Phenotypic Spectrum at Diagnosis of Age‐Related Endotypes of Type 1 Diabetes Mellitus: A Cross‐Sectional Study in China

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Abstract
Background: Emerging evidence suggests the presence of distinct endotypes of Type 1 diabetes mellitus (T1DM): T1DE1 in individuals diagnosed at age < 7 years in contrast to T1DE2 in those diagnosed at ≥ 13 years of age. We aimed to comprehensively explore the phenotypic heterogeneity of T1DM with respect to the age‐related endotypes.Methods: This cross‐sectional study was conducted in China and involved 1204 children newly diagnosed with T1DM who were admitted to the pediatric department of a tertiary hospital from January 1, 2010 to December 31, 2023. The patients were divided into three age groups: < 7 years (T1DE1), 7–12 years, and ≥ 13 years (T1DE2). A comparison was made among the age groups regarding demographic characteristics, glucose metabolism, β‐cell autoimmunity, and metabolic decompensation.Results: Patients under 7 years exhibited a shorter symptom duration before diagnosis, along with the lowest fasting and postprandial C‐peptide and C‐peptide to glucose ratio levels and the highest postprandial glucose levels. They also showed the highest insulin autoantibody positivity rate and creatine kinase‐MB levels. In contrast, patients aged 13 and older had the highest HbA1c levels and glutamate decarboxylase antibody positivity rate. In addition, this group showed the highest prevalence of TPOAb and TgAb positivity, as well as the largest proportion of abnormal liver function cases.Conclusions: The study illustrates age‐specific phenotypic heterogeneity in pediatric T1DM, indicating the presence of distinct endotypes. Further investigation of these endotypes may offer more evidence for the precise treatment of T1DM.

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