Abstract
Post-transplantation diabetes mellitus (PTDM) is a common metabolic complication after solid organ transplantation, which not only results in elevated microvascular morbidity, but also seriously impacts graft function and recipient survival. However, its underlying mechanism is not yet fully understood. In this study, an integrated liquid chromatography- mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) based-metabolomics approach was adopted to dissect the metabolic fluctuations and deduce potential mechanism associated with PTDM. 68 adult liver transplant recipients were recruited and classified as 32 PTDM and 36 non-PTDM subjects. PTDM group and non-PTDM group were well matched in gender, age, BMI, family history of diabetes, alcohol drinking history, ICU length of stay and hepatitis B infection. Peripheral blood samples from these recipients were collected and prepared for instrument analysis. Data acquired from LC-MS and GC-MS demonstrated significant metabolome alterations between PTDM and non-PTDM subjects. A total of 30 differential metabolites (15 from LC-MS, 15 from GC-MS) were screened out. PTDM patients, compared with non-PTDM subjects, were characterized with increased levels of L-leucine, L-phenylalanine, LysoPE (16:0), LysoPE (18:0), LysoPC (18:0), taurocholic acid, glycocholic acid, taurochenodeoxycholic acid, tauroursodeoxycholic acid, glycochenodeoxycholic acid, glycoursodeoxycholic acid, etc, and with decreased levels of LysoPC (16:1), LysoPC (18:2), LysoPE (22:6), LysoPC (20:4), etc. Taken collectively, this study demonstrated altered metabolites in patients with PTDM, which would provide support for enhancing mechanism exploration, prediction and treatment of PTDM.
Highlights
Solid organ transplantation (SOT), with more than 110,000 transplantations performed worldwide annually [1], is the treatment of choice for patients with end-stage organ failure
post-transplantation diabetes mellitus (PTDM) group and non-PTDM group were well matched with no significant difference in gender, age, BMI, family history of diabetes, alcohol drinking history, ICU length of stay and hepatitis B infection
Typical total ion chromatograms (TICs) of PTDM and nonPTDM recipients were presented in Supplementary Figure 1
Summary
Solid organ transplantation (SOT), with more than 110,000 transplantations performed worldwide annually [1], is the treatment of choice for patients with end-stage organ failure. The short-term outcome of SOT improved remarkably due to advances in organ preservation [2], surgical techniques [3], immunosuppression regimens [4] and so on. Metabolic complications, such as diabetes mellitus, hypertension and dyslipidemia, severely impact the long-term survival [5, 6]. PTDM is one of the major risk factors for diabetes-associated microvascular complications and infections, contributing to 1.63 times higher risk of graft failure and 1.87 times higher risk of mortality in SOT recipients [9]
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