2097-P: Age at Type 1 Diabetes Diagnosis Is an Independent Risk Factor from HLA for Development of Type 1 Diabetes in First-Degree Relatives

IF 9.3 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2026-06-11 DOI:10.2337/db26-2097-p

GREGORY POWER, MICHAEL TANSEY, CATHERINA PINNARO, ANDREW NORRIS

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引用次数: 0

Abstract

Introduction and Objective: HLA genotype is the strongest genetic predictor of T1D risk. Highest risk HLA genotypes include DR3/DR4-DQB1*03:02 (DR3 and DR4). Islet autoantibodies are a marker of additional risk. This study aims to assess whether inclusion of age of onset for T1D in first-degree relatives (FDR) improves model prediction of risk for development of T1D beyond HLA and autoantibody status. Methods: This study analyzed cohort data obtained from the TrialNet Pathway to Prevention Study. Data was collected between March 14, 2004, and July 31, 2025. This study included 3,989 individuals with a single FDR with T1D who had available HLA genotypes and islet autoantibodies. A logistic regression to predict development of T1D was created utilizing DR3 and DR4 status, number of islet autoantibodies positive at initial screen, type of FDR with T1D, and age group at which FDR was diagnosed with T1D. Statistical analyses were performed using R version 4.4.2. Results: Even after controlling for the other variables described above, FDR onset age group remained an independent and statistically significant predictor for development of T1D (Likelihood-Ratio Chi-square = 32.32 (p < 0.001)). Individuals with an FDR diagnosed prior to age 5 (n = 1033) showed significantly increased odds to develop T1D compared to individuals with an FDR diagnosed between ages 6 and 10 (n = 1306, OR [95% CI] = 1.27 [1.05 - 1.53]), between ages 11 and 18 (n = 1052, OR = 1.53 [1.26 - 1.89]), or after age 18 (n = 598, OR = 2.21 [1.66 - 2.96]). Conclusion: Age of diagnosis at time of T1D in FDRs is an independent risk factor from HLA genotype and autoantibodies for development of T1D. Individuals with an FDR diagnosed prior to age 5 have significantly increased risk for development of T1D compared to individuals with an FDR diagnosed in older age groups. Disclosure G. Power: None. M. Tansey: Research Support; Current; Novo Nordisk, Diamyd, Provention Bio, Inc. Research Support; Ended; MannKind Corporation. Research Support; Current; Lumos Pharma, Inc., Ascendis Pharma A/S, Diurnal Ltd, Acadia Pharmaceuticals Inc., Eli Lilly and Company, BioMarin Pharmaceutical Inc. C. Pinnaro: None. A. Norris: None.

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2097-P: 1型糖尿病诊断年龄是HLA对一级亲属发生1型糖尿病的独立危险因素

简介与目的：HLA基因型是T1D风险最强的遗传预测因子。高危HLA基因型为DR3/DR4- dqb1 *03:02 （DR3和DR4）。胰岛自身抗体是额外风险的标志。本研究旨在评估在一级亲属（FDR）中纳入T1D发病年龄是否能改善除HLA和自身抗体状态外T1D发展风险的模型预测。方法：本研究分析了来自TrialNet途径预防研究的队列数据。数据收集于2004年3月14日至2025年7月31日之间。本研究纳入了3989例具有可用HLA基因型和胰岛自身抗体的单一FDR T1D患者。利用DR3和DR4状态、初始筛查时胰岛自身抗体阳性的数量、FDR患有T1D的类型以及FDR被诊断为T1D的年龄组，建立了预测T1D发展的逻辑回归。采用R版本4.4.2进行统计分析。结果：即使在控制上述其他变量后，FDR发病年龄组仍然是T1D发展的独立且具有统计学意义的预测因子（似然比卡方= 32.32 (p < 0.001)）。与6 - 10岁（n = 1306, OR [95% CI] = 1.27[1.05 - 1.53]）、11 - 18岁（n = 1052, OR = 1.53[1.26 - 1.89]）或18岁以后（n = 598, OR = 2.21[1.66 - 2.96]）的FDR患者相比，5岁前确诊的FDR患者（n = 1033）患T1D的几率显著增加。结论：fdr患者诊断T1D时的年龄是HLA基因型和自身抗体之外T1D发生的独立危险因素。在5岁之前诊断出FDR的个体与在更大年龄组诊断出FDR的个体相比，患T1D的风险显著增加。G.权力：无。M. Tansey：研究支持；当前的;Novo Nordisk, Diamyd, Provention Bio, Inc.研究支持;结束;MannKind公司。研究支持;当前的;Lumos Pharma, Inc., Ascendis Pharma A/S, daily Ltd ., Acadia Pharmaceuticals Inc., Eli Lilly and Company, BioMarin Pharmaceutical Inc.。C. Pinnaro：没有。A.诺里斯：没有。

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来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.