Characteristics and impact of diabetes and prediabetes in pre- and post-liver transplantation

Introduction: Discussion is still ongoing on the prevalence and characteristics of diabetes (DM) and prediabetes (PD) [IFG and/or IGT] in patients before and after liver transplantation (LT), and the impact on post-LT outcomes. Methods: In this single centre study we evaluated 1,468 candidates for LT [(age: 56±9 yrs; M/F: 1107/361; BMI: 24.4±5.8 kg/m2; family history of diabetes (FHD): 37%; FPG: 109±36 mg/dl; HbA1c: 35±12 mmol/mol); main indications for LT: 57.7% HCV/HBV-related cirrhosis/HCC, and 27.5% dysmetabolic/esotoxic cirrhosis/HCC)]. From this cohort, 1,086 subjects underwent LT, 470 of which reached a 5-year follow-up. Results: Based on pre-LT history, FPG, HbA1c and/or OGTT, 32.5% patients from the pre-LT cohort had DM and 21.4% PD. DM and PD patients were older and predominantly males (both p<0.001). Furthermore, DM subjects had higher BMI and FHD than PD and normoglycemic subjects (NG) (both p<0.05). In the transplant cohort with 5-year follow-up, patient and graft survival was respectively 84.5% and 84.1%, and the prevalence of DM and PD increased respectively to 49% (p<0.001) and 29% (p=0.053) vs pre-LT. To identify pre-LT factors in NG associated with post-LT DM (PTDM), machine learning algorithms (both interpretable and explainable) were used (i.e. decision trees, explainable boosting machines and CatBoost) to assess multivariate correlations. Inspection of the models indicated that pre-LT FPG, BMI, smoking and eGFR were among the main factors correlated with PTDM. In addition, insulin therapy at discharge after LT was more common in NG and PD patients who later developed PTDM than in those who remained non diabetic (p<0.001). Long duration (more than 10 years) of pre-LT DM (p=0.051) and HbA1c >7% (p=0.094) tended to impact on patient survival and/or graft outcome. Conclusion: This assessment of glycemic status in a large series of subjects candidates for LT implements previous available data and demonstrates a high prevalence of DM and PD (>50%); it also identifies modifiable factors to possibly prevent PTDM; duration of pre-LT DM and its control could affect post-LT outcomes. Supported by the EC and MUR under PNRR – M4C2-I1.3 Project PE_00000019~ HEAL ITALIA.