Insulin resistance is a strong risk factor for the development of PTDM and diseases of the cardiovascular system, which significantly affect the long-term survival of patients after KT. Modifiable factors, such as weight gain in the absence of regular physical activity, contribute significantly to these insulin-resistant patients much more frequently compared to their peers in the general population (6).
It is known and verified by several studies that regular physical activity is an effective tool for the prevention and treatment of pre-diabetic conditions and type 2 DM, which clearly strengthens its position among interventional procedures in this group of patients (17, 18). Conversely, in the transplanted population, the data are severely limited. Sharif et al. in 2008 they were the first to monitor the effect of intensive lifestyle modification in patients after KT. Physical activity included 2 hours of endurance discipline per week. However, the study was designed primarily for therapeutic purposes, as subjects had already been diagnosed with IGT or PTDM. At 6-month follow-up, there was a 15% improvement in 2-hour postprandial glycemia versus 12% deterioration in the control group. In the first group, 44% of those treated with IGT developed normal glucose tolerance, while only 4% switched to PTDM and 58% of those monitored with PTDM achieved improvement (29% to IGT, 29% to normal tolerance). The study pointed out the importance and significance of active intervention in the lifestyle of these patients, both in the prevention of high-risk patients and in the treatment of already developed PTDM. However, the evaluation of sporting activity was subjective (19).
Recently, a prospective randomized study CAVIAR (Comparing Glycemic Benefits of Active Versus Passive Lifestyle Intervention in Kidney Allograft Recipients) was published, comparing the effect of a complex lifestyle change on glucose metabolism among patients after KT without PTDM. 130 recipients were randomized 1:1 into active (lifestyle counseling by a renal dietitian using a behavior change technique) and passive intervention groups. As in our study, the length of follow-up was 6 months. In terms of physical activity, patients were encouraged to increase their performance and kept a training diary. This study did not confirm a different impact of active versus passive intervention on insulin sensitivity or secretion (20). The Dutch multicenter randomized study ACT (The Active Care after Transplantation) is currently underway, comparing 3 groups of patients (classic care, physical exercise intervention and combination of diet and exercise) with the primary aim to assess the impact of lifestyle changes on quality of life as well as degree of physical condition, adipose tissue and cardio-metabolic risk factors such as blood pressure, lipids, glucose metabolism (21).
Weight gain and obesity are known risk factors for the development of IR in the post-transplant period. Oterdoom et al. in their work they state that obesity evaluated by the BMI index, but also the distribution of adipose tissue determined from the waist-to-hip ratio are the strongest determinants for the development of IR after KT. Even adipose tissue distribution is a risk factor independent of general obesity, and therefore assessment of waist circumference provides more accurate information on abdominal obesity than BMI (6). In our study, regular physical activity led to a significant reduction in waist circumference and a reduction in LDL cholesterol compared to the control group. However, the reduction in body weight, BMI, waist circumference and lipid profile parameters did not reach statistically significant in the multivariate model. In the CAVIAR study, the active intervention group achieved significant progress in weight and fat mass reduction in contrast to the passive group, which clearly contributes to improving the cardio-metabolic risk profile of these patients (20). We also demonstrated a significant difference in waist circumference value reduction between patients in the intervention group, which was achieved by the subgroup with the highest level of sports exertion, which supports a direct relationship between the degree of physical activity and cardio-metabolic risk. In 2011, Zelle et al. in a prospective study on a sample of 540 recipients after KT, they confirmed a strong independent correlation between low physical activity and cardiovascular and overall mortality (22). Recently, Byambasukh et al. published work in which recipients performing moderate to high intensity physical activity showed significantly lower cardiovascular and overall mortality compared to recipients with a sedentary lifestyle regardless of age, gender, and graft function (23).
The secondary goal of our work was to evaluate the influence of physical activity on the development of graft function. We found a significantly lower value of serum creatinine and a higher eGFR already in the 3rd month from the beginning of the follow-up in the intervention group in comparison with the control group. We assume that the length of our follow-up is relatively short in terms of graft function impact assessment. The Italian authors Totti et al. reported a significant increase in creatinine and a decrease in eGFR during the 3-year follow-up period in the passive group compared to patients exercising regularly ≥ 150 minutes per week (24).
In our study, we confirmed that regular exercise of moderate intensity of at least 150 minutes per week is sufficient to adequately prevent glucose metabolism disorders. This conclusion is in line with the ADA recommendations for high-risk patients or with prediabetes to prevent and delay the development of DM (15). The WHO (World Health Organization) also proposes the same minimum weekly sports activity limit in its 2010 recommendations for the adult population. At the same time, they state that in order to achieve an additional health effect, it is necessary to increase this activity to ≥ 300 minutes of medium intensity per week or ≥ 150 minutes of high intensity per week (25). In our study, such an effect (significant reduction in waist circumference) was achieved by a subgroup meeting the criteria of high-intensity and long-lasting exertion (≥ 300 minutes per week). In most available works, an aerobic type of sport is applied to evaluate the effect of physical activity. Both aerobic and strength training are known to promote skeletal muscle, adipose tissue and liver adaptation in association with increased insulin action (13). The combination of endurance and strength training can provide even greater improvement and appears to be superior to continuous aerobic training (26). The ADA and WHO also recommend incorporating a strength component into regular training (15, 25). By comparing the combined activity with aerobic, we did not find in our study an additional impact on the parameters of glucose metabolism or anthropometric data. At the end of the follow-up, the group with isolated aerobic activity showed a significantly lower value of triglycerides.
There are several similarities between glucose metabolism disorders in the general population and arising de novo after KT, but the transplanted population is exceptional in many aspects and needs to be approached in an individualized way. Therefore, there are no specific suggestions for prevention, but also non-pharmacological treatment of these disorders in the general recommendations for recipient care after KT, especially at a time when the KT patient is not rare in the population and a healthy lifestyle is the number one topic in most age groups. Based on the findings, we consider it necessary to apply regular physical activity, but also dietary counseling to daily practice as much as possible in order to improve the long-term survival of grafts and patients after KT.
We consider the incorporation of digital technologies for patient monitoring and thus the simple verification of data, which in our case is not based only on the questionnaire method, to be an important and unique aspect of this study. Sports bracelets, which in most cases are already part of the watch, are now widely available and commonly used from beginners to professional athletes of various ages. They use motion and thermally controlled sensors to record energy expenditure and monitor metabolic physical activity, thus providing us with an objective evaluation of each patient's athletic performance. By pairing them with a mobile application, we obtained a detailed analysis of the entire period under review, and on the other hand, we consider them to be an important factor in motivating individuals and striving to improve their results. To date, no studies have performed on the transplanted sample of patients to objectively evaluate the impact of physical activity on changes in glucose metabolism. We consider this an excellent opportunity to further monitor the impact of lifestyle modifications on the development of the cardio-metabolic profile of this risk group of patients. The possible different impact of lifestyle adjustments depending on gender remains questionable, given that in a study in 2019 by Dedinská et al. found that in men after KT, IR and metabolic syndrome are the main predictors of PTDM, while in women it is pancreatic β cell dysfunction (27). It is therefore necessary to incorporate this probably important variable into further research.
The limitation of the study is the small number of enrolled patients and the possible problem with monitoring physical activity carried out in the control group. There was significantly different time from kidney transplantation between both groups with worse kidney function however there were no differences in immunosuppression and average kidney function was excellent in both groups.