Regional Center for Pediatric Diabetes, University of Verona, Verona, Italy.
Eur J Endocrinol. 2012 Dec 10;168(1):107-11. doi: 10.1530/EJE-12-0541. Print 2013 Jan.
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.
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.
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)).
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.
探讨糖尿病家族史与糖尿病酮症酸中毒（DKA）发病频率的关系，并分析人类白细胞抗原（HLA）基因型与 DKA 之间的可能关联。
我们招募了 510 名年龄<17 岁的 1 型糖尿病（T1D）患儿和青少年，并收集了一级亲属（FDR）T1D 病史信息。DKA 和重度 DKA 的定义分别为发病时血 pH 值<7.30 和<7.10。根据各种 HLA DQA1-DQB1 单倍型组合基因型，确定 T1D 发病的危险类别。
DKA 和重度 DKA 的发病频率分别为 34.7%和 7.2%。年轻患者（<2 岁（60.0%；P<0.001））更易发生 DKA，至少有一位 FDR 患有 T1D 的儿童 DKA 发生率较低（13.0%比 37.4%，P<0.001）。Logistic 回归显示，发病年龄（<2 岁）和增加的 HLA 相关危险基因型是 DKA 的独立预测因素（P<0.01，比值比（OR）=1.068（95%置信区间（CI）1.021-1.117）；P<0.05，OR=1.606（95% CI 1.034-2.475））。在 logistic 模型中引入至少有一位 FDR 患有 T1D，DKA 与发病年龄（<2 岁；P<0.01，OR=1.072（95% CI 1.024-1.123））和无 FDR 患有 T1D（P=0.001，OR=4.287（95% CI 1.770-10.383））之间存在显著关联，但与增加的 HLA 相关危险基因型无关（P=0.06，OR=1.550（95% CI 0.992-2.423））。
HLA 相关的高危基因型与糖尿病发病时出现 DKA 的可能性较高相关。然而，至少有一位 FDR 患有 T1D 可降低 DKA 的风险，而与 HLA 基因型无关。
