Ingrid Libman, Polly J Bingley, Dorothy Becker, Jane H Buckner, Linda A DiMeglio, Stephen E Gitelman, Carla Greenbaum, Michael J Haller, Heba M Ismail, Jeffrey Krischer, Wayne V Moore, Antoinette Moran, Andrew B Muir, Vana Raman, Andrea K Steck, Frederico G S Toledo, John Wentworth, Diane Wherrett, Perrin White, Lu You, Kevan C Herold
{"title":"Hydroxychloroquine in Stage 1 Type 1 Diabetes.","authors":"Ingrid Libman, Polly J Bingley, Dorothy Becker, Jane H Buckner, Linda A DiMeglio, Stephen E Gitelman, Carla Greenbaum, Michael J Haller, Heba M Ismail, Jeffrey Krischer, Wayne V Moore, Antoinette Moran, Andrew B Muir, Vana Raman, Andrea K Steck, Frederico G S Toledo, John Wentworth, Diane Wherrett, Perrin White, Lu You, Kevan C Herold","doi":"10.2337/dc23-1096","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Innate immune responses may be involved in the earliest phases of type 1 diabetes (T1D).</p><p><strong>Research design and methods: </strong>To test whether blocking innate immaune cells modulated progression of the disease, we randomly assigned 273 individuals with stage 1 T1D to treatment with hydroxychloroquine (n = 183; 5 mg/kg per day to a maximum of 400 mg) or placebo (n = 90) and assessed whether hydroxychloroquine treatment delayed or prevented progression to stage 2 T1D (i.e., two or more islet autoantibodies with abnormal glucose tolerance).</p><p><strong>Results: </strong>After a median follow-up of 23.3 months, the trial was stopped prematurely by the data safety monitoring board because of futility. There were no safety concerns in the hydroxychloroquine arm, including in annual ophthalmologic examinations. Preplanned secondary analyses showed a transient decrease in the glucose average area under the curve to oral glucose in the hydroxychloroquine-treated arm at month 6 and reduced titers of anti-GAD and anti-insulin autoantibodies and acquisition of positive autoantibodies in the hydroxychloroquine arm (P = 0.032).</p><p><strong>Conclusions: </strong>We conclude that hydroxychloroquine does not delay progression to stage 2 T1D in individuals with stage 1 disease. Drug treatment reduces the acquisition of additional autoantibodies and the titers of autoantibodies to GAD and insulin.</p>","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":14.8000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620539/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2337/dc23-1096","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Innate immune responses may be involved in the earliest phases of type 1 diabetes (T1D).
Research design and methods: To test whether blocking innate immaune cells modulated progression of the disease, we randomly assigned 273 individuals with stage 1 T1D to treatment with hydroxychloroquine (n = 183; 5 mg/kg per day to a maximum of 400 mg) or placebo (n = 90) and assessed whether hydroxychloroquine treatment delayed or prevented progression to stage 2 T1D (i.e., two or more islet autoantibodies with abnormal glucose tolerance).
Results: After a median follow-up of 23.3 months, the trial was stopped prematurely by the data safety monitoring board because of futility. There were no safety concerns in the hydroxychloroquine arm, including in annual ophthalmologic examinations. Preplanned secondary analyses showed a transient decrease in the glucose average area under the curve to oral glucose in the hydroxychloroquine-treated arm at month 6 and reduced titers of anti-GAD and anti-insulin autoantibodies and acquisition of positive autoantibodies in the hydroxychloroquine arm (P = 0.032).
Conclusions: We conclude that hydroxychloroquine does not delay progression to stage 2 T1D in individuals with stage 1 disease. Drug treatment reduces the acquisition of additional autoantibodies and the titers of autoantibodies to GAD and insulin.
期刊介绍:
The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes.
Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.