18 Children in Western pennsylvania and around the ... - Pitt Med

18 P I T T M E DChildren in Western Pennsylvania and aroundthe world benefited from the diabetes treatmentadvances that started here and spread. AllanDrash led much of that work. He’s shown here(right) in 1985 with colleagues Trevor Orchardand Eileen LaRocca.

f e a t u r et h e d o c w h o b u i l t a d i a b e t e st r e a t m e n t a n d r e s e a r c h c e n t e rw i t h o u t p e e r | b y C h u c k S t a r e s i n i c“We HadDr. Drash”© Pittsburg h Post-Gazette, All rig hts r e se rved. R e pri nted with pe rm ission. Photo by Harry Coug hanou r 1985.Aslight 6-year-old girl from Pittsburgh’s North Side becameill with a virus one day. Her sickness was not all thatunusual—she developed a fever and was vomiting. Butwhen she failed to bounce back after several days, her parents took herto the pediatrician, who said, “She has a virus,” and sent her home withinstructions to rest and wait it out.This was in the early 1970s. She may have had a run-of-the-millviral infection initially, but something else was happening now. Shelost weight. She urinated a lot, and she was always thirsty. The parentsbypassed their pediatrician and brought her straight to Children’sHospital of Pittsburgh. It seemed like they had been in the hospital onlymoments when someone said, “This looks like diabetes.”Those were scary words. Diabetes may be manageable, but much lesswas known about how to manage it back then. All the parents knew wasthat their child was no longer just sick; she had an incurable disease. Somechildren entered the hospital in her state, continued to deteriorate, anddied. Some came home less than whole. They were frail or had damagedminds. Others survived but lost something of their childhood.At Children’s, the physicians and nurses saw it a bit differently. Therewas an acute crisis to overcome in that the girl’s blood was becomingincreasingly acidic. This was life-threatening, but if she overcame it, thefamily could manage her disease.S P R I N G 2 0 1 0 19

Ketoacidosis, as the condition is called, isthe most common, acute, and serious complicationresulting from diabetes in childhood.The crisis often leads to the initial diagnosis.The problem begins, many experts believe,when the immune system reacts to a commonvirus in an uncommon way. Rather thanfighting off the virus, then ramping downthe attack, the immune system continues itsassault, attacking cells in the pancreas.Tucked into pearly clusters in the pancreascalled islets of Langerhans, these cells produceinsulin, a hormone that metabolizes glucoseto fuel the body. When the body experiencesa glucose shortage, it begins to metabolizefat instead, causing sudden weight loss anda buildup of acidic byproducts in the bloodcalled ketones. Uncontrolled, it can lead toswelling in the brain, kidney failure, death ofbowel tissue, and heart attack.Through happenstance, the girl’s familyhad arrived at what was arguably the best placein the world for a diabetic child to go. Whatis now Children’s Hospital of Pittsburgh ofUPMC and the University of Pittsburgh werebuilding a diabetes research center withoutpeer. Children in Western Pennsylvania benefitedfrom the treatment advances that startedhere and spread around the world.The physician who walked into the roomthat day and talked with the family abouttheir daughter’s diagnosis was the one mostresponsible for the bustling hive of diabetesrelatedresearch in Pittsburgh: Allan Drash,a pediatric endocrinologist and professor ofpediatrics in the University of PittsburghSchool of Medicine. He and others had createda multifaceted center that simultaneouslyadvanced the treatment of diabetic patientsand probed the underlying epidemiology—who gets the disease, and why?The girl in our story not only recoveredfrom her bout with ketoacidosis, but she alsowent on to become a nurse and a diabeteseducator. For decades afterward, she and herparents remembered the words of Dr. Drash.He told them the disease could be managed.“Diabetes will become a part of yourlife,” he said, “but do not give up on yourdreams for your child. She can achieve anythingshe puts her mind to.”Allan Drash was a Tennessee nativewho stayed close to home for college(Vanderbilt University), then went tomedical school at the University of Virginia,trained at Johns Hopkins Hospital, and lateraccepted a position with Children’s Hospitalof Pittsburgh. He was a pediatric endocrinologistwho set about perfecting a clinic totreat children suffering from diabetes.The year was 1966, and, compared to whatwe know now, physicians had an incompleteunderstanding of the disease. They knew thatmany people experienced adult-onset diabetesin their 40s or later. These people showedinsulin resistance, meaning their insulin didn’tprocess glucose as well as it should have. Otherpeople developed diabetes in childhood orearly adulthood. Both of these groups experiencedhyperglycemia—excess sugar in theblood. But it wasn’t clear whether there weremajor differences between the two types ofdiabetes aside from the age of onset.“Diabetes will become part of your life,” he said,“but do not give up on your dreams for your child.”In 1967, one year after arriving inPittsburgh, Drash published a study confirmingthat most children with diabetes were notinsulin resistant like most adults with diabetes.The children were insulin deficient. They hadno insulin, or they had not nearly enough.The study contributed to a new understandingthat there were two types of diabetes: Type1 usually came to light in childhood and wasmarked by a deficiency of insulin. Type 2 usuallyappeared in adulthood and was marked bythe body’s resistance to the insulin it produced.Drash’s motivation was to find the besttreatment for diabetic children. Aggressivetreatment with insulin injections eventuallybecame the unquestioned standard of care fortype 1—hence the moniker insulin-dependentdiabetes. Drash was instrumental in pushingfor federal funding of the Diabetes Controland Complication Trial, which eventuallygrew to 29 sites. It demonstrated that metaboliccontrol was critically important in thedevelopment and rate of progression of vascularcomplications in people with diabetes.And it showed that an aggressive regimen thatincluded multiple daily injections of insulinwas the most important element of treatment.He quietly fomented a revolution in endocrinologyat a time when pediatric endocrinologywas a rather neglected field. Atprofessional conferences, he and other endocrinologistswho treated children typically hada session or two devoted to their interests. Hiswork on diabetes illustrated his point thatchildren were not just smaller in size thanadult patients: Diabetes, like many otherendocrine disorders, was fundamentally differentin children than it was in adults. Drashlobbied for pediatric endocrinology to betaken more seriously. And, over the course ofhis career, it was.In Pittsburgh, Drash employed a uniqueteam approach to treating diabetes. Hebelieved in treating the family, not justthe child. He enlisted nutritionists, nurses,social workers, educators, and psychologists.Physicians in his clinic were just one part ofa team that strived to educate the family andmanage the disease with aggressive monitoringand intervention.With philanthropic help, Children’sHospital provided funding so that familieswho could not otherwise afford care couldreceive the same treatment.The epidemiology of diabetes intriguedDrash. There were hints that genetics playeda role—siblings and other relatives of diabeticchildren seemed to be at higher risk of developingthe disease. Because early diagnosis andintervention were important elements of successfultreatment, Drash believed that epidemiologywas a natural extension of the clinic.In the early 1970s, Drash and epidemiologistLewis Kuller developed a registry that aimedto include every child in Allegheny Countydiagnosed with type 1 diabetes.“Allan focused very much on developingan unusual, multidisciplinary clinic that gavequality care for children,” says Kuller, whois now a Distinguished Professor of PublicHealth at Pitt. “And that helped in developingthe registry and getting families andpatients into research programs. The researchprogram just blossomed dramatically.”Epidemiologists who trained in Pittsburghinclude Ronald LaPorte, a Pitt professor ofepidemiology who led the diabetes projectfor years, and Trevor Orchard, currently theinterim chair of epidemiology at Pitt.The diabetes epidemiology group inPittsburgh exported the model worldwide,with Drash as its principal ambassador. In1990, Drash calculated that he had averaged100 days of travel per year for the precedingeight years. “We were married 38 years,” saysDiane Drash. “There were no real holidays.20 P I T T M E D

We would travel for meetings, or when hewould lecture or give a keynote address at aconference.”She recalls her husband, who died onAugust 3, 2009, visiting clinics around theworld: “I loved to watch him interact withparents and children. His whole life was builtaround trying to help children with diabetesand to reassure parents.”His travel and years of professional dutiesled to one memorable argument with histhen-teenage daughter, one of two Drashchildren. A few days later, Drash wrote a long,thoughtful letter to his daughter about hisreasons for being dedicated to his professionand his love for her.He wrote, “There is nothing more importantthan to be consumed by a sense ofdedication and responsibility to a profession,a calling, that takes one out of one’s own selfand into the service of others. It is not the jobof medicine that is demanding, but that weare demanding of ourselves.”About his dreams for her, he wrote,“Despite what the U.S. Constitution says…Happiness should not be pursued. It is thebyproduct of a meaningful, contributing life.I hope for you such a life.”At Children’s Hospital of Pittsburgh,Drash trained a long line of stellarpediatric endocrinologists. DorothyBecker is a Pitt professor of pediatrics whonow occupies Drash’s former position as chiefof pediatric endocrinology and diabetes. Shealso is the director of the diabetes programat Children’s and is principal investigatoron a multicenter trial funded by the NIH todetermine whether a cow’s-milk infant formulacan keep children from later developingtype 2 diabetes. She “continues to carry forward[Drash’s] investigative prowess,” notesOrchard. Ingrid Libman is another Drashtrainee, an MD/PhD assistant professor ofpediatrics who works in prevention and treatmentof type 2 diabetes in children. SilvaArslanian, the Richard L. Day Professor ofPediatrics, is an internationally recognizedendocrinologist and authority on the longtermconsequences of type 2 diabetes andracial disparities in its prevalence.Pitt’s diabetes epidemiology project wasprobably the largest such project in the world,Kuller says. “In our international project, wehad 155 centers in 70 countries across theworld. For a while, we were publishing 35to 40 papers a year at a time when we wereprobably responsible for 20 to 30 percent ofthe world’s literature in that area.” To offerevidence, Kuller walks to a bookshelf acrossthe hall from his office. He pulls down a fewbound sets of scientific papers, each roughly asthick as the Pittsburgh telephone book.“This is [from] the early days,” he says,paging through the bibliography in the frontof one volume. “It’s almost all Drash. It’sDrash and epidemiology group. It was a broadproject, from the basic immunology all theway up to the global work.”Pitt’s reputation has attracted expertisethroughout the health sciences schools.Linda Siminerio—a diabetes educator, facultymember in the schools of medicine andnursing, and executive director of theUniversity of Pittsburgh Diabetes Institute—was the national spokesperson for WorldDiabetes Day in 2009.Andrew Stewart, Pitt professor of medicineand chief of the Division of Endocrinologyand Metabolism, left Yale University to jointhe Pitt faculty in 1997. Stewart’s lab hasidentified the genes and proteins involved inthe creation of new insulin-producing cells.Stewart is exploring the possibility that wemight stimulate the production of new cells inpatients with diabetes, restoring their abilityto manufacture insulin.In the mid-’80s, Drash and his colleaguesrecruited Massimo Trucco, an MD immunologistand geneticist who was prepared to takethe expertise in Pittsburgh and build on it tocreate a new understanding of the basic immunologyand genetics behind type 1 diabetes.Today, Pitt’s Trucco is the Hillman Professor ofPediatric Immunology, a professor of pathology,human genetics, and epidemiology, as wellas director of the Division of Immunogenetics.Simply put, Trucco is on the trail of a curefor diabetes. He has uncovered genes thatconfer susceptibility to type 1 diabetes anddescribed some of the molecular activities inthe immune system that cause the destructionof insulin-producing cells. Trucco and hiscolleagues—notably Nick Giannoukakis, anassociate professor of pathology and immunology—havedeveloped cell and microparticlevaccines that reverse or prevent type 1diabetes in mice. The group is wrapping up asafety trial of a vaccine in recently diagnosedchildren.‘‘D I A B E T E S I N V E S T M E N T SAllan had this phenomenal commitmentto taking care of the people,”says Kuller. “It wasn’t just screeningthese kids to do an interesting genetic study.He was actually saying, ‘Hey, what are wegoing to do about it?’”For much of four decades, until his deathlast year, Drash was the doctor leading the wayfor families in Pittsburgh with diabetic children.One former patient says it’s impossibleto overstate the significance of his words andactions on her family. Drash told her parentsnot to let their child be defined by a diagnosis:“We all know what that diagnosis means.It’s this overwhelming shadow of darkness.But we never had that. We had Dr. Drash.” nChildren’s Hospital is establishing the AllanDrash Diabetes Scholarship to further thecareers of pediatric diabetes trainees andperpetuate Dr. Drash’s work. To contributecontact Chip Eagle, 412-586-6317chip.eagle@chp.eduTo protect patient privacy, some details werechanged in this story.When he was 35 years old, Allan Drash received an offer to relocate fromJohns Hopkins University to Children’s Hospital of Pittsburgh and theUniversity of Pittsburgh. One of the attractions for Drash was that, atChildren’s, the diabetes clinic had long been a priority. A $1 million fundhad been established in 1937 by Emilie Renziehausen to support the care ofdiabetic children and honor the memory of her two brothers, one of whomhad diabetes. The interest from that fund has contributed to clinical care atChildren’s for more than 70 years. The fund allows for aggressive outreach tofamilies coping with diabetes, regardless of the family’s financial situation.Additional gifts from the Renziehausen family through the years have createdan additional trust fund at Children’s to support laboratory research and education.These deep roots have nourished an extraordinary breadth and depthof diabetes research at Pitt. —CSS P R I N G 2 0 1 0 21