Postinitial remission in children with type 1 diabetes mellitus

Authors: Podoláková Kristína 1;  Lobotková Denisa 1;  Jančová Emília 1;  Podracká Udmila 1;  Barák Ubomír 1;  Staník Juraj 1,2
Authors‘ workplace: Detská klinika, Lekárska fakulta, Univerzity Komenského, a Národný ústav detských, chorôb, Bratislava 1;  DIABGENE a Oddelenie, výskumu porúch, metabolizmu, Ústav experimentálnej, endokrinológie, Biomedicínske centrum, Slovenskej Akadémie vied, Bratislava 2
Published in: Čes-slov Pediat 2022; 77 (2): 72-77.
Category: Comprehensive Report


Post-initial remission is a period that occurs shortly after the initiation of treatment for type 1 diabetes mellitus (T1D) and is characterized by a transient improvement in residual endogenous insulin secretion accompanied by a reduced need for exogenous insulin and good glycemic control. Remission occurs in more than ⅓ of children with newly diagnosed T1D, and most cases are partial remission with a reduction in daily insulin dose < 0.5 IU/kg/day; complete remission with temporary discontinuation of insulin therapy is rare. Several factors influence the development and length of remission - known factors include age and early diagnosis of T1D, when diabetic ketoacidosis is not yet developed and the residual secretory capacity of the remaining β-cells secreting insulin is better. In our review article, we discuss in more detail the factors influencing remission as well as efforts to influence the development and duration of post-initial remission pharmacologically or with new technologies.


remission – type 1 diabetes mellitus – children – T1D – factors


1. Agner T, Damm P, Binder C. Remission in IDDM: prospective study of basal C–peptide and insulin dose in 268 consecutive patients. Diabetes Care 1987; 10(2): 164–9.

2. Mortensen HB, Volund A. Application of a biokinetic model for prediction and assessment of glycated haemoglobins in diabetic patients. Scand J Clin Lab Invest 1988; 48(6): 595–602.

3. Ortqvist E, Falorni A, Scheynius A, et al. Age governs gender- dependent islet cell autoreactivity and predicts the clinical course in childhood IDDM. Acta Paediatr 1997; 86(11): 1166–71.

4. Lundberg RL, Marino KR, Jasrotia A, et al. Partial clinical remission in type 1 diabetes: a comparison of the accuracy of total daily dose of insulin of < 0.3 units/kg/day to the gold standard insulin–dose adjusted hemoglobin A1c of < /=9 for the detection of partial clinical remission. J Pediatr Endocrinol Metab 2017; 30(8): 823–830.

5. Bonfanti R, Bognetti E, Meschi F, et al. Residual beta–cell function and spontaneous clinical remission in type 1 diabetes mellitus: the role of puberty. Acta Diabetol 1998; 35(2): 91–5.

6. Komulainen J, Lounamaa R, Knip M, et al. Ketoacidosis at the diagnosis of type 1 (insulin dependent) diabetes mellitus is related to poor residual beta cell function. Childhood Diabetes in Finland Study Group. Arch Dis Child 1996; 75(5): 410–5.

7. Palmer JP, Fleming GA, Greenbaum CJ, et al. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21–22 October 2001. Diabetes 2004; 53(1): 250–64.

8. Couper JJ, Haller MJ, Greenbaum CJ, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Stages of type 1 diabetes in children and adolescents. Pediatr Diabetes 2018; 19(Suppl 27): 20–27.

9. Lombardo F, Valenzise M, Wasniewska M, et al. Two-year prospective evaluation of the factors affecting honeymoon frequency and duration in children with insulin dependent diabetes mellitus: the key-role of age at diagnosis. Diabetes Nutr Metab 2002; 15(4): 246–51.

10. Mortensen HB, Hougaard P, Swift P, et al. New definition for the partial remission period in children and adolescents with type 1 diabetes. Diabetes Care 2009; 32(8): 1384–90.

11. Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med 1998; 128(7): 517–23.

12. Chobot A, Stompor J, Szyda K, 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(3): 286–292.

13. Nagl K, Hermann JM, Plamper M, 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(6): 428–434.

14. Passanisi S, Salzano G, Gasbarro A, et al. Influence of Age on Partial Clinical Remission among Children with Newly Diagnosed Type 1 Diabetes. Int J Environ Res Public Health 2020; 17(13).

15. Chiavaroli V, Derraik JGB, Jalaludin MY, et al. Partial remission in type 1 diabetes and associated factors: Analysis based on the insulin dose–adjusted hemoglobin A1c in children and adolescents from a regional diabetes center, Auckland, New Zealand. Pediatr Diabetes 2019; 20(7): 892–900.

16. Marino KR, Lundberg RL, Jasrotia A, et al. A predictive model for lack of partial clinical remission in new–onset pediatric type 1 diabetes. PLoS One 2017; 12(5): e0176860.

17. Nwosu BU, Rupendu S, Zitek-Morrison E, et al. Pubertal lipid levels are significantly lower in youth with type 1 diabetes who experienced partial clinical remission. J Endocr Soc 2019; 3(4): 737–747.

18. Neuman V, Pruhova S, Kulich M, et al. Gluten-free diet in children with recent-onset type 1 diabetes: A 12-month intervention trial. Diabetes Obes Metab 2020; 22(5): 866– 872.

19. Pyziak A, Zmyslowska A, Bobeff K, et al. Markers influencing the presence of partial clinical remission in patients with newly diagnosed type 1 diabetes. J Pediatr Endocrinol Metab 2017; 30(11): 1147–1153.

20. Fonolleda M, Murillo M, Vazquez F, et al. Remission phase in paediatric type 1 diabetes: new understanding and emerging biomarkers. Horm Res Paediatr 2017; 88(5): 307–315.

21. Abdul-Rasoul M, Habib H, Al-Khouly M. ‚The honeymoon phase‘ in children with type 1 diabetes mellitus: frequency, duration, and influential factors. Pediatr Diabetes 2006; 7(2): 101–7.

22. Mortensen HB, Swift PG, Holl RW, 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 2010; 11(4): 218–26.

23. Pozzilli P, Mesturino CA, Crino A, et al. Is the process of beta-cell destruction in type 1 diabetes at time of diagnosis more extensive in females than in males? Eur J Endocrinol 2001; 145(6): 757–61.

24. Zamaklar M, Jotic A, Lalic N, et al. Relation between course of disease in type 1 diabetes and islet cell antibodies. Ann N Y Acad Sci 2002; 958: 251–3.

25. Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes. Diabetologia 2001; 44(7): 914–22.

26. D iabetes C, Complications Trial Research G, Nathan DM, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977–86.

27. Bunn HF, Gabbay KH, Gallop PM. The glycosylation of hemoglobin: relevance to diabetes mellitus. Science 1978; 200(4337): 21–7.

28. Wong TWC, Wong MYS , But WMB. Features of partial remission in children with type 1 diabetes using the insulin dose- adjusted A1c definition and risk factors associated with nonremission. Ann Pediatr Endocrinol Metab 2021; 26(2): 118–125.

29. Vlassara H, Striker GE. Advanced glycation endproducts in diabetes and diabetic complications. Endocrinol Metab Clin North Am 2013; 42(4): 697–719.

30. Verzijl N, DeGroot J, Thorpe SR, et al. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 2000; 275(50): 39027–31.

31. Shields BM, McDonald TJ, Oram R, et al. C-peptide decline in type 1 diabetes has two phases: an initial exponential fall and a subsequent stable phase. Diabetes Care 2018; 41(7): 1486–1492.

32. Akirav E, Kushner JA, Herold KC. Beta-cell mass and type 1 diabetes: going, going, gone? Diabetes 2008; 57(11): 2883–8.

33. Martin S, Pawlowski B, Greulich B, et al. Natural course of remission in IDDM during 1st yr after diagnosis. Diabetes Care 1992; 15(1): 66–74.

34. Simell T, Kaprio EA, Maenpaa J, et al. Randomised prospective study of short–term and long–term initial stay in hospital by children with diabetes mellitus. Lancet 1991; 337(8742): 656–60.

35. Marek-Trzonkowska N, Mysliwiec M, Iwaszkiewicz-Grzes D, et al. Factors affecting long-term efficacy of T regulatory cell-based therapy in type 1 diabetes. J Transl Med 2016; 14(1): 332.

36. Jamiolkowska-Sztabkowska M, Glowinska-Olszewska B, Luczynski W, et al. Regular physical activity as a physiological factor contributing to extend partial remission time in children with new onset diabetes mellitus - two years observation. Pediatr Diabetes 2020; 21(5): 800–807.

37. Ludvigsson J, Cheramy M, Axelsson S, et al. GAD-treatment of children and adolescents with recent-onset type 1 diabetes preserves residual insulin secretion after 30 months. Diabetes Metab Res Rev 2014; 30(5): 405–14.

38. S vensson J, Sildorf SM, Pipper CB, et al. Potential beneficial effects of a gluten-free diet in newly diagnosed children with type 1 diabetes: a pilot study. Springerplus 2016; 5(1): 994.

39. Bouillet B, Rouland A, Petit JM, et al. A low-carbohydrate high-fat diet initiated promptly after diagnosis provides clinical remission in three patients with type 1 diabetes. Diabetes Metab 2020; 46(6): 511–513.

40. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study G. Effectiveness of continuous glucose monitoring in a clinical care environment: evidence from the Juvenile Diabetes Research Foundation continuous glucose monitoring (JDRF-CGM) trial. Diabetes Care 2010; 33(1): 17–22.

41. Thrailkill KM, Moreau CS, Swearingen C, et al. Insulin pump therapy started at the time of diagnosis: effects on glycemic control and pancreatic beta-cell function in type 1 diabetes. Diabetes Technol Ther 2011; 13(10): 1023– 30.

42. Sherr JL, Tauschmann M, Battelino T, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetes technologies. Pediatr Diabetes 2018; 19 Suppl 27: 302–325.

43. de Bock M, Dart J, Roy A, et al. Exploration of the performance of a hybrid closed loop insulin delivery algorithm that includes insulin delivery limits designed to protect against hypoglycemia. J Diabetes Sci Technol 2017; 11(1): 68– 73.

44. Patton SR, Noser AE, Youngkin EM, et al. Early initiation of diabetes devices relates to improved glycemic control in children with recent-onset type 1 diabetes mellitus. Diabetes Technol Ther 2019; 21(7): 379–384.

Neonatology Paediatrics General practitioner for children and adolescents
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