Age and sex mark clinical differences in the presentation of pediatric type 1 diabetes mellitus
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Esha A. Gupta
Abstract
Objectives
Type 1 diabetes mellitus (T1D) is a heterogeneous condition. We aimed to study the associations between age and sex with clinical characteristics at the onset of pediatric T1D.
Methods
A secondary analysis was conducted on data collected retrospectively from 706 children newly diagnosed with T1D at a large tertiary hospital in southeastern USA. Age (stratified across three cohorts from 0.84 to 18.08 years), sex, and their interaction were compared for associations with clinical characteristics of T1D at presentation by multivariable regression analyses and pairwise comparisons.
Results
Within the participants (mean age 9.71 (SD 4.10), 48.3 % female, 21.0 % Hispanic, 15.3 % non-Hispanic black and 58.7 % non-Hispanic white), children under 6 years had higher glucose (p<0.001), lower hemoglobin A1c (HbA1c) (p<0.001), and lower C-peptide (p<0.001) than the older age groups. Diabetic ketoacidosis (DKA) was more prevalent in the youngest (p=0.005) and the intermediate-aged cohorts (p=0.005), compared to the oldest group. Among the children with DKA, bicarbonate was lower in the youngest (p<0.001) and middle cohorts (p=0.013), compared to the oldest group. Younger age was associated with higher prevalence of insulin autoantibodies (IAA; p<0.001) and IA-2 autoantibodies (IA-2A; p=0.006). Males had higher glucose (p=0.001), but lower HbA1c (p=0.003), lower C-peptide (p<0.001), and lower GAD autoantibody (GADA) prevalence (p=0.001) than females. There was no significant interaction between age and sex.
Conclusions
In children with new onset T1D, younger age and male sex were associated with findings suggestive of more rapid and aggressive T1D preclinical course, including poorer beta-cell function, and distinct islet autoantibody profiles.
Acknowledgments
We acknowledge Anaemy Danner De Armas for logistical assistance.
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Research ethics: The Baylor College of Medicine’s Institutional Review Board approved the study, protocol number H-27002.
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Informed consent: Informed consent was waived by the Baylor College of Medicine’s Institutional Review Board.
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Author contributions: Esha A. Gupta wrote the manuscript drafts and contributed to data analysis and interpretation. Xiaofan Huang, and Charles G. Minard ran statistical analyses and reviewed/edited the manuscript. All authors contributed to data interpretation and reviewed/approved the final version of the manuscript before submission. Maria J Redondo designed and oversaw the study, and is the guarantor of this article, taking full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript. The authors have accepted responsibility for the entire content of this manuscript and approved its submission.”
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: Authors state no conflict of interest.
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Research funding: None declared.
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Data availability: The data analyzed by this study is available from the corresponding author upon reasonable request.
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Prior presentations: Part of this manuscript was presented at the Texas Children’s Hospital annual research symposium (April 2nd, 2024) and at the annual Pediatric Endocrine Society of Texas, Oklahoma, Louisiana, and Arkansas conference (April 6th, 2024).
References
1. ElSayed, NA, Aleppo, G, Bannuru, RR, Bruemmer, D, Collins, BS, Ekhlaspour, L, et al.. 2. Diagnosis and classification of diabetes: standards of care in diabetes-2024. Diabetes Care 2024;47:S20–42. https://doi.org/10.2337/dc24-s002.Search in Google Scholar
2. Gale, EA, Gillespie, KM. Diabetes and gender. Diabetologia 2001;44:3–15. https://doi.org/10.1007/s001250051573.Search in Google Scholar PubMed
3. Mohammad, HA, Farghaly, HS, Metwalley, KA, Monazea, EM, Abd El-Hafeez, HA. Predictors of glycemic control in children with Type 1 diabetes mellitus in Assiut-Egypt. Indian J Endocrinol Metab 2012;16:796–802. https://doi.org/10.4103/2230-8210.100679.Search in Google Scholar PubMed PubMed Central
4. Bosi, E, Boulware, DC, Becker, DJ, Buckner, JH, Geyer, S, Gottlieb, PA, et al.. Impact of age and antibody type on progression from single to multiple autoantibodies in type 1 diabetes relatives. J Clin Endocrinol Metab 2017;102:2881–6. https://doi.org/10.1210/jc.2017-00569.Search in Google Scholar PubMed PubMed Central
5. Jacobsen, LM, Bocchino, L, Evans-Molina, C, DiMeglio, L, Goland, R, Wilson, DM, et al.. The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening. Diabetologia 2020;63:588–96. https://doi.org/10.1007/s00125-019-05047-w.Search in Google Scholar PubMed PubMed Central
6. Leete, P, Willcox, A, Krogvold, L, Dahl-Jørgensen, K, Foulis, AK, Richardson, SJ, et al.. Differential insulitic profiles determine the extent of β-cell destruction and the age at onset of type 1 diabetes. Diabetes 2016;65:1362–9. https://doi.org/10.2337/db15-1615.Search in Google Scholar PubMed
7. Battaglia, M, Ahmed, S, Anderson, MS, Atkinson, MA, Becker, D, Bingley, PJ, et al.. Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diabetes Care 2020;43:5–12. https://doi.org/10.2337/dc19-0880.Search in Google Scholar PubMed PubMed Central
8. Redondo, MJ, Morgan, NG. Heterogeneity and endotypes in type 1 diabetes mellitus. Nat Rev Endocrinol 2023;19:542–54. https://doi.org/10.1038/s41574-023-00853-0.Search in Google Scholar PubMed
9. You, W, Yang, J, Liu, Y, Wang, W, Zhu, L, Wang, W, et al.. Fulminant type 1 diabetes mellitus: two case reports. Medicine 2019;98:e14319. https://doi.org/10.1097/md.0000000000014319.Search in Google Scholar PubMed PubMed Central
10. Krischer, JP, Cuthbertson, DD, Greenbaum, C. Male sex increases the risk of autoimmunity but not type 1 diabetes. Diabetes Care 2004;27:1985–90. https://doi.org/10.2337/diacare.27.8.1985.Search in Google Scholar PubMed
11. Vehik, K, Bonifacio, E, Lernmark, Å, Yu, L, Williams, A, Schatz, D, et al.. Hierarchical order of distinct autoantibody spreading and progression to type 1 diabetes in the TEDDY study. Diabetes Care 2020;43:2066–73. https://doi.org/10.2337/dc19-2547.Search in Google Scholar PubMed PubMed Central
12. Decochez, K, De Leeuw, IH, Keymeulen, B, Mathieu, C, Rottiers, R, Weets, I, et al.. IA-2 autoantibodies predict impending type I diabetes in siblings of patients. Diabetologia 2002;45:1658–66. https://doi.org/10.1007/s00125-002-0949-8.Search in Google Scholar PubMed
13. So, M, O’Rourke, C, Ylescupidez, A, Bahnson, HT, Steck, AK, Wentworth, JM, et al.. Characterising the age-dependent effects of risk factors on type 1 diabetes progression. Diabetologia 2022;65:684–94. https://doi.org/10.1007/s00125-021-05647-5.Search in Google Scholar PubMed PubMed Central
14. Tojjar, J, Cervin, M, Hedlund, E, Brahimi, Q, Forsander, G, Elding, LH, et al.. Sex differences in age of diagnosis, HLA genotype, and autoantibody profile in children with type 1 diabetes. Diabetes Care 2023;46:1993–6. https://doi.org/10.2337/dc23-0124.Search in Google Scholar PubMed
15. Flores, MGV, Islam, H, Puttagunta, SM, Islam, R, Kundu, S, Jha, SB, et al.. Association between type 1 diabetes mellitus and celiac disease: autoimmune disorders with a shared genetic background. Cureus 2022;14:e22912. https://doi.org/10.7759/cureus.22912.Search in Google Scholar PubMed PubMed Central
16. Conrad, N, Misra, S, Verbakel, JY, Verbeke, G, Molenberghs, G, Taylor, PN, et al.. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet 2023;401:1878–90. https://doi.org/10.1016/s0140-6736(23)00457-9.Search in Google Scholar
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/jpem-2024-0451).
© 2024 Walter de Gruyter GmbH, Berlin/Boston
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