732 Diabetes Care Volume 40, June 2017

Mark A. Atkinson1 and Mary Tyler Moore (1936–2017): 2 Concepcion R. Nierras Diabetes Educator and Advocate Diabetes Care 2017;40:732–735 | https://doi.org/10.2337/dci17-0015 PROFILES IN PROGRESS

Having a dream is what keeps you alive. Award for Best Actress in a Leading Role. Overcoming the challenges makes life Whether performing on television, in a worth living. film, or on a theater stage, Ms. Moore dMary Tyler Moore loved her craft and felt called to use her talents, time, and fame to help others. “Who can turn the world on with her smile?” So began the theme song for AN UNEXPECTED DIAGNOSIS the popular The Mary Tyler Moore Ms. Moore’s commitment to bringing Show, which aired on the CBS television about positive change for others was network from 1970 to 1977. With the manifest in her openness about dealing ’ passing of Mary Tyler Moore, the show s with life’s challenges, including her diag- star, on 25 January 2017, the diabetes nosis with diabetes. community lost an individual who for de- At the age of 33 years, during her time cades not only brought smiles to her au- on The Mary Tyler Moore Show,shewas diences, but also changed the world for diagnosed with type 1 diabetes (6). Later, people living with diabetes, researchers she described being initially incredulous, seeking its cure, and health care providers having never expected that something for those with the disease. like this could happen to her. It took her only a short time, however, to fully appre- A LIFE IN THE SPOTLIGHT ciate the seriousness of her diagnosis, and Born in Brooklyn, NY, in 1936, young Mary Mary Tyler Moore delivering testimony at a U.S. her response was to become vigilant moved with her family to Los Angeles, CA, Senate hearing for JDRF’s Children’s Congress, about managing the disease. Her public when she was 8 years old (1,2). There, she 2003. statements about type 1 diabetes human- developed a love of show business, and ized the condition and gave voice to the her early efforts as a dancer opened doors forward-thinking, fearless yet vulnera- thoughts and experiences of many others into the world of television. Many trib- ble producer at a local Minneapolis, living with the disease. Her acknowledg- utes published since her passing have MN, television news station who spoke ment of her diagnosis became their ac- highlighted Ms. Moore’s creativity and her mind but also fostered teamwork knowledgment. Her acceptance that success as a performer; her remarkable and a sense of camaraderie among her living with type 1 diabetes would be an talent encompassed dancing, acting, and quirky coworkers (4). For her dramatic all day, every day undertaking with no singing. From 1961 to 1966, she played role as Beth Jarrett in the acclaimed vacations helped them to accept their Laura Petrie, the wife, mother, and home- 1980 film Ordinary People, in which she own condition. Her courage in the face maker on The Dick Van Dyke Show (3). In convincingly conveyed a parent’sheart- of constant fear of long-term complica- the 1970s, on The Mary Tyler Moore breaking challenge of surviving a child tions lent courage to others facing the Show,shewasMaryRichards,themodern, (5), she was nominated for an Academy same fear.

1Department of Pathology, Immunology, and Laboratory Medicine, and Department of Pediatrics, University of Florida Diabetes Institute, Universityof Florida, Gainesville, FL 2Past Senior Director, International Partnerships and Cure Therapeutics, JDRF, New York, NY Corresponding author: Mark A. Atkinson, atkinson@ufl.edu. © 2017 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. care.diabetesjournals.org Atkinson and Nierras 733

A CHAMPION OF EDUCATION parents of children with type 1 diabetes for increased funding for the National In- Ms. Moore’s openness about her life with (known then as the Juvenile Diabetes stitutes of Health (NIH) and, in particular, diabetes, as well as her struggles to con- Foundation and now simply as JDRF). By for special funding for type 1 diabetes re- trol her blood glucose, did not just make 1984, she had become its International search. In 1999, JDRF launched its first her a role model for people with the dis- Chairman (7). Ms. Moore knew that being Children’s Congress, with Ms. Moore de- ease; she was also tireless in encouraging active in this position would mean inter- lighting in being the most senior “child everyone to learn more about the disor- acting with young people, and she rel- delegate” participating. She would later der. She championed the understanding ished the opportunity. She was not only explain that the idea for the Children’s that individuals with type 1 diabetes do one of them, but also someone whose life Congress came from another child dele- not look any different from others and proved that a person with type 1 diabetes gate, Tommy Solo, who, at the age of that they hold a unique position from could achieve anything. Although this 9 years, asked, “Why should adults go to which to educate friends, neighbors, message may seem obvious today, one Congress to ask for funding? Kids with di- schoolmates, coworkers, and colleagues must recall that, at the time of her diag- abetes should go and tell them what it’s that type 1 diabetes is not “just” adisor- nosis, that was not the case. Back then, like, because we know better than any- der in which one cannot eat sweets and people diagnosed with type 1 diabetes one. Maybe then they’ll hurry up and help for which the major challenge involves were widely considered to be bound for us find a cure.” Ms. Moore encouraged overcoming a fear of injections. To be unacceptable morbidity, early mortality, participants in the Children’s Congress very clear, Ms. Moore knew that people and a lifestyle that in many ways was pre- to ask members of Congress to, as the would say, “Mary Tyler Moore has diabe- scribed to be devoid of life. Simply put, campaign’s slogan said, “Promise to Re- tes.” Nonetheless, she accepted the risk Ms. Moore helped to change that view. member Me” when appropriating funds that her transparency about living with for type 1 diabetes research. type 1 diabetes might negatively affect A TIRELESS ADVOCATE In response to these and other persis- her career and chose to act on the bold Ms. Moore’simpactonpeoplewith tent charm offensives and advocacy ini- notion that her fame could help raise type 1 diabetes did not end theredfar tiatives, from fiscal year 1998 through awareness for the greater benefitofev- from it. Beginning in 1995, she led a group 2017, Congress appropriated a cumula- eryone with the disease. of government relations volunteers, indi- tive total of $2.46 billion in special fund- In the early 1980s, she became in- viduals with diabetes, and their family ing for type 1 diabetes research, with volved with an organization founded by members to petition the U.S. Congress an additional equal amount to support

Ms. Moore at a press conference in the U.S. Capitol Building in Washington, DC, to help launch the inaugural Fall 2006 issue of the magazine NIH Medline Plus, of which she was featured on the cover. 734 Profiles in Progress Diabetes Care Volume 40, June 2017

diabetes and education programs for Na- being associated with type 1 diabetes (8). detailed studies of the human pancreas tive Americans, who are disproportion- The pathways controlled by these genes and immune system in those with or at ately affected by type 2 diabetes. The are being studied for how they contribute risk for the disease (13). to the development of type 1 diabetes, so-called Special Diabetes Program (SDP) b how environmental factors may interact Example 3: -Cell Replacement funding to the NIH augments regularly In 2005, the NIH Immune Tolerance Net- with them to affect disease development, appropriated funds that the U.S. Depart- work completed the first multicenter clini- and how they may be related to other ment of Health and Human Services re- cal trial demonstrating that transplantation autoimmune disorders in addition to ceives for diabetes research. The SDP has of pancreatic islets from a deceased donor type 1 diabetes. fostered unique collaborations among can restore glycemic control in individuals the NIH, the Centers for Disease Control Example 2: Epidemiology, Disease with type 1 diabetes (14). The Clinical Islet and Prevention, and the broader research Prediction, and Pathogenesis Transplantation Consortium has con- community to accelerate the pace of Today, data from both TEDDY (The Environ- ducted clinical trials with associated progress in type 1 diabetes research. mental Determinants of Diabetes in the mechanistic studies to test new strategies ’ Thanks largely to Ms. Moore s leadership, Young study) (9) and Type 1 Diabetes for improving islet transplantation and to the diabetes research community has TrialNet Pathway to Prevention Study (10) facilitate the transition of islet transplanta- fi bene ted greatly from the opportunities have led to improved disease risk classifi- tion into clinical practice (15). Today, new made possible by the SDP, as illustrated cations,leadinginturntoarecommenda- methods for large-scale laboratory pro- in a few examples below. tion for a new type 1 diabetes staging duction of b-cells, including from stem classification (11) for at-risk individuals cells, are being discovered, and re- A LEGACY OF RESEARCH that provides a framework for research searchers are investigating strategies to Example 1: Genetic Discovery into and development of preventive ther- protect these cells from autoimmune at- In 2003, only three genes were known apies. Clinical trials are ongoing in which tack once they are implanted into a to be associated with type 1 diabetes. immune therapies are being tested for person with type 1 diabetes. Other ap- Through research supported by SDP funds their ability to help people with newly di- proaches for regenerating b-cells are be- and other sources, more than 50 genes or agnosed diabetes (12). Researchers also ing studied, and innovative technologies gene regions have now been identified as now have access to resources that enable for testing therapies are being developed.

Ms. Moore testifies at a U.S. Senate hearing for JDRF’s Children’s Congress 2005. The panel to her left includes Douglas Wick (producer, Red Wagon Entertainment, Culver City, CA), Gary Hall, Jr. (Olympic gold medal swimmer, Miami, FL), and Allen M. Spiegel, MD (director of the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases), each of whom also testified about the need for increased type 1 diabetes research funding. Photo credit: Larry Lettera, Camera One. care.diabetesjournals.org Atkinson and Nierras 735

Example 4: Complications Prevention she is well worthy of such tributes. How- 6. Moore MT. Growing Up Again: Life, Loves, and and Treatment ever, her impact on research progress in Oh Yeah, Diabetes. New York, St. Martin’s Press, The SDP also enabled the establishment diabetes should be given equal praise. In- 2009 7. JDRF. Celebrate Mary Tyler Moore [Internet]. of large-scale collaborative research deed, because of Ms. Moore, individuals Available from http://www.jdrf.org/blog/2017/ groups that seek to better understand with type 1 diabetes are able to live 01/25/celebrate-mary-tyler-moore. Accessed and prevent the complications of diabe- better lives with ever-increasing hopeda 18 March 2017 tes. The Epidemiology of Diabetes Inter- priceless gift. In her own unique way, 8. Onengut-Gumuscu S, Chen WM, Burren O, ventions and Complications (EDIC) study Ms. Moore summarized her view of deal- et al.; Type 1 Diabetes Genetics Consortium. “ ’ Fine mapping of type 1 diabetes susceptibility is an ongoing follow-up to the landmark ing with diabetes, often saying, You can t loci and evidence for colocalization of causal var- Diabetes Control and Complications Trial be brave if you’ve only had wonderful iants with lymphoid gene enhancers. Nat Genet (DCCT) (16) that has shown that intensive things happen to you.” 2015;47:381–386 blood glucose control can reduce the risk So, thank you, Mary Tyler Moore, for 9. Lee H-S, Burkhardt BR, McLeod W, et al.; of cardiovascular complications of type 1 your bravery, your leadership, and your TEDDY study group. Biomarker discovery study design for type 1 diabetes in The Environmental diabetes. The Diabetic Retinopathy Clin- ability to make us smile. We will be smil- Determinants of Diabetes in the Young (TEDDY) ical Research Network (17) demon- ing as we move forward to fulfill your study. Diabetes Metab Res Rev 2014;30:424– strated that anti–vascular endothelial passion to find a cure for diabetes and 434 growth factor (VEGF) therapy is a more its complications and realize your vision 10. Xu P, Krischer JP; Type 1 Diabetes TrialNet fi effective treatment for diabetic macular of a world without type 1 diabetes. Study Group. Prognostic classi cation factors as- sociated with development of multiple autoanti- edema than laser treatment alone. This bodies, dysglycemia, and type 1 diabetes: a result dramatically changed clinical recursive partitioning analysis. Diabetes Care practice, and anti-VEGF therapy has Acknowledgments. The authors thank Dr. S. 2016;39:1036–1044 ’ quickly become a standard treatment Robert Levine (Ms. Moore s husband of 33 years), 11. Insel RA, Dunne JL, Atkinson MA, et al. Staging Dr. Amanda Posgai of the University of Florida, presymptomatic type 1 diabetes: a scientific for individuals with vision loss from di- and Ms. Mara Buxbaum of ID PR (Ms. Moore’s abetic macular edema. Additional trials statement of JDRF, the Endocrine Society, and publicist) for their editorial and literary contribu- the American Diabetes Association. Diabetes demonstrated that three different anti- tions to this work. Care 2015;38:1964–1974 VEGF therapies are equally effective in Duality of Interest. This article was prepared by 12. Chatenoud L, Warncke K, Ziegler AG. Clinical people with mild vision loss (18), a result Concepcion R. Nierras in her personal capacity. immunologic interventions for the treatment of The opinions expressed in this article are those type 1 diabetes. Cold Spring Harb Perspect Med that will certainly inform personalized fl of the authors and do not re ect the views of 2012;2:a007716 treatment. the NIH, the Department of Health and Human 13. Kaddis JS, Pugliese A, Atkinson MA. A run on Services, or the U.S. government. The progress enabled by this long-term the biobank: what have we learned about type 1 investment in diabetes research under- diabetes from the nPOD tissue repository? scores the power of partnership among References Curr Opin Endocrinol Diabetes Obes 2015;22: government, foundations, scientists, and 1. Finn ML. Mary Tyler Moore.NewYork,Chelsea 290–295 people with diabetesdan alliance that House Publishers, 1996 14. Shapiro AMJ, Ricordi C, Hering BJ, et al. In- ternational trial of the Edmonton protocol for islet counted Ms. Moore among its most ef- 2. CNN. Mary Tyler Moore Fast Facts [Internet]. Available from http://www.cnn.com/2013/07/ transplantation. N Engl J Med 2006;355:1318– fective leaders. The cumulative effect of 11/us/mary-tyler-moore-fast-facts. Accessed 1330 all of these research efforts has been 18 March 2017 15. Jamiolkowski RM, Guo LY, Li YR, Shaffer SM, that long-term survival of individuals 3. Moore MT. After All. New York, Putnam Pub- Naji A. Islet transplantation in type I diabetes mel- – with type 1 diabetes has dramatically im- lishing Group, 1995 litus. Yale J Biol Med 2012;85:37 43 4. Academy of Television Arts and Sciences. Mary 16. Nathan DM; DCCT/EDIC Research Group. proved, and a foundation of knowledge The Diabetes Control and Complications Trial/ Tyler Moore [Internet]. Available from http:// has been generated that offers more op- Epidemiology of Diabetes Interventions and Com- www.emmys.com/bios/mary-tyler-moore. Ac- portunities for research advancement plications study at 30 years: overview. Diabetes cessed 21 March 2017 Care 2014;37:9–16 and greater promise for the future. 5. Kroll K. But seriously: 18 comedians who went 17. Baker CW, Jiang Y, Stone T. Recent advance- A GRATEFUL COMMUNITY dramatic for Oscar [Internet]. Rolling Stone ments in diabetic retinopathy treatment from the 13 February 2015. Available from http://www Remembrances of Ms. Moore since her Diabetic Retinopathy Clinical Research Network. .rollingstone.com/movies/lists/18-comedians- Curr Opin Ophthalmol 2016;27:210–216 recent passing have and will continue to who-went-serious-for-oscar-20150213/mary- 18. Dhoot DS, Avery RL. Vascular endothelial include accolades for her work as a per- tyler-moore-ordinary-people-1980-20150212. growth factor inhibitors for diabetic retinopathy. former and an icon for social progress; Accessed 18 March 2017 Curr Diab Rep 2016;16:122