Goldfine, Allison B.

Lopez, Ximena

Phua, Eng-Joo

Ramus, Julia

Diabetes Care

Harvard University - DASH 

 Cromolyn Sodium for Insulin-Induced Lipoatrophy: Old Drug,New Use  (Article begins on next page)The Harvard community has made this article openly available.Please share how this access benefits you. Your story matters.Citation Phua, Eng-Joo, Ximena Lopez, Julia Ramus, and Allison B.Goldfine. 2013. “Cromolyn Sodium for Insulin-InducedLipoatrophy: Old Drug, New Use.” Diabetes Care 36 (12): e204-e205. doi:10.2337/dc13-1123. http://dx.doi.org/10.2337/dc13-1123.Published Version doi:10.2337/dc13-1123Accessed February 17, 2015 8:08:02 AM ESTCitable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:13581128Terms of Use This article was downloaded from Harvard University's DASHrepository, and is made available under the terms and conditionsapplicable to Other Posted Material, as set forth athttp://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAAOBSERVATIONSCromolyn Sodium forInsulin-InducedLipoatrophy: OldDrug, New UseLocal insulin-induced lipoatrophy,an immune-mediated loss of sub-cutaneous adipose tissue at insulinadministration sites, is now a rare com-plication of insulin therapy in patientswith diabetes. Lipoatrophy incidence,previously noted in 10–55% of patientsusing animal-derived insulins (1), de-clined considerably with the advent ofand improved purity of modern insulins.Yet, it continues to be reported with in-sulin analogs (2,3) and poses a clinicalchallenge owing to erratic insulin absorp-tion at affected areas and distressing cos-metic issues.Wepreviouslydemonstratedincreaseddegranulating tryptase/chymase-positivemastcellsinbiopsies frominsulin-inducedlipoatrophic sites and reported that topi-cal cromolyn sodium (prepared with 4%cromolyn sodium in petrolatum solventfor topical administration twice daily toaffected areas) was efﬁcacious therapy in asmall series (4). Since this report, we werecontacted by 34 health care providers,caregivers, and patients worldwide, towhom we administered surveys to stan-dardize evaluation of their treatmentexperiences. The study was approved bythe institutional review board of the JoslinDiabetes Center.Twenty-one responded, providingdata on 24 patients with insulin-inducedlipoatrophy. Ten patients used cromolyn,while the remaining attempted othertherapeutic interventions or observation(Table 1). Ten respondents reported atrial of cromolyn administration. Of the10 cromolyn users, all had type 1 diabe-tes and 70% were male, with mean age16.1 6 5.0 years, age of diabetes diagno-sis 6.1 6 4.4 years, age when lipoatrophywas ﬁrst noticed 12.2 6 6.4 years, dura-tion of insulin use prior to onset of lipoat-rophy 6.1 6 5.2 years, and duration oflipoatrophy 3.9 6 3.4 years. Three pa-tients had Hashimoto thyroiditis andone other had hyperthyroidism as associ-ated autoimmune diseases.Insulin preparations associated withlipoatrophy included aspart (n 5 4),lispro (n 5 5), regular human insulin(n 5 1), NPH insulin (n 5 1), glargine(n 5 2), and detemir (n 5 1), with threepatients reporting use of more than oneinsulin preparation. Lipoatrophy oc-curred in regions corresponding to com-mon insulin injection sites: abdomen(n 5 6), thighs (n 5 5), and buttocks(n 5 3), with sizes ranging from 2 3 2cm to 8 3 10 cm. Eight patients reportedmultiple lipoatrophic sites.Among the 10 cromolyn users, 3 ini-tially attempted to treat lipoatrophy byswitching insulins, while 2 changed frominjections to continuous subcutaneousinsulin infusion without improvement.All patients who used cromolyn found itto be at least partially effective; six re-ported complete resolution of lipoatro-phic sites, while four reported partialresolution. These improvements wereattributed to cromolyn use by the healthcare providers or patients. The mean timefrom initiating cromolyn to noticeableclinical response was 3.1 6 0.9 months.No side effects or adverse events were re-ported in association with cromolyn.Switching insulins and cromolynwere the most frequent therapeutic inter-ventions for lipoatrophy in this series.Cromolyn was reported to be moresuccessful in enabling complete resolutionof lipoatrophy than other interventions.To our knowledge, this is the largestcaseseriestodateofpatientswithinsulin-induced lipoatrophy. The retrospectivestudy design, patient/provider qualitativeresponse, and use of multiple interven-tionsforlipoatrophyinnoncromolynuserscould have restricted the interpretationof results. Nonetheless, topical cromolynsodium appears to be a well-tolerated andeffective option for managing insulin-induced lipoatrophy.ENG-JOO PHUA, MBBS1,2XIMENA LOPEZ, MD3JULIA RAMUS, RN1ALLISON B. GOLDFINE, MD1,2From the1Joslin Diabetes Center, Boston, Massachu-setts; the2Harvard Medical School, Boston, Massa-chusetts; and the3Department of Pediatrics,University of Texas Southwestern, Dallas, Texas.Corresponding author: Allison B. Goldﬁne, allison.goldﬁne@joslin.harvard.edu.DOI: 10.2337/dc13-1123© 2013 by the American Diabetes Association.Readers may use this article as long as the work isproperly cited, the use is educational and not forproﬁt, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ fordetails.Acknowledgments—This work was sup-ported by grant P30DK036836 from theNational Institutes of Health. E.-J.P. receivedfellowship funding as part of the HealthManpower Development Plan award fromAlexandra Health Pte. Ltd. (Singapore).No potential conﬂicts of interest relevant tothis article were reported.E.-J.P.researcheddata,performedstatisticalanalysis, contributed to the discussion, andwrote and edited the manuscript. X.L. and J.R.researcheddata,contributedtothediscussion,and reviewedthe manuscript. A.B.G. designedthe study, researched data, contributed to thediscussion, and reviewed and edited themanuscript. A.B.G. is the guarantor of thiswork and, as such, had full access to all of thedata in the study and takes responsibility fortheintegrityofthedataandtheaccuracyofthedata analysis.The authors thank the health care providers,caregivers, and patients who shared their expe-rience by participating in the study survey.ccccccccccccccccccccccccReferences1. Reeves WG, Allen BR, Tattersall RB. Insulin-induced lipoatrophy: evidence for animmune pathogenesis. BMJ 1980;280:1500–15032. Holstein A,Stege H, Kovacs P. Lipoatrophyassociatedwiththeuseofinsulinanalogues:Table 1—Therapeutic interventions for insulin-induced lipoatrophyIntervention PatientsCompleteresolution Partial resolution No changeTopical cromolyn sodium 10 6 4 0Noncromolyn users*Changed insulin preparation 10 2 6 2Continuous subcutaneousinsulin infusion 4 2 0 2Glucocorticoid use 2 1 0 1Spontaneous resolution 1 1 0 0Data are n. *Noncromolyn users exceed 14 cases, as patients may have used more than one treatment option.e204 DIABETES CARE, VOLUME 36, DECEMBER 2013 care.diabetesjournals.orgONLINE LETTERSa new case associated with the use of insulinglargine and review of the literature. ExpertOpin Drug Saf 2010;9:225–2313. Babiker A, Datta V. Lipoatrophy with insu-lin analogues in type I diabetes. Arch DisChild 2011;96:101–1024. LopezX,CastellsM,RickerA,VelazquezEF,MunE, Goldﬁne AB. Human insulin analog–inducedlipoatrophy. Diabetes Care 2008;31:442–444care.diabetesjournals.org DIABETES CARE, VOLUME 36, DECEMBER 2013 e205Online Letters

Cromolyn Sodium for Insulin-Induced Lipoatrophy: Old Drug, New Use

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Cromolyn Sodium for Insulin-Induced Lipoatrophy: Old Drug, New Use

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