Çocukluk çağı başlangıçlı tip 1 diyabette inflamatuar kan belirteçleri diyabetin prezantasyon şekli ve kümülatif glisemik kontrol durumunu yansıtabilir mi?

Öz

Amaç: Tip 1 diyabetes mellitus (T1DM), çocukluk çağının en sık görülen diyabet formudur ve sistemik inflamasyonla ilişkili otoimmün β-hücre yıkımı ile karakterizedir. Bu çalışmanın amacı, inflamatuvar hematolojik indekslerin (SII, SIRI, NLR, PLR) çocukluk başlangıçlı T1DM’de başvuru tipi ve uzun dönem glisemik kontrolü yansıtma potansiyelini değerlendirmektir. Gereç ve Yöntemler: Nisan 2021 – Haziran 2024 tarihleri arasında, 2–18 yaş aralığında T1DM tanılı çocuklar ve yaş ile cinsiyet açısından eşleştirilmiş sağlıklı kontroller üzerinde kohort çalışması yürütüldü. Tanı anında hastalar klinik başvuru şekline göre diyabetik ketoasidoz (DKA), asidozsuz ketozis veya izole hiperglisemi olarak sınıflandırıldı. Hematolojik inflamasyon parametreleri (SII, SIRI, NLR, PIV, PDW, PCT, MPV) tanı anında ve bir yıllık takip sonunda ölçüldü. Tanı dönemi dışındaki ölçümler esas alınarak, bir yıllık ortalama HbA1c değerleri kümülatif glisemik kontrolü değerlendirmede kullanıldı. Buna göre hastalar iyi (<%7), orta (7–9%) ve kötü (>%9) metabolik kontrol gruplarına ayrıldı. Bulgular: Toplam 137 katılımcı (ortalama yaş 10,4±4,1 yıl; %51,1 kız (n: 67)] çalışmaya dahil edildi. T1DM’li hastaların %57,8’i DKA, %26,0’ı diyabetik ketozis ve %16,2’si izole hiperglisemi ile başvurdu. Tanı anında nötrofil ve lökosit sayıları ile birlikte SII, SIRI, NLR ve PLR düzeyleri DKA grubunda diğer alt gruplara ve kontrollere göre anlamlı derecede yüksekti (p<0,001). İnflamatuvar belirteçlerin takip döneminde metabolik kontrol düzeylerini ayırt etmede anlamlı bir değeri bulunmadı ve kümülatif HbA1c ile bu indeksler arasında korelasyon saptanmadı. ROC analizinde SII (AUC=0.793; %95 GA: 0.685–0.901) ve SIRI (AUC=0.780; %95 GA: 0.668–0.893) DKA’yı ayırt etmede en yüksek tanısal güce sahipti; optimal kesim değerleri sırasıyla 614.9 (sensitivite %76.9, spesifisite %75.9) ve 0.95 (sensitivite %85.4, spesifisite %65.5) olarak belirlendi. Sonuç: İnflamatuvar kan belirteçleri, özellikle SII ve SIRI, T1DM başlangıcında DKA varlığını belirlemede yararlı olabilir; ancak uzun dönem metabolik kontrolün öngörülmesinde değerli görünmemektedir.

Anahtar Kelimeler

• Tip 1 diyabetes mellitus
• glisemik kontrol
• hematolojik inflamasyon indeksi
• nötrofil-lenfosit oranı
• sistemik immün inflamasyon indeksi

Can inflammatory blood markers reflect presentation type and cumulative glycemic control status in childhood-onset type 1 diabetes?

Öz

Aim: Type 1 diabetes mellitus (T1DM) is the most common form of childhood diabetes and involves autoimmune β-cell destruction associated with systemic inflammation. This study aimed to evaluate the potential of inflammatory hematological indices (SII, SIRI, NLR, PLR) to indicate presentation type and long-term glycemic control in childhood- onset T1DM. Material and Methods: A longitudinal cohort study was conducted on children aged 2-18 years with T1DM and along with age- and sexmatched healthy controls, recruited between April 2021 and June 2024. At diagnosis, patients were categorized according to clinical presentation as diabetic ketoacidosis (DKA), ketosis without acidosis, or isolated hyperglycemia. Hematological inflammatory parameters (SII, SIRI, NLR, PIV, PDW, PCT, MPV) were measured at diagnosis and one-year follow- up. Mean HbA1c values obtained over the one-year follow-up period, excluding those from initial presentation, were used to assess cumulative glycemic control. Based on these values, patients were categorized into good (<7%), moderate (7–9%), and poor (>9%) metabolic control groups. Results: A total of 137 participants (mean age 10,4±4,1 years; %51,1 female (n: 67)] were included. Among T1DM patients, 57.8% presented with DKA. Seventy-seven children with T1DM and 60 healthy controls were included. Among the patients, 57.8% presented with DKA, 26.0% with diabetic ketosis, and 16.2% with isolated hyperglycemia. At diagnosis, neutrophil and leukocyte counts, as well as SII, SIRI, NLR, and PLR, were significantly higher in the DKA group than in the other subgroups and controls (p<0.001). Inflammatory markers were not useful in distinguishing metabolic control categories during follow-up, and no correlation was found between cumulative HbA1c and inflammatory indices at one year. In the ROC analysis, SII (AUC = 0.793; 95% CI: 0.685–0.901) and SIRI (AUC = 0.780; 95% CI: 0.668–0.893) demonstrated the highest diagnostic performance in distinguishing DKA; their optimal cut-off values were 614.9 (sensitivity 76.9%, specificity 75.9%) and 0.95 (sensitivity 85.4%, specificity 65.5%), respectively. Conclusion: Inflammatory blood markers, particularly SII and SIRI, appear to be valuable in identifying DKA at T1DM onset but not in predicting long-term metabolic control.

Anahtar Kelimeler

• Type 1 diabetes mellitus
• glycemic control
• hematological inflammatory index
• neutrophil-lymphocyte ratio
• systemic immune inflammation index

Kaynakça

1. Sperling MA, Wolfsdorf JI, Menon RK, Tamborlane WV, Maahs D, Battelino T, et al. Diabetes mellitus. In: Sperling Pediatric Endocrinology; 2021. p. 814-883. https://doi.org/10.1016/B978-0-323-62520-3.00021-X
2. Morales AE, She JX, Schatz DA. Genetics of Type 1 Diabetes. In: Pescovitz O.H, Eugster E.A (eds).Pedaitric Endocrinology. 1 edition. Philadelphia (USA): Lippincott Williams and Wilkins; 2004. p.403-10.
3. Tihić-Kapidžić S, Čaušević A, Fočo-Solak J, Malenica M, Dujić T, Hasanbegović S, et al. Assessment of hematologic markers and their correlation to hemoglobin A1c among Bosnian children with type 1 diabetes mellitus and their healthy peers. J Med Biochem. 2021;40(2):181-192. https://doi.org/10.5937/jomb0-25315
4. Korkmaz O. Assessment of the Platelet Parameters in Children With Type 1 Diabetes Mellitus. J Endocrinol Metab. 2018; 8(6): 144-8. https://doi.org/10.14740/jem537
5. Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J. Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Pro-ject Group. Diabetes Care.2000;23(10):1516-1526.2. https://doi.org/10.2337/diacare.23.10.1516
6. Baghersalimi A, Koohmanaee S, Darbandi B, Farzamfard V, Hassanzadeh Rad A, Zare R, et al. Platelet Markers Alterations in Children With Type 1 Diabetes Mellitus. J Pediatr Hematol Oncol. 2019;41(4):e227-e232. https://doi.org/10.1097/MPH.0000000000001454
7. Ersoy M, Selcuk Duru HN, Elevli M, Ersoy O, Civilibal M. Intima-Media Thickness and Mean Platelet Volume in Children With Type 1 Diabetes Mellitus. Iran J Pediatr. 2015;25(2): e368. https://doi.org/10.5812/ijp.368
8. Huang J, Xiao Y, Xu A, Zhou Z. Neutrophils in type 1 diabetes. J Diabetes Investig. 2016;7(5):652-663. https://doi.org/10.1111/jdi.12469

9. Sharma M, Narang S, Nema SK. Study of altered platelet morphology with changes in glycaemic status. Int J Res Med Sci (Internet). 2016;4(3):757-761. https://doi.org/10.18203/2320-6012.ijrms20160513
10. Özer S, Yılmaz R, Sönmezgöz E, Karaaslan E, Taşkın S, Bütün İ, et al. Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever. Med Sci Monit. 2015;21:298-303. https://doi.org/10.12659/MSM.892289
11. Mangoni AA, Zinellu A. The diagnostic role of the systemic inflammation index in patients with immunological diseases: a systematic review and meta-analysis. Clin Exp Med. 2024;24(1):27. https://doi.org/10.1007/s10238-024-01294-3
12. 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. Pediatr Diabetes. 2022;23(8):1270-1276. https://doi.org/10.1111/pedi.13455
13. Cao LF, Xu QB, Yang L. Systemic immune indicators for predicting renal damage in newly diagnosed type 1 diabetic children. World J Diabetes. 2025;16(5):104482. https://doi.org/10.4239/wjd.v16.i5.104482
14. Aygün F, Efe D. Association of neutrophil/lymphocyte ratio with obstructive coronary artery disease and coronary artery calcium score detected by multislice computed tomography in type 2 diabetes mellitus patients. Patient Prefer Adherence. 2015;9:1023-1031. https://doi.org/10.2147/PPA.S85577
15. Sochett E, Noone D, Grattan M, Slorach C, Moineddin R, Elia Y, et al. Relationship between serum inflammatory markers and vascular function in a cohort of adolescents with type 1 diabetes. Cytokine. 2017;99:233-239. https://doi.org/10.1016/j.cyto.2017.07.013
16. Hu B, Yang XR, Xu Y, Sun YF, Sun C, Guo W, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20(23):6212-6222. https://doi.org/10.1158/1078-0432.CCR-14-0442
17. Kourilovitch M, Galarza-Maldonado C. Could a simple biomarker as neutrophil-to-lymphocyte ratio reflect complex processes orchestrated by neutrophils? J Transl Autoimmun. 2022;6:100159. https://doi.org/10.1016/j.jtauto.2022.100159
18. Karavanaki K, Karanika E, Georga S, Bartzeliotou A, Tsouvalas M, Konstantopoulos I, et al. Cytokine response to diabetic ketoacidosis (DKA) in children with type 1 diabetes (T1DM). Endocr J. 2011;58(12):1045-1053. https://doi.org/10.1507/endocrj.EJ11-0024
19. Ozde S, Akture G, Ozel MA, Yavuzyilmaz F, Arslanoglu I, Ozde C, et al. 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. J Pediatr Endocrinol Metab. 2024;37(7):635-643. https://doi.org/10.1515/jpem-2024-0043
20. Aon M, Aoun AH, Alshami A, Alharbi A, Alshammari F, Alnajjar M, et al. Association of the systemic immune-inflammation index (SII) and severity of diabetic ketoacidosis in patients with type 1 diabetes mellitus: a retrospective cohort study. Ann Med Surg (Lond). 2024;86(7):3865-3872. https://doi.org/10.1097/MS9.0000000000002185
21. Nicoară DM, Munteanu AI, Scutca AC, Mang N, Juganaru I, Brad GF, et al. Assessing the Relationship between Systemic Immune-Inflammation Index and Metabolic Syndrome in Children with Obesity. Int J Mol Sci. 2023;24(9):8414. https://doi.org/10.3390/ijms24098414
22. Apostolopoulou M, Lambadiari V, Roden M. Insulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance. Endocr Rev. 2025;46(3):317-348. https://doi.org/10.1210/endrev/bnae032
23. Scutca AC, Nicoară DM, Mărăzan M, Brad GF, Mărginean O. Neutrophil-to-Lymphocyte Ratio Adds Valuable Information Regarding the Presence of DKA in Children with New-Onset T1DM. J Clin Med. 2022;12(1):221. https://doi.org/10.3390/jcm12010221
24. İsmail NA, Abeer M, El Baky NED. Neutrophil-lymphocyte ratio, platelet-lymphocyte ratio in well controlled and uncontrolled children and adolescents with type 1 diabetes mellitus. Res J Pharm Biol Chem. 2021;12:13.
25. Abo T, Kawamura T. Immunomodulation by the autonomic nervous system: therapeutic approach for cancer, collagen diseases, and inflammatory bowel diseases. Ther Apher. 2002;6(5):348-357. https://doi.org/10.1046/j.1526-0968.2002.00452.x
26. Serés-Noriega T, Perea V, Amor AJ. Screening for Subclinical Atherosclerosis and the Prediction of Cardiovascular Events in People with Type 1 Diabetes. J Clin Med. 2024;13(4):1097. https://doi.org/10.3390/jcm13041097
27. Mariaca K, Serés-Noriega T, Viñals C, Perea V, Conget I, Mesa A, et al. Neutrophil-to-lymphocyte ratio is independently associated with carotid atherosclerosis burden in individuals with type 1 diabetes. Nutr Metab Cardiovasc Dis. 2024;34(2):395-403. https://doi.org/10.1016/j.numecd.2023.09.017
28. Liu J, Liu X, Li Y, Quan J, Wei S, An S, et al. The association of neutrophil to lymphocyte ratio, mean platelet volume, and platelet distribution width with diabetic retinopathy and nephropathy: a meta-analysis. Biosci Rep. 2018;38(3):BSR20180172. https://doi.org/10.1042/BSR20180172
29. Zeng J, Chen M, Feng Q, Wan H, Wang J, Yang F, et al. The Platelet-to-Lymphocyte Ratio Predicts Diabetic Retinopathy in Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes. 2022;15:3617-3626. https://doi.org/10.2147/DMSO.S378284
30. Scutca AC, Nicoară DM, Mang N, Jugănaru I, Brad GF, Mărginean O. Correlation between neutrophil-to-lymphocyte ratio and cerebral edema in children with severe diabetic ketoacidosis. Biomedicines. 2023;11(11):2976. https://doi.org/10.3390/biomedicines11112976
31. Erbaş İM, Hajikhanova A, Besci Ö, Acinikli KY, Demir K, Böber E, et al. Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2022;35(5):593-602. https://doi.org/10.1515/jpem-2021-0564
32. Salah NY, Radwan N, Atif HM. Leukocytic dysregulation in children with type 1 diabetes: relation to diabetic vascular complications. Diabetology International. 2022;13(3):538-547. https://doi.org/10.1007/s13340-021-00568-5
33. Söbü E, Demir Yenigürbüz F, Özçora GDK, Köle MT. Evaluation of the Impact of Glycemic Control on Mean Platelet Volume and Platelet Activation in Children with Type 1 Diabetes. J Trop Pediatr. 2022;68(4):fmac063. https://doi.org/10.1093/tropej/fmac063