Case Control Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2024; 15(8): 1717-1725
Published online Aug 15, 2024. doi: 10.4239/wjd.v15.i8.1717
Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes
Jorge M Molina, Patricia G Medina, Rita A Gomez, Julia R Herrera, Nancy L Martínez, Brenda Hernández, Yesenia García
Jorge M Molina, Patricia G Medina, Department of Endocrinology, Children’s Hospital Federico Gomez, Mexico 06720, Mexico
Rita A Gomez, National Medical Center "Siglo XXI", UMAE Hosp Especialidades, Unidad Invest Med Epidemiol Clin, Mexican Social Security Institute, Mexico 06720, Mexico
Julia R Herrera, Research Division, UMAE Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Mexican Institute of Social Security, Mexico 06720, Mexico
Nancy L Martínez, Brenda Hernández, Epidemiology Research Unit in Endocrinology and Nutrition, Federico Gómez Children’s Hospital, Mexico 06720, Mexico
Yesenia García, Department of Endocrinology, Comprehensive Health Unit for Trans Persons, Mexico 11340, Mexico
Author contributions: Molina JM recruited, compiled, wrote, and edited the manuscript; Gómez RA and Herrera JR contributed to the writing of the protocol and the manuscript; Medina PG supervised the development of the study; Martínez NL and Hernández B participated in the processing of the antibodies; García Y participated in the recruitment of patients. All authors have read and approved the final manuscript.
Supported by Mexican Federal Funds HIM, No. 2018/068 SSA152.
Institutional review board statement: The study aligned with the General Health Law, article 17 in research, respecting universal principles of ethics, and complied with the Official Mexican Standard NOM-012-SSA2-2012 that establishes criteria for the execution of research projects in humans. The study was approved by the research, ethics, and biosafety committee of the Federico Gómez Children's Hospital in Mexico, registered under the HIM 2018/068 protocol.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Data sharing statement: Research data is not shared.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jorge M Molina, PhD, Doctor, Department of Endocrinology, Children’s Hospital Federico Gomez, Dr. Márquez 162, Colonia Doctores, Cuauhtemoc, Mexico 06720, Mexico. dereck79@live.com.mx
Received: April 4, 2024
Revised: May 28, 2024
Accepted: June 26, 2024
Published online: August 15, 2024
Processing time: 113 Days and 2.6 Hours
Abstract
BACKGROUND

Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus (T2DM), that is, patients who have insulin resistance, obesity, and other cardiovascular risk factors, suggesting that the presence of glutamic acid decarboxylase (anti-GAD65), islet antigen 2 (anti-IA2), and zinc transporter 8 (anti-Zn8T) antibodies could have deleterious effects on beta cell function, causing failure and earlier requirement for insulin treatment.

AIM

To evaluate anti-GAD65, anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM.

METHODS

This was a case–control study in patients with clinically diagnosed with T2DM (68 cases and 64 controls with and without early insulin dependence respectively), male and female, aged 12–18 years. Somatometry, blood pressure, glucose, insulin, C-peptide, glycated hemoglobin A1c, and lipid profiles were assessed. ELISA was used to measure anti-GAD65, anti-IA2, and anti-Zn8T antibodies. Descriptive statistics, Pearson's χ2 test, Student's t test, and logistic regression was performed. P < 0.05 was considered statistically significant.

RESULTS

There were 132 patients (53.8% female), with a mean age was 15.9 ± 1.3 years, and there was a disease evolution time of 4.49 ± 0.88 years. The presence of anti-GAD65, anti-IA2, and anti-Zn8T positivity was found in 29.5%, 18.2%, and 15.9%, respectively. Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity: anti-GAD65 odds ratio (OR): 2.42 (1.112–5.303, P = 0.026); anti-IA2: OR: 1.55 (0.859–2.818, P = 0.105); and anti-Zn8T: OR: 7.32 (2.039–26.279, P = 0.002).

CONCLUSION

Anti-GAD65 positivity was high in our study. Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype, leading to an increased risk of early insulin dependence.

Keywords: Diabetes; Obesity; Adolescents; Autoimmunity; Beta cell; Insulin requirements

Core tip: We found that adolescent patients with type 2 diabetes mellitus (T2DM) showed a more aggressive phenotype of the disease, with a significant depletion of beta cell function, and where antibodies against pancreatic beta cells were associated with lower levels of insulin and C-peptide conferring a higher risk of early dependence on exogenous insulin. Therefore, in a pediatric patient with T2DM phenotype, the determination of pancreatic antibodies can be a clinical tool to predict early insulin requirements, leading to closer control of the disease to avoid chronic complications.