Potential Mechanism Associated with Post-Heart Transplantation Diabetes Mellitus in Chinese Patients

Posttransplantation diabetes mellitus (PTDM) is a common metabolic complication following heart transplantation (HT), which not only leads to elevated microvascular morbidity, but also seriously affects graft function and recipient survival. However, the specific metabolites and underlying mechanisms are not yet fully understood.

This study aimed to preliminarily screen out differentially expressed metabolites that are associated with PTDM in HT recipients and elucidate its potential pathophysiological mechanisms by using a global metabolomics approach, and provide a basis for the management of PTDM.

A total of 106 adult HT recipients (56 PTDM and 50 non-PTDM) who were followed for more than 1 year were enrolled in the study. Untargeted metabolomics was performed by ultra-high-performance liquid chromatography-tandem mass spectrometry. Demographics, clinical data, and drug information were collected at the time of sample collection.

PTDM patients were older (P = .003), with higher body mass index scores (P = .010), higher triglyceride levels (P = .007), and a higher prevalence of hypertension (P = .001) than non-PTDM patients. A total of 1174 metabolites were detected, of which 99 metabolites showed significantly differentially abundant (VIP > 1; P < .05; FC > 1.5 or <0.67). KEGG functional enrichment analysis showed these differently expressed metabolites could be further enriched in ABC transporter, carbon metabolism, retrograde endocannabinoid signaling, and phospholipase D signaling pathway. Compared with the non-PTDM group, glutamate, diacylglycerol, and D-sorbitol were significantly changed in PTDM through metabolomics.

These findings may provide a novel understanding of the pathological mechanism of PTDM and could be used to predict the development and progression of PTDM.