Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Diabetes. Aug 15, 2026; 17(8): 122649
Published online Aug 15, 2026. doi: 10.4239/wjd.122649
Serum elemental profiles and their associations with glycemic control in pediatric type 1 and type 2 diabetes
Ahmed Abdelbaset-Ismail, Xiaodan Hui, Qian Lin, Chunjie Gu, Jason Xu, Sara Watson, Lu Cai, Yi Tan, Kupper A Wintergerst
Ahmed Abdelbaset-Ismail, Xiaodan Hui, Chunjie Gu, Jason Xu, Sara Watson, Lu Cai, Yi Tan, Kupper A Wintergerst, Pediatric Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY 40202, United States
Ahmed Abdelbaset-Ismail, Xiaodan Hui, Yi Tan, Phoenix Children’s Research Institute, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ 85004, United States
Qian Lin, Touchstone Diabetes Center, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, United States
Sara Watson, Lu Cai, Yi Tan, Kupper A Wintergerst, Wendy Novak Diabetes Institute, Norton Children’s Hospital, Norton Children’s Endocrinology, University of Louisville School of Medicine, Louisville, KY 40202, United States
Sara Watson, Lu Cai, Kupper A Wintergerst, Center for Integrative Environmental Health Sciences, University of Louisville School of Medicine, Louisville, KY 40202, United States
Lu Cai, Yi Tan, Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States
Lu Cai, Department of Radiation Oncology, University of Louisville School of Medicine, Louisville, KY 40202, United States
Co-corresponding authors: Yi Tan and Kupper A Wintergerst.
Author contributions: Tan Y, Wintergerst KA, and Cai L conceived and designed the study; Tan Y, Wintergerst KA are the co-corresponding authors of this manuscript; Tan Y, Wintergerst KA, Cai L, and Watson S requested samples; Xu J, Hui X, Lin Q, Gu C, and Abdelbaset-Ismail A prepared samples and conducted inductively coupled plasma mass spectrometer trace elemental analysis; Abdelbaset-Ismail A, Xu J, Cai L, and Tan Y analyzed data; Abdelbaset-Ismail A, Tan Y, and Cai L wrote the manuscript; Hui X, Lin Q, Gu C, Wintergerst KA, Cai L, and Tan Y edited the manuscript; Wintergerst KA, Cai L, and Tan Y supervised this study; all authors have approved the final version of the manuscript.
AI contribution statement: The authors take full responsibility and accountability for all content of this manuscript. AI tools were not used to generate any part of the manuscript, produce original scientific data, perform independent scientific analyses, or draw scientific conclusions.
Supported by the National Institutes of Health (NIH), No. X01DK125891, No. R01HL125877, and No. P30ES030283; and the Jewish Heritage Fund for Excellence Research Enhancement Grant Program at the University of Louisville School of Medicine.
Institutional review board statement: The study protocol was also reviewed and approved by the University of Louisville institutional review board (approval No. 19.0542).
Informed consent statement: Written informed consent was obtained from parents/guardians, along with written assent from participants < 18 years of age, as required by local institutional review board regulations.
Conflict-of-interest statement: None of the authors has any conflict of interest relating to this study.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The data supporting the findings of this study were obtained from the Pediatric Diabetes Consortium Registry. Data are not publicly available because of participant privacy and institutional restrictions but may be available from the corresponding author upon reasonable request and with appropriate approvals from the Pediatric Diabetes Consortium.
Corresponding author: Yi Tan, PhD, Professor, Phoenix Children’s Research Institute, Department of Child Health, University of Arizona College of Medicine, 475 N 5th St, Phoenix, AZ 85004, United States.
yitan@arizona.edu
Received: April 27, 2026
Revised: June 11, 2026
Accepted: June 29, 2026
Published online: August 15, 2026
Processing time: 102 Days and 18.7 Hours
BACKGROUND
Trace element dyshomeostasis has been implicated in the progression of diabetes mellitus (DM) in adults. However, data on elemental imbalances in children and adolescents with type 1 DM (T1DM) and type 2 DM (T2DM) remain limited.
AIM
To characterize serum elemental profiles and investigate their relationships with hemoglobin A1c (HbA1c) in diabetic children and adolescents.
METHODS
This observational study was conducted as a secondary analysis of 421 children and adolescents (221 with T1DM, 200 with T2DM) enrolled in the Pediatric Diabetes Consortium Registry. Demographics and clinical characteristics were briefly evaluated, and serum elemental profiles were analyzed and compared between the T1DM and T2DM and across demographic subgroups. Relationships between HbA1c and common serum elements or elemental ratios were assessed.
RESULTS
Serum magnesium (Mg), cobalt (Co), and antimony (Sb) levels were significantly lower in T2DM than in T1DM (all P < 0.0001), whereas copper (Cu) and zinc (Zn) levels were higher in T2DM compared to T1DM (both P < 0.0001). The Zn/iron (Fe) ratio was significantly lower in T1DM than in T2DM. By correlation analysis, in both T1DM and T2DM, HbA1c was positively associated with serum Cu (T1DM: ρ = 0.16, P = 0.02; T2DM: ρ = 0.31, P < 0.0001) and inversely associated with Zn/Cu ratio (T1DM: ρ = -0.21, P = 0.002; T2DM: ρ = -0.23, P = 0.001). In T1DM, HbA1c was also inversely associated with Zn (ρ = -0.16, P = 0.02) and the Zn/Fe ratio (ρ = -0.19, P = 0.01). In T2DM, HbA1c was positively associated with calcium and selenium, and inversely associated with Mg and barium. Significant ethnicity-related differences in the Zn/Cu ratio were observed in both T1DM and T2DM, and sex-related differences were identified in T2DM.
CONCLUSION
Youth with diabetes exhibit distinct serum elemental profiles, with significant alterations in Mg, Cu, Zn, Zn/Fe ratio, Co, and Sb. Multiple elements and elemental ratios were associated with HbA1c, including Cu, Zn, Zn/Fe, and Zn/Cu. This suggests that elemental dyshomeostasis may contribute to glycemic regulation and the pathophysiology of disease in pediatric diabetes. Further longitudinal studies involving healthy control groups are needed to clarify the clinical significance of these findings.
Core Tip: Trace elements play important roles in glucose metabolism, insulin action, and oxidative stress, yet their relationships to glycemic control in pediatric diabetes remain incompletely understood. This study comprehensively evaluated serum elemental profiles in children and adolescents with type 1 diabetes mellitus and type 2 diabetes mellitus. Distinct alterations in zinc, copper, magnesium, selenium, and trace-element ratios were identified, and several elements showed significant associations with glycated hemoglobin. These findings provide new insights into elemental dysregulation in pediatric diabetes and highlight potential biomarkers for glycemic control.
