Tip 1 Diyabette Uzun Dönem Glisemik Kontrol ile Remisyon Dönemi Arasındaki İlişki: Retrospektif Bir Çalışma

Abstract

Amaç: Parsiyel remisyon (PR), tip 1 diyabet (T1D) tanısından kısa süre sonra izlenen ve diyabet yönetimine dair önemli etkileri olan bir süreçtir. T1D'de PR ile uzun dönem hemoglobin A1c (HbA1c) sonuçları arasındaki ilişkiyi araştırmayı amaçladık. Ayrıca uzun süreli glisemik kontrolü etkileyebilecek demografik ve klinik faktörleri de analiz ettik. Gereç ve yöntem: T1D'li 131 çocuk ve adolesanın 5 yıllık takip süresindeki HbA1c düzeylerini retrospektif olarak değerlendirdik. Hastalar düşük (<%7.5) ve yüksek (≥%7.5) uzun dönem HbA1c gruplarına ayrılarak gruplar uygun istatistiksel yöntemlerle karşılaştırıldı. Bulgular: Ortalama HbA1c±SD tanı anında %12,1±2,4, 1. yılda %8,1±1,3; 2. yılda %8,9±1,6; 3. yılda %9,1±1,6; 4. yılda %9,3±1,7 ve 5. yılda %9,5±1,4 idi. Hastaların %87,8'inde uzun dönem ortalama HbA1c düzeyleri yüksekti. 75 olguda (%57,3) parsiyel remisyon izlendi. Takip sırasında, PR izlenen T1D'lilerde HbA1c düzeyleri diğerlerine göre anlamlı olarak daha düşüktü (%8,9±1,3 ve %9,6 ±1,6; p=0.006). Düşük uzun dönem HbA1c grubu, yüksek HbA1c grubuna göre daha yüksek bazal açlık C-peptid seviyelerine sahipti [0,48 (0,12-1,4) ng/ml ve 0,28 (0,05-1,5) ng/ml; p=0,048]. Ayrıca diğer gruba kıyasla tanıdan 3 ay, 6 ay, 9 ay ve 12 ay sonraki HbA1c seviyeleri de daha düşüktü (p≤0,001 ya da p=0,004). Sonuç: Glisemik kontrol takip süresi boyunca suboptimaldi. HbA1c seviyeleri, T1D teşhisi sonrası ilk 2 yıl boyunca (ilk birkaç aydan sonra) istikrarlı olarak arttı ancak daha sonra stabil seyretti. PR izlenen olguların izlemdeki HbA1c düzeyleri PR izlenmeyenlere göre daha düşüktü. T1D’de HbA1c seyrinin anlaşılması, klinik sonuçları iyileştirmek ve T1D yönetimini düzenlemek için imkânlar sunar.

Keywords

• Tip 1 diyabet
• parsiyel remisyon
• glisemik kontrol
• hemoglobin A1c

The Relationship Between Long-Term Glycemic Control and Partial Remission in Type 1 Diabetes: A Retrospective Study

Abstract

Aim: Partial remission (PR) is a significant period in the early course of type 1 diabetes (T1D) with implications for diabetes management. We aimed to investigate whether long-term hemoglobin A1c (HbA1c) outcomes in T1D differed as a result of experiencing PR. We also analyzed the demographic and clinical factors that may influence long-term glycemic control. Material and methods: We retrospectively tracked the HbA1c values of 131 children and adolescents with T1D over a 5-year period. Patients were stratified into low (<7.5%) and high (≥7.5%) long-term HbA1c groups, and groups were compared using appropriate statistical procedures. Results: Mean HbA1c±SD was 12.1±2.4% at diagnosis, 8.1±1.3% at 1 yr, 8.9±1.6% at 2 yr, 9.1±1.6% at 3 yr, 9.3±1.7% at 4 yr, and 9.5±1.4% at 5 yr from diagnosis. Of the patients, 87.8% had high long-term mean HbA1c levels. There were 75 remitters (%57.3). During follow-up, HbA1c levels were significantly lower in those with T1D who experienced PR than those who did not (8.9±1.3% vs. 9.6% ±1.6%, p=0.006). The group with low long-term HbA1c had higher fasting C-peptide levels at baseline than the higher HbA1c group [0.48 (0.12-1.4) ng/ml vs. 0.28 (0.05-1.5) ng/ml, p=0.048)]. They also had lower HbA1c levels at 3 months, 6 months, 9 months, and 12 months after diagnosis compared to the other group (p≤0.001 or p=0.004). Conclusion: Glycemic control was suboptimal throughout the follow-up period. After the first few months, HbA1c levels increased steadily through the first 2 years of T1D diagnosis but tended to stabilize in a "track" afterward. The trajectory of youth who experienced PR was lower than those who didn't. Understanding the HbA1c trajectory helps to identify opportunities for the intensification of T1D management to improve clinical outcomes.

Keywords

• Type 1 diabetes
• partial remission
• glycemic control
• hemoglobin A1c

References

1. 1. Giordano C, Amato MC, Ciresi A, Citarrella R, Mantione L, Accidenti M, et al. Predictors of microvascular complications in type 1 diabetic patients at onset: The role of metabolic memory. Eur J Intern Med [Internet]. 2011 Jun;22(3):266–74. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0953620511000409
2. 2. Pihoker C, Badaru A, Anderson A, Morgan T, Dolan L, Dabelea D, et al. Insulin Regimens and Clinical Outcomes in a Type 1 Diabetes Cohort. Diabetes Care [Internet]. 2013 Jan 1;36(1):27–33. Available from: https://diabetesjournals.org/care/article/36/1/27/38259/Insulin-Regimens-and-Clinical-Outcomes-in-a-Type-1
3. 3. Clements MA, Foster NC, Maahs DM, Schatz DA, Olson BA, Tsalikian E, et al. Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry. Pediatr Diabetes [Internet]. 2016 Aug 1;17(5):327–36. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.12295
4. 4. Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, DiMeglio LA, et al. Current State of Type 1 Diabetes Treatment in the U.S.: Updated Data From the T1D Exchange Clinic Registry. Diabetes Care [Internet]. 2015 Jun 1;38(6):971–8. Available from: https://diabetesjournals.org/care/article/38/6/971/37394/Current-State-of-Type-1-Diabetes-Treatment-in-the
5. 5. Steffes MW, Sibley S, Jackson M, Thomas W. β-Cell Function and the Development of Diabetes-Related Complications in the Diabetes Control and Complications Trial. Diabetes Care [Internet]. 2003 Mar 1;26(3):832–6. Available from: http://diabetesjournals.org/care/article-pdf/26/3/832/665500/dc0303000832.pdf
6. 6. Effect of Intensive Therapy on Residual β-Cell Function in Patients with Type 1 Diabetes in the Diabetes Control and Complications Trial. Ann Intern Med [Internet]. 1998 Apr 1;128(7):517. Available from: https://www.acpjournals.org/doi/abs/10.7326/0003-4819-128-7-199804010-00001
7. 7. Hamman RF, Bell RA, Dabelea D, D’Agostino RB, Dolan L, Imperatore G, et al. The SEARCH for Diabetes in Youth Study: Rationale, Findings, and Future Directions. Diabetes Care [Internet]. 2014 Dec 1;37(12):3336–44. Available from: https://diabetesjournals.org/care/article/37/12/3336/29405/The-SEARCH-for-Diabetes-in-Youth-Study-Rationale
8. 8. Dovc K, Telic SS, Lusa L, Bratanic N, Zerjav-Tansek M, Kotnik P, et al. Improved Metabolic Control in Pediatric Patients with Type 1 Diabetes: A Nationwide Prospective 12-Year Time Trends Analysis. Diabetes Technol Ther [Internet]. 2014 Jan 1;16(1):33–40. Available from: http://www.liebertpub.com/doi/10.1089/dia.2013.0182

9. 9. Shalitin S, Phillip M. Which factors predict glycemic control in children diagnosed with type 1 diabetes before 6.5 years of age? Acta Diabetol [Internet]. 2012 Oct 25;49(5):355–62. Available from: https://doi.org/10.1007/s00592-011-0321-x
10. 10. Nirantharakumar K, Mohammed N, Toulis KA, Thomas GN, Narendran P. Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis. Diabetologia [Internet]. 2018 May 24;61(5):1064–70. Available from: http://link.springer.com/10.1007/s00125-018-4574-6
11. 11. Araujo MB, Mazza CS. Assessment of risk factors of poor metabolic control in type 1 diabetic children assisted in a public hospital in Argentina. Pediatr Diabetes [Internet]. 2008 Oct;9(5):480–7. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1399-5448.2008.00388.x
12. 12. Mazarello Paes V, Barrett JK, Taylor‐Robinson DC, Chesters H, Charalampopoulos D, Dunger DB, et al. Effect of early glycemic control on HbA1c tracking and development of vascular complications after 5 years of childhood onset type 1 diabetes: Systematic review and meta‐analysis. Pediatr Diabetes [Internet]. 2019 Apr 24;20(5):pedi.12850. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.12850
13. 13. 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 [Internet]. 2018 Oct 1;19:7–19. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.12773
14. 14. 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 [Internet]. 2009 Aug 1;32(8):1384–90. Available from: http://care.diabetesjournals.org/cgi/content/full/dc08-1987/DC1.
15. 15. Demir K, Özen S, Konakçı E, Aydın M, Darendeliler F. A Comprehensive Online Calculator for Pediatric Endocrinologists: ÇEDD Çözüm/TPEDS Metrics. J Clin Res Pediatr Endocrinol [Internet]. 2017 Jun 1;9(2):182–4. Available from: http://www.cdc.gov/growthcharts/percentile_data_files.htm
16. 16. Shubrook J, Butts A, Chamberlain JJ, Johnson EL, Leal S, Rhinehart AS, et al. Standards of Medical Care in Diabetes—2017 Abridged for Primary Care Providers. Clin Diabetes [Internet]. 2017 Jan 1;35(1):5–26. Available from: http://diabetesjournals.org/clinical/article-pdf/35/1/5/500736/5.pdf
17. 17. Care D, Suppl SS. 13. Children and Adolescents: Standards of Medical Care in Diabetes—2019. Diabetes Care [Internet]. 2019 Jan 1;42(Supplement_1):S148–64. Available from: https://diabetesjournals.org/care/article/42/Supplement_1/S148/31023/13-Children-and-Adolescents-Standards-of-Medical
18. 18. Dean AG, Sullivan KM, Soe MM. OpenEpi: Open Source Epidemiologic Statistics for Public Health, Version. www.OpenEpi.com, updated 2013/04/06, accessed 2022/10/19.
19. 19. Prahalad P, Yang J, Scheinker D, Desai M, Hood K, Maahs DM. Hemoglobin A1c Trajectory in Pediatric Patients with Newly Diagnosed Type 1 Diabetes. Diabetes Technol Ther [Internet]. 2019 Aug 1;21(8):456–61. Available from: https://www.liebertpub.com/doi/10.1089/dia.2019.0065
20. 20. Cengiz E, Connor CG, Ruedy KJ, Beck RW, Kollman C, Klingensmith GJ, et al. Pediatric diabetes consortium T1D New Onset (NeOn) study: Clinical outcomes during the first year following diagnosis. Pediatr Diabetes. 2014;15(4):287–93.
21. 21. 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 [Internet]. 2018 Sep 1;41(9):2026–44. Available from: https://doi.org/10.2337/dci18-0023
22. 22. 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 [Internet]. 2018 Oct 1;19:105–14. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.12737
23. 23. Piccini B, Schwandt A, Jefferies C, Kordonouri O, Limbert C, Arslanoglu I, et al. Association of diabetic ketoacidosis and HbA1c at onset with year‐three HbA1c in children and adolescents with type 1 diabetes: Data from the International SWEET Registry. Pediatr Diabetes [Internet]. 2020 Mar 19;21(2):339–48. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.12946
24. 24. Redondo MJ, Libman I, Maahs DM, Lyons SK, Saraco M, Reusch J, et al. The Evolution of Hemoglobin A1c Targets for Youth With Type 1 Diabetes: Rationale and Supporting Evidence. Diabetes Care [Internet]. 2021 Feb 1;44(2):301–12. Available from: https://diabetesjournals.org/care/article/44/2/301/35481/The-Evolution-of-Hemoglobin-A1c-Targets-for-Youth
25. 25. Prahalad P, Schwandt A, Besançon S, Mohan M, Obermannova B, Kershaw M, et al. Hemoglobin A1c trajectories in the first 18 months after diabetes diagnosis in the SWEET diabetes registry. Pediatr Diabetes [Internet]. 2022 Mar 21;23(2):228–36. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.13278
26. 26. Lawes T, Franklin V, Farmer G. HbA1c tracking and bio-psychosocial determinants of glycaemic control in children and adolescents with type 1 diabetes: retrospective cohort study and multilevel analysis. Pediatr Diabetes [Internet]. 2014 Aug;15(5):372–83. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.12100
27. 27. Samuelsson U, Steineck I, Gubbjornsdottir S. A high mean-HbA1c value 3-15 months after diagnosis of type 1 diabetes in childhood is related to metabolic control, macroalbuminuria, and retinopathy in early adulthood-a pilot study using two nation-wide population based quality registries. Pediatr Diabetes [Internet]. 2014 May;15(3):229–35. Available from: http://www.ndr.nu
28. 28. Mortensen HB, Swift PG, Holl RW, Hougaard P, Hansen L, Bjoerndalen H, et al. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis. Pediatr Diabetes [Internet]. 2009 Aug 25;11(4):218–26. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1399-5448.2009.00566.x
29. 29. Duca LM, Reboussin BA, Pihoker C, Imperatore G, Saydah S, Mayer-Davis E, et al. Diabetic ketoacidosis at diagnosis of type 1 diabetes and glycemic control over time: The SEARCH for diabetes in youth study. Pediatr Diabetes [Internet]. 2019 Mar 1;20(2):172–9. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.12809
30. 30. Nielens N, Pollé O, Robert A, Lysy PA. Integration of Routine Parameters of Glycemic Variability in a Simple Screening Method for Partial Remission in Children with Type 1 Diabetes. J Diabetes Res [Internet]. 2018;2018:1–9. Available from: https://doi.org/10.1155/2018/5936360
31. 31. Nwosu BU. Partial Clinical Remission of Type 1 Diabetes Mellitus in Children: Clinical Applications and Challenges with its Definitions. Eur Med journal Diabetes [Internet]. 2019 Mar;4(1):89–98. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31069088%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6502244
32. 32. Yazidi M, Mahjoubi S, Oueslati I, Chaker F, Chihaoui M. The remission phase in adolescents and young adults with newly diagnosed type 1 diabetes mellitus: prevalence, predicting factors and glycemic control during follow-up. Arch Endocrinol Metab [Internet]. 2022 Mar 23;66(2):222–30. Available from: https://orcid.org/0000-0001-7991-9885
33. 33. Niedzwiecki P, Pilacinski S, Uruska A, Adamska A, Naskret D, Zozulinska-Ziolkiewicz D. Influence of remission and its duration on development of early microvascular complications in young adults with type 1 diabetes. J Diabetes Complications [Internet]. 2015 Nov;29(8):1105–11. Available from: https://www.sciencedirect.com/science/article/pii/S1056872715003724
34. 34. Redondo MJ, Connor CG, Ruedy KJ, Beck RW, Kollman C, Wood JR, et al. Pediatric Diabetes Consortium Type 1 Diabetes New Onset (NeOn) Study: factors associated with HbA1c levels one year after diagnosis. Pediatr Diabetes [Internet]. 2014 Jun;15(4):294–302. Available from: https://onlinelibrary.wiley.com/doi/10.1111/pedi.12061
35. 35. Forst T, Kunt T, Wilhelm B, Weber MM, Pfützner A. Role of C-Peptide in the Regulation of Microvascular Blood Flow. Exp Diabetes Res [Internet]. 2008;2008:1–8. Available from: http://www.hindawi.com/journals/jdr/2008/176245/
36. 36. Sørensen JS, Johannesen J, Pociot F, Kristensen K, Thomsen J, Hertel NT, et al. Residual β-Cell Function 3–6 Years After Onset of Type 1 Diabetes Reduces Risk of Severe Hypoglycemia in Children and Adolescents. Diabetes Care [Internet]. 2013 Nov 1;36(11):3454–9. Available from: http://diabetesjournals.org/care/article-pdf/36/11/3454/614465/3454.pdf
37. 37. Nakanishi K, Watanabe C. Rate of β-Cell Destruction in Type 1 Diabetes Influences the Development of Diabetic Retinopathy: Protective Effect of Residual β-Cell Function for More Than 10 Years. J Clin Endocrinol Metab [Internet]. 2008 Dec 1;93(12):4759–66. Available from: https://academic.oup.com/jcem/article/93/12/4759/2627335
38. 38. 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 [Internet]. 2021 Oct 26;34(10):1311–7. Available from: https://www.degruyter.com/document/doi/10.1515/jpem-2021-0048/html
39. 39. Urbach SL, LaFranchi S, Lambert L, Lapidus JA, Daneman D, Becker TM. Predictors of glucose control in children and adolescents with type 1 diabetes mellitus. Pediatr Diabetes [Internet]. 2005 Jun;6(2):69–74. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1399-543X.2005.00104.x
40. 40. CİMBEK EA, ÖZTÜRK MA, KARAGÜZEL G. Preservation of C-Peptide Levels in Children with New-Onset Type 1 Diabetes: A Comparison Based on Body Mass Index. Turkish J Diabetes Obes [Internet]. 2022 Apr 30;6(1):32–8. Available from: https://dergipark.org.tr/en/doi/10.25048/tudod.1059061
41. 41. Zucchini S, Scaramuzza AE, Bonfanti R, Buono P, Cardella F, Cauvin V, et al. A Multicenter Retrospective Survey regarding Diabetic Ketoacidosis Management in Italian Children with Type 1 Diabetes. J Diabetes Res [Internet]. 2016;2016:1–6. Available from: http://www.hindawi.com/journals/jdr/2016/5719470/
42. 42. Dabelea D, Rewers A, Stafford JM, Standiford DA, Lawrence JM, Saydah S, et al. Trends in the prevalence of ketoacidosis at diabetes diagnosis: The search for diabetes in youth study. Pediatrics. 2014;133(4).
43. 43. Duca LM, Wang B, Rewers M, Rewers A. Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes Predicts Poor Long-term Glycemic Control. Diabetes Care [Internet]. 2017 Sep 1;40(9):1249–55. Available from: http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0558/-/DC1.
44. 44. Seo Y-J, Kum CD, Rho JG, Shim YS, Lee HS, Hwang JS. Comparison of the clinical characteristics and outcomes of pediatric patients with and without diabetic ketoacidosis at the time of type 1 diabetes diagnosis. Ann Pediatr Endocrinol Metab [Internet]. 2022 Jun 30 [cited 2022 Sep 3];27(2):126–33. Available from: http://e-apem.org/journal/view.php?doi=10.6065/apem.2142174.087
45. 45. Emilia K, Aneta S, Barbara M, Małgorzata J, Aleksandra H, Paulina B, et al. Is diabetic ketoacidosis a good predictor of 5-year metabolic control in children with newly diagnosed type 1 diabetes? BMC Endocr Disord [Internet]. 2021 Dec 2;21(1):218. Available from: https://bmcendocrdisord.biomedcentral.com/articles/1