Post-transplant diabetes mellitus (PTDM) is a prevalent and significant complication following organ transplantation, notably affecting 30% to 56% of liver transplant recipients (LTRs). PTDM arises partly due to immunosuppressive therapies, which impair insulin secretion, and corticosteroid use, which decreases insulin sensitivity. The presence of PTDM correlates with detrimental long-term outcomes, including impaired graft function, increased cardiovascular risks, infections, rejection episodes, and elevated mortality rates.

Sedentary behavior (SB) and physical activity (PA) are well-established factors influencing diabetes risk in the general population. Prolonged sedentary time increases diabetes incidence, while moderate-to-vigorous physical activity (MVPA) offers protective benefits. Despite this, LTRs commonly exhibit sedentary lifestyles with low PA levels, influenced by pre-transplant frailty, immunosuppressive therapy side effects, and reduced exercise tolerance. However, previous research in LTRs has mainly focused on PA’s impact on physical function and quality of life rather than its relationship with PTDM, and often without considering the interdependence between sedentary time and PA.

To address this gap, the study employed isotemporal substitution analysis, a statistical method that models the health impact of substituting time spent in one activity (e.g., sedentary behavior) with another (e.g., light or moderate-to-vigorous physical activity). This approach allows a nuanced understanding of how reallocating time affects PTDM risk in LTRs.

PTDM was diagnosed retrospectively from medical records using standard criteria: fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5%.

Participants wore a triaxial accelerometer (Active Style Pro) on their waist for seven consecutive days during waking hours, excluding water activities. Valid data required ≥10 hours of wear time per day. The device captured sedentary time (≤1.5 METs), light-intensity PA (LPA, >1.5 but <3 METs), and MVPA (≥3 METs).

Demographic and health data included age, sex, BMI, primary liver disease, time since transplantation, immunosuppressive regimens, employment status, and comorbidities (hypertension, dyslipidemia).

Participants were grouped by PTDM status. Sedentary time was categorized into <8 h, 8–<10 h, and ≥10 h/day. LPA and MVPA were dichotomized based on thresholds of 330 min/day and 150 min/week, respectively. Logistic regression models adjusted for covariates analyzed associations between sedentary time, PA, and PTDM risk. Isotemporal substitution models estimated changes in PTDM odds when replacing 30 minutes of sedentary time with LPA or MVPA.

Participant Characteristics and Activity Levels
The mean age was 63.4 years with 41% males. The majority underwent transplantation due to viral hepatitis (56%), with a mean post-transplant duration of 9 years. The median daily sedentary time was 8.4 hours, with 60% achieving ≥330 min/day of LPA and 27% achieving ≥150 min/week of MVPA. The accelerometer was worn approximately 15.5 hours daily.

Incidence of PTDM and Associations
PTDM prevalence was 54%. Onset occurred mostly beyond three years post-transplant (65%), emphasizing its chronic nature. Those with sedentary time ≥8 h/day had a 60% higher odds of PTDM compared to those with <8 h/day (adjusted OR 1.60, 95% CI 1.15–1.78, p = 0.015). No other demographic or health factors showed significant differences between PTDM and non-PTDM groups.

Isotemporal Substitution Analysis
Replacing 30 minutes of sedentary time with LPA reduced the odds of PTDM by 19% (adjusted OR 0.81, 95% CI 0.70–0.92, p = 0.001), while substituting with MVPA led to a 72% risk reduction (adjusted OR 0.28, 95% CI 0.09–0.69, p = 0.002). Conversely, replacing LPA or MVPA with sedentary time increased PTDM odds substantially.

This pioneering study objectively measured sedentary behavior and physical activity in living donor LTRs and found a strong association between prolonged sedentary time and increased PTDM risk. The results align with broader population studies that link sedentary behavior to type 2 diabetes but highlight an even greater vulnerability in transplant recipients due to metabolic challenges and immunosuppressive treatments.

Notably, the study revealed a non-linear relationship between sedentary time and PTDM risk, with a plateau effect beyond 8 hours daily, possibly due to biological saturation or sample size limitations. Compared to healthy populations, LTRs showed markedly reduced MVPA levels, indicating a critical area for intervention.

While MVPA offers the most potent protection against PTDM, achieving recommended MVPA levels may be challenging for LTRs due to fatigue, fear of harming the graft, and physical limitations. Thus, promoting light-intensity physical activity, such as standing or gentle walking, emerges as a feasible and beneficial strategy. Recent evidence supports LPA’s potential to improve cardiometabolic markers and reduce diabetes risk.

The study emphasizes the importance of using objective measures like accelerometers and tailored interventions to reduce sedentary time and incrementally increase physical activity in LTRs. Wearable devices and validated questionnaires can assist clinicians in counseling and monitoring patients to improve long-term metabolic outcomes.

The cross-sectional design limits causal inference. The single-center, small sample size restricts generalizability. Attrition bias may exist due to dropouts who were younger and less post-transplant time. Key confounders such as dietary intake were not assessed, and immunosuppressive therapy adjustments post-PTDM diagnosis complicate interpretations.

Prolonged sedentary behavior (≥8 hours/day) significantly increases PTDM risk in liver transplant recipients. Substituting sedentary time with light or moderate-to-vigorous physical activity is associated with substantial reductions in PTDM risk. Given the feasibility of promoting light-intensity activity, clinical strategies should focus on reducing sedentary time and gradually increasing physical activity to improve metabolic outcomes after transplantation.

Share this post