O N L I N E L E T T E R S COMMENTS AND mographic or clinical characteristics be- DIABETESINTERVENTIONSAND tween the 175 participants and the 56 COMPLICATIONS(DCCT/EDIC)RESEARCH RESPONSES nonparticipants at baseline. Complete GROUP* baselinedataareavailableuponrequest. From the 1Joslin Diabetes Center, Boston, Massa- Perlmuter et al. also stated that our chusetts;the2DepartmentofPsychiatry,Harvard article was unclear regarding the ages of MedicalSchool,Boston,Massachusetts;the3De- Glycemic Control and partmentofPsychiatry,UniversityofPittsburgh theindividualsduringeachseverehypo- School of Medicine, Pittsburgh, Pennsylvania; Hypoglycemia: Is the glycemicepisode:ByEDICyear12,there the 4Biostatistics Center, George Washington Loser the Winner? were294eventsin87subjects(33events, University,Washington,D.C.;5RainbowBabies ages 13–16 years; 71, 17–19 years; 152, and Children’s Hospital, Case Western Reserve 20–29 years; and 38, 30–39 years). As University, Cleveland, Ohio; 6Diabetes Clinical Research&Programs,UniversityofIowa,Iowa ResponsetoPerlmuteretal. notedonpage1936ofourarticle,thetim- City, Iowa; 7St. Joseph’s Health Care London, ingofseverehypoglycemiceventsdidnot UniversityofWesternOntario,London,Ontario, affect performance on any of the eight Canada;andthe8DepartmentofPediatricEndo- TheeditorialbyPerlmuteretal.(1)in cognitivedomainsevaluated. crinologyandMetabolism,WashingtonUniver- the October 2008 issue of Diabetes Finally, Perlmuter et al. expressed sityinSt.Louis,St.Louis,Missouri. Corresponding author: Gail Musen, gail.musen@ Care commented on the long-term concern regarding the synergistic ef- joslin.harvard.edu. effectsofseverehypoglycemiaandraised fects of hyperglycemia and hypoglyce- *Acompletelistoftheindividualsandinstitutionspar- concerns about our study (2), which re- mia and stated that statistical support ticipatingintheDCCT/EDICResearchGroupap- portedthatwithinthecohortofsubjects for these effects was not reported. The pearsinthefollowingarticle:JacobsonAM,Ryan CM,ClearyP,WaberskiB,BurwoodA,WeingerK, who entered the Diabetes Control and synergistic effects of hypoglycemia and BaylessM,DahmsW,HarthJ:Long-termeffects ComplicationsTrial(DCCT)duringado- hyperglycemia on cognitive function ofdiabetesanditstreatmentoncognitivefunc- lescence, there was no relationship be- were evaluated using the interaction tion.NEnglJMed356:1842–1852,2007. tween subsequent episodes of severe term in an ANCOVA model. We found †Deceased. hypoglycemiaandcognitiveperformance nostatisticallysignificanteffect. Thecontentofthisarticleissolelytheresponsibility measured(cid:1)20yearsafterstudyentry.Be- Inconclusion,ourresearchquestion oftheauthorsanddoesnotnecessarilyrepresent theofficialviewsoftheNationalInstituteofDia- low,weoutlinetheirfivemajorconcerns related to the long-term effects of severe betesandDigestiveandKidneyDiseasesorthe andprovidesupportinginformation. hypoglycemicepisodesoncognitiveper- NationalInstitutesofHealth. One concern of Perlmuter et al. was formance associated with intensive insu- DOI: 10.2337/dc08-2264. Clinical trial reg. no. NCT00360893,clinicaltrials.gov. the exclusion of potential participants lin therapy during the DCCT and post- © 2009 by the American Diabetes Association. from the DCCT if they had a history of DCCT period. Our results indicate that Readersmayusethisarticleaslongastheworkis severehypoglycemia,thuslimitinggener- forpatientssimilartothoseoftheDCCT properlycited,theuseiseducationalandnotfor alizability. However, a history of severe adolescent cohort, intensive diabetes profit, and the work is not altered. See http:// hypoglycemiawasnotanabsoluteexclu- therapycanbeimplementedwithoutun- creativecommons.org/licenses/by-nc-nd/3.0/ for details. sion criterion for participation in the due concern for development of long- DCCT. Indeed, 24% of the 175 partici- term cognitive deficits during the pantshadpreviouslyexperienced1–5ep- follow-upperiod.Despitethisfinding,in- Acknowledgments—Fundingforthisstudy isodesofseverehypoglycemiawithlossof tensive diabetes therapy must be prac- was provided by NIH grant 5R01-DK- consciousness before entry into the ticed with caution because severe 062218-02andcontractswiththeDivisionof DCCT. hypoglycemia can cause short-term cog- Diabetes, Endocrinology, and Metabolic Dis- TheeditorialbyPerlmuteretal.also nitive impairment that affects ability to easesoftheNationalInstituteofDiabetesand DigestiveandKidneyDiseasesandbytheGen- suggestedthatnonparticipationmayhave carry out daily activities and can lead to eral Clinical Research Centers Program, Na- beenduetocognitivedeteriorationorse- seizureorcoma.Moreover,effectsofhy- tionalCenterforResearchResources. vere hypoglycemic events. However, the poglycemiaatayoungeragewerenotas- Nopotentialconflictsofinterestrelevantto 56nonparticipantsremainedactiveinthe sessed.Insum,thegoalofachievingtight thisarticlewerereported. Epidemiology of Diabetes Interventions glycemic control while avoiding severe andComplications(EDIC)protocol,and hypoglycemia is appropriate for adoles- ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● data are available on their frequency of centpatients. References severe hypoglycemia. The frequency dis- 1. Perlmuter LC, Flanagan BP, Shah PH, tribution of severe hypoglycemia episodes GAILMUSEN,PHD1,2 SinghSP:Glycemiccontrolandhypoglyce- is similar between the 56 nonparticipants ALANM.JACOBSON,MD1,2 mia:istheloserthewinner?DiabetesCare andthe175participants(5vs.9%,respec- CHRISTOPHERM.RYAN,PHD3 31:2072–2076,2008 tively).Therefore,dropoutduetocognitive PATRICIAA.CLEARY,MS4 2. MusenG,JacobsonAM,RyanCM,Cleary deterioration is unlikely. A comparison of BARBARAH.WABERSKI,MS4 PA,WaberskiBH,WeingerK,DahmsW, cognitive performance between baseline KATIEWEINGER,EDD1,2 Bayless M, Silvers N, Harth J, White N, andDCCTyear5forbothgroupsshowed WILLIAMDAHMS,MD5† theDiabetesControlandComplications the same scores on seven domains, with MEGBAYLESS,RN6 Trial/EpidemiologyofDiabetesInterven- tions and Complications (DCCT/EDIC) participantsscoringmodestlybetteronlyon NANCYSILVERS,RN3 Research Group: Impact of diabetes and problemsolving(P(cid:2)0.01). JUDITHHARTH,RN7 itstreatmentoncognitivefunctionamong Perlmuteretal.assertedthatbaseline NEILWHITE,MD,CDE8 adolescentswhoparticipatedintheDia- data for the dropouts would have been FORTHEDIABETESCONTROLAND betes Control and Complications Trial. useful: There were no differences in de- COMPLICATIONSTRIAL/EPIDEMIOLOGYOF DiabetesCare31:1933–1938,2008 e46 DIABETESCARE,VOLUME32,NUMBER4,APRIL2009