Diabetic ketoacidosis in children newly diagnosed with type 1 diabetes mellitus: Role of demographic, clinical, and biochemical features along with genetic and immunological markers as risk factors. A 20‐year experience in a tertiary Belgian center

Abstract

Background: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes (T1D). Little is known about the association between genetic and immunological markers and the risk for DKA at onset of T1D. The aim of this study was to create a model foreseeing the onset of DKA in newly diagnosed patients.Methods: This retrospective study included 532 T1D children (aged <18 years at diagnosis) recruited in our hospital, from 1995 to 2014. DKA and its severity were defined according to the criteria of ISPAD. Genetic risk categories for developing T1D were defined according to the Belgian Diabetes Registry. Multivariate statistical analyses were applied to investigate risk factors related to DKA at diagnosis.Results: Overall 42% of patients presented DKA at diagnosis. This study outlined the major risk of DKA at diagnosis for younger children (<3 years) and for those belonging to ethnic minorities. Children carrying neutral genotypes had a 1.5-fold increased risk of DKA at diagnosis than those with susceptible or protective genotypes, a paradoxical observation not previously reported. Only solitary positive IA-2A increased the risk of DKA at diagnosis. The proposed model could help to predict the probability of DKA in 70% of newly diagnosed cases. Conclusions:This was the first reported implication of IA-2A positivity and neutral genotypes predisposing to DKA at diagnosis regardless of its severity. Earlier diagnosis through genetic and immunological screening of high-risk children could decrease DKA incidence at diabetes onset.

Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes?

“…A recent report has found a correlation between the number of positive antibodies and the severity of ketoacidosis [48], which supports the relation of DKA to the intensity of destruction of pancreatic β-cells. Other reports have found a greater risk of DKA associated with different specific antibodies [48,49]. However, most of the published data find no difference in rates of DKA and presence or absence of autoimmunity [50,51] which substantiates the relationship of DKA to delayed diagnosis rather than to the expression of antigenicity.…”

Epidemiological and clinical factors influencing the presence of ketoacidosis in inaugural Type 1 Diabetes in children : review of the last ten years in a center for pediatric diabetology in Brussels (HUDERF), cross-sectional study

“…La symptomatologie classique de lhyperglycémie (polyurie, polydipsie, perte de poids) est trouvée dans la majorité des cas au diagnostic de DT1 2,14 . Dans notre étude, nous trouvons que celle-ci est plus marquée en cas dACD que sans ACD, ce qui est déjà rapporté dans la littérature 9 . Les signes cliniques de lACD décrits par lISPAD sont des nausées, vomissements, douleurs abdominales et/ou altération de la conscience 4 .…”

“…Linfluence du sexe dans lacidocétose diabétique nest pas universelle. Une revue de la littérature rapporte tant des études avec plus de filles en ACD ou sans différence entre les deux sexes 9,10,15,16 .…”

“…Les facteurs épidémiologiques prédisposant les plus souvent retrouvés sont : le faible niveau socio-économique, un âge situé entre 0 et 4 ans et la situation géographique 8 . Les facteurs immunologiques, décrits par Vicinanza , sont la présence dauto-anticorps IA-2A 9 . Dautres facteurs diminuent le risque dACD : la présence dans lentourage proche dune personne ayant un diabète de type 1 et le haut niveau déducation parentale 10 .…”

Parent Preferences for Delaying Insulin Dependence in Children at Risk of Stage III Type 1 Diabetes

“…1 Because presymptomatic disease is difficult to detect without blood tests, most affected individuals progress to Stage III disease unaware of their condition and then present to the emergency department with very high blood glucose values and, quite often, in a state of diabetic ketoacidosis (DKA). [2][3][4] Beyond the immediate health care costs of DKA, the presence of DKA at T1D onset is associated with an increased risk of hospitalization and negative long-term outcomes, including poor glycemic control and adverse neurocognitive impacts. [5][6][7] Therefore, preventing DKA at T1D diagnosis may provide long-term value.…”