Whole Blood Metabolome Profiling for Stratification of Type 2 Diabetes Patients and Identification of Biomarkers for Diabetic Kidney Disease in Asian Indian Adults

Type
2 diabetes mellitus is a heterogeneous disease with broader
metabolic perturbation beyond hyperglycemia, resulting in varied prognoses.
Additionally, patients are at risk of complications, such as diabetic
kidney disease (DKD), which often remains asymptomatic in early stages.
Metabolomics offers a comprehensive assessment of metabolic dysregulation,
surpassing conventional biomarkers such as glucose and creatinine.
In this case-control study, we used mass spectrometry coupled to liquid
(LCMS) and gas chromatography (GCMS) to profile metabolites from the
whole blood samples from a cohort of Asian Indians belonging to three
groups: nondiabetic, type 2 diabetes, and DKD. We identified 290 metabolites
using LCMS and GCMS, of which 26 and 20 metabolites were significantly
associated with type 2 diabetes and DKD, respectively, after false
discovery rate correction. Clustering analyses revealed two distinct
subgroups within the type 2 diabetes group, with nine metabolites
linked to the disease severity. Additionally, seven metabolites exhibited
progressive changes from nondiabetic to type 2 diabetes to DKD, suggesting
potential prognostic markers for DKD. Our study highlights the role
of metabolome profiling for patient stratification and early diagnosis
of DKD in Indian patients with type 2 diabetes.