Exploring the synergistic effects of exercise and vitamin D in type 2 diabetes

Background:

Type 2 diabetes (T2D) is a chronic disease characterized by insulin resistance and impaired pancreatic insulin production. In 2021, its global prevalence was above 500 million [1]. The rapid growth of this epidemic reflects socioeconomic trends, including changes in environmental factors such as high-calorie intake, low levels of physical activity (PA) and an increased incidence of obesity [2,3]. In this regard, it has been observed that obesity and lack of regular exercise or a sedentary lifestyle are major causes of chronic disease [4] and global mortality on [1], in which PA plays a very significant role [5]. Aerobic and resistance training with exercise is the most effective way to increase CRF, and people with T2D clearly respond to training with this adaptation [5]. Aerobic exercise interventions have dominated the literature on the effects of exercise on glycaemic parameters, in T2D [6]. For example, a combination of aerobic and resistance training (but not aerobic or resistance training alone) improved HbA1c levels in T2D patients [7]. Moderate to vigorous aerobic exercise (65-90% of maximum heart rate) improves VO2 max (oxygen consumption) and cardiac output. This is associated with a significant reduction in the risk of cardiovascular and all-cause mortality in people with T2D [8]. Results from studies evaluating the effects of 12 weeks resistance training in T2D have shown improvements of HbA1c and 10% to 15% in strength, bone mineral density, blood pressure, lipid profiles, cardiovascular health, insulin sensitivity and muscle mass [7,9]. Additionally, due to the increased prevalence of T2D with age and the age-related loss of muscle mass, known as sarcopenia, resistance training may have additional health benefits for older adults [10]. Exercise provides additional benefits for glycaemic control. It has been established as an important therapy in the prevention, management and treatment of T2D and its associated complications [11,12]. Resistance training has also been observed to reduce abdominal fat, a factor that may be particularly important in the prevention of T2D. This recommendation is consistent with the American Diabetes Association's resistance training guidelines for exercising all major muscle groups [13].
Vitamin D (VitD) is a fat-soluble vitamin innately present in some foods. VitD promotes intestinal calcium absorption, maintains adequate serum calcium and phosphate concentrations to afford normal bone mineralisation, and prevents hypocalcemic tetany. Low blood levels of VitD have emerged as a risk factor for T2D; it is often associated with metabolic alterations, such as an increased risk of glucose intolerance [14]. It has also been observed that obesity is inversely correlated with VitD status, which can be attributed to the sequestration of soluble vitamins by adipose tissue [15].
Few studies evaluated the effects of VitD and exercise in patients with T2D. Kim et al. combined, in a group of elderly diabetic women, VitD supplementation with a 12-week training circuit. The combination showed positive effects on abdominal fat and blood lipid profiles, but the metabolic characterization of the patients was limited, and the results were inconclusive [16]. Dadrass et al. combined VitD with a 3-month resistance training program in patients with T2D. VitD supplementation, in addition to resistance training, had positive effects on some inflammatory markers (interleukin 6, tumor necrosis factor α and C-reactive protein) in men with T2D and VitD insufficiency but they did not analyze any non-inflammatory metabolic parameters [17, 18]. In conclusion, although some studies link VitD and aerobic or endurance exercise, the analyses are scattered and inconsistent, with incomplete metabolic characterization, low numbers of patients, and generally unreliable conclusions.
Herein, the present study aims to identify the effect of aerobic and resistance training in T2D patients on a VitD regime and compare it to patients not exercising or exercising but not on VitD treatment. The results of this study could provide a useful understanding to improve the treatment of this disease.

Objectives:

The aim of this study is to analyze the effects of aerobic and resistance training in patients with T2D on VitD on clinical parameters.
The specific objectives are:
1. To evaluate the effect of aerobic and resistance training in patients with T2D on a VitD treatment on blood biomarkers (insulin, glucose, glycosylated hemoglobin, HDL, LDL, total cholesterol, triglycerides, hepatic profile, microalbuminuria, hemogram, renal function, C-reactive protein, erythrocyte sedimentation rate, ferritin, HOMA-IR and HOMA-B).
2. To evaluate the synergistic effect of aerobic and resistance training in patients with T2D on a VitD treatment on anthropometric measures (weight, body mass index, waist circumference, waist hip-ratio, skinfold measurements).
3. To assess and quantify adherence to the Mediterranean dietary pattern before the intervention, and to assess the psychological well-being among patients with T2D before and after the intervention.
4. To evaluate the role of the pharmacist in the follow-up of medication, interventions and in the development of a clinical study

Methods:

The study will include a total of 80 individuals of both sexes (female, male) with a diagnosis of T2D. Among them, 40 individuals will be required to be on a VitD treatment for at least, 6 months. The other 40 will serve as controls. Subjects during usual medical care will be recruited in a convenience-based by the collaborating physicians from the Primary Care Center (CAP) Sant Rafael in Barcelona, Spain.
Subsequently, they will be randomly assigned to different intervention groups: VitD, No VitD, VitD+training, and No VitD+No training
Inclusion criteria for the subjects of this study are detailed below:
- Adults (females or males) older than 18 years old with a diagnosis of T2D
- Patients who have been taking the combination therapy of metformin + sodium-glucose transport protein 2 inhibitors (iSGLT2), as recommended by the redGDPS 2023, with stable medication for the past 6 months.
- Diabetic patients taking prescribed VitD treatment for at least 6 months (intervention group) and diabetic patients not taking prescribed VitD (control group)
- Patients who signed the informed consent
- Patients capable of performing mild to moderate physical activity (to walk steadily and independently for at least 6 minutes)
Exclusion criteria of subjects are summarized below
- Patients taking other medication different than metformin + iSGLT2 (including combinations and insulin).
- Patients with diagnosed osteoporosis
- Patients taking polyvitaminic supplementation at the inclusion for at least, 1 month before the intervention
- Female subjects who are pregnant
- Patients who did not sign the informed consent

Variables include gender, height, weight, food consumption and adherence to the Mediterranean diet, activity degree, psychological well-being and clinical blood parameters.

This is a home training program where sessions are conducted online by the investigator and personal trainer (Elnaz Dardashtipour, PhD student). This program will run for 16 weeks and three sessions every week.

During the first visit at the CAP, the current medication of diabetic patients will be a by the participating physicians. This information will serve as baseline data and aid in the interpretation of outcomes, adjustment in statistical analyses, and support a more individualized approach to patient care. Additionally, the data can be utilized to identify common treatment patterns, assess adherence to prescribed therapies, and explore the relationship between medication regimens and patient outcomes.

A total of 5 visits are expected per each participant. After initial inclusion at the Primary Care Centers, patients will be contacted by the investigators. They will explain the study protocol using the patient information sheet and will set a meeting at the community pharmacy. Community pharmacists of the geographical area of the study will be invited to collaborate in the study. A total of 4 visits at the community pharmacy with the investigator pharmacist (Aina Surroca, PhD student) are expected for each participant. An initial visit at the pharmacy will be performed (in person) with the participants. During this visit, the investigator pharmacist will obtain the informed consent, collect basic sociodemographic data (age, weight, high, and gender), and will perform que nutritional and well-being questionnaires and duration of current medication. Further, information about the personal trainer (Elnaz Dardashtipour), the training schedule and the corporate Teams meeting links and password will be provided. During the first meeting, the participant will be provided with 2 documents: The recommendations for a healthy diet by the Spanish Society of Diabetes and a nutritional proposal based on the abovementioned guidelines.
Two additional monthly check-ups, consisting in a short interview (covering any adverse events, general well-being, etc.) will be performed 2 and 3 months after study initiation.
A final 4th visit at month 4, will be performed at the end of the study, in the pharmacy office where the well-being questionnaire and a satisfaction questionnaire will be provided.

Ethics:

This trial was approved by the Ethics and Research Committee of the Faculty of Psychology, Education Sciences and Sport Blanquerna of the Ramon Llull University (2122007D) and the Ethics Committee of the Primary Health Care IDIAP Jordi Gol 24/142-EOm).

Project expenses for the URL project:

The next step for this project involves the publication of the clinical protocol in an open-access, peer-reviewed journal. The clinical protocol is already under review at the Frontiers in Endocrinology Journal (Q1). In addition, we need to cover all clinical blood test expenses, as agreed with the Servei d’Anàlisi Clínica de la Vall d’Hebron. Part of the expenses are internally covered by another project.
Finally, results from the PhD student have been submitted for presentation at the XX Congreso Internacional de la Sociedad Española de Medicina del Deporte, to be held in Bilbao in November 2025.


References:

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