Evaluation of the systemic-immune inflammation index (SII) and systemic immune-inflammation response index (SIRI) in children with type 1 diabetes mellitus and its relationship with cumulative glycemic exposure

Sukriye Ozde; Gulsah Akture; Mehmet Ali Ozel; Fatma Yavuzyilmaz; Ilknur Arslanoglu; Cem Ozde; Osman Kayapinar; Gokhan Coskun

doi:10.1515/jpem-2024-0043

Article

Evaluation of the systemic-immune inflammation index (SII) and systemic immune-inflammation response index (SIRI) in children with type 1 diabetes mellitus and its relationship with cumulative glycemic exposure

Sukriye Ozde , Gulsah Akture , Mehmet Ali Ozel , Fatma Yavuzyilmaz , Ilknur Arslanoglu , Cem Ozde , Osman Kayapinar and Gokhan Coskun

Published/Copyright: June 3, 2024

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 7

Abstract

Objectives

In this study, the systemic proinflammatory status was assessed using the systemic immune-inflammation index (SII) and SIRI systemic immune-inflammatory response index (SIRI) in children and adolescents with type 1 diabetes mellitus (T1DM).

Methods

The study involved 159 patients aged between 6 and 16 years. The SII and SIRI values were calculated based on the complete blood count. Basic blood biochemistry evaluated, and carotid intima-media thickness (cIMT) was measured and recorded. The cumulative glycemic exposure was calculated by multiplying the value above the normal reference range of the HbA_1c value. The sum of all these values obtained from the time of diagnosis to obtain the cumulative glycemic exposure. All findings were compared statistically. All statistically significant parameters were evaluated in the multivariate logistic regression analysis.

Results

The analysis revealed that only cIMT (Exp(B)/OR: 0.769, 95 % CI: 0.694–0.853, p<0.001), high-density lipoprotein (Exp(B)/OR: 3.924, 95 % CI: 2.335–6.596, p<0.001), monocyte count (Exp(B)/OR: 1.650, 95 % CI: 1.257–2.178, p<0.001), hematocrit (Exp(B)/OR: 0.675, 95 % CI: 0.523–0.870, p<0.001), and SIRI (Exp(B)/OR: 1.005, 95 % CI: 1.002–1.008, p<0.001) were significantly associated with T1DM. A statistically significant positive association was found between cumulative glycemic exposure and SIRI only (r=0.213, p=0.032). To our knowledge, this is the first study to evaluate SII and SIRI in children with type 1 diabetes.

Conclusions

These findings indicate that SIRI could serve as a potential biomarker for detecting early-onset proatherosclerotic processes in diabetic children. However, further clinical studies are required to confirm this.

Keywords: type 1 diabetes; children; inflammation

Corresponding author: Osman Kayapinar, MD, Department of Cardiology, Düzce University Faculty of Medicine, Ciftepinarlar mahallesi, 39.sokak. no:4/1 Konuralp/Duzce 8100, Düzce, Türkiye, E-mail: osmankayapinar@gmail.com

Research ethics: The authors confirm that they adhered to the tenets of the World Medical Association Declaration of Helsinki on the ethical conduct of research involving human subjects. The local Ethics Committee approved the study.
Informed consent: Written informed consent was obtained from the families of all subjects.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

References

1. Pettitt, DJ, Talton, J, Dabelea, D, Divers, J, Imperatore, G, Lawrence, JM, et al.. SEARCH for diabetes in youth study group: prevalence of diabetes in U.S. Youth in 2009: the SEARCH for diabetes in youth study. Diabetes Care 2014;37:402–8. https://doi.org/10.2337/dc13-1838.Search in Google Scholar PubMed PubMed Central

2. Sharma, H, Lencioni, M, Narendran, P. Cardiovascular disease in type 1 diabetes. Cardiovasc Endocrinol Metab 2019;8:28–34. https://doi.org/10.1097/xce.0000000000000167.Search in Google Scholar PubMed PubMed Central

3. Dabelea, D, Stafford, JM, Mayer-Davis, EJ, D’Agostino, RJr, Dolan, L, Imperatore, G, et al.. Association of type 1 diabetes versus type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA 2017;317:825–35. https://doi.org/10.1001/jama.2017.0686.Search in Google Scholar PubMed PubMed Central

4. Rawshani, A, Sattar, N, Franzén, S, Rawshani, A, Hattersley, AT, Svensson, A-M, et al.. Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet 2018;392:477–86. https://doi.org/10.1016/s0140-6736(18)31506-x.Search in Google Scholar PubMed PubMed Central

5. de Ferranti, SD, Steinberger, J, Ameduri, R, Baker, A, Gooding, H, Kelly, AS, et al.. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American heart association. Circulation 2019;139:e603–34. https://doi.org/10.1161/cir.0000000000000618.Search in Google Scholar

6. Libby, P, Ridker, PM, Hansson, GK. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 2009;54:2129–38. https://doi.org/10.1016/j.jacc.2009.09.009.Search in Google Scholar PubMed PubMed Central

7. Ross, R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340:115–26. https://doi.org/10.1056/nejm199901143400207.Search in Google Scholar

8. Snell-Bergeon, JK, West, NA, Mayer-Davis, EJ, Liese, AD, Marcovina, SM, D’Agostino, RBJr, et al.. Inflammatory markers are increased in youth with type 1 diabetes: the SEARCH case-control study. J Clin Endocrinol Metab 2010;95:2868–76. https://doi.org/10.1210/jc.2009-1993.Search in Google Scholar PubMed PubMed Central

9. Liu, Y, Ye, T, Chen, L, Jin, T, Sheng, Y, Wu, G, et al.. Systemic immune-inflammation index predicts the severity of coronary stenosis in patients with coronary heart disease. Coron Artery Dis 2021;32:715–20. https://doi.org/10.1097/mca.0000000000001037.Search in Google Scholar PubMed

10. Xia, Y, Xia, C, Wu, L, Li, Z, Li, H, Zhang, J., et al.. Systemic immune inflammation index (SII), system inflammation response index (SIRI) and risk of all-cause mortality and cardiovascular mortality: a 20-year follow-up cohort study of 42,875 US adults. J Clin Med 2023;12(3):1128. https://doi.org/10.3390/jcm12031128.Search in Google Scholar PubMed PubMed Central

11. Mayer-Davis, EJ, Kahkoska, AR, Jefferies, C, Dabelea, D, Balde, N, Gong, CX, et al.. ISPAD clinical practice consensus guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2018;19:7–19. https://doi.org/10.1111/pedi.12773.Search in Google Scholar PubMed PubMed Central

12. DiMeglio, LA, Acerini, CL, Codner, E, Craig, ME, Hofer, SE, Pillay, K, et al.. ISPAD clinical practice consensus guidelines 2018: glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes 2018;19:105–14. https://doi.org/10.1111/pedi.12737.Search in Google Scholar PubMed

13. Donaghue, KC, Marcovecchio, ML, Wadwa, RP, Chew, EY, Wong, TY, Calliari, LE, et al.. ISPAD clinical practice consensus guidelines 2018: microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes 2018;19:262–74. https://doi.org/10.1111/pedi.12742.Search in Google Scholar PubMed PubMed Central

14. Rabago Rodriguez, R, Gómez-Díaz, RA, Tanus Haj, J, Avelar Garnica, FJ, Ramirez Soriano, E, Meguro, EN, et al.. Carotid intima-media thickness in pediatric type 1 diabetic patients. Diabetes Care 2007;30:2599–602. https://doi.org/10.2337/dc07-0922.Search in Google Scholar PubMed

15. Orchard, TJ, Forrest, KY, Ellis, D, Becker, DJ. Cumulative glycemic exposure and microvascular complications in insulin dependent diabetes mellitus: the glycemic threshold revisited. Arch Intern Med 1997;157:1851–6. https://doi.org/10.1001/archinte.157.16.1851.Search in Google Scholar

16. Margeirsdottir, HD, Stensaeth, KH, Larsen, JR, Brunborg, C, Dahl-Jørgensen, K. Early et al signs of atherosclerosis in diabetic children on intensive insulin treatment: a population-based study. Diabetes Care 2010;33:2043–8. https://doi.org/10.2337/dc10-0505.Search in Google Scholar PubMed PubMed Central

17. Santos, RD, Gidding, SS, Hegele, RA, Cuchel, MA, Barter, PJ, Watts, GF, et al.. International atherosclerosis society severe familial hypercholesterolemia panel. Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the international atherosclerosis society severe familial hypercholesterolemia panel. Lancet Diabetes Endocrinol 2016;4:850–61. https://doi.org/10.1016/s2213-8587(16)30041-9.Search in Google Scholar

18. Raitakari, O, Pahkala, K, Magnussen, CG. Prevention of atherosclerosis from childhood. Nat Rev Cardiol 2022;19:543–54. https://doi.org/10.1530/ey.19.14.17.Search in Google Scholar

19. Borén, J, Chapman, MJ, Krauss, RM, Packard, CJ, Bentzon, JF, Binder, CJ, et al.. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2020;41:2313–30. https://doi.org/10.1093/eurheartj/ehz962.Search in Google Scholar PubMed PubMed Central

20. Gusev, E, Zhuravleva, Y. Inflammation: a new look at an old problem. Int J Mol Sci 2022;23:4596. https://doi.org/10.3390/ijms23094596.Search in Google Scholar PubMed PubMed Central

21. Tylutka, A, Morawin, B, Walas, Ł, Michałek, M, Gwara, A, Zembron-Lacny, A, et al.. Assessment of metabolic syndrome predictorsin relation to inflammation and visceral fat tissue in older adults. Sci Rep 2023;13:89. https://doi.org/10.1038/s41598-022-27269-6.Search in Google Scholar PubMed PubMed Central

22. Henein, MY, Vancheri, S, Longo, G, Vancheri, F. The role of inflammation in cardiovascular disease. Int J Mol Sci 2022;23:12906. https://doi.org/10.3390/ijms232112906.Search in Google Scholar PubMed PubMed Central

23. Zhou, Q, Su, S, You, W, Wang, T, Ren, T, Zhu, L., et al.. Systemic inflammation response index as a prognostic marker in cancer patients: a systematic review and meta-analysis of 38 cohorts. Dose Response 2021;19:1–14. https://doi.org/10.1177/15593258211064744.Search in Google Scholar PubMed PubMed Central

24. Krantz, JS, Mack, WJ, Hodis, HN, Liu, CR, Liu, CH, Kaufman, FR, et al.. Early onset of subclinical atherosclerosis in young persons with type 1 diabetes. J Pediatr 2004;145:452–7. https://doi.org/10.1016/j.jpeds.2004.06.042.Search in Google Scholar PubMed

25. Bjornstad, P, Donaghue, KC, Maahs, DM. Macrovascular disease and risk factors in youth with type 1 diabetes: time to be more attentive to treatment? Lancet Diabetes Endocrinol 2018;6:809–20. https://doi.org/10.1016/s2213-8587(18)30035-4.Search in Google Scholar

26. Lorenz Matthias, W, Markus Hugh, S, Bots Michiel, L, Rosvall, M, Sitzer, M. Prediction of clinical cardiovascular events with carotid intima-media thickness. Circulation 2007;115:459–67. https://doi.org/10.1161/circulationaha.106.628875.Search in Google Scholar PubMed

27. Singh, TP, Groehn, H, Kazmers, A. Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus. J Am Coll Cardiol 2003;41:661–5. https://doi.org/10.1016/s0735-1097(02)02894-2.Search in Google Scholar PubMed

28. Shah, AS, Dabelea, D, Fino, NF, Dolan, LM, Paul Wadwa, R, D’Agostino, RJr, et al.. Predictors of increased carotid intima-media thickness in youth with type 1 diabetes: the SEARCH CVD study. Diabetes Care 2016;39:418–25. https://doi.org/10.2337/dc15-1963.Search in Google Scholar PubMed PubMed Central

29. Larsen, J, Brekke, M, Sandvik, L, Arnesen, H, Hanssen, KF, Dahl-Jorgensen, K. Silent coronary atheromatosis in type 1 diabetic patients and its relation to long-term glycemic control. Diabetes 2002;51:2637–41. https://doi.org/10.2337/diabetes.51.8.2637.Search in Google Scholar PubMed

30. Nathan, DM, Lachin, J, Cleary, P, Orchard, T, Brillon, DJ, Backlund, JY, et al.. Diabetes control and complications trial, epidemiology of diabetes interventions and complications research group. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med 2003;348:2294–303. https://doi.org/10.1056/NEJMoa022314.Search in Google Scholar PubMed PubMed Central

31. Nathan, DM, Cleary, PA, Backlund, JY, Genuth, SM, Lachin, JM, Orchard, TJ, et al.. Diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study research group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353:2643–53. https://doi.org/10.1056/NEJMoa052187.Search in Google Scholar PubMed PubMed Central

32. Heier, M, Margeirsdottir, HD, Brunborg, C, Hanssen, KF, Dahl-Jørgensen, K, Seljeflot, I, et al.. Inflammation in childhood type 1 diabetes; influence of glycemic control. Atherosclerosis 2015;238:33–7. https://doi.org/10.1016/j.atherosclerosis.2014.11.018.Search in Google Scholar PubMed

33. Weber, KS, Nowotny, B, Strassburger, K, Pacini, G, Müssig, K, Szendroedi, J, et al.. The role of markers of low-grade inflammation for the early time course of glycemic control, glucose disappearance rate, and β-cell function in recently diagnosed type 1 and type 2 diabetes. Diabetes Care 2015;38:1758–67. https://doi.org/10.2337/dc15-0169.Search in Google Scholar PubMed

34. Gordon, T, Castelli, WP, Hjortland, MC, Kannel, WB, Dawber, TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977;62:707–14. https://doi.org/10.1016/0002-9343(77)90874-9.Search in Google Scholar PubMed

35. Orchard, TJ, Costacou, T, Kretowski, A, Nesto, RW, Forrest, KY-Z, Smithline, KL, et al.. Type 1 diabetes and coronary artery disease. Diabetes Care 2006;29:2528–38. https://doi.org/10.2337/dc06-1161.Search in Google Scholar PubMed

36. Chiesa, ST, Charakida, M, McLoughlin, E, Nguyen, HC, Georgiopoulos, G, Motran, L, et al.. Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation. Eur Heart J 2019;40:3559–66. https://doi.org/10.1093/eurheartj/ehz114.Search in Google Scholar PubMed PubMed Central

37. Abdel-Moneim, A, Zanaty, MI, El-Sayed, A, Khalil, RG, Rahman, HA. Relation between oxidative stress and hematologic abnormalities in children with type 1 diabetes. Can J Diabetes 2020;44:222–8. https://doi.org/10.1016/j.jcjd.2019.07.153.Search in Google Scholar PubMed

38. Coregliano-Ring, L, Goia-Nishide, K, Rangel, ÉB. Hypokalemia in diabetes mellitus setting. Medicina 2022;58:431. https://doi.org/10.3390/medicina58030431.Search in Google Scholar PubMed PubMed Central

Received: 2024-01-22

Accepted: 2024-05-11

Published Online: 2024-06-03

Published in Print: 2024-07-26

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Articles in the same Issue

https://doi.org/10.1515/jpem-2024-0043

Keywords for this article

type 1 diabetes; children; inflammation