Sport Physiology

Sport Physiology

The Effect of Combined Exercise Sequence on Cardiovascular Risk Factors, C-Reactive Protein, Homocysteine, and Insulin Resistance in Obese Women with Type 2 Diabetes

Document Type : Research Paper

Authors
1 Department of Physical Education, Boj.C., Islamic Azad University, Bojnourd, Iran
2 Department of Sport Sciences, Faculty of Humanity, Bojnourd University, Bojnourd, Iran
3 Department of Endocrinology and Internal Medicine, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
Abstract
Background and Purpose
Abdominal obesity, in particular, represents a cluster of risk factors that significantly increase the likelihood of developing cardiovascular disease and type 2 diabetes. At present, in addition to the classical cardiovascular risk factors—including obesity, hypertension, hypercholesterolemia, metabolic syndrome, physical inactivity, and smoking—several novel risk markers such as homocysteine and C-reactive protein have been identified, which independently and more strongly predict the risk of cardiovascular diseases compared with traditional risk factors.C-reactive protein (CRP) is a member of the pentraxin family composed of five 23-kDa subunits, derived from the liver and the endothelium of coronary arteries, and it contributes to vascular injury and an increased risk of atherosclerosis through mechanisms such as enhancing the generation of reactive oxygen species, reducing nitric oxide activity, and stimulating macrophage-mediated uptake of low-density lipoprotein (LDL) cholesterol. Homocysteine, a sulfur-containing amino acid produced during methionine metabolism, induces endothelial dysfunction by promoting LDL oxidation, suppressing nitric oxide activity and impairing arterial vasodilation, inhibiting nitric oxide synthase function, activating platelets, and generating oxidative stress; its metabolism is dependent on several nutritional and genetic factors. Elevated levels of homocysteine can lead to a prothrombotic state, oxidative stress, and endothelial dysfunction . Numerous studies have demonstrated that hyperhomocysteinemia is a significant risk factor for the development of cardiovascular diseases . However, limited data exist regarding the impact of elevated plasma homocysteine levels on the increased risk of cardiovascular disease in individuals with diabetes. Several studies have reported higher homocysteine concentrations in diabetic patients compared with non-diabetic individuals. According to a meta-analysis of prospective studies, a 5 μmol/L increase in circulating homocysteine levels is associated with a 33.6% rise in all-cause mortality risk.Among the various factors influencing serum homocysteine and CRP concentrations, exercise and physical activity play a significant role. Physical activity induces several biochemical changes that may affect homocysteine metabolism, with oxidative stress likely serving as a major mediator in this process . Aerobic training, a specific form of exercise, is commonly employed to enhance maximal oxygen consumption. The combination of resistance and aerobic training has been suggested as an effective strategy to improve overall performance. Evidence from research indicates that combined resistance–aerobic training, compared with performing each type of exercise alone, elicits distinct resistance-related adaptations that are closely linked to hormonal responses. Relevant studies addressing these effects individually are summarized below.Findings from existing research highlight the dual nature of the immune response to exercise. Intense and prolonged physical activity, characterized by high mechanical stress and eccentric loading, can cause muscle damage and trigger the release of cytokines, whereas exercise involving lower mechanical stress is associated with reduced CRP levels. Currently, limited evidence exists regarding the effects of resistance training—particularly when combined with endurance training—on cardiovascular and immune markers. Therefore, based on these considerations, the present study was conducted to address the central question of whether the sequence of combined training influences cardiovascular risk factors, including C-reactive protein, homocysteine, and insulin resistance, in obese women with type 2 diabetes.
Materials and Methods
This study employed a quasi-experimental pre-test and post-test design. A total of 36 women aged 40–60 years from Bojnord voluntarily participated and were recruited based on the required research criteria through announcements and informed instructions. After initial assessments and completion of questionnaires, participants were randomly assigned into three groups of 14, which, after attrition, were reduced to 12 per group: a control group that did not perform any exercise, an experimental group that performed aerobic training before resistance training, and a second experimental group that performed aerobic training after resistance training. Following the completion of medical questionnaires, informed consent forms, and readiness assessments, participants were admitted to the study based on inclusion criteria such as absence of medication or supplement use, no history of cardiovascular disease or infections affecting immune factors, and no engagement in regular or intense exercise in the preceding six months. All participants confirmed their readiness to adhere to the training protocol. Blood samples were collected from all three groups during both pre-test and post-test stages, and participants were instructed to refrain from engaging in strenuous physical activity for at least 48 hours before blood collection.
Results
In this study, the highest mean age was observed in the aerobic–resistance group at 49.7 years. The lowest mean height also belonged to the aerobic–resistance group at 154.2 cm, while the highest mean weight was recorded in the same group at 71.6 kg. The results indicated that ten weeks of combined aerobic–resistance training produced significant effects on HbA1c, homocysteine (Hcy), C-reactive protein (CRP), and insulin resistance in women with type 2 diabetes. In contrast, ten weeks of combined resistance–aerobic training did not significantly affect Hcy levels, although it had significant effects on insulin resistance, CRP, and HbA1c. No significant changes were observed in the control group. The results also showed that ten weeks of combined aerobic–resistance training had no significant effects on the lipid profile (LDL, HDL, TG, TC) of women with type 2 diabetes, except for HDL and TC. Similarly, combined resistance–aerobic training did not significantly affect the lipid profile (LDL, HDL, TG, TC) except for HDL. No significant changes were observed in the control group.
Conclusion
The findings of this study demonstrated significant differences in HbA1c, homocysteine (Hcy), CRP, and insulin resistance indices before and after aerobic–resistance training. In contrast, ten weeks of resistance–aerobic training did not significantly affect Hcy but did produce significant improvements in insulin resistance, CRP, and HbA1c. Insulin levels before and after training were not significantly different in either experimental group, and no significant differences were observed between the experimental and control groups. Comparison of HbA1c values showed a significant reduction following aerobic–resistance training, whereas no significant change was observed with resistance–aerobic training. After ten weeks of aerobic–resistance training, total cholesterol decreased significantly while HDL increased significantly, whereas in the resistance–aerobic group, only HDL showed a significant increase. These results suggest that aerobic–resistance training may help improve insulin resistance through reductions in fasting glucose and insulin levels.
Article Message
The sequence of combined exercises significantly affects metabolic and inflammatory markers in obese women with type 2 diabetes. Performing aerobic exercise before resistance training yields greater improvements in insulin resistance, homocysteine, and CRP levels, offering a practical approach for glycemic control and cardiovascular risk reduction.
Ethical Considerations
All stages of this study were conducted in accordance with the ethical principles of human research approved by the Islamic Azad University. Before participation, informed written consent was obtained from all subjects, and they were assured that their personal information and collected data would be used solely for research purposes. Participants were free to withdraw at any time, and all training sessions were performed under safe conditions and medical supervision.
Authors’ Contributions
Conceptualization: Sheida Naghizadeh
Data Collection and Exercise Protocol Implementation: Shida Naghizadeh and Habibeh-Sadat Shakeri
Laboratory Experiments and Sample Preparation: Habibeh-Sadat Shakeri
Data Analysis and Interpretation of Results: Shida Naghizadeh and Habibeh-Sadat Shakeri
Manuscript Writing: Shida Naghizadeh
Review and Editing: Ali Golestani and Habibeh-Sadat Shakeri
Literature Review: Ali Golestani and Habibeh-Sadat Shakeri
Project Management: Ali Golestani and Habibeh-Sadat Shakeri
Conflict of Interest
The authors declare that there is no conflict of interest regarding the authorship and publication of this article.
Acknowledgments
The authors thanks all participants for their cooperation and contribution to the study.
 
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Volume 17, Issue 68
Winter 2026
Pages 74-90

  • Receive Date 01 May 2025
  • Revise Date 05 October 2025
  • Accept Date 04 November 2025