Beta Cell Dysfunction and Insulin Resistance in Posttransplant Diabetes Mellitus

A BSTRACT Introduction: Posttransplant diabetes mellitus (PTDM) is a major determinant of renal allograft dysfunction, posttransplant infections, and increased risk of cardiovascular morbidity and mortality, and can significantly affect the clinical outcome of the transplant recipients. We aimed to determine the incidence, risk factors, and underlying mechanisms of PTDM in kidney transplant recipients. Methods: In a single-center, prospective, observational cohort study of 80 nondiabetic kidney transplant recipients (2023–2024), the clinical, metabolic, immunosuppressive, and infectious parameters were recorded. Pretransplant fasting plasma glucose, glycosylated hemoglobin (HbA1C), lipid profile, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Homeostatic Model Assessment of β-cell Function (HOMA-β), and tacrolimus trough levels at 1.5 and 3 months posttransplant were analyzed. Logistic regression and receiver operating characteristic curves defined predictors. Results: PTDM developed in 23.8% ( n = 19). Significant risk factors included family history of diabetes and hypertension, smoking, higher pretransplant Body Mass Index, waist circumference, fasting blood glucose, HbA1c, lipid abnormalities, and high net immunosuppression. Independent predictors of PTDM were pretransplant triglycerides >134.5 mg/dL (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01–1.10) and trough tacrolimus level ≥7.5 ng/mL at 1.5 months (OR– 2.1, 95% CI 1.06–4.14). HOMA-β was significantly lower than HOMA IR in the PTDM group ( P < 0.001), suggesting beta-cell dysfunction as the predominant pathophysiologic mechanism. Conclusion: PTDM occurred in 23.8% of kidney transplant recipients in our cohort, with the majority developing PTDM within the 1 st -year posttransplantation. Pretransplant hypertriglyceridemia and high early tacrolimus exposure were independently associated with the development of PTDM. Beta-cell dysfunction appears to be the main contributor. Early metabolic screening and individualized immunosuppression may mitigate PTDM risk.