Exercise and Prediabetes After Renal Transplantation (EXPRED-I): A Prospective Study.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) beyond 12 months (late PTDM) is a severe complication after renal transplantation. Late PTDM develops mostly in subjects with prediabetes. Although exercise may have a potential role in preventing late PTDM, there are no previous data on the effect of exercise in patients with prediabetes. MATERIAL AND METHODS: The design was a 12-month exploratory study to test the capacity of exercise in reverting prediabetes in order to prevent late-PTDM. The outcome was the reversibility of prediabetes, assessed every 3 months with oral glucose tolerance tests (OGTT). The protocol included an incremental plan of aerobic and/or strength training as well as an active plan for promoting adherence (telephone calls, digital technology, and visits). A priori, a sample size cannot be calculated which makes this an exploratory analysis. Based on previous studies, the spontaneous reversibility of prediabetes was 30% and the reversibility induced by exercise will account for another 30%, a total reversibility of 60% (p value < 0.05, assuming a potency of 85%). Ad interim analysis was performed during follow-up to test the certainty of this sample calculation. Patients beyond 12 months after renal transplantation with prediabetes were included. RESULTS: The study was interrupted early due to efficacy after the evaluation of the follow-up of 27 patients. At the end of follow-up, 16 (60%) patients reverted to normal glucose levels at fasting (from 102.13 mg/dL ± 11 to 86.75 ± 6.9, p = 0.006) and at 120 min after the OGTTs (154.44 mg/dL ± 30 to 113.0 ± 13.1, p = 0.002) and 11 patients had persistent prediabetes (40%). Also, insulin sensitivity improved with the reversibility of prediabetes, compared to those with persistent prediabetes: 0.09 [0.08-0.11] versus 0.04 [0.01-0.07], p = 0.001 (Stumvoll index). Most needed at least one increment in the prescription of exercise and compliance. Finally, measures aimed at the improvement of compliance were successful in 22 (80%) patients. CONCLUSION: Exercise training was effective to improve glucose metabolism in renal transplant patients with prediabetes. Exercise prescription must be conducted considering both the clinical characteristics of the patients and pre-defined strategy to promote adherence. The trial registration number of the study was NCT04489043.

Post-Transplant Diabetes Mellitus and Prediabetes in Renal Transplant Recipients: An Update.

Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20-30% of renal transplant recipients and increases the risk for cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of ß-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.

Exercise and Prediabetes after Renal Transplantation (EXPRED): Protocol Description.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a frequent and severe complication after renal transplantation. In fact, PTDM is a risk factor for both infection and cardiovascular diseases. The prevalence and incidence of PTDM have a bimodal evolution: early (up to 3 months) and late PTDM (beyond 12 months). The majority of late PTDM occurs in subjects with prediabetes after transplantation. So, treating patients with prediabetes, a potentially reversible condition, might help preventing PTDM. In the general population, exercise prevents the evolution from prediabetes to diabetes. However, in renal transplantation, not enough evidence is available in this field. OBJECTIVES: We designed an exploratory analysis to evaluate the feasibility of exercise to reverse prediabetes as a first step in the design of a trial to prevent PTDM. METHODS: Only patients with prediabetes beyond 12 months after transplantation with capacity to perform exercise will be included. Prediabetes will be diagnosed based on fasting glucose levels and oral glucose tolerance tests (OGTTs). Patients will be treated with a stepped training intervention, starting with aerobic exercise training (brisk walking, swimming, and cycling) 5 times per week and 30 min/day. Aerobic exercise training will be gradually increased to 60 min/day or eventually combined with anaerobic exercise training in case of persistent prediabetes. The reversibility/persistence of prediabetes will be measured with fasting glucose and OGTTs every 3 months. This study will last for 12 months.