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Children’s Di abetes Foundation at Denver Summer 1997 Scientific Advisory Board: Richard S. Abrams, M.D. Associate Clinical Professor of Medicine, University of Colorado School of Medicine; Rose Medical Center, Denver Jules Amer, M.D. Clinical Professor of Pediatrics, University of Colorado School of Medicine; Partner, Children’s Medical Center, Denver M. Douglas Jones, Jr., M.D. Professor and Chairman, Department of Pediatrics, University of Colorado School of Medicine; Pediatrician in Chief, The Children’s Hospital, Denver Brian Kotzin, M.D. Professor of Immunology, University of Colorado School of Medicine; National Jewish Center for Immunology and Respiratory Medicine, Denver Ake Lernmark, M.D., Ph.D. Robert H. William Professor, Department of Medicine, University of Washington School of Medicine, Seattle Ali Naji, M.D., Ph.D. J. William White Professor of Surgery, Hospital of University of Pennsylvania, Philadelphia Gerald Nepom, M.D., Ph.D. Scientific Director and Director of Immunology and Diabetes Research Programs, Virginia Mason Research Center, Seattle Julio Santiago, M.D. Professor of Medicine and Pediatrics, Washington University, St. Louis, Missouri; St. Louis Children’s Hospital Advisory Board: Mrs. Alan Angelich Mr. and Mrs. Rand V. Araskog Mrs. John Aylsworth Mr. Michael Bolton Mrs. Joseph Broughton Mrs. Franklin L. Burns Mr. Michael Caine The Honorable Ben Nighthorse Campbell, U. S Senate, Colorado Ms. Natalie Cole Mr. Phil Collins Mr. Lodwrick M. Cook Mrs. John Cowee Mr. and Mrs. Robert A. Daly Mrs. Thomas P. D’Amico Mr. Tony Danza Mr. Neil Diamond Mr. Placido Domingo Miss Donna Douglas President and Mrs. Gerald R. Ford Mrs. Joseph Franzgrote Mr. David Foster Mr. Kenny G Mr. David Geffen Mr. Merv Griffin Mr. Bob Hope Ms. Whitney Houston Mrs. Walter Imhoff Mr. Michael Jackson Mr. and Mrs. John H. Johnson Mr. Quincy Jones Mrs. Michael Jultak Dr. Henry A. Kissinger Mrs. Robert Knisely Mr. Howard W. Koch Kevin J. Lafferty, Ph.D. The Honorable and Mrs. Richard D. Lamm Ms. Sherry Lansing Mr. Jay Leno Mr. Paul Marciano Mr. Walter Matthau Miss Dina Merrill Mr. Myron M. Miller Mr. Roger Moore Evelyn and Mo Ostin Mr. Ronald O. Perelman The Honorable Federico Peña Mr. Sidney Poitier President and Mrs. Ronald Reagan Mr. Lionel Richie Mrs. Sheldon Roger Mr. Kenny Rogers The Honorable Roy Romer Governor, State of Colorado Mrs. Roy Romer Miss Diana Ross Mr. Lewis Rudin Mr. George Schlatter Ms. Maria Shriver and Mr. Arnold Schwarzenegger Alan and Sandra Silvestri Mr. Steven Spielberg and Ms. Kate Capshaw Mrs. Robert J. Stewart Mrs. Robert Tucker Mrs. Thomas N. Tucker Miss Joan van Ark Mrs. Peter Weingarten The Honorable Wellington E. Webb Mayor, City of Denver Mrs. Luanne Wells Ms. Barbera Thornhill and Mr. Gary L. Wilson The Honorable Pete Wilson Governor, State of California Mr. Henry Winkler Mr. Stevie Wonder Executive Board: Mrs. Marvin Davis Chairperson Richard S. Abrams, M.D. Jules Amer, M.D. Miss Amy Davis Steven Farber, Esq. The Honorable Sherman G. Finesilver Mr. Gerald S. Gray Charles Halgrimson, M.D. Associate Dean, University of Colorado School of Medicine Mrs. A. Barry Hirschfeld M. Douglas Jones, Jr., M.D. Mrs. Dana Davis Lipman Mrs. Nancy Davis Rickel Ex-officio Member: George S. Eisenbarth, M.D., Ph.D. Executive Director, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center; Professor of Pediatrics and Medicine, University of Colorado School of Medicine Continued on page 2 THE RESEARCH PROGRAM — John Hutton, Ph.D., Research Director 1997 RESEARCH EDITION T he Barbara Davis Center has the status of an internationally renowned scientific research organization with particular expertise in the area of immunology of diabetes. Many fellows who have trained with Center staff now hold leading clinical and search posts all over the world, Photo: ©1997 Martin Crabb
Transcript

Children’s Diabetes Foundation at Denver Summer 1997

Scientific Advisory Board:Richard S. Abrams, M.D.Associate Clinical Professor of Medicine,University of Colorado School ofMedicine; Rose Medical Center, DenverJules Amer, M.D.Clinical Professor of Pediatrics,University of Colorado School ofMedicine; Partner, Children’s MedicalCenter, DenverM. Douglas Jones, Jr., M.D.Professor and Chairman, Department ofPediatrics, University of Colorado Schoolof Medicine; Pediatrician in Chief,The Children’s Hospital, DenverBrian Kotzin, M.D.Professor of Immunology,University of Colorado School ofMedicine; National Jewish Center forImmunology and Respiratory Medicine,DenverAke Lernmark, M.D., Ph.D.Robert H. William Professor, Departmentof Medicine, University of WashingtonSchool of Medicine, SeattleAli Naji, M.D., Ph.D.J. William White Professor of Surgery,Hospital of University of Pennsylvania,PhiladelphiaGerald Nepom, M.D., Ph.D.Scientific Director and Director ofImmunology and Diabetes ResearchPrograms, Virginia Mason ResearchCenter, SeattleJulio Santiago, M.D.Professor of Medicine and Pediatrics,Washington University, St. Louis,Missouri; St. Louis Children’s Hospital

Advisory Board:Mrs. Alan AngelichMr. and Mrs. Rand V. AraskogMrs. John AylsworthMr. Michael BoltonMrs. Joseph BroughtonMrs. Franklin L. BurnsMr. Michael CaineThe Honorable Ben NighthorseCampbell, U. S Senate, Colorado

Ms. Natalie ColeMr. Phil CollinsMr. Lodwrick M. CookMrs. John CoweeMr. and Mrs. Robert A. DalyMrs. Thomas P. D’AmicoMr. Tony DanzaMr. Neil DiamondMr. Placido DomingoMiss Donna DouglasPresident and Mrs. Gerald R. FordMrs. Joseph FranzgroteMr. David FosterMr. Kenny GMr. David GeffenMr. Merv GriffinMr. Bob HopeMs. Whitney HoustonMrs. Walter ImhoffMr. Michael JacksonMr. and Mrs. John H. JohnsonMr. Quincy JonesMrs. Michael JultakDr. Henry A. KissingerMrs. Robert KniselyMr. Howard W. KochKevin J. Lafferty, Ph.D.The Honorable and Mrs.Richard D. Lamm

Ms. Sherry LansingMr. Jay LenoMr. Paul MarcianoMr. Walter MatthauMiss Dina MerrillMr. Myron M. MillerMr. Roger MooreEvelyn and Mo OstinMr. Ronald O. PerelmanThe Honorable Federico PeñaMr. Sidney PoitierPresident and Mrs. Ronald ReaganMr. Lionel RichieMrs. Sheldon RogerMr. Kenny RogersThe Honorable Roy RomerGovernor, State of Colorado

Mrs. Roy RomerMiss Diana RossMr. Lewis RudinMr. George SchlatterMs. Maria Shriver andMr. Arnold Schwarzenegger

Alan and Sandra SilvestriMr. Steven Spielberg andMs. Kate Capshaw

Mrs. Robert J. StewartMrs. Robert TuckerMrs. Thomas N. TuckerMiss Joan van ArkMrs. Peter WeingartenThe Honorable Wellington E. WebbMayor, City of Denver

Mrs. Luanne WellsMs. Barbera Thornhilland Mr. Gary L. Wilson

The Honorable Pete WilsonGovernor, State of California

Mr. Henry WinklerMr. Stevie Wonder

Executive Board:Mrs. Marvin DavisChairpersonRichard S. Abrams, M.D.Jules Amer, M.D.Miss Amy DavisSteven Farber, Esq.The Honorable Sherman G.Finesilver

Mr. Gerald S. GrayCharles Halgrimson, M.D.Associate Dean, University ofColorado School of MedicineMrs. A. Barry HirschfeldM. Douglas Jones, Jr., M.D.Mrs. Dana Davis LipmanMrs. Nancy Davis RickelEx-officio Member:George S. Eisenbarth, M.D., Ph.D.Executive Director, Barbara DavisCenter for Childhood Diabetes,University of Colorado HealthSciences Center; Professor ofPediatrics and Medicine, Universityof Colorado School of Medicine Continued on page 2

THE RESEARCH PROGRAM— John Hutton, Ph.D., Research Director

1997 RESEARCH EDITION

The Barbara Davis Center hasthe status of an internationallyrenowned scientific research

organization with particular expertisein the area of immunology of diabetes.Many fellows who have trained withCenter staff now hold leading clinicaland search posts all over the world,

Photo:©1997

MartinCrabb

including Australia (PeterColman, Charles Verge), theUnited Kingdom (KevinDocherty), Israel (Pnina Vardi),Germany (Anette Ziegler), andJapan (Hiroshi Ikegami). Theseformer fellows continue theirassociation through collabora-tive interdisciplinary researchprograms and have provided asteady flow of new post-doctoralfellows to the Center. Thesealumni have also created uniqueopportunities for research, asexemplified by a study of dia-betes susceptibility genes in alarge Bedouin Arab family inIsrael. The Center also trainsgraduate students within theUniversity of Colorado in thedepartments of Pediatrics,Endocrinology, Immunology andCell and Structural Biology.

The susceptibility to developtype I diabetes is strongly herita-ble and is controlled by a numberof genes, the majority of whichhave not been identified. Studiesare currently concentrating onfour groups: identical twins ofpatients with type I diabetes, apopulation-based Coloradocohort of young, at-risk individu-als, a family with a geneticdefect that alters the productionof insulin from proinsulin, andother unique families with multi-ple generations affected by typeI diabetes. Investigations hereaim to locate the genetic muta-tions that account for the dis-ease association which will ulti-

mately contribute to our abilityto identify at-risk individuals.

The onset of type I diabetes ispreceded by a long period with-out symptoms when progressiveautoimmune destruction of thepancreatic B-cell occurs. Newautoantibody tests developed atthe Center are helping to deter-mine who is susceptible to thedisease so that therapy might beinstituted before the diseasedevelops. This has set the stagefor trials for the prevention ofthe disease, and a series ofstudies evaluating variousmodes of insulin administrationis being conducted on 60,000people as part of the DPT-1National Diabetes PreventionTrial. The Center has recruiteda large proportion of the individ-uals entering the trial and per-forms key genetic and autoanti-body assays for it.

The Center remains at the fore-front of research aimed at iden-tifying the immune cells (T lym-phocytes) responsible for thepathogenesis of the disease.The major thrust of this workcomes from investigations withthe NOD (non-obese diabetic)mouse, an experimental animalwhich serves as an excellentmodel of the disease in humans.The nature of the T cells andtheir molecular targets arebeing identified in order todevelop new strategies for aneffective vaccine against the dis-ease which will hopefully trans-

late into clinical trials in thenear future.

The treatment of type I diabetesby transplantation from cadaver-ic donors is a practical proce-dure, though at the moment it isusually restricted to individualswho need a kidney because oflife-threatening diabetic kidneydisease. For young patients, themedical problems introduced byimmunosuppressive drugs out-weigh the benefits that would begained. A major goal of thework of the Center’s TransplantImmunobiology Division is theachievement of islet transplan-tation using minimal recipientimmunosuppression. This isnow feasible in non-diabeticmice and even in the autoimmuneNOD mouse by a number ofnovel strategies. In conjunctionwith the Department of Surgeryat the University of Colorado, weaim to translate this knowledgeinto clinical practice.

Successful islet transplantationrequires an abundant supply ofislet tissue from a source otherthan human cadavers, but whatsource? Graft tissue from ani-mals whose organs have beengenetically manipulated to makethem acceptable for transplanta-tion into the human body is onepotential avenue. Another pos-sibility is to genetically engineercultured insulin producing cellsfor implantation. A third is torecreate in the adult the normalprocess whereby the islets aregenerated in fetal life. Each ofthese approaches is being inves-tigated by Center personnel incollaboration with Universitybio-engineering groups anddevelopmental biologists. Thegroup shares the belief thatsuch interdisciplinary researchwill achieve an effective treat-ment for type I diabetes that issafe and available to all.

Research

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Continued from cover page

George S. Eisenbarth, M.D.,Ph.D.,Executive Director

H. Peter Chase, M.D., Clinical Director

Photos:©1997

MartinCrabb

RESEARCH UPDATES:BDC LABORATORIES

George S. Eisenbarth,M.D., Ph.D.Executive DirectorOne ultimate goal for the pre-vention of childhood diabetes isthe development of immunologicvaccines which have the poten-tial with a single administrationto prevent the autoimmunitywhich leads to diabetes. Duringthe past year, vaccine trials indiabetes prone mice and clinicalgenetic and immunologic studieshave advanced to a stage wherewe can now design initial vacci-nation trials. In particular, it isnow apparent that as many asone in two relatives of patientswith type I diabetes, whoexpress high risk genes on chro-mosome 6, will develop anti-islet autoimmunity by two yearsof age. Often such anti-isletautoantibodies appear in thefirst year of life. Expression of acombination of more than one ofthese antibodies indicates a riskof diabetes of more than 90%.Such high risk children are mostlikely to benefit from future vac-cination trials.

In a unique Bedouin Arab familyfrom Israel with 18 memberswith type I diabetes, we have (incollaboration with Dr. PninaVardi of Israel) identified aregion on chromosome 10which, in concert with the abovegenes on chromosome 6, gives arisk of diabetes of almost 30%.Members of this family haveother genetic autoimmune dis-eases, including celiac diseaseand thyroid autoimmunity.

Approximately one in ten chil-dren and young adults with dia-betes have the intestinal disor-der celiac disease, or the adren-al disease Addison’s disease.Both of these disorders are often

not diagnosed prior to perma-nent harm and both are relative-ly easy to treat. We currentlyscreen all of our patients forautoantibodies predicting thesediseases. (See the BDC Webpage - http://www.uchsc.edu/misc/diabetes/bdc.html)

Given the appearance of anti-islet autoantibodies in the firstyears of life, the search isunderway to identify therapiesto prevent diabetes. We carriedout pilot studies and are nowcontributing to the large nation-al DPT-1 trial for diabetes pre-vention which is studying lowdose subcutaneous and oralinsulin. In animal models, asmall piece of the insulin mole-cule (amino acids 9 to 23 of theB chain) can be used as a vac-cine to prevent diabetes. Thewhite blood cells which recog-nize this piece of insulin aredirected to islets (see Wegmann,et al) and these T cells areunusual in sharing in common asegment of their T cell receptor.

To develop trials of diabetes pre-vention in man by immunologicvaccination will require a stagedapproach. Initial studies will bein patients who have just devel-oped diabetes and for whom thegoal will be to prevent furtherdestruction of the cells whichproduce insulin. Such trials willbe followed by prevention trialsfor relatives with high riskautoantibodies, and these trialswill be followed by trials in therelatives with high genetic riskwho do not yet express antibod-ies. These are the childrendescribed in the first paragraphwith a one in two risk of activat-ing autoimmunity early in life.Finally, if the vaccines prove safeand effective, it may be possibleto “simply” vaccinate large pop-ulations to prevent diabetes.

John C. Hutton, Ph.D.Research DirectorThe area of pancreatic islet mol-ecular and cellular biology hasseen some remarkable develop-ments in the past two years withthe discovery of genes which arecritical to the growth and differ-entiation of the islet.Manipulation of these genesholds promise in the future forthe regeneration of islets from adiseased pancreas or the pro-duction of insulin by cells otherthan those derived from the pan-creas. One of our collaboratorsat the University of Coloradohas, for example, identifiedNeuroD, a gene transcriptionfactor which when deletedresults in diabetes due to a fail-ure of fetal insulin-producingcells to form islets. We haveidentified another genetic defectassociated with diabetes in theenzyme PC1 which is responsi-ble for the conversion of proin-sulin to insulin. These resultscame from a detailed analysis ofa single individual in whom ges-tational diabetes was accompa-nied by a reproductive disorderand childhood diabetes.

Our ongoing search for newdiagnostic markers for preclini-cal type I diabetes has recentlyrevealed four new candidateautoantigens to which autoanti-bodies are present in new onsetpatients. These proteins appearto be components of the insulinsecretory granule membrane.Future investigations are aimedat molecular characterizationsof these autoantigens, refine-ment of the assays for measur-ing autoantibodies to them inpatients and evaluation of theirimportance to the pathogenesisof diabetes using the NODmouse model.

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Ron Gill, Ph.D.Nature of islet allograft immuni-ty and tolerance: These studiesdeal with the mechanisms bywhich transplanted islets aredestroyed by one set of immunesystem cells (CD8 T cells) andthe role of another set (CD4 Tcells) in facilitating the destruc-tion. In parallel, a majoremphasis is on the study of theinduction of tolerance to trans-planted islets. The hypothesisbeing explored is that toleranceto islet transplants is controlledby regulatory molecules(cytokines) produced by immunecells.

Nature of islet xenograftingimmunity: This area of researchfocuses on the nature of T cellimmunity to islets transplantedfrom other species (xenografts)with particular emphasis oncomparing this process with theresponse to islets from the samespecies (allografts). These stud-ies have indicated that xenograftand allograft immunity are quitedifferent processes in that allo-graft responses appear todepend particularly on CD8 Tcells, whereas the xenograftresponse is more dependent onCD4 T cells. One implication ofthis research is that it couldultimately enable us to useislets from other species as atreatment for human diabetesand thus solve the problem offinding adequate numbers ofislets to treat all patients withthis disease.

Nature of islet damage inautoimmune diabetes: Thesestudies address the mechanismof islet damage initiated byautoimmune T cells derived fromnon-obese diabetic (NOD) mice.In collaboration with DaleWegmann, Ph.D., the mechanismof islet damage triggered by Tcells that react against insulin isbeing examined. Such cells

make up a large proportion ofthe T cells found in the pancre-atic islets of NOD mice and cantrigger islet destruction regard-less of the donor source of theislets. This in turn suggeststhat the mechanism of damagein this system appears to bevery similar to the type of dam-age proposed for islet xenograftdestruction. We will continue toexamine the mechanisms bywhich autoimmune T cells actu-ally recognize and destroy islettransplants.

Anthony Hayward,M.D., Ph.D.Work in this laboratory hasrecently focused on the conse-quences to non-immune cells ofCD40-CD40L interactions. Weare testing the hypotheses thatislet cell destruction is mediatedthrough CD40 and that immunityto certain intracellularpathogens (CMV and cryp-tosporidia) is similarly mediat-ed. These studies use mice withmutated genes for CD40, CD40Land Bax and have required thedevelopment of new collabora-tions with Drs. Flavell,Korsmeyer and Kikutani. Recentprogress includes the findingthat CD40L knockout mice donot eradicate cryptosporidiafrom their biliary tree. We havean in vitro model system usingHepG2 cells, which undergoapoptosis when their surfaceCD40 is ligated, while proteinsynthesis (specifically, Bcl-2 andBcl-x) is inhibited.

One extension of these findingshas involved apoptosis in isletcells triggered by CD40 ligation.Protein synthesis, and againBcl-2 and Bcl-x, can protect theislet cell lines from CD40L-trig-gered apoptosis. Our long-termaim will be to see if apoptosis-deficient islets can survive inNOD mice. To this end, we tried

to breed Bax knockouts for Dr.Gill to transplant their isletsinto NOD recipients.

The lab is also pursuing theinduction of transplantation tol-erance in human fetuses byinjection of bone marrow stemcells. The diseases selected fortreatment are homozygous tha-lassemia syndromes (a and b)and lysosomal storage disor-ders. The end point for study isthe development of chimerismand/or abolition of conventionalCMI responses such as alloanti-gen-specific T cell proliferationand cytotoxicity. Additionalstudies to understand when thehuman T cell repertoire diversi-fies are in progress, using PCRto identify TCR messages inhuman fetal lymphocytes.

Studies are also in progress onimmune responses to infectiousorganisms, specifically respira-tory syncytial virus, varicellazoster virus and BCG. The lat-ter is in the context of a clinicaltrial to delay progression of isletcell destruction in new onsettype I diabetics.

Kathryn Haskins, Ph.D.The major thrust of our researchcontinues to be directed towardthe understanding of mecha-nisms of pathogenesis and regu-lation of autoimmune diabetesin the NOD mouse. Our toolsfor this research are a panel ofislet-specific diabetogenic T cellclones and several NOD strainvariations, including the dia-betes-resistant NOD strain, dia-betes-resistant NOD congenics,the NOD-scid, and a TCR trans-genic mouse on the NOD back-ground. One important projectis to isolate and identify thebeta cell antigen(s) for the path-ogenic T cell clones we haveproduced. A second project isthe comprehensive analysis ofrequirements for disease induc-

Research

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tion by T cell clones and how toinhibit this process. A third pro-ject is to investigate regulatorymechanisms through compara-tive analysis of cytokine produc-tion, costimulatory moleculefunction, and antigen presenta-tion in the diabetes-prone NODand related diabetes-resistantstrains.

Our major achievements duringthe past year include (1) demon-stration of an antigen-presentingcell functional defect in the NODand localizing this deficiency tosplenic macrophages; (2) deter-mining differences in cytokineprofiles between NOD mice anddiabetes-resistant strains; and(3) isolation of islet-reactivelines and clones with a Th2 phe-notype as shown by in vitrocytokine production. Our direc-tions in the coming year will beto further characterize the regu-latory defects in antigen presen-tation and cytokine productionin NOD mice and to investigatethe in vivo activity of the Th2clones. We are also endeavoringthrough a collaborative effort toproduce a second TCR trans-genic mouse and hope to begincharacterization of this animal.

Dale Wegmann, Ph.D.It is now clear that humaninsulin dependent diabetes mel-litus (IDDM) is the result of anautoimmune disorder in which aparticular type of white bloodcell, a T lymphocyte or T cell,attacks and destroys the insulinproducing beta cells of the pan-creas. There is also an inbredmouse strain, the nonobese dia-betic (NOD) mouse, that devel-ops insulin dependent diabetesas a result of T cell attack onbeta cells. Our laboratory hasspent the last several yearsinvestigating the T cell responseof NOD mice to beta cells andhave found that insulin is one ofthe proteins recognized by

autoimmune T cells. In a subse-quent analysis, we found that asmall fragment of the insulinmolecule (B:9-23) is the partthat is actually recognized bythe great majority of T cells thatrecognize insulin. More impor-tantly, we have found that thisfragment will protect NOD micefrom diabetes. We are in theprocess of determining if thisfragment of insulin is recognizedby T cells from human subjectswho either have IDDM or areclassified as at risk in screeningassays. Other experiments areaimed at determining the mech-anism by which B:9-23 confersprotection.

The major research efforts of mylaboratory over the past severalyears have been directed towardcharacterization of the T cellresponse to islets in NOD micein several different situations:first, as it is reflected in theislet infiltrates that accumulateduring the spontaneous diseaseprocess; second, in the infil-trates that develop and rapidlydestroy islet isografts placed inspontaneously diabetic mice andreferred to as “disease recur-rence;” third, as it develops inthe draining lymph nodes of ani-mals protected from IDDM byintranasal or subcutaneous B:9-23; and fourth, the nature of thechanges within islet infiltratesof mice that have been protectedfrom diabetes by B:9-23 or othertreatments. The overall goals ofthese investigations are tounderstand the development ofthe immune response to isletsduring the disease process indetail, and to understand whatalterations are induced in thisresponse by antigen-specifictherapies that result in protec-tion of NOD mice from diabetes.In addition to the mouse work,we have been attempting to iso-late and characterize T cellclones and lines from new onset

or prediabetic individuals thatmight have some relevance tothe disease process. This workhas been progressing and wehave recently confirmed thatB:9-23 is an epitope in at leastDR4/4 individuals.

Don Bellgrau, Ph.D.Immunobiology of type I dia-betes: Our overall workinghypothesis at present is thatdefective T cell function isinvolved in disease. A majorfocus of our laboratory researchis the study of candidate autore-active T cells that are unusuallyresistant to regulation. Our goalis to determine the function ofdiabetogenic genes.

Immunology of privileged sites:The work on the immunobiologyof type I diabetes has providedus with important insights intothe special characteristics ofautoreactive T cells and providesan experimental means toexplore the issues of transplan-tation tolerance, transplantationrejection and the immunobiologyof privileged sites. Central tothis issue is our finding thatimmune privilege in the testisrequires the production by thetestis tissue of CD95 ligand.Our goal is to determine if CD95expression by testis tissue is notonly necessary but sufficient toconvey immune privilege to nor-mally immunogenic tissue.

T cell signalling: In our studiesof the BB rat and NOD mousemodels of type I diabetes, wehave discovered that autoreac-tive T cells may be defective intyrosine kinase mediated T cellsignalling. We hypothesize thatthese signalling defects influ-ence the function of T cells thatregulate autoreactive T cells.Our goal is to define thesedefects both biochemically andmolecularly. This work shouldprovide important insights into

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the nature of the defects in reg-ulatory T cells and/or effector Tcells involved in autoimmunity.

Autoimmunity: While the pre-vailing view at this time may bethat autoimmune disorders aremore different than alike, ourown bias is that many differentautoimmune disorders may havecommon pathways of initiationin that they share cells thatcause the destruction of target-ed tissue. This area is beingpursued experimentally in ourlaboratory by comparing the cel-lular and molecular immunologyof the diabetes-prone and dia-betes-resistant BB rats to eachother, as well as to the diabetes-prone NOD mouse and diabetichumans. This work is helpingus define the “ground rules” thatcontrol autoimmunity. At thislevel it should be possible todesign reagents that are effec-tive on multiple autoimmunedisorders.

CLINICAL RESEARCH

H. PETER CHASE, M.D.Clinical Director

Diabetes PreventionTrialOver the past year, the clinichas been very involved in theNational Diabetes PreventionTrial (DPT-1). The BarbaraDavis Center is one of 10 cen-ters nationwide participating inthis trial. H. Peter Chase M.D.and George S. Eisenbarth M.D.,Ph.D. are serving on the nine-teen-member steering commit-tee for this trial.

Approximately 40,000 peoplehave been screened, with over8,000 screened at our Center.Approximately 160 people (witha greater than 50 percent risk ofdeveloping diabetes within fiveyears) have been entered into

the parenteral trial, with almostone-fourth of the total partici-pants coming from our Center.

The second part of the trial (forpeople with a 35 to 50 percentrisk for developing diabetes inthe next five years) began inSeptember, 1996. To date, ourCenter has admitted 18 of thefirst 69 subjects nationwide.This research is funded by NIH(National Institutes of Health)and has been the major focus ofDr. Peter Chase and SherrieHarris, R.N., DPT-1 researchnurse. The assistance of theNIH-funded Children’s ClinicalResearch Center at TheChildren’s Hospital in Denverhas also been of great help.

Prevention of the Eyeand KidneyComplications ofDiabetesSatish Garg, M.D. and Dr. Chasehave published over 20 articlesin this area and are continuingtheir longitudinal studies. InJanuary, 1997, the first of threearticles related to 24-hourambulatory blood pressure mon-itoring (ABPM) was published inThe American Journal ofHypertension. The article dealtwith controls who were studiedin order to obtain better normaldata to compare with data frompeople with diabetes who camefrom different ethnic groups.Surprisingly, it was found thatAfrican-American teenagersalready had some significantlyhigher blood pressure findingscompared to age-matched Angloor Hispanic youth. As it isknown that adult African-Americans have a higher risk forhypertension, this study sug-gests that prevention of hyper-tension will need to start at ayoung age in this population.

Studies of 24-hour blood pres-sure monitoring and the eyecomplications of diabetes arenow in press. Of the findings,elevated resting (sleeping) dias-tolic blood pressure was thefinding most closely associatedwith both diabetic eye and kid-ney changes.

A longitudinal (three-year) fol-low-up of the eye and renalchanges in people receiving thenew insulin, Humalog® (insulinlispro), was reported by Drs.Garg and Chase at the nationalAmerican Diabetes Associationmeeting (June, 1997) and at theInternational Congress ofDiabetes (August, 1997). It wasimportant to make sure that thisnew insulin analogue would nothasten the eye and kidney com-plications of diabetes.Fortunately, their findings donot show any evidence of this.

As reported elsewhere in thisissue of NEWSNOTES, a new“double-blind” trial of the effectsof antioxidants on the eye andkidney complications of diabeteshas now begun. It is anticipatedthat this will be a three-yeartrial.

New Insulin TrialsThe use of Humalog® (insulinlispro) in preschoolers one tofour years old has been studiedby Ms. Succhari Rutledge and byDr. Chase and others at theCenter. It was found that thenew insulin was even moreeffective when given to preschool-ers after the meal, in compari-son to Regular insulin given upto 30 minutes before the meal.This will allow parents to judgethe toddlers’ insulin dose onwhat is eaten and will help toprevent eating problems relatedto an insulin dose having alreadybeen given, with the preschoolerthen refusing to eat.

Research

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Photo:©1997

MartinCrabb

SELECTED MEETINGS,GRANTS AND HONORSRECEIVED

GEORGE S. EISENBARTH,M.D., Ph.D.Executive Director

Selected meetings attended:

Invited speaker, First International SCMCISymposium on Type I Diabetes, Tel Aviv,Israel, March, 1996.

Invited speaker, European Association forthe Study of Diabetes Satellite Symposium,Vienna, Austria, September, 1996.

Co-organizer, American Diabetes Association31st Research Symposium, Estes Park, CO,September, 1996.

Invited speaker, 75th Anniversary Discoveryof Insulin, Toronto, Canada, October, 1996.

Grant Support:

Principal Investigator. NIH, DiabetesPrevention Trial, HLA laboratory subcon-tract, 11/1/93-8/31/98, annual direct costs$73,520.

Principal Investigator. NIH, Natural historyof pre-diabetic autoimmunity, 7/1/93-6/30/97, annual direct costs $323,683.

Principal Investigator. NIH, Genetic andenvironmental causes of celiac disease,10/1/95-9/30/00, annual direct costs$156,152.

Principal Investigator. NIH, Antibodies torecombinant autoantigens:prediction/immunogenetics, 12/1/95-11/30/00, annual direct costs $33,200.

Blum-Kovler Fellowship, 7/1/97-6/30/98,$30,000.

ADA mentor-based postdoctoral fellowshipprogram grant, 7/1/95-6/30/98, annual directcosts $30,000.

Prizes, Awards, other Merits:

Francis D. W. Lukens Medal, Penn. ChapterAmerican Diabetes Assoc., 1995.

Robert E. Bolinger Citation for AcademicDistinction, Kansas School Med., 1996.

David Rumbaugh Award of the JuvenileDiabetes Foundation, Miami, Florida. Theaward was given jointly to Dr. Eisenbarthand Dr. Ali Naji. June 1997.

JOHN C. HUTTON, Ph.D.Research Director

Selected meetings attended:

Clore Laboratory 3rd InternationalSymposium, Buckingham, UK, July, 1996.

Gordon Research Conferences, NewHampton, NH, July, 1996.

European Association for the Study ofDiabetes 32nd Annual Meeting, Vienna,Austria, September, 1996.

Immunology of Diabetes Workshop,Canberra, Australia, December, 1996.

Keystone Symposium, Taos, NM, March,1997.

Keystone Symposium, Keystone, CO, April,1997.

International Diabetes Federation SatelliteMeeting, Helsingor, Denmark, July, 1997.

Grant Support:

Principal Investigator. JDFI, Molecularscreening for novel autoantigens in type Idiabetes, 9/1/96-8/31/98, annual direct costs$50,000.

Principal Investigator. JDFI, Sorting of theprohormone convertase PC3 and proinsuli-naemia, 9/1/96-8/31/98, annual direct costs$50,000.

Principal Investigator. University of ColoradoBiomedical Engineering. Development ofartificial pancreas for diabetic therapy,7/15/96-7/14/97, $20,000.

ADA mentor-based postdoctoral fellowshipprogram grant, 7/1/97-6/31/00, annual directcosts $30,000.

Principal Investigator. NIH, Cloning of themolecular targets of cell mediated autoim-munity in type I diabetes, 12/14/96-11/30/00, annual direct costs $138,274.

Principal Investigator. NIH, large equipmentgrant. Molecular Dynamics STORM 860Imager, 4/1/97-3/31/98, $85,000.

Prizes, Awards, other Merits:

Appointed Professor of Cellular & StructuralBiology, UCHSC, September, 1996.

RON GILL, Ph.D.

Selected meetings attended:

“T Lymphocyte-Dependent Pathogenesis inIslet Transplantation,” University of Alberta,Department of Surgery. Edmonton, Alberta,Canada, March, 1997.

”Tolerance Does Not Require Clonal Deletionof Antigen-Specific T Cells,” 15th PlenarySession, Immunology of Diabetes Workshop,Canberra, Australia, December, 1996.

”The Role of CD4 T Cells in Pancreatic IsletTransplantation Immunity,” SmithKlineBeecham Pharmaceuticals-sponsoredTransplantation Symposium, Collegeville, PA,May, 1996.

”T Cell-Dependent Pathogenesis inPancreatic Islet Transplantation,” AlbertaHeritage Foundation for Medical Research,University of Alberta, Edmonton, Canada,March, 1996.

”T Cell-Dependent Damage in PancreaticIslet Transplants,” University of MarylandMedical Center Transplantation Program,Baltimore, MD, February, 1996.

Grant Support:

Principal Investigator. NIH, Reversal of dia-betes by islet transplantation, 4/1/94-3/31/98, annual direct costs $186,928.

Principal Investigator. NIH, Immunobiologyof pancreatic islet xenografting, 1/1/93-12/31/97, annual direct costs $109,835.

Principal Investigator. JDFI, Protection fromautoimmune-mediated islet injury throughgene therapy, 9/1/95-8/31/97, annual directcosts $45,345.

Principal Investigator. Baxter HealthcareCorporation, Autoimmune triggering and reg-ulation by immunoisolated islet antigens,7/13/96-7/12/97, annual direct costs$19,073.

KATHRYN HASKINS, Ph.D.

Selected meetings attended:

Invited Speaker, Symposium onAutoimmunity in IDDM, Royal Society ofMedicine, London, UK, April, 1996.

Research

7

RESEARCH DIVISION

European Immunology Conference, LesEmbiez, France, May, 1996.

Invited Speaker, IDDM Symposium,Copenhagen, Denmark, November, 1996.

Mini-symposium Chair, AAI Annual Meeting,San Francisco, CA, February, 1997.

Symposium Speaker, 16th InternationalDiabetes Federation Congress, Helsinki,Finland, July, 1997.

Immunology Division, Cambridge University,Cambridge, England, April, 1996.

Pasteur Institute, Paris, France, June, 1996.

Erasmus University, Rotterdam, Netherlands,July, 1996

Joslin Diabetes Center, Boston, MA, March,1997.

Grant Support:

JDFI Research, Autoreactive T cells in theNOD mouse, 9/1/95-8/31/96

Principal Investigator. JDFI, Role of Th2 Tcells in immunoregulation of IDDM, 9/1/95-8/31/97, annual direct costs $50,000.

Principal Investigator. NIH, Training programin immunology, 8/1/96-7/31/01, annual directcosts $167,831.

Principal Investigator. NIH, Antigen specifici-ty of T cell clones from the NOD mouse,5/1/92-4/30/98, annual direct costs$196,698.

Principal Investigator. NIH, Autoreactive Tcells in the NOD mouse, 9/1/96-8/31/00,annual direct costs $234,881.

ANTHONY HAYWARD, M.D.,Ph.D.

Selected meetings attended:

Invited speaker, NIH Fetal Stem CellTransplantation Meeting, Bethesda, MD,June, 1996.

Invited speaker, NIH Fetal Stem CellTransplantation Meeting, Reno, NV,September, 1996.

Invited speaker, APS/SPR meeting,Washington, DC, June, 1996.

Visiting Professor, University of Florida,Gainesville, FL, February, 1996.

Grant Support:

Co-investigator. NIH, General clinicalresearch centers program of NCRR, 12/1/95-11/30/00. $1,516,121.

Principal Investigator. NIH, Training programin pediatric immunology, 9/1/95-8/31/00,annual direct costs $62,422.

Principal Investigator. NIH, Fetal stem celltransplantation for alpha thalassemia, 6/1/96-5/31/97, annual direct costs $129,004.

Co-investigator. NIH, Natural and vaccineimmunity to RSV in man and monkeys,12/1/94-11/30/98, annual direct costs$209,000.

Principal Investigator. Colorado CancerCampaign, CD40-CD40L interactions andsusceptibility to hepatobiliary cancer, 7/96-6/98, annual direct costs $18,500.

DALE WEGMANN, Ph.D.

Selected meetings attended:

Invited speaker, Clinical Immunology SocietyAnnual Meeting, New Orleans, LA, May, 1996.

Invited Co-chair, “Cytokines andAutoimmunity.” American Association ofImmunologists Annual Meeting, NewOrleans, LA, June, 1996.

Invited speaker, “Who Killed the Beta Cell?,”American Diabetes Association AnnualMeeting, San Francisco, CA, June, 1996.

Invited speaker, “Protection of NOD Micefrom Diabetes by Insulin B:9-23.” EuropeanAssociation for the Study of Diabetes,Satellite Symposium, Vienna, Austria,August, 1996.

Invited speaker, “Insulin ImmunomodulationTherapy,” American Diabetes Association31st Research Symposium, Prevention ofType I Diabetes in the General Population,Estes Park, CO, September, 1996.

Symposium Co-chair, “Autoantigens inIDDM,” 15th Immunology of DiabetesSociety, Canberra, Australia, December, 1996.

Grant Support:

Principal Investigator. NIH, Regulation ofdiabetes in the NOD mouse. $101.000,5/1/96-4/30/97.

Principal Investigator. NIH, Analysis of theislet-specific T cell response in NOD mice8/1/94-7/31/97, annual direct costs $125,988.

Principal Investigator. JDFI,Characterization of GAD-specific T cellsfrom NOD mice, 9/1/95-8/31/97, annualdirect costs $45,450.

DONALD BELLGRAU, Ph.D.

Selected meetings attended:

The Second International Conference on NewTrends in Clinical and ExperimentalImmunology, Geneva, Switzerland, February,1996.

European Federation Meeting on theMolecular Basis of Autoimmunity, Lengries,FRG, October, 1996.

The Third Gordon Conference onNeuroendocrine Immunology, Ventura, CA,January, 1997.

AAAAI/AAI/CIS Joint Meeting, Mini-sympo-sium Chairman, “Mechanisms of OrganSpecific Autoimmunity,” San Francisco, CA,February, 1997.

Harvard Medical School Dept. ofImmunology, “Immune Privilege and CD95Ligand,” Cambridge, MA, February, 1996.

Biotransplant Inc., “A Role for CD95 Ligandin Transplantation,” Boston, MA, February,1996.

The Second International Conference on NewTrends in Clinical and ExperimentalImmunology, “Fas Ligand-BasedImmunosuppression,” Geneva, Switzerland,February, 1996.

Sandoz Pharmaceuticals, “Fas Ligand andthe Immunology of Privileged Sites,” Basel,Switzerland, February, 1996.

The Basel Institute for Immunology, “TheImmunology of Privileged Sites,” Basel,Switzerland, February, 1996.

Grant Support:

Principal Investigator. NIH, Autoreactive Tcells resistant to tolerance induction,12/1/94-11/30/98, annual direct costs$115,000.

Principal Investigator. JDFI, Fas ligand-based tolerance induction, 9/31/96-8/30/98,annual direct costs $45,000.

Principal Investigator. Colorado Institute forResearch in Biotechnology. “CD95 Ligand:A Novel Immunosuppressive Agent to CreateArtificial Immune Privileged Sites,” 7/1/96-6/30/97, annual direct costs $35,000.

8

Research

H. PETER CHASE, M.D.Clinical Director

Selected meetings attended:

Diabetes Prevention Trial SteeringCommittee, Washington, DC, January andJune, 1997.

American Diabetes Association, Boston, MA,June, 1997.

Course Director, Management of Diabetes inthe 1990’s, Vail, CO, August, 1996.

Thirty-first ADA Research Symposium,“Prevention of Type I Diabetes in the GeneralPopulation,” Estes Park, CO, September,1996.

Central Plains Clinic Symposium, “Topics inClinical Medicine,” Sioux Falls, SD, April,1997.

Grant Support:

Principal Investigator. NIH, NationalDiabetes Prevention Trial (DPT-1), 1994-2002, annual direct costs $200,000.

Principal Investigator. Becton-Dickensonpen needle study, 1997, $10,000.

Prizes, Awards and OtherMerits:

University of Wisconsin, annual MedicalSchool Alumni Award, Outstanding Alumnus,May, 1997.

American Association of University Women’s“Trailblazer” Award for work as co-chairmanof the four-state Commission on Poverty inChildren. 1997.

President, Colorado Chapter of the AmericanDiabetes Association. 1997.

GEORGEANNAKLINGENSMITH, M.D.Director of Pediatric Clinics

Selected meetings attended:

Selected to present the ADA Council of YouthSymposium at the ADA meeting. Topic: “TheTreatment of Non-type I Diabetes in Youth,”1997.

Presented a portion of the DAISY studyresearch at the Fifth International Congressof the Juvenile Diabetes FoundationInternational. Topic: “The PsychosocialImpact of Diabetes Risk Identification,” 1997.

Grant Support:

Principal Investigator. Genentech clinicalresearch grant for ongoing clinical trial,6/1/97, approximately $94,000.

Prizes, Awards and otherMerits:

Selected to the American Board ofPediatrics, the sub-board of PediatricEndocrinology, a national board of nine pedi-atric endocrinologists responsibile for prepa-ration of the certification examination for allpediatric endocrinologists. 1997.

Chairperson of the National AmericanDiabetes Association Council for Diabeteson Youth from 1994 to 1996.

PHILLIPE WALRAVENS, M.D.

Selected meetings attended:

Workshop on “Insulin Injection Techniques”sponsored by Becton Dickinson in France.June 7th and 8th, 1997.

Grant Support:

Principal Investigator. Grant from BristolMeyers Squibb to study the effects of usingGlucophage®, an oral hypoglycemic agent, inaddition to insulin, in adolescents with type Idiabetes, 10/97-12/98, $70,000.

Prizes, Awards and otherMerits:

Appointed Professor of Pediatrics, UCHSC.1997.

SELECTED RESEARCHPAPERS PUBLISHED OR INPRESS

Bailyes, E. M., K. I. J. Shennan, E. F. Usac,S. D. Arden, P. C. Guest, K. Docherty and J.C. Hutton. 1995. Differences between thecatalytic properties of recombinant humanPC2 and endogenous rat PC2. Biochem J309:587-594.

Bellgrau, D., D. Gold, H. Selawry, J. Moore,A. Franzusoff and R. Duke. 1995. A role forCD95 ligand in preventing graft rejection.Nature 377:600-602.

Chase, H. P., S. K. Garg, G. Icaza, J. A.Carmain, C. F. Walravens and G. Marshall.1995. 24-h ambulatory blood pressure mon-itoring in healthy young adult Anglo,Hispanic, and African-American subjects.Am J of Hypertension 10:18-25.

Daniel, D., R. G. Gill, N. Schloot and D.Wegmann. 1995. Epitope specificity,cytokine production profile and diabetogenicactivity of insulin-specific T cell clones iso-lated from NOD mice. Euro J Immuno25:1056-1062.

Eisenbarth, G. S. and M. Rewers. 1995.Refining genetic analysis of type I diabetes.J Clin Endocrinol Metab 80:2564-2566.

Garg, S. K., H. P. Chase, H. Shapiro, S.Harris and I. M. Osberg. 1995. Exercise ver-sus overnight albumin excretion rates insubjects with type I diabetes. Diab Res ClinPrac 28:51-55.

Gianani, R., D. U. Rabin, C. F. Verge, L. Yu,S. Babu, M. Pietropaolo, and G. S.Eisenbarth. 1995. ICA512 Autoantibodyradioassay. Diabetes 44:1340-1344.

Gold, D. P., S. T. Shaekewitz, D. Mueller, J.R. Redd, K. S. Sellins, A. Pettersson, A.Lernmark and D. Bellgrau. 1995. T cellsfrom BB-DP rats show a unique cytokineprofile associated with the IDDM1 suscepti-bility gene, Lyp. Autoimmunity 22:149-161.

Guest, P. C., S. D. Arden, N. G. Rutherfordand J. C. Hutton. 1995. The post-translation-al processing and intracellular sorting ofcarboxypeptidase H in the islets ofLangerhans. Mol Cell Endocrinol 113:99-108.

Healey, D., P. Ozegbe, S. D. Arden, P.Chandler, J. C. Hutton and A. Cooke. 1995.In vivo activity and in vitro specificity ofCD4+ Th1 and Th2 cells derived from thespleens of diabetic NOD mice. J Clin Invest95:2979-2985.

Penfold, J., H. P. Chase, G. Marshall, C. F.Walravens, P. A. Walravens and S. K. Garg.1995. Final adult height and its relationshipto blood glucose control and microvascularcomplications in IDDM. Diab Med 12:129-133.

Rewers, M. and R. F. Hamman. Risk factorsfor non-insulin dependent diabetes. In: NDDG(ed.) Diabetes in America 1995; 9, pp. 1-43.

Schloot, N. and G. S. Eisenbarth. 1995.Isohormonal therapy of endocrine autoimmu-nity. Immunol Today 16:289-294.

Research

9

CLINICAL DIVISION

Photo:©1997

MartinCrabb

Van Horssen, A. M., W. H. Van den Hurk, E.M. Bailyes, J. C. Hutton, G. J. M. Martensand I. Lindberg. 1995. Identification of theregion within the neuroendocrine polypep-tide 7B2 responsible for the inhibition ofprohormone convertase PC2. J Biol Chem270:14292-14296.

Arden, S. D., B. O. Roep, P. I. Neophytou, E.F. Usac, G. Duinkerken, R. R. P. de Vries andJ. C. Hutton. 1996. Imogen 38: a novel 38kDislet mitochondrial autoantigen recognizedby T cells from a newly diagnosed insulin-dependent diabetic patient. J Clin Invest97:551-561.

Bellgrau, D., D. Stenger, C. Richards and F.Bao. 1996. The diabetic BB rat. Neither Th1nor Th2? Hormone Metabol Res 28:299-301.

Bergman, B. and Haskins K. 1997.Autoreactive T cell clones from the nonobesediabetic (NOD) mouse. Proc Soc Exp BiolMed 214:27.

Boguniewicz, M. and A. R. Hayward. 1996.Atopy, airway responsiveness and genes.Thorax.

Cook, J. L., T. A. Potter, D. Bellgrau and B.A. Routes. 1996. E1A Oncogene expressionin target cells induces cytolytic susceptibilityat a post recognition stage in the interactionwith killer lymphocytes. Oncogene :13833-42.

Coulombe, M., H. Yang, S. Guerder, R. A.Flavell, K. J. Lafferty and R. G. Gill. 1996.Tissue immunogenicity: the role of MHCantigen and the lymphocyte costimulatorB7-1. J Immunol 157:4790-4795.

Coulombe, M. and R. G. Gill. 1996. T lym-phocyte indifference to extrathymic isletallografts. J Immunol 156:1998-2003.

Creemers, J. W. M., E. F. Usac, N. A. Bright,W. Van de Loo, W. J. M. Van de Ven and J. C.Hutton. 1996. Identification of a transferablesorting domain for the regulated pathway inthe prohormone convertase PC2.J Biol Chem 271:25284-25291.

Daniel, D. and D. Wegmann. 1996.Intranasal administration of insulin peptideB:9-23 protects NOD mice from diabetes.Annals NY Acad Sci 778:371.

Daniel, D. and D. Wegmann. 1996.Protection of NOD mice from diabetes fromintranasal or subcutaneous administration ofinsulin peptide B:9-23. Proc Nat Acad Sci(USA) 93:956.

Duke, R. C., A. Franzusoff, and D. Bellgrau.1996. CD95 ligand in graft rejection. Nature379:682-83.

Eisenbarth, G. S. and M. Stegall. 1996. Isletand pancreas transplantation: autoimmunityand alloimmunity. New Engl J Med 335:888-890.

Fisher, D. A. and G. S. Eisenbarth. 1996.Identification of individuals at risk for type Iinsulin-dependent diabetes mellitus.Diagnostic Endocrinol Metabol 14:211-214.

Garg, S. K., J. A. Carmain, K. C. Braddy, J.H. Anderson, L. Vignati, M. K. Jennings andH. P. Chase. 1996. Pre-meal insulin ana-logue insulin Lispro vs Humulin® insulintreatment in young subjects with type I dia-betes. Diab Med 13:47-52.

Garg, S. K., G. J. Klingensmith and G. S.Eisenbarth. Autoimmune polyglandular syn-dromes. 1996. In: G. S. Eisenbarth and K. J.Lafferty (eds.), type I Diabetes: Molecular,Cellular and Clinical Immunology. Chapter8, 153-171, Oxford University Press, NewYork.

Garg, S. K., C. E. Hiar, L. M. Pennington, I.M. Osberg, M. K. Jennings, A. Chu, H. P.Chase and R. M. Hamilton. 1996. A reliable,accurate, and rapid method for estimation ofurinary albumin excretion rate. J Amer Socof Nephrol 7:1358.

Gianani, R., C. F. Verge, R. I. Gianani, L. Yu,A. Pugliese, and G. S. Eisenbarth. 1996.Limited loss of tolerance to islet autoanti-gens in ICA+ first degree relatives ofpatients with type I diabetes expressing theHLa DQB1*0602 allele. J Autoimmunity9:423-426.

Gill, R. G., M. Coulombe and K. J. Lafferty.1996. Pancreatic islet allograft immunityand tolerance: the two-signal hypothesisrevisited. Immunol Reviews 149:75-96.

Gottlieb, P. A. and G. S. Eisenbarth. 1996.Mouse and man: multiple genes and multipleautoantigens in the aetiology of type I DMand related autoimmune disorders.J Autoimmunity 9:277-281.

Haskins, K. and D. Wegmann. 1996.Diabetogenic T cell clones. Diabetes45:1299.

Hawkes C. J., C. Wasmeier, M. R. Christieand J. C. Hutton. 1996. Identification of the37k-antigen in insulin-dependent diabetes as

a tyrosine-phosphatase-like protein(phogrin) related to IA-2. Diabetes 45:1187-1197.

Kawasaki, E., J. C. Hutton, and G. S.Eisenbarth. 1996. Molecular cloning andcharacterization of the human transmem-brane protein tyrosine phosphatase homo-logue, Phogrin, an autoantigen of type I dia-betes. Bio Biophys Res Comm 7:227:440-447.

Hayward, A. R., K. Buda, M. Jones, C. J.White, and M. J. Levin. 1996. VZV Specificcytotoxicity following secondary immuniza-tion with live or killed vaccine. ViralImmunol 9:241-245.

Kawasaki, E., G. S. Eisenbarth, C.Wasmeier, and J. C. Hutton. 1996.Autoantibodies to protein tyrosine phos-phatase-like proteins in type I diabetes:overlapping specificities to phogrin andICA512/IA-2. Diabetes 45:1344-1349.

McKeever U., S. Khandekar, J. Newcomb, J.Naylor, P. Gregory, P. Brauer., M. Jesson, B.Bettencourt, E. Burke, A. Alderson, J.Banerji, K. Haskins, and B. Jones. 1996.Immunization with soluble BDC-2.5 T cellreceptor-immunoglobulin (TCR-IgG1)chimeric protein: antibody specificity andprotection of non-obese diabetic (NOD) miceagainst adoptive transfer of diabetes bymaternal immunization. J Exp Med184:1755.

Neophytou, P. I., E .M. Muir and J. C. Hutton.1996. T-cell epitope analysis using subtract-ed expression libraries. Application to a38kDa autoantigen recognized by T cellsfrom a newly diagnosed insulin-dependentdiabetic patient. Proc Natl Acad Sci USA93:2014-2018.

Neophytou, P. I., E. M. Muir and J. C. Hutton.1996. A subtractive cloning approach to theidentification of mRNA’s specificallyexpressed in pancreatic B-cells. Diabetes45:127-133.

Neophytou, P. I., P. Ozegbe, D. Healey, R.Quartey-Papafio, A. Cooke and J. C. Hutton.1996. Development of a procedure for thedirect cloning of T cell epitopes using bacte-rial expression systems. J Immunol Methods196:63-72.

Norris, J. M., B. Beaty, G. Klingensmith, L.Yu, M. Hoffman, H. P. Chase, H. A. Erlich, R.F. Hamman, G. S. Eisenbarth, and M.Rewers. 1996. Lack of association betweenearly exposure to cow’s milk protein and

Research

10

Photo:©1997

MartinCrabb

beta-cell autoimmunity: DiabetesAutoimmunity Study in the Young (DAISY).JAMA 276:609-614.

Peterson, J. D. and Haskins, K. 1996.Transfer of diabetes in the NOD-scid mouseby CD4 T cell clones: differential require-ment for CD8 T cells. Diabetes 45:328.

Roep, B. O. and J. C. Hutton. 1996. 38kDaB-cell protein as target of the autoimmuneresponse in insulin-dependent diabetes mel-litus. Diab Nutr Metab 9:233-236.

Rewers, M., T. L. Bugawan, J. M. Norris, A.Blair, B. Beaty, M. Hoffman, R. S. McDuffie,R. F. Hamman, G. Klingensmith, G. S.Eisenbarth, and H. A. Erlich. 1996. Newbornscreening for HLA markers associated withIDDM: Diabetes Autoimmunity Study in theYoung (DAISY). Diabetologia 39:807-812.

Rewers, M., J. M. Norris, G. S. Eisenbarth,H. A. Erlich, B. Beaty, G. Klingensmith, M.Hoffman, L. Yu, T. L. Bugawan, A. Blair, R.F. Hamman, M. Groshek, and R. S. Mc DuffieJr. 1996. Beta cell autoantibodies in infantsand toddlers without IDDM Relatives:Diabetes Autoimmunity Study in the Young(DAISY). J Autoimmunity 9:(3)405-410.

Schloot, N., D. Daniel and D. Wegmann.1996. Peripheral T cell clones from NODmice specific for GAD65 peptides: Lack ofislet reponsiveness and diabetogenicity.J Autoimmunity 9:367-373.

Sellins, K. S., D. P. Gold and D. Bellgrau.1996. Resistance to tolerance induction inthe diabetes prone Biobreeding rat as onemanifestation of abnormal responses tosuperantigens. Diabetologia 39:28-36.

Simone E. and Eisenbarth G. S. 1996.Chronic autoimmunity of type I diabetes.Hormone Metabol Res 28:332-336.

Stegall, M. D., Z. Loberman, A. Ostrowska,M. Coulombe and R. G. Gill. 1996.Autoimmune destruction of islet grafts in theNOD mouse is resistant to 15-deoxysper-gualin but sensitive to anti-CD4 antibody.J Surg Res 64:156-160.

Stegall, M. D., K. J. Lafferty, I. Kam and R.G. Gill. 1996. Evidence of recurrent autoim-munity in human allogeneic islet transplan-tation. Transplantation 61:1272-1274.

Verge, C. F., R. Gianani, E. Kawasaki, L. Yu,M. Pietropaolo, R. A. Jackson, H. P. Chase,and G. S. Eisenbarth. 1996. Number ofautoantibodies (against insulin, GAD or

ICA512/IA2) rather than particular autoanti-body specificities determines risk of type Idiabetes. J Autoimmunity 9:379-383.

Verge, C. F., R. Gianani, E. Kawasaki, L. Yu,M. Pietroapolo, R. A. Jackson, H. P. Chase,and G. S. Eisenbarth. 1996. Prediction oftype I diabetes in first-degree relatives usinga combination of insulin, GAD, andICA512bdc/IA-2 autoantibodies. Diabetes45:926-933.

Wasmeier, C. and J. C. Hutton. 1996.Molecular cloning of phogrin, a protein tyro-sine phosphatase homologue localized toinsulin secretory granule membranes.J Biol Chem 271:18161-18170.

Wegmann, D.,D. Daniel, J. D Peterson,. andK. Haskins. 1996. The role of T cells in betacell damage in NOD mice and humans intype I diabetes: Molecular, cellular and clin-ical immunology. G. S. Eisenbarth, K. J.Lafferty (eds.) Oxford University Press.

Wegmann, D. R. 1996. The immune responseto islets in experimental diabetes and insulindependent diabetes mellitus. CurrentOpinion in Immunology 8:860.

Yu, L., M. Rewers, R. Gianani, E. Kawasaki,Y. Zhang, C. Verge, P. Chase, G. Klingensmith,H. Erlich, J. Norris, and G. S. Eisenbarth.1996. Anti-islet autoantibodies developsequentially rather than simultaneously.J Clin Endocrinol Metab 81:4264-4267.

Bergman, B. and K. Haskins. 1997.Autoreactive T cell clones from the nonobesediabetic mouse. Proc Soc Exp Biol Med214:41-48.

Crawford, M., D. Daniel, D. Wegmann, H.Yang and R.G. Gill. 1997. Autoimmune isletdamage mediated by insulin-specific T cells.Transpl Proc 29:758-759.

Coulombe, M., H. Yang and R. G. Gill. 1997.Adoptive transfer of CD4 T cell dependentallograft tolerance. Transpl Proc 29:1166-1167.

Graves, P. M., M. Pallansch, J. M. Norris, I.Gerling and M. Rewers. 1997. The role ofenteroviral infections in the development ofIDDM: Limitations of current approaches.Diabetes 46:161-168.

Guest, P. C., E. M. Bailyes and J. C. Hutton.1997. Endoplasmic Reticulum Ca 2+ isimportant for the proteolytic processing andintracellular transport of proinsulin in thepancreatic beta cell. Biochem J 323:445-450.

Kawasaki, E., L. P. Yu, R. Gianani, C. F.Verge, S. Babu, E. Bonifacio and G. S.Eisenbarth. 1997. Evaluation of islet cellantigen (ICA) 512/IA-2 autoantibody radioas-says using overlapping (ICA)512/IA-2 con-structs. J Clin Endocrinol Metab 82:375-380.

Pietropaolo, M., J. C. Hutton and G. S.Eisenbarth. 1997. Protein tyrosine phos-phatase-like proteins: Link with IDDM.Diabetes Care 20:208-214.

Pugliese, A., M. Zeller, A. Fernandez, L. J.Zalcberg, R. J. Bartlett, C. Ricordi, M.Pietropaolo, G. S. Eisenbarth, S. T. Bennettand D. D. Patel. 1997. The insulin gene istranscribed in the human thymus and tran-scription levels correlate with allelic varia-tion at the INS VNTR-IDDM susceptibilitylocus for type I diabetes. Nature Genetics15:293-297.

Schloot, N. C., B. O. Roep, D. R. Wegmann,L. Yu, T. B. Wang and G. S. Eisenbarth.1997. T-cell reactivity to GAD65 peptidesequences shared with coxsackie virus pro-tein in recent-onset IDDM, post-onset IDDMpatients and control subjects. Diabetologia40:332-338.

Simone, E., D. Daniel, N. Schloot, P.Gottlieb, S. Babu, E. Kawasaki, D. Wegmannand G. S. Eisenbarth. 1997. T cell receptorrestriction of diabetogenic autoimmune NODT cells. Proc Natl Acad Sci 94:2518-2521.

Slover, R. H. and G. S. Eisenbarth, 1997.Prevention of type I diabetes and recurrentbeta cell destruction of transplanted islets.Endocrine Rev 18:241-258.

Research

11

Photo:K.C.Keefer

NEW CLINICAL TRIALOF ANTIOXIDANTSAND MICRONUTRIENTS

— H. Peter Chase, M.D.Clinical Director

A new research trial at theBarbara Davis Center began inJuly 1997 to evaluate the possi-ble role of antioxidants in pre-venting the eye and kidney com-plications of diabetes. Althoughhigh HbA1c levels, elevatedblood pressure and smoking areall known to be related to themicrovascular complications ofdiabetes, other factors not yetidentified may also be impor-tant. One possible explanationrelates to the formation ofadvanced glycosylation endproducts (AGEs) which formfrom sugar attaching to bodyproteins as with the HbA1c val-ues, hemoglobin and glucose,formed when blood sugars arehigh. Although the HbA1c val-ues, and red blood cells, turnover every three months, theAGEs tend to remain in thebody.

Oxidation is believed importantin creating the AGEs and is alsobelieved important in allowingthe AGEs to form irreversiblebonds (cross-links) between pro-teins. A recent article inDiabetes Self-Management(March/April 1997) noted:“There is preliminary researchin animals that suggests antioxi-dants may help slow the pro-gression of diabetic retinopa-thy.” The Center has joinedhands with a commercial com-pany, LiForce International, Inc.,to evaluate the role of antioxi-dants in diabetic eye and kidneydisease. There is no evidence inhumans at this time that theseagents are beneficial.

One hundred subjects with typeI diabetes will be asked to par-

ticipate in the double-blind trial.All subjects will be asked totake four tablets twice daily.Half of the subjects will receivea tablet containing antioxidants,e.g.: vitamins A, C and E, andmicro-nutrients, e.g.: zinc, mag-nesium, potassium, all of whichare available “over-the-counter”and are not prescription medi-cines. The other half of the sub-jects will receive a placebo(inert) tablet, as this is howresearch must be done to deter-mine if there is an effect.People taking various vitaminsmust discontinue them for 30days prior to entering the trial.The Human Subjects Committeerequires all trial participants tobe told that, “There is no evi-dence that the present study willoffer any benefits to you.” Thisis a routine statement requiredfor all research trials.

A unique aspect of this trial isthat people with type I diabetesages 14 to 50 years will be invit-ed to participate. This meansthat in some cases teenagers aswell as their parents may jointhe trial. Those who enter willreceive the most modern andcomplete eye and kidney evalua-tions possible. The eye examswill include photographs usingthe new digital-imaging (TV)equipment at the Center. Thisallows retinal pictures to belooked at as they are taken andprevents the need to retake pic-tures a week later due to poorquality. The urine microalbu-mins will be done similarly witha new immunologic method thatobtains results in seven minutesrather than in three weeks.

Qualified individuals who areinterested in participating in thetrial may phone Kevin Wanebo,Research Associate at theCenter (303-315-8796), formore information. People whosmoke, or who were previous

smokers, are excluded. Womenwho plan on starting a family inthe near future are also exclud-ed. This will be a three-yeartrial, so people who expect tomove out of the area in the nearfuture will also be asked not toparticipate. Participants will bepaid $250 for the first year and$200 for the second and thirdyears to help defray travel, park-ing and other costs.

Clinic Review

12

THE BDCCALENDAR

October 17Grandparents Workshop

$25, full day

October 21Toddler Support Group

no fee,11:30 a.m. to 1:30 p.m.

November 14School Nurse ProgramProfessional Program

”Taking Diabetes to School”Approximately $60,8 a.m. to 4 p.m.

NOTE DATE CHANGE:The original date for theProfessional Programhas been changed from

November 7th toNovember 14th.(303) 315-8796

FOR REGISTRATION

QUESTIONS &ANSWERS

— H. Peter Chase, M.D.Clinical Director

Q. With all of the good glu-cose meters having memoriesof blood sugar values whichcan be printed out in clinic,do I still need to write downevery blood sugar value?

A. Unfortunately, the answer isYES. It is just as important towrite values down now as it wasseven years ago when metersdid not have memories. It isimportant to look for “trends” inblood sugar levels to know whento make changes in insulindosages. If a person or familydoes not do this, they are notdoing a good job of home dia-betes management. One of mytop “pet peeves” in diabetescare is to have a patient or fami-ly do blood sugars and to con-stantly have values that are toohigh or too low, but who don’tmake changes between clinicvisits or fax the values to some-one who can make suggestions.

Our general rule of thumb isthat if more than half of the val-ues at any time of day are abovethe upper level (usually 180 for5 to 17 years old, or above 150if 18 years or older), anincrease in the insulin dose isneeded. For example, if a 12year-old has all morning valuesabove 180 mg/dl (10mmol/L) fora week, the evening long-actinginsulin should be increased byone unit. Similarly, if the pre-dinner values are all above 180mg/dl (10mmol/L) for a week,the morning long-acting insulindose should be increased by oneor two units. If the values arenot being recorded in such away that values done at thesame time of day can be easilycompared, it is possible thatthese trends will be missed.The sheets on pages 40 and 41

in the 8th Edition ofUnderstanding Insulin-Dependent Diabetes are idealfor this (and can be copied fromthe book as often as desired).The converse is also true that ifthere are more than one or twovalues in a week below 60 mg/dl(3.24mmol/L) at any time of theday, the insulin dose working atthat time can be reduced.Pages 40 and 41 are designedfor easy faxing, and if there is aquestion whether the dosesshould be changed, the page canbe faxed to the health-careprovider (most schools and workplaces now have fax machines).The faxing of the blood sugarssaves valuable doctor/nursetime in having to sit at a phoneand write down results. OurCenter now averages over twen-ty patient faxes per day, and it isconsidered part of the service ofthe clinic visits every threemonths.

For the young child or teen whodoes not want to write valuesdown, it is often acceptable forthe parent to push the “M”(memory) button at the end ofthe day and record the values.This is a way for the parents tostay involved, and mostteenagers agree to accept thishelp. The parent is often thefamily member who does thefaxing to the health team aswell.

Q. Is it true that growth isreduced by poor sugar con-trol?

A. Research published from ourCenter in 1995 (DiabeticMedicine, Vol. 12, 129-133)was one of the first studies touse longitudinal HbA1c values toshow that optimal growth is notreached if longitudinal HbA1cvalues are not in a good range.In addition to the growth rate ofthe person with diabetes, thefinal adult height was comparedto that of siblings as well as theexpected adult height based onthe parents’ heights. All werereduced in people withincreased HbA1c values. In con-trast, growth was not altered inpeople who kept their HbA1cvalues in a good range.

Q. How can I predict whatmy final adult height will be?

A. Looking at your growth chartwhen you are in clinic is oneway to estimate final height.Knowing when your parents hadtheir growth spurts is oftenhelpful.

For people with diabetes, thelongitudinal HbA1c values willcause a reduction in this esti-mate if the HbA1c values havebeen high.

Questions & Answers

13

THERE ARE FORMULAS THAT SOME PEOPLE USE TOESTIMATE FINAL ADULT HEIGHT, i.e.:

FOR GIRLS:

Father’s height, minus 5”, plus Mom’s height, ÷ total by 2 = final adult height

AND FOR BOYS:

Mom’s height, plus 5”, plus Father’s height, ÷ total by 2 = final adult height

THE BARBARA DAVISCENTER ON THEWORLDWIDE WEB

— H. Peter Chase, M.D.Clinical Director

Some of you might like to visitthe Center’s Web site at:http://www.uchsc.edu/misc/diabetes/bdc.html

In February 1997, we had 1500people enter our site, or 1500“hits.” The Web site includes thetext of the 8th edition of oureducational book, UnderstandingInsulin-Dependent Diabetes. Italso includes the Foundation’snewsletter, NEWSNOTES, whichcontains nutrition informationand wonderful recipes, ongoingresearch, clinic news, trainingprograms, publications and DPTinformation. In NEWSNOTES,you will also find BDC patientnews, activities for children andyoung adults with diabetes,scholarship information, calen-dar of events and access toother diabetes-related Web sites.

Surprisingly, people who havebeen in the Web site often sende-mail to the Center. An exam-ple of a message we received isshown below:

Mail*Link SMTPExercise & DiabetesDiagnosed diabetic recently atthe age of 40, I have beeninjecting insulin now for fourmonths and am still finding myway with regard to exercise. Ithas been tremendous help read-ing your page on the Web (viaAOL) as I am a keen soccerplayer and am having troublecombining exercise and diabetescontrol. But you are helping melearn. Thank you very much.Best wishes,

Malcolm Bryant,Hull, England

A VOTE OF THANKSTO SKI TRIPVOLUNTEERS!Each year some very specialpeople give countless hours oftheir time to make the BDC skitrips a huge success. The CDFSki Program presents a greatopportunity for skiers of all lev-els, ages 8 to 18, to enjoy daytrips to beautiful Winter Parkand includes expert supervisionby BDC staff members and theProgram Coordinator, BobOwen, who has enthusiasticallyorganized these trips time and

again. Bob, CDF and the BDCextend their hearty thanks to thefollowing BDC staff members:Dr. Peter Chase, Dr. PeterGottlieb, Dr. Phillipe Walravens,Dr. Marian Rewers, Dr. EricSimone, and Sandy Hoops, P.A.We couldn’t have done it withoutyour help, and the kids had ablast!

M0MS CLUB FIGHTSDIABETESThe Children’s DiabetesFoundation at Denver is gratefulto the “MOMS Club” of BoyntonBeach, Florida for their continu-ing contributions to the BrassRing Fund totaling $244, and forsending information about theirnon-profit national organizationwhich provides support formothers.

Gail Mazzaferro, Vice Presidentof the Boynton Beach Chapter,said the goals of MOMS Clubsaround the nation are to provide:moral support to at-home moth-ers; a forum for topics of inter-est; a voice in the communityfrom mothers; and a chance toparticipate in service projects,many of which benefit children.Thank you MOMS!

Barbara Davis Center

14Members of the “MOMS Club” of Boynton Beach, FL sold T-shirts and donatedproceeds to the Brass Ring Fund

http://www.uchsc.edu/misc/diabetes/bdc.html

Cindy Barton ‘97

ELIMINATORCHALLENGE ATHUNDERINGSUCCESSOnlookers were thrilled by theamazing sights and sounds atCDF’s drag race extravaganza atBandimere Speedway onSaturday, June 21st, benefittingthe Children’s DiabetesFoundation at Denver and pro-moting public awareness of thesymptoms of diabetes. Fundsraised at the event benefited theclinical care and research pro-grams at the Barbara DavisCenter. The electrifying event atBandimere Speedway inMorrison, Colorado featureddragsters, jet cars, funny carsand the mesmerizing EliminatorChallenge, a 16-car challengerace featuring guest celebritydrivers, special guest U.S.Senator Ben NighthorseCampbell; Dave Aguilera-Channel 4; Brien Allen and RonAllen-Channel 7; Jeff Barlowand Tom Laugeson-Mike Shaw•Chevrolet•Geo•Buick; ToddRomero and Joe Franzgrote-9NEWS; Ed Lozano and ErnestGurulé-Channel 2; Mike Haynes,Voice of the Avalanche; GaryScrivner and Jim Lakin-Lakin/Scrivner; Marta Dillon andChaz Smith-Rocky MountainNews; and Victoria Taunton-fiancée of Mike Haynes.

Generous corporate sponsorswere: Rocky Mountain News;Jim and Elaine Lakin, Linda andGary Scrivner; Mike

Shaw•Chevrolet•Geo•Buick;John and Nancy Cowee; Lee andVictoria Cooper; King Soopers;Olé and Marty Jensen; Medved

Autoplex; Villano Brothers; EASof Golden; ContinentalVolkswagen; Frito-Lay®; Pepsi®;and Gateway Mazda. Our sin-cere thanks to the wonderfulpeople at Bandimere Speedway,to our celebrity drivers and cor-porate sponsors, the media andvolunteers for helping toincrease awareness of diabetes.

CDF’s Eliminator Challenge pro-vided spectacular entertainmentfor all and raised essential funds

to improve the quality of life forcourageous children and youngadults afflicted with diabetes.

Carousel Days

15

Nancy and John Cowee, Co-Chairmenof the Eliminator Challenge

Ernest Gurulé, Joe Franzgrote, Todd Romero and Brien Allen are geared up to raceat Bandimere

A popular celebrity guest at Bandimere, Senator BenNighthorse Campbell, on his custom Harley Davidson

High-powered dragsters prepare to race at the Bandimere event

Photos:TomMasamori

SCHOOL LUNCH: BUYIT OR BAG IT?— Markey Swanson, R.D., C.D.E.

With the new school year uponus, it’s the age old question:What to do about school lunch?Most parents really don’t have aclue when it comes to knowingwhat their child consumes atschool lunchtime. If they buylunch—do they eat it? If they“brown bag”—do they trade it?When your child has diabetes,this information is important,though many times parentswould really rather NOT know!The choices made at lunch timeare often not what you wouldchoose for your child.

For starters, let’s look at whatschool lunches usually provide.Schools must offer 8 ounces ofmilk, 2 ounces of meat or ameat alternative, two servings offruit and/or vegetable (3/4 to 1cup, depending upon child’s age)and a minimum of one serving ofgrain/starch per day. In a oneweek period, 12-15 servings ofgrain/starch must be provided,depending upon age. Schoolsmust offer five food choices asoutlined, but children arerequired to take only three tofour choices, depending uponthe requirements of the localschool food authority. As youcan see, intake will vary, espe-cially in the amount of carbohy-drate.

As we all know, many schoolsoffer food choices other than“traditional” lunches, especiallyas children progress to middleschool and into high school.Often various fast food items areavailable. Some of the morepopular choices, along with car-bohydrate information are listedhere.

Keep in mind, the items listedare quite high in FAT! In addi-

tion, other items such as bagelsand soft serve ice cream willmost likely be available. Whilethese choices are usually low infat, the portions are often largeand the amount of carbohydrateis much more than you mightcalculate.

The best you can do as a parent,is to encourage your child to eata healthy lunch. For gradeschool children with diabetes, agood rule is to ask that yourchild consume at least half ofthe lunch provided and drink themilk before rushing out forrecess. (Lunchroom attendants

may be able to assist with this.)When you are aware that yourchild is not making the greatestfood choice at lunch, allow forthis and assist with insulin man-agement. Your best defense isto provide healthy food choicesin your home.

Just for fun, some bag lunchrecipes follow . . . and they’renot the usual PBJ. Add a drinkand a couple of extra items(string cheese, fruit, yogurt) andyou’ve got lunch!

Nutrition News BDC Dietitians Cook’s Corner

16

RESTAURANT FOOD/PORTION CARBOHYDRATE GMS.

PEANUT BUTTER MUFFINS

INGREDIENTS

2 cups all purpose flour1-1/2 teaspoons baking soda1/8 teaspoon salt1/2 cup crunchy peanut butter1/4 cup dark brown sugar1 egg1 cup skim milk

PREPARATION

Preheat oven to 350 degrees. Line muffin cups with paper liners. Insmall bowl, combine flour, soda and salt and set aside. Cream peanutbutter and brown sugar and add egg, mixing completely. Alternate addingthe flour mixture and the milk to the peanut butter mixture, stirring aftereach addition and ending with flour mixture. Spoon into paper-lined muf-fin cups and bake 20 minutes or until done.

Pizza Hut

Subway

Taco Bell

McDonald’s

1 slice PepperoniPersonal Pan, Pepperoni

(1) 6” Cold Cut

1 Soft Taco1 Bean Burrito

NachosCinnamon Twists

1 Quarter Pounder w/cheeseChicken McNuggets

1 pkt sauce

28 gms69 gms

43 gms

19 gms58 gms37 gms20 gms

37 gms16 gms12 gms

NUTRITION INFORMATION

Number of Servings: 12Serving Size: 1 muffin130 calories per serving21 grams carbohydrate4.5 grams protein3 grams fat

Winner’s Circle

17

SKIER FOCUSES ONOLYMPIC GOALFourteen-year-old Ryan Robertsis a member of the SteamboatSprings Winter Sports Club andis a terrific skier who participat-ed in the Junior Olympics in Vail.He has diabetes and managesall of his activities while over-seeing the precise managementof his disease. On April 16th,Ryan was awarded The RitterMemorial Courage Cup by theSteamboat Springs Winter SportsClub. The award was given toRyan for his special courage andfor being an inspiration to oth-ers.

Up to seven times a day, Ryanpricks his finger to test hisblood sugar and gives himself ashot of insulin three times daily.He sometimes has to miss outon favorite activities to stickwith his testing schedule. Ryan

accepts this routine as a neces-sary part of his life to keep himhealthy. Due to the stress andrigorous physical demands ofskiing, he follows a differentschedule on days when he racesand tests more often, beginningjust before his training starts.On those challenging days, heeats more carbohydrates, car-ries more fluids like LTPGatoradeand brings along some candyjust in case. His teammateshave learned the signs andsymptoms of low blood sugar,and if Ryan is exhausted or pale,they know what to do.

Ryan learned to ski at age two,and nothing has stopped himfrom doing what he loves. Nowhe is aiming for the Olympic SkiTeam. With the capable manage-ment of his diabetes, coupledwith his determination and zestfor life, Ryan Roberts willprobably do just that! We’re allrooting for you, Ryan. GO FORTHE GOLD!

SALUTE TO BDCVOLUNTEERSThe Denver Country Club wasthe setting on May 15th for theBDC Volunteer Luncheon honor-ing the hard-working ClinicVolunteers. The special lun-cheon was expertly organized byGuild President-Elect MartyJensen.

KANGAROO POCKETPITAS

INGREDIENTS

Whole pita bread, cut in half2-6” lettuce pieces1/2 cup grated carrot2 tablespoons peanut butter1 tablespoon raisins1 tablespoon sunflower nuts1/2 Jonathan apple, chopped

PREPARATION

Line each half pita with lettucepiece. Mix all remaining ingre-dients and divide into two equalportions. Stuff each pita pocketwith one portion of filling.

NUTRITION INFORMATION

Makes two sandwichesPortion: 1 sandwich25 grams carbohydrate7 grams protein5 grams fat

1997 Ritter Trophy winner Ryan Roberts

Ryan Roberts at the 1997 JuniorOlympics at Vail

BDC volunteers, standing from left Bea Bugelli, StellaGrimes, Judy Villano, Herb Bartlett, Nancy Reed, FriedaEisenbarth, Dolores Sullivan, Nancy Michener. Seated Lto R, Doris Stathopulos, BDC volunteer coordinatorKathy Griffis, Faye Glick, Sarita List, Marilyn Friedrich.

Cindy Barton ‘97

122222223

122222223

Photo:LindaHuebner

Guild President Linda Broughtonpresented Barbara Davis Centervolunteer Sarita List with a spe-cial gift for 15 years of dedicat-ed service. Attendees alsoincluded BDC volunteers NancyMichener, Stella Grimes, JudyVillano, Doris Stathopulos, BeaBugelli, Faye Glick, HerbBartlett, Frieda Eisenbarth,Dolores Sullivan, StaceyPreblud, Nancy Reed, MarilynFriedrich, Lynn Bentsen, BDCvolunteer coordinator KathyGriffis and Sue Palandri, CDFDirector of Finance.

In her message of thanks tohonored guests, Marty Jensencompared the centerpieces com-prised of vigorous strawberryplants spreading their tendrils,to the BDC volunteers whoreach far beyond what is askedof them to dedicate countlesshours to help children afflictedwith diabetes. Clinic Volunteersare a source of tremendous helpto the Center’s busy staff mem-bers. They brighten the day forclinic patients by making themfeel welcome and helping themduring their visits to the Center.

PARENT SUPPORTGROUPS NEEDEDMany phone calls have beenreceived from families askingabout local support groups. We

are looking for parents and/orguardians of children with type Idiabetes to organize or join aparent support group in the fol-lowing areas: Denver, Littleton,Englewood, Lakewood,Wheatridge, Arvada, Aurora,Highlands Ranch and Golden. Anew support group has formedin the Boulder area. Ten fami-lies have already joined theBoulder group and are enjoyingpotluck suppers, sharing ideasand giving support to one anoth-er while their children play. Ifyou are interested in joining theBoulder group, call SoniaCooper at 444-1345. For addi-tional information on joining ororganizing a new support group,call Sue Palandri or LindaSchneider at the Foundationoffice, (303) 863-1200.

CONGRATULATIONSCHARLOTTE TUCKERSCHOLARSHIPWINNERS!The Wellshire Inn was the set-ting for The Guild’s luncheonhonoring college-boundCharlotte Tucker Scholarshipwinners and their parents. Theselection of scholarship winnersfrom many impressive candi-dates involves detailed consider-ation of the records of each stu-dent by scholarship committeemembers. This year’s annualScholarship Awards Luncheonwas arranged by chairpersonsSharon Whiton Gelt and JuliaPeay. Chairperson for TheGuild’s Scholarship Committeewas Judy Villano.

18

BOOK ORDER FORMName

Address

City/State

Zip Phone

Understanding Insulin-Dependent Diabetes $10 per copy(includes postage) _____ Quantity

A Coloring Book About Diabetes $4 per copy (includespostage) _____ Quantity

Kid’s Cupboard: A cookbook chock full of treats for all ages$10 per copy (includes postage) _____ Quantity

Make check payable to: The Guild–CDF at Denver

All orders must be paid in full before delivery. Books aremailed 4th class book rate – allow 1 to 3 weeks for delivery.Large orders are shipped UPS.

Canadian and Foreign Purchasers: Please include sufficientfunds to equal U.S. currency exchange rates and internationalpostage.

For additional information call (303) 863-1200 or (800) 695-2873.

Mailing address: The Guild of theChildren’s Diabetes Foundation777 Grant Street, Suite 302Denver, CO 80203

Guild Guide — Linda HuebnerGuild Guide Editor

L to R, Guild President-Elect Marty Jensen, 15-year vol-unteer Sarita List, and Guild President Linda Broughton

Photo:LindaHuebner

Each year, $1,000 awards aregiven by The Guild of CDF tohelp defray college expenses for30 students treated through pro-grams at the Barbara DavisCenter. The Charlotte TuckerScholarship program was estab-lished in 1990 as an ongoingtribute to a past president ofThe Guild, who inspired andencouraged BDC patients to berelentless in their pursuit ofhigher education to help themreach their goals in life.

Following the luncheon, eachstudent spoke about plans,hopes and dreams for collegeand beyond. The Barbara DavisCenter joins the Children’sDiabetes Foundation in extend-ing hearty congratulations to theenterprising 1997 scholarshipwinners.

19

Guild Guide

GUILD CALENDAR

September 11Brass Ring Luncheon*

& Fashion ShowHyatt Regency DenverNeiman Marcus presents“THE ART OF FASHION”

*An event of the DenverNuggets Community Fund tobenefit charities such as theChildren’s Diabetes Foundation

at Denver. The DenverNuggets Community Fund is a

fund of the Robert R.McCormick Tribune

Foundation.�888

October Halloween Party -date to be announced

303-862-1200 OR800-695-2874

FOR INFORMATION

GUILDMEMBERSHIP FORM

YOUTH MEMBERSHIP Any youth 18 yearsof age or under: Annual dues of $2.00 perperson

ASSOCIATE MEMBERSHIP Annual dues of$30.00 per person

PATRON MEMBERSHIP Annual dues of$50.00 per person

LIFETIME MEMBERSHIP One-time dues of$250.00 per person

Name _________________________________

Address _______________________________

City/State/Zip __________________________

To actively participate in The Guild as avolunteer, please check your choice(s) below:

_____Barbara Davis Center Patient Check-In_____Barbara Davis Center Playroom_____Brass Ring Luncheon_____Halloween Party

Make check payable to:The Guild – CDF at Denver, and mail to:The Guild, Children's Diabetes Foundation777 Grant Street, Suite 302Denver, CO 80203

For information, call (303) 863-1200 or(800)695-2873

L to R, Guild President Linda Broughton, ScholarshipChairman Judy Villano and Scholarship Awards LuncheonCo-Chairmen, Julia Peay and Sharon Whiton Gelt

Some of the 1997 scholarship winners L to R, rear, Adam Waterman, Davis Moore,Tim Deal, Scott Coulter, Corey Shaw, Patrick Cochran; front row, Jeanette Larsen,Kristen Noel, Nicole Pike, Maggie Zochol

Photos:LindaHuebner

Guild Guide

20Jeanette Larsen,Ricks College

Britney Bancroft,Montana State University

Robert Antonelli,Mesa State College

Molly Buster,Colorado State University

Renee Bender,Colorado State University

Melody Conrads,Colorado State University

Patrick Cochran,Colorado Institute of Art

Bridget GreerUniversity of N.Colorado

Tessa Jenkins,Northwest College

Tim Deal,Colorado State University

Corey Hostetler, MetropolitanState College of Denver

Jazzmine Hall, The AmericanMusical and Dramatic Academy

Sarah Covell,Davidson College

Scott Coulter,University of N. Colorado

The CharlotteTuckerScholarshipprogram wasestablished inmemory of aGuild memberwho encouragedthe children ofthe BarbaraDavis Center tofollow highercarrer and/oreducational pur-suits of theirchoice. Forinformation andapplications, callthe CDF office at(303) 863-1200or 800-695-2873.

1997CHARLOTTE TUCKER

SCHOLARSHIPWINNERS!

The Children’s DiabetesFoundation and

the Barbara Davis Centercongratulate the winners of the

1997 Charlotte TuckerScholarship awards!

Ryan Mandeville, GonzagaUniversity of Spokane WA

21

Guild Guide

Tim McMahan,Colorado State University

Davis Moore,University of Wyoming

Kristen Noel,University of CO at Boulder

Casey Olsen,Dawson Community College

Nicole Pike,University of CO at Boulder

Micah Risher,Cornell College

Zachary Sexton,Northland College

Corey Shaw,University of Wyoming

Joe Sprowls,Colorado State University

Amber Townsend,University of Wyoming

Luke Schuessler,Wisconsin Lutheran College

Paul SchuesslerWisconsin Lutheran College

Michael SchwabHastings College

Adam Waterman,University of Colorado

Ron Wright,Colorado State University

Maggy Zochol, Universityof Nebraska at Lincoln

COURAGEOUSFIREFIGHTER SENDSMESSAGE OF HOPE

— Robin and Dan Mulroney

Once a young person becomes asenior in high school, peoplebegin asking the big question,“What are your career goals andhow are you going to achievethem?” By the time JoshuaMulroney finished his senioryear at Highlands Ranch HighSchool, he’d come up with hisanswer . . . “I’m going to be afirefighter.” Then his journeybegan.

Josh was diagnosed with dia-betes when he was five yearsold. Three months later, he wasinsisting on giving his own injec-tions. That’s when we knew thisyoung boy would be the one incontrol and not the disease.

In high school, Josh chose oneof the more difficult sports a

diabetic could be a part of,wrestling. At the time, Josh wasone of the youngest students tomake the varsity wrestling team.He carefully kept track of hisblood sugars and at the sametime maintained his weight,which is an important aspect ofthe sport.

After graduation, Josh receivedthe Charlotte Tucker ScholarshipAward and used the opportunityto receive his EmergencyMedical Technician Certificationat Arapahoe Community College.During that time, he attendedthe Vail Fire Academy and tookthe entrance exam with the VailFire Department. He had to gothrough an Oral Board Reviewand was timed against appli-cants in a physical agility testwhich required running, climb-ing ladders and lifting and carry-ing heavy hoses. Josh was theyoungest person to take the testand the only diabetic. Out of 18participants, Josh came in third,and in May 1997, Josh packedup his car and moved to Vail foryet another step toward his goal.

Josh now lives at the FireStation in Vail. This summer heis taking classes such asHazardous Materials, BuildingInspections and SprinklerControls at Colorado MountainCollege. On weekends, he mustalso attend training sessionswith the fire department and beon duty four days a month. Joshalso works at a local retail storewhen he can squeeze in the time.

None of this would be possiblefor Josh without the proper careand maintenance of his dia-betes. Besides eating well andmonitoring glucose levels, Joshhas had to make some plans forthose “just in case” times. Hehas stocked a backpack withglucose tablets and snacks. Ifhe goes out on a “call,” he will

be able to maintain his needswhile caring for others.

Joshua is going to be a leader inthis challenging career as a fire-fighter with diabetes. He hasalready run into some prejudicewith regard to his career choice,but he answers each skeptic thesame way . . . “Watch me, andsee what a diabetic can do.”

ARIELLA GOLDMANMANAGES DIABETESWITH CONFIDENCEMy name is Ariella Goldman. Iam nine years old and going intothe fourth grade. I’ve had dia-betes for 21⁄2 years and I needthree shots of insulin a day. I’vebeen giving myself shots forabout two years. My doctor’sname is Marian Rewers. At firsthe said I shouldn’t give my ownshots. Before I had my firstshot, my Dad let me give him ashot with an empty syringe. Ihit a nerve, but he didn’t tell meat the time because he didn’twant me to get scared.

When I first found out that I haddiabetes, I was sort of shockedbecause I never heard of any-thing like it. I thought I wouldnever be able to eat candyagain! About a year ago Ilearned how to read the ingredi-ents on cereal, candy, and other

Winner’s Circle

22

BDC patient, Ariella Goldman

Dedicated firefighter, Joshua Mulroney, during strenu-ous career training at Vail, CO

food boxes, so I could figure out howmuch I could eat. On days we havebirthday snacks at school, I alwayslook at the ingredients. If we havecake, I scrape the icing off.

For two years I’ve been walking theBoulder Bolder. It is 6.2 miles andfinishes at the CU stadium. Last yearI got low, but this year I drankLTPGatorade, because every few blocksthere were cups of it. I don’t justwalk—I bike, swim every Thursday,and I take Tae Kwon Do. On the com-puter, my dad makes these slidingscales so I know how much insulin Ishould get. One time on the WallStreet Journal’s website, we found anarticle on diabetes. It was really cool.

All I hope for is a cure for diabetes.Still, I know not to keep my hopes uptoo high. Ariella Goldman, 9.

Note: Ariella, the Barbara DavisCenter is filled with hope and determi-nation to find the cure, but in themeantime, keep up the great workyou’re doing with managing your dia-betes!

BDC PATIENT SARAH HILLEXCELS AT VIOLACOMPETITIONSIn May, I participated in the solo andensemble viola competition inBrighton, CO and played a solo, a duetand two ensembles on my viola. Themarks I received were “1” on each ofmy entries (the best score possible),and a “1” in the large group contestmy orchestra participated in this

spring. I received five medals and twotrophies, both at school and in variouscontests. Sarah Hill, 13.

Note from H. Peter Chase, M.D.:Sarah was diagnosed with IDDM twoyears ago and has done an excellentjob of managing her diabetes. Shemade friends with Sarah Swann fromEngland at diabetes camp last summerand is looking forward to seeing heragain this summer. Diabetes hasobviously not slowed Sarah down!

23

A child reaching for the brassring on a carousel is symbolicof the most important goal ofthe Children’s DiabetesFoundation — a cure. Your con-tribution on behalf of a loved onewill make a difference. It willsupport treatment programs toassist children with diabetes inleading healthier lives; and it willfund research to help CDF “catchthe brass ring” by finding a cure.

Mark an anniversary, birthday,special occasion, express appreci-ation or make a memorial tributein honor of someone special witha contribution — for any amount— to the Children’s DiabetesFoundation at Denver.Donations are tax deductible.Tax ID #84-0745008

NEWSNOTES is published threetimes per year by the Children’sDiabetes Foundation at Denver.We welcome your comments.If you would like to submit anarticle or a letter to NEWSNOTESsend information to:

Children’s DiabetesFoundation at Denver777 Grant Street, Suite 302Denver, CO 80203

Christine LernerEditor

Linda HuebnerManaging EditorThe Guild Guide Editor

Cindy BartonGraphic Designer

Dorothy HarringtonAssociate Editor

Alice GreenClinic News Liaison

Know the symptoms ofChildhood Diabetes:• Loss of weight• Extreme thirst• Excessive irritability• Frequent urination

Enclosed is my Contribution of $ _________________

In memory of ____________________________________Or in honor of ___________________________________Occasion _______________________________________

Please send acknowledgements to:(Amount of gift will not be mentioned)

Name ___________________________________________Address _________________________________________City ________________ State _______ Zip ____________

From:Name ___________________________________________Address _________________________________________City ________________ State _______ Zip ____________

The Brass RingFund

Remember a loved one ––Help CDF “Catch the Brass Ring”

Children’s Diabetes Foundation at Denver777 Grant Street, Suite 302, Denver, CO 80203

Sarah Hill with Doran Azari, Judge at the Brighton, Colorado competition

Printed on recycled paper

Nonprofit Org.

U.S. POSTAGE

PAIDDenver, CO

Permit No. 1752

Children’s DiabetesFoundation at Denver, CO

777 Grant Street, Suite 302Denver, CO 80203

Address CorrectionRequested

NEIMAN MARCUS AND DENVER NUGGETS JOINFOR ANNUAL BRASS RING LUNCHEON*

The Brass Ring Luncheon Kick-off,chaired by Jan Cortez, was heldJune 3rd at the Hyatt Regency

Denver. Christel Dikeman and NancyHusted of Neiman Marcus presentedan exciting preview of styles which willbe highlighted at the Brass RingLuncheon set for September 11th atthe Hyatt Regency Denver.

Chairman of the prestigiousSeptember event is Diane Sweat. Thetheme of the luncheon is THE ART OFFASHION, featuring The Best ofNeiman Marcus, and headlining theAmerican and European Collections ofOgnibene Zendman, Giorgio Armani,Escada, John Paul Gautier, Gucci,Donna Karan, Badgley Mischka,Moschino, Oscar de la Renta, St.John, Valentino and Emanuel Ungaro.Cocktails and hors d’oeuvres will beserved prior to the start of the fashionshow.

The Patron Reception, chaired byMarsha Bolen, will be at Neiman

Marcus on the day following the eventfor platinum and gold ticket holders.Two fabulous door prizes from theHyatt Regency Denver can be won byattending the Brass Ring Luncheonand Fashion Show: A weekend nightfor two, with dinner at the Hyattrestaurant, “1876,” or two nights at aspectacular Hyatt Regency Resort.Proceeds of the event support essen-tial research, treatment and educa-tional programs at the Barbara DavisCenter for Childhood Diabetes.

Ticket prices are:Platinum-$250Gold-$150Brass Ring-$65

A sellout is expected. Tickets maybe purchased by calling303-863-1200.

*An event of the Denver Nuggets CommunityFund to benefit charities such as theChildren’s Diabetes Foundation at Denver.The Denver Nuggets Community Fund is afund of the Robert R. McCormick TribuneFoundation.

L to R, Jan Cortez, Kick-off Chairman withDiane Sweat, Chairman of the Brass RingLuncheon and Fashion Show

Photo:LindaHuebner


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