin diabe-tologist and historian. “Thanks to her perse-verance, 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, approach-ing where it stands today—approximately 95 percent. With extraordinary devotion to her patients, she was with them during child-birth. When she retired, the hallways of Joslin were flooded with thankful mothers and off-spring 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 dia-betes onset, duration, and presence of heart, kidney and eye complications.

Today, the Pregnancy Pro-gram 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 dia-betes or gestational diabetes. Their diabetes is monitored closely in concert with their obstetric team.

In pregnancy, the placenta makes hor-mones that increase the body’s resistance to insulin, causing the mother’s blood glucose to rise. This can cause preeclamp-sia, 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 nine-

month 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 follow-

ing generations in ways not based on parental

DNA, but possibly on factors such as poor

nutrition or reduced muscle mass. {

Thank you for 50 yearsM. 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.” {

L e a D i n g P a T h W a y s


Children, teens, young adults

The new normalServing 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.

1898Elliott 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.

1922After 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?”

1923When 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).

1931Dr. Joslin receives a $1 donation from a shoeshine boy with diabetes (p. 24).

1932Modeled 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

The Elliott P. Joslin Camp for Boys is founded in Charleton, Mass. Operated by a nonprofit organization, both camps are still active today.

1970sHome blood glucose monitoring, smaller insulin needles and disposable syringes are now available, making it easier to accept therapies requiring multiple insulin doses.

1970sJoslin 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.

1980s–90sJoslin introduces and expands usage of insulin pumps among pediatric patients. Today more than 60% receive insulin- pump therapy.

2002Ann 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.

2003Online discussion boards are started for teens and their families to learn more about living with diabetes.

2007Research 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.

2010Joslin begins the New Onset Program for children with type 1 diabetes whose condition at onset allows for outpatient care rather than hospitalization.

2012Joslin launches Young Adult Support Program, addressing specific challenges of the teen years and easing the transition to adult diabetes care.

9


Use CGM to best advantageJoslin 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 smartlyPediatric 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 wellPediatric 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.

Joslin’s pediatric program offers exceptional expertise to young patients of all ages, from infants to teenagers and into early adulthood. Family team-

work is vital, and Joslin’s family-centered approaches—validated by research find-ings—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 do-it-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. {

‘Grow, play and make noise’ P e D i a T r i cP a T h W a y s

Handprints of pediatric patients cover the clinic's ceiling


Preventingcomplications

Defying the oddsSignificant 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.

1931With 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. 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–70sJoslin physicians devise revolutionary surgical and medical approaches for saving feet and limbs damaged by diabetes, a success record unsurpassed anywhere in the world.

1983Joslin 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.

1985George King, M.D., who pioneers the use of cell-culture models to study diabetes complications, shows insulin is protective of blood vessels.

1989Dr. 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.

1991When 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.

1993The landmark Diabetes Control and Complications Trial (DCCT) confirms Dr. Joslin’s long-held belief that good blood glucose control helps prevent diabetes-related complications.

1994Dr. 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.

1995Joslin clinical researchers identify blood glucose levels that limit kidney disease.

2005Joslin formally launches the 50-Year Medalist Study to learn how people survive diabetes 50 years or longer with surprisingly few complications (see opposite page).

2008C. Ronald Kahn, M.D., identifies insulin resistance in the liver as a key factor in the cause of metabolic syndrome and associated atherosclerosis.

2009Edward 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.

2010Hillary 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.

2011Andrzej 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.

2012Amy 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.

10


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.

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. {

5 0 - y e a r M e D a L i s T s T u D y

Seeking protective factors

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. {

1931Joslin Life Expectancy

10-Year Medal

1948Joslin Quarter-Century

Victory Medal

1970Joslin

50-Year Medal

1995Joslin Victory Award

75-Year Medal

2013Joslin

80-Year Medal


Eye research and care

Vascular victoriesCalled 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.

1931Insulin 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.

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.

1966The 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.

1968Dr. 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.

1971Joslin 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.

1979With 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.

1993The landmark Diabetes Control and Complications Trial confirms that good blood glucose control can stave off diabetes-related complications, including blindness.

1994Lloyd 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.

1998Dr. 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.

2010Based 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.

2012Edward 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.

11


Carrying the torch

To 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

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. {

e y e 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. {


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 chapterJoslin’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.

Letter from a shoeshine boy


director Jeffrey Bright

writer & editor Christine Paul

Historical consultant Donald M. Barnett, M.D.

design Richard Chiarella, Innovative Resource Group

photography John Soares Stephanie M. McPherson

Joslin Legacy is produced by the Communications Department at Joslin Diabetes Center.

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

One Joslin Place, Boston, MA 02215 www.joslin.org (617) 309-2400

Computer-generated image of insulin molecule

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Joslin Legacy - Joslin Diabetes Center · | joslin legacy 1 ... concentrated effort to prevent, treat and cure diabetes. ... new “miracle drug.”