Review

Prevention of Type 1 Diabetes

Jay S. Skyler¹, Jeffrey P. Krischer², Dorothy J. Becker³, Marian Rewers⁴

Catherine C. Cowie¹, Sarah Stark Casagrande², Andy Menke², Michelle A. Cissell³, Mark S. Eberhardt⁴, James B. Meigs⁵, Edward W. Gregg⁶, William C. Knowler⁷, Elizabeth Barrett-Connor⁸, Dorothy J. Becker⁹, Frederick L. Brancati¹⁰, Edward J. Boyko¹¹, William H. Herman¹², Barbara V. Howard¹³, K. M. Venkat Narayan¹⁴, Marian Rewers¹⁵, Judith E. Fradkin¹⁶

, editors.

In: Diabetes in America. 3rd edition. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 37.

Affiliations

¹ Dr. Jay S. Skyler is Professor of Medicine at the Diabetes Research Institute, University of Miami Miller School of Medicine, University of Miami, Miami, FL
² Dr. Jeffrey P. Krischer is Professor at the University of South Florida College of Medicine, and Director of the USF Diabetes Center and USF Health Informatics Institute, Tampa, FL
³ Dr. Dorothy J. Becker is Professor of Pediatrics in the Division of Endocrinology and Diabetes, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA
⁴ Dr. Marian Rewers is Professor of Pediatrics and Medicine at the Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO

Book Affiliations

¹ Senior Advisor and Director for Diabetes Epidemiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
² Senior Research Analyst, Social & Scientific Systems, Inc., Silver Spring, MD
³ Science Writer/Editor, Chicago, IL
⁴ Epidemiologist, Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD
⁵ Professor of Medicine, Harvard Medical School, and Physician, Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA
⁶ Chief, Epidemiology and Statistics Branch, Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA
⁷ Chief, Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ
⁸ Distinguished Professor, Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA
⁹ Professor of Pediatrics, Division of Endocrinology and Diabetes, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA
¹⁰ Distinguished Service Professor of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD
¹¹ Professor, University of Washington, and Staff Physician, Veterans Affairs Puget Sound, Seattle, WA
¹² Professor, Departments of Internal Medicine and Epidemiology, University of Michigan, Ann Arbor, MI
¹³ Professor of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University Hospital, and Senior Scientist, MedStar Health Research Institute, Hyattsville, MD
¹⁴ Director, Emory Global Diabetes Research Center, Ruth and O.C. Hubert Professor of Global Health and Epidemiology, Rollins School of Public Health, and Professor of Medicine, School of Medicine, Emory University, Atlanta, GA
¹⁵ Professor of Pediatrics and Medicine, Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO
¹⁶ Director, Division of Diabetes, Endocrinology, and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

PMID: 33651549
Bookshelf ID: NBK567991

Free Books & Documents

Review

Prevention of Type 1 Diabetes

Jay S. Skyler et al.

Free Books & Documents

In: Diabetes in America. 3rd edition. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 37.

Authors

Jay S. Skyler¹, Jeffrey P. Krischer², Dorothy J. Becker³, Marian Rewers⁴

Book Editors

Affiliations

¹ Dr. Jay S. Skyler is Professor of Medicine at the Diabetes Research Institute, University of Miami Miller School of Medicine, University of Miami, Miami, FL
² Dr. Jeffrey P. Krischer is Professor at the University of South Florida College of Medicine, and Director of the USF Diabetes Center and USF Health Informatics Institute, Tampa, FL
³ Dr. Dorothy J. Becker is Professor of Pediatrics in the Division of Endocrinology and Diabetes, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA
⁴ Dr. Marian Rewers is Professor of Pediatrics and Medicine at the Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO

Book Affiliations

¹ Senior Advisor and Director for Diabetes Epidemiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
² Senior Research Analyst, Social & Scientific Systems, Inc., Silver Spring, MD
³ Science Writer/Editor, Chicago, IL
⁴ Epidemiologist, Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD
⁵ Professor of Medicine, Harvard Medical School, and Physician, Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA
⁶ Chief, Epidemiology and Statistics Branch, Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA
⁷ Chief, Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ
⁸ Distinguished Professor, Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA
⁹ Professor of Pediatrics, Division of Endocrinology and Diabetes, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA
¹⁰ Distinguished Service Professor of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD
¹¹ Professor, University of Washington, and Staff Physician, Veterans Affairs Puget Sound, Seattle, WA
¹² Professor, Departments of Internal Medicine and Epidemiology, University of Michigan, Ann Arbor, MI
¹³ Professor of Medicine, Department of Medicine, Division of Endocrinology and Metabolism, Georgetown University Hospital, and Senior Scientist, MedStar Health Research Institute, Hyattsville, MD
¹⁴ Director, Emory Global Diabetes Research Center, Ruth and O.C. Hubert Professor of Global Health and Epidemiology, Rollins School of Public Health, and Professor of Medicine, School of Medicine, Emory University, Atlanta, GA
¹⁵ Professor of Pediatrics and Medicine, Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO
¹⁶ Director, Division of Diabetes, Endocrinology, and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

PMID: 33651549
Bookshelf ID: NBK567991

Excerpt

Type 1 diabetes is a progressive disease. There is a genetic predisposition to type 1 diabetes, particularly conferred by alleles present within the major histocompatibility complex (HLA region) on the short arm of chromosome six. It is thought that in susceptible individuals, an environmental trigger initiates an immune response. Immune infiltration into pancreatic islets results in beta cell damage, impairment of beta cell function, and potential destruction of beta cells. One would expect that if type 1 diabetes is an immunologically mediated disease, then immune intervention should alter the natural history of the disease and potentially abrogate the clinical syndrome.

Intervention trials have been conducted at a number of stages of the disease process. Primary prevention trials have been conducted in individuals with a genetic predisposition who have not yet developed immunologic markers (“Pre-Stage 1”). Secondary prevention trials have been conducted in individuals with two or more diabetes-related autoantibodies, either during Stage 1 of type 1 diabetes (normal metabolic function) or Stage 2 of type 1 diabetes (abnormal metabolic function). Intervention trials, also called tertiary prevention trials, have been conducted in individuals with Stage 3 of type 1 diabetes (clinical hyperglycemia), usually shortly after clinical onset of disease.

This chapter provides brief summaries of the randomized controlled clinical trials that have been conducted and also mentions some non-randomized pilot studies. Unfortunately, none of the primary or secondary prevention trials have clearly arrested the disease process. Some tertiary intervention trials have demonstrated improved beta cell function, at least for some period of time, after which beta cell function has generally declined in parallel to that in the respective control group. This could be a consequence of most studies focusing on only a single immunologic mechanism; whereas, what may be required are studies that deal with multiple immunologic mechanisms, including attempting to improve regulatory immunity, while also addressing beta cell function by including interventions that improve beta cell health.

PubMed Disclaimer

Conflict of interest statement

DUALITY OF INTEREST

Dr. Skyler received personal fees from Dexcom, Debiopharm, Genentech, ImmunoMolecular Therapeutics, Intarcia, Intrexon, INNODIA, Eli Lilly and Company, Merck, Novo Nordisk, Orgenesis, and Sanofi Genzyme outside the submitted work. Drs. Krischer, Becker, and Rewers reported no conflicts of interest.

Sections

References

1. Eisenbarth GS: Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314:1360–1368, 1986 - PubMed
1. Bluestone JA, Herold K, Eisenbarth G: Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 464:1293–1300, 2010 - PMC - PubMed
1. Atkinson MA, Eisenbarth GS, Michels AW: Type 1 diabetes. Lancet 383:69–82, 2014 - PMC - PubMed
1. Atkinson MA, Bluestone JA, Eisenbarth GS, Hebrok M, Herold KC, Accili D, Pietropaolo M, Arvan PR, Von Herrath M, Markel DS, Rhodes CJ: How does type 1 diabetes develop? The notion of homicide or β-cell suicide revisited. Diabetes 60:1370–1379, 2011 - PMC - PubMed
1. Nerup J, Platz P, Andersen OO, Christy M, Lyngsoe J, Poulsen JE, Ryder LP, Nielsen LS, Thomsen M, Svejgaard A: HL-A antigens and diabetes mellitus. Lancet 2:864–866, 1974 - PubMed

Publication types

Actions

LinkOut - more resources

Full Text Sources
- NCBI Bookshelf
Research Materials
- NCI CPTC Antibody Characterization Program

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Prevention of Type 1 Diabetes

Affiliations

Book Affiliations

Prevention of Type 1 Diabetes

Authors

Book Editors

Affiliations

Book Affiliations

Excerpt

Conflict of interest statement

Sections

References

Publication types

LinkOut - more resources

Full Text Sources

Research Materials