DOI: https://dx.doi.org/10.18203/2394-6040.ijcmph20221512
Published: 2022-05-27

Stable rates of diabetic ketoacidosis at the initial episode of type 1 diabetes mellitus are associated with a shift towards younger age at diagnosis: 8 years’ experience of a large Portuguese centre

Francisco Branco Caetano, Ana Lança, Cláudia Rodrigues, Ana M. Garcia, Sofia Bota, Catarina Diamantino, Ana L. Fitas, Júlia Galhardo, Rosa Pina, Lurdes Lopes, Catarina Limbert

Abstract


Background: The rate of diabetic ketoacidosis in new-onset type 1 diabetes mellitus depends on multiple factors and is very heterogeneous between countries. An inverse relationship between the incidences of T1D and DKA seems to exist. Moreover, DKA is reported to be more common in children under 5 years old. Current data on Portuguese pediatric DKA incidence in new-onset T1D is limited. We aimed to determine the rate of DKA incidence in this population, as well as risk and protective factors.

Methods: Review of data from children aged 18 years or younger with new onset T1D, referred to a pediatric endocrinology unit between January 1st, 2013 and December 31th, 2020 (8 years).

Results: 276 patients were included with a median age of 9.6 years-old (0.5-17.9 years): 15,6% aged between 2 and 5 years-old and 3,6% under two years. A mean incidence of 34,5 new cases per year was observed, with an upward trend. One hundred and five (38%) presented with DKA, which was considered severe in 9,4%; 50 patients (18,1%) presented only with hyperglycemia. Non-DKA at presentation was associated with family history of T1D (p=0.016). DKA at presentation was more frequent in the age group under 2 years old (p=0.005).

Conclusions: DKA’s frequency at new onset T1D is still high, although only a small proportion of cases was considered severe. A family history of T1D correlated with a non-DKA presentation, while an age under 2 years presented as a risk factor for DKA.


Keywords


Type 1 diabetes, Diabetic ketoacidosis, Incidence trend, Risk factors

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References


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;19(27):155-77.

Usher-Smith JA, Thompson MJ, Sharp SJ, Walter FM. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: A systematic review. BMJ. 2011; 343(7815):1-16.

Usher-Smith JA, Thompson M, Ercole A, Walter FM. Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia. 2012;55:2878-94.

Lévy-Marchal C, Patterson CC, Green A. Europe and Diabetes. Geographical variation of presentation at diagnosis of type I diabetes in children: the EURODIAB study, European and Diabetes. Diabetologia. 2001;44(3):B75-80.

Szypowska A, Dżygało K, Wysocka-Mincewicz M, Mazur A, Lisowicz L, Ben-Skowronek I, et al. High incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes among Polish children aged 10-12 and under 5 years of age: A multicenter study. Pediatr Diabetes. 2017;18:722-8.

Große J, Hornstein H, Manuwald U, Kugler J, Glauche I, Rothe U. Incidence of Diabetic Ketoacidosis of New-Onset Type 1 Diabetes in Children and Adolescents in Different Countries Correlates with Human Development Index (HDI): An Updated Systematic Review, Meta-Analysis, and Meta-Regression. Horm Metab Res. 2018;50:209-22.

Duca L, Wang B, Rewers M, Rewers A. Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes Predicts Poor Long-term Glycemic Control. Diabetes Care 2017;40:1249-55

Vanelli M, Chiari G, Ghizzoni L, Costi G, Giacalone T, Chiarelli F. Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices. Diabetes Care. 1999;22:7-9.

Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet. 2009;373:2027-33.

Soltesz G, Patterson CC, Dahlquist G. Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology? Pediatr Diabetes. 2007;8(6):6-14.

Steck AK, Armstrong TK, Babu SR, Eisenbarth GS. Stepwise or linear decrease in penetrance of type 1 diabetes with lower-risk HLA genotypes over the past 40 years. Diabetes. 2011;60(3):1045-9.

Rush T, McGeary M, Sicignano N, Buryk MA. A plateau in new onset type 1 diabetes: Incidence of pediatric diabetes in the United States Military Health System. Pediatr Diabetes. 2018;19(5):917-22.

Haynes A, Bulsara MK, Jones TW, Davis EA. Incidence of childhood onset type 1 diabetes in Western Australia from 1985 to 2016: Evidence for a plateau. Pediatr Diabetes. 2018;19(4):690-2.

Observatório da Diabetes. Diabetes: Factos e Números – O Ano de 2015 − Relatório Anual do Observatório Nacional da Diabetes. 2016. Sociedade Portuguesa de Diabetologia. Available at: http://www.spd.pt/images/ bolsas/dfn2015.pdf. Accessed on 22 November 2021.

Ace E, Group S. Variation and trends in incidence of childhood diabetes in Europe. EURODIAB ACE Study Group. Lancet. 2000;355(9207):873-6.

Patterson CC, Gyürüs E, Rosenbauer J, Cinek O, Neu A, Schober E, et al. Trends in childhood type 1 diabetes incidence in Europe during 1989-2008: Evidence of non-uniformity over time in rates of increase. Diabetologia. 2012;55(8):2142-7.

Chobot A, Polanska J, Brandt A, et al. Updated 24-year trend of Type 1 diabetes incidence in children in Poland reveals a sinusoidal pattern and sustained increase. Diabet Med. 2017;34(9):1252-8.

Usher-Smith JA, Thompson M, Ercole A, Walter FM. Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: A systematic review. Diabetologia. 2012;55:2878-94.

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. 2016;2016.

Groe J, Hornstein H, Manuwald U, Kugler J, Glauche I, Rothe U. Incidence of diabetic ketoacidosis of new-onset type 1 diabetes in children and adolescents in different countries correlates with human development index (hdi): an updated systematic review, meta-analysis, and meta-regression. Horm Metab Res. 2018;50:209-22.

Stipancic G, Sepec MP, La Grasta Sabolic L, Radica A, Skrabic V, Severinski S, et al. Clinical characteristics at presentation of type 1 diabetes mellitus in children younger than 15 years in Croatia. J Pediatr Endocrinol Metab. 2011;24(9-10):665-70.

Fritsch M, Schober E, Rami-Merhar B, Hofer S, Fröhlich–Reiterer E, Waldhoer T, et al. Diabetic Ketoacidosis at Diagnosis in Austrian Children: A Population-Based Analysis, 1989-2011. J Pediatr. 2013;163:1484-8.

Conde Barreiro S, Rodríguez Rigual M, Bueno Lozano G, López Siguero JP, González Pelegrín B, Rodrigo Val MP, et al. Epidemiology of type 1 diabetes mellitus in children in Spain. An Pediatr. 2014;81:189.e1-12.

Hanberger L, Birkebaek N, Bjarnason R, Drivvoll AK, Johansen A, Skrivarhaug T, et al. Childhood diabetes in the Nordic countries: A comparison of quality registries. J Diabetes Sci Technol. 2014;8:738-44.

Rewers A, Dong F, Slover RH, Klingensmith GJ, Rewers M. Incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes in colorado youth, 1998-2012. JAMA. 2015;313:1570-2.

Unsworth R, Wallace S, Oliver N. New-onset type 1 diabetes in children during COVID-19: multicenter regional findings in the UK. Diabetes Care. 2020;43:e170-1.

Roche EF, Menon A, Gill D, Hoey H. Clinical presentation of type 1 diabetes. Pediatr Diabetes. 2005;6:75-8.

Couper J, Haller M, Greenbaum, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Stages of type 1 diabetes in children and adolescents. Pediatric Diabetes. 2018;19(27):20-7.

Samuelsson U, Stenhammar L. Clinical characteristics at onset of Type 1 diabetes in children diagnosed between 1977 and 2001 in the south-east region of Sweden. Diabetes Res Clin Pract. 2005;68(1):49-55.

Veijola R, Reijonen H, Vähäsalo P, Sabbah E, Kulmala P, Ilonen J, et al. HLA-DQB1-defined genetic susceptibility, beta cell autoimmunity, and metabolic characteristics in familial and nonfamilial insulin-dependent diabetes mellitus. J Clin Invest. 1996;98:2489-95.

Szypowska A, Skórka A. The risk factors of ketoacidosis in children with newly diagnosed type 1 diabetes mellitus. Pediatr Diabetes. 2011;12(4.1):302-6.

King BR, Howard NJ, Verge CF, Jack MM, Govind N, Jameson K, et al. A diabetes awareness campaign prevents diabetic ketoacidosis in children at their initial presentation with type 1 diabetes. Pediatr Diabetes. 2012;13:647-51.

Vanelli M, Chiari G, Ghizzoni L, Costi G, Giacalone T, Chiarelli F. Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices. Diabetes Care. 1999;22:7-9.

Battaglia M, Ahmed S, Anderson M, et al. Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes. Diab Care. 2020;43(1):5-12.