Risk Factors for Type 1 Diabetes

Marian Rewers; Lars C. Stene; Jill M. Norris

Risk Factors for Type 1 Diabetes

Review

In: Diabetes in America. 3rd edition. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 11.

Authors

Marian Rewers¹, Lars C. Stene², Jill M. Norris³

Book Editors

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

Affiliations

¹ 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
² Dr. Lars C. Stene is Senior Scientist at the Department of Child Health, Norwegian Institute of Public Health, Oslo, Norway
³ Dr. Jill M. Norris is Professor of Epidemiology at the Colorado School of Public Health, University of Colorado, 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: 33651530
Bookshelf ID: NBK567965

Excerpt

The incidence of type 1 diabetes is increasing at an annual rate of 3%–5%, which suggests a major environmental exposure has changed, by either the gradual introduction of a susceptibility factor or the removal of a protective factor, during the past 60 or more years. Outbreaks and seasonality of type 1 diabetes may suggest an infectious cause, perhaps related to increasing sanitation and loss of herd immunity. Early childhood diet and environmental toxins are also of interest.

Prospective studies following high-risk children from birth to development of the subclinical phase of the disease (islet autoimmunity) and diabetes have been the most reliable source of information regarding risk factors for type 1 diabetes. Prenatal and early post-natal exposures appear to be critical, as the incidence of islet autoimmunity peaks in the second year of life. Among the infectious agents, enteroviral infections (particularly if they are persistent and acquired in early childhood) have gained most interest. Early leads suggesting the role of cow’s milk exposure in the initiation of islet autoimmunity have not been confirmed by large prospective studies and a large randomized clinical trial. While numerous studies have reported 1.5–2-fold increases in the risk of islet autoimmunity or type 1 diabetes with various components of early childhood diet and infectious exposures, none of the associations appears particularly strong or universal across different populations.

In the United States, 1 in 300 children and adolescents develop type 1 diabetes by age 20 years, but 1 in 40 offspring of mothers with type 1 diabetes and 1 in 15 offspring of fathers with type 1 diabetes develop type 1 diabetes. The disease is likely caused by the interplay of genetic and environmental factors. Systematic investigation of gene-environment interactions in large, prospectively followed cohorts of young children may help to identify and fully characterize modifiable risk factors and design trials to fully evaluate the strongest candidate triggers of autoimmunity.

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