Aims/hypothesis

Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual’s clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis.

Methods

Data were collected from the large INNODIA cohort of individuals (aged 1.0–45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA_1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10–17 years; and ≥18 years.

Results

The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0–382.0) pmol/l (AUC 749.3 [466.2–1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA_1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001).

Conclusions/interpretation

In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline.

Graphical Abstract

中文翻译：

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INNODIA 1 型糖尿病自然史研究：欧洲新诊断儿童、青少年和成人队列

目标/假设

1 型糖尿病是一种异质性疾病。解释个体临床病程和治疗反应差异的特征因素将具有重要的临床和研究意义。我们的目的是通过诊断后前 12 个月内的临床特征、自身抗体、β 细胞功能和血糖结果来评估 1 型糖尿病的异质性，以及它与诊断时年龄的关系。

方法

数据收集自新诊断为 1 型糖尿病的 INNODIA 大型个体（年龄 1.0-45.0 岁）队列，随访 3 个月，以评估临床特征、C 肽、HbA _1c和糖尿病相关抗体及其变化。诊断后的前 12 个月内，跨越三个年龄组：<10 岁； 10-17岁；且≥18岁。

结果

研究人群包括 649 人（57.3% 为男性；年龄 12.1±8.3 岁），其中 96.9% 的一种或多种糖尿病相关抗体呈阳性。空腹 C 肽基线 (IQR) 为 242.0 (139.0–382.0) pmol/l (AUC 749.3 [466.2–1106.1] pmol/l × min)，水平随着年龄的增长而增加 ( p <0.001)。随着时间的推移，10 岁以下参与者的 C 肽仍然较低，但在所有年龄组中均有所下降。与此同时，血糖水平逐渐升高。较低的基线空腹 C 肽、BMI SD 评分和诊断时糖尿病酮症酸中毒的存在与随着时间的推移较低的刺激 C 肽相关。 HbA _1c在前 3 个月内下降 ( p <0.001)，而胰岛素需求量从诊断后 3 个月开始增加 ( p <0.001)。

结论/解释

在这个新诊断的 1 型糖尿病的大型队列中，我们发现了临床和生化变量中与年龄相关的差异。值得注意的是，C 肽在年龄较小的儿童中较低，但其下降率没有主要的年龄差异。

图形概要