Department of Computer Science & Engineering, Indian Institute of Technology Kharagpur, Kharagpur, India.
Department of Cell Biology and Physiology, Indian Institute of Chemical Biology CSIR, Kolkata, West Bengal, India.
BMJ Open Diabetes Res Care. 2022 Feb;10(1). doi: 10.1136/bmjdrc-2021-002654.
Inadequate glycemic control among patients with type 2 diabetes mellitus (T2DM) poses an enormous challenge. Whether this uncontrolled T2DM population is a heterogenous mix of disease subtypes remains unknown. Identification of these subtypes would result in a customized T2DM management protocol thereby paving the way toward personalized therapy.
Electronic health records of 339 patients with uncontrolled T2DM patients followed up for a median period of 14 months were analyzed using Uniform Manifold Approximation and Projection followed by density-based spatial clustering of applications with noise. Baseline clinical features and final diagnoses with drug combinations were selected in the analysis. A 30 min oral glucose tolerance test was next performed for assessing the underlying insulin resistance and β cell dysfunction.
Three major clusters were identified. The first cluster characterized by recent onset T2DM had moderately preserved β cell function. The second cluster with a longer duration of T2DM and associated hypertension showed the best glycemic control with dual antidiabetic therapy. The third cluster with the longest history of T2DM and no history of hypertension had the worst glycemic control in spite of the highest percentage of patients on triple therapy (34.58%) and quadruple therapy (8.41%).
Uncontrolled T2DM comprises a heterogeneous population with respect to disease duration, presence of co-morbidities and β cell function without significant difference in insulin resistance. Stratifying them on the basis of pathoclinical features is the first step toward a personalized management in T2DM.
2 型糖尿病(T2DM)患者血糖控制不佳是一个巨大的挑战。目前尚不清楚这些未得到控制的 T2DM 患者是否是疾病亚型的异质混合人群。如果能够识别出这些亚型,就可以为 T2DM 患者制定个体化的管理方案,从而为个性化治疗铺平道路。
对 339 例血糖控制不佳的 T2DM 患者的电子病历进行了分析,中位随访时间为 14 个月。采用统一流形逼近和投影(UMAP),然后应用基于密度的空间聚类算法进行分析。在分析中选择了基线临床特征和最终诊断药物组合。接下来进行 30 分钟口服葡萄糖耐量试验,以评估潜在的胰岛素抵抗和β细胞功能障碍。
确定了三个主要的聚类。第一个聚类以近期发病的 T2DM 为特征,β细胞功能中度保留。第二个聚类 T2DM 病程较长,伴有高血压,联合使用两种降糖药可获得最佳的血糖控制。第三个聚类 T2DM 病程最长,且无高血压病史,尽管接受三联或四联治疗的患者比例最高(分别为 34.58%和 8.41%),但血糖控制最差。
血糖控制不佳的 T2DM 人群在疾病持续时间、合并症存在和β细胞功能方面存在异质性,而胰岛素抵抗无显著差异。根据病理临床特征对其进行分层是 T2DM 个体化管理的第一步。