Abstract
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. 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. 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. 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.
Highlights
Diabetic ketoacidosis (DKA) is a potentially life-threatening acute complication of type 1 diabetes (T1D) characterized by a biochemical triad of hyperglycemia, ketonemia, and acidemia.Diabetic ketoacidosis is still the leading cause of morbidity and mortality in children with T1D
HLAassociated risk categories for developing T1D were defined according to the results reported by a genetic risk assessment Belgian study.[14]
The ROC curve in our study showed that this model would be able to correctly predict the probability of DKA at diagnosis in almost 70% of cases (Figure 3), preventing admissions to pediatric intensive care unit and reducing hospital lengths of stay and costs
Summary
Diabetic ketoacidosis (DKA) is a potentially life-threatening acute complication of type 1 diabetes (T1D) characterized by a biochemical triad of hyperglycemia, ketonemia (ketonuria), and acidemia.Diabetic ketoacidosis is still the leading cause of morbidity and mortality in children with T1D. A decreasing rate of DKA at diagnosis has been observed over time.[6] Increasing medical information and awareness might have resulted in changes in the clinical presentation of T1D in developed countries.[3,7,8]. Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes (T1D). This study outlined the major risk of DKA at diagnosis for younger children (
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