Baylor College of Medicine, Texas Children's Hospital, Houston, TX
University of South Florida, Tampa, FL.
Diabetes Care. 2018 Feb;41(2):311-317. doi: 10.2337/dc17-0961. Epub 2017 Oct 12.
The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 () single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis.
We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available rs4506565 and rs7901695 SNP data ( = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders.
The rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old ( = 504; OR 2.12 [1.29, 3.47], = 0.003) but not younger ones ( = 306, = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) ( = 0.008) and lower mean glucose AUC ( = 0.0127). The results were similar for the rs7901695 SNP.
In this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms.
1 型糖尿病的表型多样性提示其发病机制存在异质性。我们研究了与 2 型糖尿病相关的转录因子 7 样 2（）单核苷酸多态性（SNP）与 1 型糖尿病诊断时免疫和代谢特征的关系。
我们研究了新诊断为自身免疫性 1 型糖尿病的 TrialNet 参与者，这些参与者有可获得的 rs4506565 和 rs7901695 SNP 数据（=810；中位年龄 13.6 岁；范围 3.3-58.6）。我们构建了携带 变异体（即携带 1 或 2 个次要等位基因）对糖尿病诊断时胰岛自身抗体数量以及口服葡萄糖耐量试验（OGTT）刺激的 C 肽和血糖测量的影响模型。所有分析均调整了已知的混杂因素。
rs4506565 变异体是诊断时表达单个而非多个自身抗体的显著独立因素（比值比[OR]1.66[95%可信区间 1.07-2.57]，=0.024）。交互分析表明，这种关联仅在≥12 岁的参与者中具有显著性（=504；OR2.12[1.29-3.47]，=0.003），而在年龄较小的参与者中则不具有显著性（=306，=0.73）。rs4506565 变异体与 C 肽曲线下面积（AUC）升高（=0.008）和平均血糖 AUC 降低（=0.0127）相关。rs7901695SNP 的结果也相似。
在本队列新诊断的 1 型糖尿病患者中，2 型糖尿病相关的 变异体与单自身抗体（在≥12 岁的患者中）、OGTT 时 C 肽 AUC 升高和血糖 AUC 降低相关。因此，携带 变异体的个体在 1 型糖尿病诊断时具有较轻的免疫和代谢表型，这可能部分是由 2 型糖尿病样发病机制驱动的。
