Objective: To explore the relationship between family history of diabetes and frequency of diabetic ketoacidosis (DKA) at diagnosis and to analyze the possible association between HLA genotypes and DKA. Design and methods: We recruited 510 children and adolescents aged <17 years with type 1 diabetes (T1D) and collected information on first-degree relative (FDR) history of T1D. DKA and severe DKA were defined as blood pH <7.30 and <7.10 at diabetes onset respectively. Risk categories for developing T1D were determined according to various HLA DQA1-DQB1 haplotype combination genotypes. Results: The frequency of DKA and severe DKA at diagnosis was 34.7 and 7.2% respectively. DKA was more frequent in younger patients (<2 years (60.0%; P<0.001)) and occurred less in children with at least one FDR affected by T1D (13.0 vs 37.4%, P<0.001). The logistic regression showed that age at diagnosis (<2 years) and increased HLA-associated risk genotypes were independent predictors of DKA (P<0.01, odds ratio (OR) =1.068 (95% confidence interval (CI) 1.021-1.117); P<0.05, OR=1.606 (95% CI 1.034-2.475)). Introducing the presence of T1D in at least one FDR in the logistic model, a significant association between DKA and age at diagnosis (<2 years; P<0.01, OR=1.072 (95% CI 1.024-1.123)) and absence of FDRs with T1D (P=0.001, OR=4.287 (95% CI 1.770-10.383)) was found, but no more with increased HLA-associated risk genotype (P=0.06, OR=1.550 (95% CI 0.992-2.423)). Conclusions: HLA-associated high-risk genotypes are associated with a high chance of presenting DKA at diabetes onset. However, having at least one FDR with T1D reduced the risk of DKA regardless of HLA genotype
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