Pediatrik tip 1 diyabette kısmi remisyonun başlangıcını ve seyrini etkileyen klinik ve immünolojik faktörler

Yıl 2025, Cilt: 50 Sayı: 3, 863 - 871

Semine Özdemir Dilek , İhsan Turan , Fatih Gürbüz , Eda Mengen , Can Celiloğlu , Bilgin Yüksel

https://doi.org/10.17826/cumj.1712723

Öz

Amaç: Bu çalışmada yeni tanı konmuş tip 1 diyabetli (T1D) çocuk ve ergenlerde parsiyel remisyonun (PR) başlangıcını ve seyrini şekillendiren klinik ve immünolojik faktörleri incelenmiştir.
Gereç ve Yöntem: Çalışmaya T1D tanısı almış toplam 201 pediatrik hasta dahil edildi. PR, insülin dozu ile ayarlanmış HbA1c (IDAA1c) ≤9 olarak tanımlandı. Katılımcılar parsiyel remisyon yaşayanlar (PR grubu) ve remisyon yaşamayanlar (NR grubu) olmak üzere iki gruba ayrıldı.
Bulgular: Parsiyel remisyon 138 (%69) hastada gözlendi. PR grubunda tanı anındaki ortalama yaş 9,4 ± 3,8 yıl olup, remisyon başlangıcı tanıdan ortalama 1,6 ± 1,4 ay sonra gerçekleşmiş ve ortalama 7,3 ± 5,2 ay sürmüştür. Fazla kilolu/obez olmak PR ile güçlü bir şekilde ilişkiliydi; fazla kilolu/obez hastaların %81’inde parsiyel remisyon görüldü. Anti-glutamik asit dekarboksilaz (anti-GAD) antikor pozitifliği PR grubunda daha sık saptandı (%63,0 iken %33,3). Daha uzun remisyon süresi ergenlik dönemindeki, fazla kilolu/obez olan veya çölyak hastalığı pozitif olan hastalarda gözlenirken; anti-GAD ve adacık hücre antikoru pozitifliği daha kısa remisyon ile ilişkiliydi.
Sonuç: Bulgularımız, anti-GAD ve ICA gibi iyi bilinen belirteçlerin bile, çocukluk çağı T1D'de PR’nin seyri üzerinde farklı yönlü etkiler gösterebileceğini, bu belirteçlerin öngörüsel karmaşıklığını ve klinik önemini vurgulamaktadır. Ayrıca obezite, ergenlik ve çölyak hastalığı arasındaki etkileşim, T1D’nin başlangıç döneminde PR yönetiminde immünometabolik yaklaşımların gerekliliğini ortaya koymaktadır.

Anahtar Kelimeler

: parsiyel remisyon , anti-glutamik asit dekarboksilaz antikoru , adacık hücresi antikoru , ergenlik , fazla kilo , obezite

Clinical and immunological factors influencing the onset and course of partial remission in pediatric type 1 diabetes

Öz

Purpose: This study examined key clinical and immunological factors influencing the onset and course of partial remission (PR) in children and adolescents with newly diagnosed type 1 diabetes(T1D).
Materials and Methods: A total of 201 pediatric patients with T1D were enrolled. PR was defined as an insulin dose-adjusted HbA1c(IDAA1c) of≤9. Participants were categorized into two groups: PR and NR (non-remission).
Results: Partial remission occurred in 138 (69%) patients. In the PR group, the mean age at diagnosis was 9.4 ± 3.8 years, with PR onset occurring 1.6 ± 1.4 months after diagnosis and lasting for a mean duration of 7.3 ± 5.2 months. Overweight/obesity was strongly associated with PR, as 81% of overweight/obese patients achieved remission. Anti-glutamic acid decarboxylase (anti-GAD) antibody positivity was more frequent in the PR group (63.0% vs. 33.3%). Longer remission was seen in patients with puberty, overweight/obesity, or coeliac disease, whereas positivity for anti-GAD and islet cell antibodies was associated with shorter remission.
Conclusion: Anti-GAD and ICA antibodies have distinct effects on PR, reflecting the complexity of autoimmune activity in pediatric T1D. The presence of obesity, puberty, and celiac disorder supports the need for a immuno-metabolic strategy for the early prediction and management of PR in pediatric T1D.

Anahtar Kelimeler

partial remission , anti-glutamic acid decarboxylase antibody , islet cell antibody

Kaynakça

• Couper JJ, Haller MJ, Greenbaum CJ, Ziegler AG, Wherrett DK, Knip M et al. ISPAD Clinical Practice Consensus Guidelines 2018: Stages of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2018;27:20-7.
• Cimbek EA, Bozkır A, Usta D, Beyhun NE, Ökten A, Karagüzel G. Partial remission in children and adolescents with type 1 diabetes: an analysis based on the insulin dose-adjusted hemoglobin A1c. J Pediatr Endocrinol Metab. 2021;34:1311-7.
• Pyziak A, Zmyslowska A, Bobeff K, Malachowska B, Fendler W et al. Markers influencing the presence of partial clinical remission in patients with newly diagnosed type 1 diabetes. J Pediatr Endocrinol Metab. 2017;30:1147-53.
• Collier JJ, Wasserfall CH, Brehm MA, Karlstad MD. Partial remission of type 1 diabetes: Do immunometabolic events define the honeymoon period? Diabetes Obes Metab. 2025;27:4092-4101.
• Sokołowska-Gadoux M, Jarosz-Chobot P, Polanska J, Kalemba A, Chobot A. Body mass index and partial remission in 119 children with type 1 diabetes-a 6-year observational study. Front Endocrinol (Lausanne). 2023;14:1257758.
• Schölin A, Törn C, Nyström L, Berne C, Arnqvist H, Blohmé G et al. Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in type 1 diabetes. Diabet Med. 2004;21:447-53.
• Zhong T, Tang R, Gong S, Li J, Li X, Zhou Z. The remission phase in type 1 diabetes: changing epidemiology, definitions, and emerging immuno-metabolic mechanisms. Diabetes Metab Res Rev. 2020;36:e3207.
• Kueh MTW, Chew NWS, Al-Ozairi E, le Roux CW. The emergence of obesity in type 1 diabetes. Int J Obes (Lond). 2024;48:289-301.
• Van der Schueren B, Ellis D, Faradji RN, Al-Ozairi E, Rosen J, Mathieu C. Obesity in people living with type 1 diabetes. Lancet Diabetes Endocrinol. 2021;9:776-85.
• 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;27:7.
• Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018;27:155-77.
• Husby S, Koletzko S, Korponay-Szabó I, Kurppa K, Mearin ML, Ribes-Koninckx C et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr. 2020;70:141-56.
• Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child. 1976;51:170.
• Neyzi O, Bundak R, Gökçay G, Günöz H, Furman A, Darendeliler F et al. Reference values for weight, height, head circumference, and body mass index in Turkish children. J Clin Res Pediatr Endocrinol. 2015;7:280-93.
• 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;23:1270-6.
• Mortensen HB, Hougaard P, Swift P, Hansen L, Holl RW, Hoey H et al. New definition for the partial remission period in children and adolescents with type 1 diabetes. Diabetes Care. 2009;32:1384-90.
• Chobot A, Stompór J, Szyda K, Sokołowska M, Deja G, Polańska J et al. Remission phase in children diagnosed with type 1 diabetes in years 2012 to 2013 in Silesia, Poland: an observational study. Pediatr Diabetes. 2019;20:286-92.
• Patterson C, Guariguata L, Dahlquist G, Soltész G, Ogle G, Silink M. Diabetes in the young - a global view and worldwide estimates of numbers of children with type 1 diabetes. Diabetes Res Clin Pract. 2014;103:161-75.
• Acerini CL, Williams RM, Dunger DB. Metabolic impact of puberty on the course of type 1 diabetes. Diabetes Metab. 2001;27:19-25.
• Nagl K, Hermann JM, Plamper M, Schröder C, Dost A, Kordonouri O et al. Factors contributing to partial remission in type 1 diabetes: analysis based on the insulin dose-adjusted HbA1c in 3657 children and adolescents from Germany and Austria. Pediatr Diabetes. 2017;18:428-34.
• Maddaloni E, Tuccinardi D. Obesity in type 1 diabetes: an overlooked immune-metabolic issue. Expert Rev Endocrinol Metab. 2024;19:295-7.
• Corbin KD, Driscoll KA, Pratley RE, Smith SR, Maahs DM, Mayer-Davis EJ et al. Obesity in type 1 diabetes: pathophysiology, clinical impact, and mechanisms. Endocr Rev. 2018;39:629-63.
• Vilarrasa N, San Jose P, Rubio MÁ, Lecube A. Obesity in patients with type 1 diabetes: links, risks and management challenges. Diabetes Metab Syndr Obes. 2021;14:2807-23.
• Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev. 2014;13:981-1000.
• Dooley J, Tian L, Schonefeldt S, Delghingaro-Augusto V, Garcia-Perez JE, Pasciuto E et al. Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes. Nat Genet. 2016;48:519-27.
• Ozen G, Zanfardino A, Confetto S, Piscopo A, Casaburo F, Tinto N et al. The association of autoimmune diseases with type 1 diabetes mellitus in children depends also by the length of partial clinical remission phase (honeymoon). Int J Endocrinol. 2020;2020:2630827.
• Larsen J, Dall M, Antvorskov JC, Weile C, Engkilde K, Josefsen K et al. Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion. Eur J Immunol. 2014;44:3056-67.
• Ejsing-Duun M, Josephsen J, Aasted B, Buschard K, Hansen AK. Dietary gluten reduces the number of intestinal regulatory T cells in mice. Scand J Immunol. 2008;67:553-9.
• Eland I, Klieverik L, Mansour AA, Al-Toma A. Gluten-free diet in co-existent coeliac disease and type 1 diabetes mellitus: is it detrimental or beneficial to glycemic control, vascular complications, and quality of life? Nutrients. 2022;15:199.
• McGill DE, Levitsky LL. Management of hypoglycemia in children and adolescents with type 1 diabetes mellitus. Curr Diab Rep. 2016;16:88.
• Camilo DS, Pradella F, Paulino MF, Baracat ECE, Marini SH, Guerra G Jr et al. Partial remission in Brazilian children and adolescents with type 1 diabetes: association with a haplotype of class II human leukocyte antigen and synthesis of autoantibodies. Pediatr Diabetes. 2020;21:606-14.
• Pecheur A, Barrea T, Vandooren V, Beauloye V, Robert A, Lysy PA. Characteristics and determinants of partial remission in children with type 1 diabetes using the insulin-dose-adjusted A1C definition. J Diabetes Res. 2014;2014:851378.
• Pörksen S, Laborie LB, Nielsen L, Andersen MLM, Sandal T, de Wet H et al. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD and IA-2 antibodies. BMC Endocr Disord. 2010;10:16.
• Pöllänen PM, Lempainen J, Laine AP, Toppari J, Veijola R, Vähäsalo P et al. Characterisation of rapid progressors to type 1 diabetes among children with HLA-conferred disease susceptibility. Diabetologia. 2017;60:1284-93.
• Niechciał E, Szypowska A, Sieradzka-Kempa A, Piątkowska E, Lipska-Ziętkiewicz BS, Gach A et al. Autoantibodies against zinc transporter 8 are related to age and metabolic state in patients with newly diagnosed autoimmune diabetes. Acta Diabetol. 2018;55:287-94.
• Felton JL, Nayak AU, Snape AE, Shields BM, Burren CP, Williams AJ et al. Islet autoantibodies as precision diagnostic tools to characterize heterogeneity in type 1 diabetes: a systematic review. Commun Med. 2024;4:66.