Extended Abstract

1. Introduction and Purpose

The prevalence of diabetes is directly related to age and is recognized as the most common chronic disease of old age. This condition can influence the levels of Growth Differentiation Factor-15 (GDF-15). An increase in this variable may be due to the hormone's anti-inflammatory effects, which provide an overall protective effect on the disease process. Furthermore, reports indicate that elevated GDF-15 levels have a strong correlation with certain anthropometric and diabetes-related indices, where increased circulating GDF-15 has been observed in obese individuals with Type 2 Diabetes Mellitus (T2DM) due to elevated glucose and insulin levels. While exercise can increase plasma GDF-15 and improve glucose metabolism in men, the results regarding the effect of exercise training on GDF-15 are contradictory. Although studies have demonstrated the role of various types of exercise in improving and controlling T2DM and reducing inflammatory biomarkers, the effect of combined training (aerobic + resistance) on the inflammatory biomarker GDF-15 in elderly patients with T2DM has not been thoroughly investigated. Moreover, the lack of information regarding the response of this research variable in diabetic elderly individuals highlights the necessity of this study. Therefore, this research aims to investigate the effect of a period of combined training (resistance + aerobic) on the serum level of GDF-15 in elderly men with T2DM.

2. Materials and Methods

This semi-experimental study included 16 elderly men with T2DM (66.50 \pm 1.41 years) who were assigned to two groups: combined training (aerobic + resistance) and a control group. Inclusion criteria comprised: not having COVID-19, T2DM duration between 1 and 10 years, using no more than one type of oral antidiabetic drug per day (all subjects consumed an equal dose of Metformin), not receiving insulin therapy, a baseline glycosylated hemoglobin (HbA1c) level between 6.6% and 9.9%, a fasting blood glucose (FBG) level between 160 to 250\ \text{mg/dL}, and absence of cardiovascular, renal, or ocular diseases, any diabetes complications, smoking, ability to perform exercise, and no participation in regular exercise for at least 6 months prior to the study. Exclusion criteria included: unwillingness to participate, use of nutritional supplements, irregular attendance at training sessions (maximum three absences), changes in current daily medical treatment per physician’s advice (changes in the dose or type of medication), and injury. Initially, subjects' weight and height were measured using a Seca scale model, BMI was calculated as weight divided by the square of height, and finally, body fat percentage was assessed and recorded using a caliper based on the Jackson and Pollock seven-site formula. The training protocol lasted 8 weeks (3 sessions per week, 90 minutes per session), including: 10 minutes of warm-up. 10–30 minutes of aerobic training (at an intensity between 50% and 70% of maximum heart rate. 30–40 minutes of resistance training (at an intensity between 40% and 70% of one-repetition maximum (1RM)). Before each blood sampling, subjects rested in a seated position for a few minutes. Then, 10 cc of blood was rapidly drawn by a laboratory specialist from the cubital vein of the left arm between 8:00 AM and 9:00 AM. Serum GDF-15 level was measured in all subjects before and after the exercise intervention. The data were analyzed using dependent t-tests and Analysis of Covariance (ANCOVA) at a significance level of P < 0.05.

3. Results

The between-group results using ANCOVA showed a significant difference between the two groups in the values of GDF-15 (P=0.001), glucose (P=0.001), insulin (P=0.001), and insulin resistance (P=0.001) indices. The within-group findings indicated a significant increase in serum GDF-15 level and a significant decrease in glucose, insulin, and insulin resistance levels in the post-test compared to the pre-test (P < 0.05).

4. Conclusion

The results of the present study demonstrated a significant increase in Growth Differentiation Factor-15 in the experimental group after a period of combined training (resistance + aerobic). A systematic review and meta-analysis stated that acute exercise significantly increases this factor, while chronic exercise did not have a significant effect. The probable mechanism suggests that exercise leads to a transient and short-term increase in GDF-15, which may contribute to the beneficial metabolic effects of physical activity. Consistent findings can be referenced in the studies by Moghaddasi et al. (2020) and Zhang et al. (2019). Conversely, the results of this study are inconsistent with some findings, such as those of Naderi et al. (2021), where a significant decrease in this variable was found in the continuous training group compared to the pre-test in a comparison of interval and continuous training methods in women with T2DM. Regardless of the source of GDF-15 secretion, it has been shown that an exercise-induced increase in this variable may have anti-inflammatory effects and improve insulin sensitivity. This variable likely exerts different biological effects depending on the conditions that lead to its secretion, which is transiently increased in response to exercise, leading to improved insulin sensitivity and reduced inflammation. In the findings of this research, a significant increase in these indices likely occurred due to the presence of a pathological condition (T2DM) and the effect of combined exercise training. It appears that combined exercise training can be effective in reducing diabetes-related indices and body composition factors by influencing the GDF-15 factor. Despite the important clinical findings of the present study, several limitations are apparent. Due to the limited number of available studies, subgroup analyses to understand the effects of various exercise types were not feasible. This was a two-group study, which inherently limits clinical value and generalizability.

5. Acknowledgment & Funding

We hereby express our gratitude to the participants.

6. Ethical Consideration

This study was conducted in compliance with ethical guidelines and has the ethical approval number IR.UMA.REC.1401.002 from Mohaghegh Ardabili university

7. Contribution of authors

All authors have been actively participated in the process the study and writing the article.

8. Conflict of interest

The authors declare no conflict of interest.