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World J Diabetes. Jan 15, 2020; 11(1): 13-25
Published online Jan 15, 2020. doi: 10.4239/wjd.v11.i1.13
Current understandings of the pathogenesis of type 1 diabetes: Genetics to environment
Adebola Matthew Giwa, Rizwan Ahmed, Zahra Omidian, Neha Majety, Kagan Ege Karakus, Sarah M Omer, Thomas Donner, Abdel Rahim A Hamad
Adebola Matthew Giwa, Department of Pediatrics, Johns Hopkins Medical Center, Baltimore, MD 21287, United States
Rizwan Ahmed, Zahra Omidian, Neha Majety, Sarah M Omer, Abdel Rahim A Hamad, Department of Pathology, Johns Hopkins Medical Center, Baltimore, MD 21205, United States
Kagan Ege Karakus, School of Medicine, Koc University, Istanbul 34450, Turkey
Thomas Donner, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
Author contributions: Giwa AM drafted, performed the literature review and analysis, critical revision, editing, writing and final approval of the final version; Ahmed R, Omidian Z, Majety N, Karakus KE, and Omer SM contributed with the literature review, analysis, and writing; Hamad ARA and Donner T contributed with critical revision, editing, and approval of the final version.
Supported by NIH grant AI R01966987 (Hamad ARA).
Conflict-of-interest statement: All the authors have nothing to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Abdel Rahim A Hamad, PhD, Associate Professor, Department of Pathology, Johns Hopkins Medical Center, Ross 66G, 720 Rutland Ave, Baltimore, MD 21205, United States. ahamad@jhmi.edu
Received: September 17, 2019
Peer-review started: September 18, 2019
First decision: October 13, 2019
Revised: November 1, 2019
Accepted: November 25, 2019
Article in press: November 25, 2019
Published online: January 15, 2020
Processing time: 90 Days and 8.4 Hours
Abstract

Type 1 diabetes (T1D) is an autoimmune disease that usually strikes early in life, but can affect individuals at almost any age. It is caused by autoreactive T cells that destroy insulin-producing beta cells in the pancreas. Epidemiological studies estimate a prevalence of 1 in 300 children in the United States with an increasing incidence of 2%-5% annually worldwide. The daily responsibility, clinical management, and vigilance required to maintain blood sugar levels within normal range and avoid acute complications (hypoglycemic episodes and diabetic ketoacidosis) and long term micro- and macro-vascular complications significantly affects quality of life and public health care costs. Given the expansive impact of T1D, research work has accelerated and T1D has been intensively investigated with the focus to better understand, manage and cure this condition. Many advances have been made in the past decades in this regard, but key questions remain as to why certain people develop T1D, but not others, with the glaring example of discordant disease incidence among monozygotic twins. In this review, we discuss the field’s current understanding of its pathophysiology and the role of genetics and environment on the development of T1D. We examine the potential implications of these findings with an emphasis on T1D inheritance patterns, twin studies, and disease prevention. Through a better understanding of this process, interventions can be developed to prevent or halt it at early stages.

Keywords: Type 1 diabetes genetics; Type 1 diabetes epigenetics; Role of genetics in type 1 diabetes; Diabetes prevention; Type 1 diabetes environment; Type 1 diabetes twin studies; Type 1 diabetes concordance; Type 1 diabetes discordance

Core tip: Type 1 diabetes (T1D) is one of the most common childhood chronic conditions with its incidence increasing annually. Its arduous management requires vigilance to avoid complications that impact quality of life and health care costs. A better understanding of how T1D develops can help find a way to prevent it from developing at all. In this review, we discuss the current understanding of the complex relationship between the roles of genetics and the environment in the development of T1D.