Salivary β1-Adrenergic Receptor-Related Immunoreactivity in Pediatric Type 1 Diabetes Mellitus
Abstract
Introduction: Type 1 diabetes mellitus is associated with several oral complications, including salivary gland dysfunction and alterations in salivary composition. Adrenergic pathways are involved in the regulation of salivary secretion; however, salivary β1-adrenergic receptor-related immunoreactivity has not been well investigated in children with type 1 diabetes mellitus. This exploratory case-control study aimed to compare salivary β1-adrenergic receptor immunoreactivity between children with type 1 diabetes mellitus and systemically healthy controls. Materials and Methods: This observational case-control study included 66 children aged 7-13 years, comprising 33 children with type 1 diabetes mellitus and 33 systemically healthy controls within the same age range. Children with type 1 diabetes mellitus were clinically stable at enrollment and had acceptable metabolic control based on screening records and pediatric endocrinology evaluation. These glycemic criteria were used only for eligibility screening and were not included as analytic variables. Unstimulated whole saliva was collected using the spitting method after a minimum fasting period of 2 hours. Salivary β1-adrenergic receptor immunoreactivity was measured using a sandwich enzyme-linked immunosorbent assay. Data normality was assessed using the Shapiro-Wilk test, and the between-group comparison was performed using the Mann-Whitney U test. Results: Salivary β1-adrenergic receptor immunoreactivity was significantly higher in children with type 1 diabetes mellitus than in healthy controls. The median salivary β1-adrenergic receptor immunoreactivity was 81.56 ng/L (IQR: 62.12-92.31) in the type 1 diabetes mellitus group and 36.43 ng/L (IQR: 27.56-45.92) in the control group. The between-group difference was statistically significant (Mann-Whitney U = 137.0, p = 1.79 × 10⁻⁷). The range of values was wider in the type 1 diabetes mellitus group (19.96-615.28 ng/L) compared with controls (4.67-188.29 ng/L). Conclusion: Children with type 1 diabetes mellitus showed higher salivary β1-adrenergic receptor-related immunoreactivity than systemically healthy controls. This finding should be interpreted as preliminary evidence of altered salivary biomarker profiles rather than direct evidence of increased adrenergic receptor expression, receptor function, or sympathetic nervous system activity. Further studies with larger samples, community-based or matched controls, salivary flow rate measurement, oral health indices, and detailed diabetes-related variables are required to clarify the biological source and clinical relevance of this finding. Keywords: Type 1 diabetes mellitus; Pediatric diabetes; Saliva; Salivary biomarkers; β1-adrenergic receptor; Immunoreactivity; ELISA.
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17. Triebl Z, Bencze B, Bányai D, Rózsa N, Hermann P, Végh D. Poor glycemic control impairs oral health in children with type 1 diabetes mellitus-a systematic review and meta-analysis. BMC Oral Health. 2024;24(1):748.
18. Liu T, Wei Y, Zhu Y, Yang W. Caries status and salivary alterations of type-1 diabetes mellitus in children and adolescents: a systematic review and meta-analysis. Journal of Evidence Based Dental Practice. 2021;21(1):101496.
19. Catamo E, Tornese G, Navarra C, Aldegheri L, Zanotta N, Comar M, et al. Oral health and salivary inflammatory markers in children and adolescents with type 1 diabetes: A cross-sectional study. Journal of Endocrinological Investigation. 2026:1-10.
20. Cui L, Zheng J, Lu Y, Lin P, Lin Y, Zheng Y, et al. New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases. Journal of Nanobiotechnology. 2024;22(1):171.
21. Boulestreau J, Molina L, Ouedraogo A, Laramy L, Grich I, Van TNN, et al. Salivary extracellular vesicles isolation methods impact the robustness of downstream biomarkers detection. Scientific Reports. 2024;14(1):31233.
22. Mortazavi H, Yousefi-Koma A-A, Yousefi-Koma H. Extensive comparison of salivary collection, transportation, preparation, and storage methods: a systematic review. BMC Oral Health. 2024;24(1):168.
2. Moreira A, Passos I, Sampaio F, Soares M, Oliveira R. Flow rate, pH and calcium concentration of saliva of children and adolescents with type 1 diabetes mellitus. Brazilian Journal of Medical and Biological Research. 2009;42:707-11.
3. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine. 2010;38(11):602-6.
4. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. The lancet. 2014;383(9911):69-82.
5. Group DP. Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabetic medicine. 2006;23(8):857-66.
6. Al-Maskari AY, Al-Maskari MY, Al-Sudairy S. Oral manifestations and complications of diabetes mellitus: a review. Sultan Qaboos University Medical Journal. 2011;11(2):179.
7. Ben-Aryeh H, Cohen M, Kanter Y, Szargel R, Laufer D. Salivary composition in diabetic patients. Journal of Diabetic Complications. 1988;2(2):96-9.
8. Rajakumar G, Scarpace PJ. βAdrenergic Signal Transduction in Aging Parotid and Submandibular Salivary Glands. Journal of Gerontology. 1991;46(6):B249-B51.
9. Aps JK, Martens LC. The physiology of saliva and transfer of drugs into saliva. Forensic science international. 2005;150(2-3):119-31.
10. Zhou G, Shu X, Long Y, Cao Y, Wang J, Liao G, et al. Dental caries and salivary alterations in patients with type 2 diabetes: A systematic review and meta-analysis. Journal of Dentistry. 2024;150:105321.
11. Marques RCR, da Silva JR, Lima CPV, Stefani CM, Dame-Teixeira N. Salivary parameters of adults with diabetes mellitus: a systematic review and meta-analysis. Oral surgery, oral medicine, oral pathology and oral radiology. 2022;134(2):176-89.
12. Hand AR. Salivary glands. Dental Science for the Medical Professional: An Evidence-Based Approach. 2023:49-66.
13. Song EAC, Chung SH, Kim JH. Molecular mechanisms of saliva secretion and hyposecretion. European Journal of Oral Sciences. 2024;132(2):e12969.
14. Proctor GB, Carpenter GH. Salivary secretion: mechanism and neural regulation. Monogr Oral Sci. 2014;24:14-29.
15. Steenhuis P, Huntley R, Gurenko Z, Yin L, Dale B, Fazel N, et al. Adrenergic signaling in human oral keratinocytes and wound repair. Journal of dental research. 2011;90(2):186-92.
16. Gholizadeh N, Rezayi A, Mirzaii-Dizgah I, Sheykhbahaei N. Saliva Levels of Adrenergic Receptors in Relation to Psychological Factors in Patients with Oral Lichen Planus. Chinese Journal of Dental Research. 2023;26(3).
17. Triebl Z, Bencze B, Bányai D, Rózsa N, Hermann P, Végh D. Poor glycemic control impairs oral health in children with type 1 diabetes mellitus-a systematic review and meta-analysis. BMC Oral Health. 2024;24(1):748.
18. Liu T, Wei Y, Zhu Y, Yang W. Caries status and salivary alterations of type-1 diabetes mellitus in children and adolescents: a systematic review and meta-analysis. Journal of Evidence Based Dental Practice. 2021;21(1):101496.
19. Catamo E, Tornese G, Navarra C, Aldegheri L, Zanotta N, Comar M, et al. Oral health and salivary inflammatory markers in children and adolescents with type 1 diabetes: A cross-sectional study. Journal of Endocrinological Investigation. 2026:1-10.
20. Cui L, Zheng J, Lu Y, Lin P, Lin Y, Zheng Y, et al. New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases. Journal of Nanobiotechnology. 2024;22(1):171.
21. Boulestreau J, Molina L, Ouedraogo A, Laramy L, Grich I, Van TNN, et al. Salivary extracellular vesicles isolation methods impact the robustness of downstream biomarkers detection. Scientific Reports. 2024;14(1):31233.
22. Mortazavi H, Yousefi-Koma A-A, Yousefi-Koma H. Extensive comparison of salivary collection, transportation, preparation, and storage methods: a systematic review. BMC Oral Health. 2024;24(1):168.
| Files | ||
| Issue | Vol 13, No 2 (Spring 2026) | |
| Section | Original Article(s) | |
| Keywords | ||
| Type 1 diabetes mellitus; Pediatric diabetes; Saliva; Salivary biomarkers; β1-adrenergic receptor; Immunoreactivity; ELISA. | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Khayamzadeh M, Alipour F, Sanei S, Baniebrahimi G. Salivary β1-Adrenergic Receptor-Related Immunoreactivity in Pediatric Type 1 Diabetes Mellitus. J Craniomaxillofac Res. 2026;2026(2):194-202.
