Relationship between Insulin Dosage and Metabolic Control (HbA1c) in Children and Adolescents with Type 1 Diabetes Mellitus

Chegini, Victoria; Oveisi, Sonia; Saffari, Fatemeh

doi:10.22038/jpp.2026.96670.5687

Relationship between Insulin Dosage and Metabolic Control (HbA1c) in Children and Adolescents with Type 1 Diabetes Mellitus

Document Type : original article

Authors

Victoria Chegini ¹

Sonia Oveisi ²

Fatemeh Saffari ³

¹ Department of Pediatric Critical Care Medicine, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

² Clinical Research Development Unit of Advanced Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

³ Non-communicable Diseases Research Center, Research Institute for Prevention of Non-communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.

10.22038/jpp.2026.96670.5687

Abstract

Background: Insulin requirements in pediatric type 1 diabetes mellitus (T1DM) vary according to age, pubertal status, and metabolic factors; however, the relationship between insulin dose and glycemic control remains complex.
Objective: This study aimed to evaluate the association between total daily insulin dose and metabolic control in children and adolescents with T1DM.
Methods: In this cross-sectional study, 471 children and adolescents with T1DM attending an endocrine clinic were evaluated. HbA1c was measured on two separate occasions at a three-month interval. Insulin dose was recorded at each monthly visit over the three-month observation period. Associations between total daily insulin dose (U/kg/day), HbA1c, body mass index (BMI), diabetes duration, and pubertal stage were analyzed.
Results: The mean age was 12.37 ± 3.95 years (range, 2.25–17.8 years), and the mean duration of diabetes was 4.69 ± 3.36 years. A significant positive correlation was observed between total daily insulin dose and HbA1c (r = 0.18, p < 0.001). Insulin requirements increased significantly across pubertal stages (p < 0.001). BMI showed a positive correlation with insulin dose among male participants (r = 0.20, p = 0.008). In multivariable regression analysis, total insulin dose was significantly associated with HbA1c (β = 0.74, 95% CI: 0.22–1.26, p = 0.006), whereas age, sex, diabetes duration, and pubertal stage were not significant predictors.
Conclusion: Higher insulin doses were associated with poorer glycemic control, likely reflecting compensatory dose escalation rather than improved metabolic regulation. Pubertal status and BMI significantly influenced insulin requirements in children and adolescents with T1DM.

Keywords

Body mass index

Insulin

Glycated hemoglobin

Puberty

Microalbuminuria

Type 1 diabetes mellitus

1. Ogle GD, James S, Dabelea D, Pihoker C, Svennson J, Maniam J, et al. Global estimates of incidence of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Atlas. Diabetes research and clinical practice. 2022 Jan 1;183:109083.

2. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. The lancet. 2014 Jan 4;383(9911):69-82.

3. DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. The Lancet. 2018 Jun 16;391(10138):2449-62.

4. American Diabetes Association Professional Practice Committee: Draznin B, Aroda VR, Bakris G, Benson G, Brown FM. Freeman R, et al. Facilitating Behavior Change and Well-being to Improve Health Outcomes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S60-82.

5. Hirsch IB, Sherr JL, Hood KK. Connecting the dots: validation of time in range metrics with microvascular outcomes. Diabetes Care. 2019 Feb 12;42(3):345.

6. Apostolopoulou M, Lambadiari V, Roden M, Dimitriadis GD. Insulin resistance in type 1 diabetes: pathophysiological, clinical, and therapeutic relevance. Endocrine Reviews. 2025 Jun;46(3):317-48.

7. Rasmussen VF, Vestergaard ET, Schwandt A, Beltrand J, Rami-Merhar B, O'Riordan SM, et al. Proportion of basal to total insulin dose is associated with metabolic control, body mass index, and treatment modality in children with type 1 diabetes—a cross-sectional study with data from the International SWEET registry. The Journal of Pediatrics. 2019 Dec 1;215:216-22.

8. Beckers M, Polle O, Gallo P, Bernard N, Bugli C, Lysy PA. Determinants and Characteristics of Insulin Dose Requirements in Children and Adolescents with New‐Onset Type 1 Diabetes: Insights from the INSENODIAB Study. Journal of Diabetes Research. 2023;2023(1):5568663.

9. Karamanakos G, Kokkinos A, Dalamaga M, Liatis S. Highlighting the role of obesity and insulin resistance in type 1 diabetes and its associated cardiometabolic complications. Current obesity reports. 2022 Sep;11(3):180-202.

10. Wiegand S, Raile K, Reinehr T, Hofer S, Näke A, Rabl W, et al. Daily insulin requirement of children and adolescents with type 1 diabetes: effect of age, gender, body mass index and mode of therapy. European journal of endocrinology. 2008 Apr;158(4):543-9.

11. Chiang JL, Maahs DM, Garvey KC, Hood KK, Laffel LM, Weinzimer SA, et al. Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes care. 2018 Aug 13;41(9):2026.

12. Rica I, Mingorance A, Gómez-Gila AL, Clemente M, González I, Caimari M, et al. Achievement of metabolic control among children and adolescents with type 1 diabetes in Spain. Acta diabetologica. 2017 Jul;54(7):677-83.

13. Cree-Green M, Stuppy JJ, Thurston J, Bergman BC, Coe GV, Baumgartner AD, et al. Youth with type 1 diabetes have adipose, hepatic, and peripheral insulin resistance. The Journal of Clinical Endocrinology & Metabolism. 2018 Oct;103(10):3647-57.

14. Lan YY, Kovinthapillai R, Kędzia A, Niechciał E. Age-based challenges to type 1 diabetes management in the pediatric population. Frontiers in pediatrics. 2024 Sep 2;12:1434276.

15. Litwin A, Le Thi TG, El‐Lababidi N, Kindermann A, Pancheva R, Gerasimidis K, et al. Celiac disease diagnosis in clinical practice: ESPGHAN quality of care survey from 129 pediatric hospitals across 28 countries. Journal of pediatric gastroenterology and nutrition. 2025 Sep;81(3):606-17.

16. Fröhlich‐Reiterer E, Elbarbary NS, Simmons K, Buckingham B, Humayun KN, Johannsen J, et al. ISPAD Clinical Practice Consensus Guidelines 2022: Other complications and associated conditions in children and adolescents with type 1 diabetes. Pediatric diabetes. 2022 Dec 1;23(8):1451.

17. Jia Q, Zhang Y, Zhang B, An X. Reassessing type 2 diabetes in adolescents and its management strategies based on insulin resistance. Frontiers in endocrinology. 2024 Jun 19;15:1377918.

18. Mazzotta FA, Lucaccini Paoli L, Rizzi A, Tartaglione L, Leo ML, Popolla V, et al. Unmet needs in the treatment of type 1 diabetes: why is it so difficult to achieve an improvement in metabolic control?. Nutrition & Diabetes. 2024 Aug 2;14(1):58.

19. de Bock M, Codner E, Craig ME, Huynh T, Maahs DM, Mahmud FH, et al. ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes. Pediatric diabetes. 2022 Dec 20;23(8):1270.

20. Gregory JW, Cameron FJ, Joshi K, Eiswirth M, Garrett C, Garvey K, et al. ISPAD clinical practice consensus guidelines 2022: diabetes in adolescence. Pediatric diabetes. 2022 Oct 17;23(7):857.

21. Mohammed O, Alemayehu E, Bisetegn H, Debash H, Gedefie A, Ebrahim H, et al. Prevalence of microalbuminuria among diabetes patients in africa: a systematic review and meta-analysis. Diabetes, Metabolic Syndrome and Obesity. 2023 Dec 31:2089-103.

22. Lešović S. Effect of age, sex and the insulin regiment on insulin needs in children and adolescents suffering from diabetes mellitus type 1. Medicinski glasnik Instituta za štitastu žlezdu i metabolizam" Zlatibor". 2016 Jan 1.

23. Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV. Impaired insulin action in puberty. New England Journal of Medicine. 1986 Jul 24;315(4):215-9.

24. Hong CP. Insulin resistance during puberty: results from clamp studies in 357 children. Diabetes. 1999 Jan 1.

25. Kliegman RM, St. Geme JW III, eds. Nelson Textbook of Pediatrics. 22nd ed. Philadelphia: Elsevier; 2025. Chapter 629, Type 1 Diabetes Mellitus.

26. Beck RW, Bergenstal RM, Cheng P, Kollman C, Carlson AL, Johnson ML, et al. The relationships between time in range, hyperglycemia metrics, and HbA1c. Journal of diabetes science and technology. 2019 Jul;13(4):614-26.

27. He BB, Liu ZZ, Xu RY, Fan L, Guo R, Deng C, et al. Glycated hemoglobin is not enough: The role of glycemia risk index for glycemic control assessment in type 1 diabetes. World Journal of Diabetes. 2025 Jun 15;16(6):104024.