Type 2 DiabetesEx-GM-T2DNCT06562842
Exercise, Gut Microbiota and Type 2 Diabetes
A study testing Regular exercise in people with Type 2 Diabetes, run by University of Thessaly at 1 site in Greece.
Trial summary
This randomized, parallel, controlled study, will investigate the effect of regular exercise on GM composition, inflammatory status, and insulin sensitivity, in the progression from normal glucose tolerance (NGT), to prediabetes (pre-D), to type 2 diabetes (T2D). Read more about this study
- Who is it for?
- Ages 45 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Regular exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteGreece
- Study dates
- 10 Mar 2025to 30 May 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 45 and 65 years old
- Sedentary lifestyle or insufficient daily physical activity according to guidelines for T2D
- Abstinence of anti-inflammatory drugs and/or antibiotics and/or dietary supplements that could affect GM composition before the study (>3 months)
- No other chronic diseases and/or musculoskeletal injuries (>6 months)
Who cannot join
- Age <45 years or >65 years
- Physically active individuals
- Consumption of anti-inflammatory drugs and/or antibiotics and/or dietary supplements that could affect GM composition before the study (<3 months)
- Other chronic diseases ot recent history of musculoskeletal injury (<6 months)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Athanasios Z Jamurtas, PhD contact
Greece1 site, 1 recruiting
- Recruiting
Department of Physical Education and Sport Science, Uninersity of Thessaly
Trikala, 42100
Chariklia K. Deli, Phd, delixar@pe.uth.gr
About this study
Official title: The Effects of Regular Exercise on Gut Microbiota Composition in Individuals with Type 2 Diabetes
This randomized, parallel, controlled study, will investigate the effect of regular exercise on GM composition, inflammatory status, and insulin sensitivity, in the progression from normal glucose tolerance (NGT), to prediabetes (pre-D), to type 2 diabetes (T2D). Following baseline assessment of glucose tolerance, the participants will be randomly assigned to either a 12-week, thrice-weekly exercise training program followed by 4 weeks of detraining, or will remain sedentary for the 16-week intervention. Thus, the six study groups will be: 1) NGT group (NGT), NGT individuals - no exercise, 2) NGT exercise group (NGT+Ex), NGT individuals that will participate in training and detraining, 3) pre-D group (pre-D), pre-D individuals - no exercise, 4) pre-D exercise group (Pre-D+Ex), pre-D individuals that will participate in training and detraining, 5) T2D group (T2D), T2D individuals - no exercise, and 6) T2D exercise group (T2D+Ex), T2D individuals that will participate in training and detraining. Assessment of physiological measures, anthropometric characteristics, body composition, glucose tolerance, insulin sensitivity, complete blood count, lipidemic profile, GM composition, inflammatory status, oxidative stress, and muscle performance, will be conducted before and following 12 weeks of the exercise training intervention and following 4 weeks of detraining for all participants.
Read the detailed description
Type 2 diabetes is a global metabolic epidemic and a major global health threat. In 2021, 537 million adults aged 20-79 years worldwide had diabetes. T2D, is related with life threatening microvascular and macrovascular health complications that contribute tremendously to the burden of mortality and disability worldwide. T2D is defined by fasting hyperglycemia which is largely secondary to inadequate action of insulin. T2D is usually preceded by a state of intermediate hyperglycemia or Pre-D, which is characterized by impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both, and greatly increases the risk for T2D. In T2D, although insulin levels are normal or high, tissues such as liver, skeletal muscle, and adipose tissue become resistant to insulin resulting in high levels of blood glucose. T2D is associated with a systemic inflammatory response which seems to be an independent risk factor for the development of T2D. Additionally, individuals with T2D tend to have a more oxidative internal environment than healthy subjects. Hyperglycemia-induced oxidative stress has been found to affect the insulin signaling cascade and decrease GLUT4 gene transcription and also alter mitochondrial activity. T2D pathophysiology has also been associated with GM composition. Dysbiosis of GM is suggested to have a central role in the pathogenesis of insulin resistance and T2D through several mechanisms.
The important role of regular exercise for the prevention and treatment of T2D has been established. Most benefits of exercise on T2D management and prevention are realized through the adaptations to skeletal muscle which in turn induce acute and chronic improvements in insulin action. Exercise also exerts anti-inflammatory effects. Emerged evidence suggests that exercise may also favorably affect T2D by improving GM composition. The most promising effect of regular exercise is the alteration of GM towards a healthier microbial composition by producing a more diverse GM, decreasing pathogenic bacterial communities and increasing SCFAs-producing bacteria. However, the impact of exercise on the GM structure and function of T2D individuals is poorly understood, as only a limited number of studies exist in this area, so far.
According to a preliminary power analysis (a probability error of 0.05 and a statistical power of 80%), a sample size of 8-10 participants/group was considered appropriate to detect statistically meaningful changes between trials. Thus, ≥60 middle-aged individuals will be assessed for eligibility to participate in the study. The study will be conducted in a parallel, randomized, controlled design. The participants, will be primarily informed of the study procedures, as well as the benefits and possible risks, and they will also sign an informed consent form for participation in the study. All eligible individuals will provide blood samples for the determination of fasting blood glucose, glycosylated hemoglobin (HbA1c), and fasting plasma insulin, and will take an oral glucose tolerance test (OGTT) to determine their glycemic profile, according to which, they will be characterized as normal glucose tolerance (NGT) individuals, or pre-diabetes (pre-D) individuals, or type 2 diabetes (T2D) individuals. Physical activity levels will also be assessed through the International Physical Activity Questionnaire (IPAQ). Afterwards, the participants of each glucose tolerance stage will be randomly assigned to either the 12 weeks of regular combined aerobic and resistance exercise according to the guidelines for pre-D and T2D individuals, or remain sedentary for 12 weeks. Thus, six intervention groups will be as follows: i) NGT group (NGTG), NGT individuals - no exercise, ii) NGT exercise group (NGTG+Ex), NGT individuals that will participate in training and detraining, iii) pre-D group (pre-DG), pre-D individuals - no exercise, iv) pre-D exercise group (Pre-DG+Ex), pre-D individuals that will participate in training and detraining, v) T2D group (T2DG), T2D individuals - no exercise, and vi) T2D exercise group (T2DG+Ex), T2D individuals that will participate in training and detraining. Randomization of the conditions will be done by a software generating random integers available on the internet (Random.org).
Baseline measurements will take place at the Laboratory of Biochemistry, Physiology and Nutrition of Exercise (SmArT Lab), Department of Physical Education and Sports, University of Thessaly: physiological measures (resting heart rate, resting systolic and diastolic blood pressure, resting metabolic rate), anthropometric characteristics (body height, body mass, body mass index), body composition (amount of body fat, lean body mass, fat mass, bone density), muscle performance [aerobic capacity (VO2max), isokinetic strength of the lower extremities (isometric, concentric and eccentric torque of the knee extensors and knee flexors), handgrip strength, muscle power (countermovement jump)]. Additionally, the participants will provide feces for the determination of GM composition and GM metabolites [short chain fatty acids (SCFAs)], as well as blood samples for the determination of complete blood count (CBC), systemic inflammation [tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-reactive protein (CRP), zonulin, lipopolysaccharides-binding protein (LBP)], blood redox status [total antioxidant capacity (TAC), catalase (CAT), protein carbonyls (PC), reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, malondialdehyde (MDA), uric acid, bilirubin], and lipid profile [total cholesterol (CHO-T), low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG)]. In addition, the participants will record their diet via a 7-days recall before their participation in the first experimental condition, and dietary data will be analyzed. All of the above measurements will be repeated following the 12-weeks of exercise intervention, as well as following the 4-weeks of detraining period. The participants that will be allocated into the regular exercise, except for VO2max, they will further undergo estimation of maximal strength of the main muscle groups for the determination of intensity of each participant's exercise program; aerobic capacity and muscle strength determination will also be repeated after four weeks of the regular exercise for the necessary intensity adjustments of the exercise program.
- Conditions
- Type 2 Diabetes
- Being tested
- Regular exercise, Control comparator
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regular exerciseOther
Participants will perform regular exercise training for 12 weeks, followed by 4 weeks of detraining.
Control comparatorOther
Participants will remain sedentary throughout the 16-weeks intervention period.
| Study group | Role | What they receive |
|---|---|---|
| NGT - Exercise | Experimental | Regular exercise for 12 weeks and detraining for 4 weeks Receives: Other: Regular exercise |
| NGT - Control comparator | Active comparator | Sedentary behavior for 16 weeks Receives: Other: Control comparator |
| Pre-D - Exercise | Experimental | Regular exercise for 12 weeks and detraining for 4 weeks Receives: Other: Regular exercise |
| Pre-D - Control comparator | Active comparator | Sedentary behavior for 16 weeks Receives: Other: Control comparator |
| T2D - Exercise | Experimental | Regular exercise for 12 weeks and detraining for 4 weeks Receives: Other: Regular exercise |
| T2D - Control comparator | Active comparator | Sedentary behavior for 16 weeks Receives: Other: Control comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in gut microbiota composition
Gut microbiota composition will be assessed in feces via Next generation sequencing
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in butyrate
Butyrate will be assessed in feces via HPLC/MS
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in propionate
Propionate will be assessed in feces via HPLC/MS
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in acetate
Acetate will be assessed in feces via HPLC/MS
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in White blood cells (WBC)
WBC will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Lymphocytes (LYM)
LYM will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Monocytes (MON)
MON will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Granulocytes (GRA)
GRA will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in percent Lymphocytes (LYM%)
LYM% will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in percent Monocytes (MON%)
MON% will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in percent Granulocytes (GRA%)
GRA% will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Red blood cells (RBC)
RBC will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Hemoglobin (HGB)
HGB will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Hematocrit (HCT)
HCT will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Mean corpuscular volume (MCV)
MCV will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Mean corpuscular hemoglobin (MCH)
MCH will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Mean corpuscular hemoglobin concentration (MCHC)
MCHC will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Red cell distribution width (RDW)
RDW will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Platelets (PLT)
PLT will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Mean platelets volume (MPV)
MPV will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Plateletcrit (PCT)
PCT will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in Plateletcrit distribution width (PDW)
PDW will be assessed in whole blood via hematological analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in TNF-α concentration
TNF-α concentration will be assessed in serum via ELISA
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in IL-6 concentration
IL-6 concentration will be assessed in serum via ELISA
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in high-sensitivity C-reactive protein concentration
C-reactive protein concentration will be assessed in serum via ELISA
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in lipopolysacharides-binding protein (LBP) concentration
LBP concentration will be assessed in serum via ELISA
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in zonulin concentration
Zonulin concentration will be assessed in serum and in feces via ELISA
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in protein carbonyls (PC) concentration
PC concentration will be assessed in plasma via a spectrophotometer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in malondialdehyde (MDA) concentration
MDA concentration will be assessed in plasma via HPLC
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in reduced glutathione (GSH) concentration
GSH concentration will be assessed in red blood cells lycate via a spectrophotometer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in oxidized glutathione (GSSG) concentration
GSSG concentration will be assessed in red blood cells lycate via a spectrophotometer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in GSH/GSSG ratio
GSH/GSSG ratio will be calculated by dividing GSH concentration with GSSG concentration
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in catalase concentration
Catalase concentration will be assessed in red blood cells lycate via a spectrophotometer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in total antioxidant capacity (TAC)
TAC will be assessed in red blood cells lycate via a spectrophotometer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in uric acid concentration
Uric acid concentration will be assessed in serum via a biochemical analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in bilirubin concentration
Bilirubin concentration will be assessed in serum via a biochemical analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in glycosylated hemoblobin (HbA1c) concentration
HbA1c concentration will be assessed in whole blood via a HbA1c analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in fasting plasma glucose
Fasting plasma glucose will be assessed in plasma via a biochemical analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in fasting plasma insulin
Fasting plasma insulin will be assessed in plasma via a biochemical analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in insulin resistance
Insulin resistance will be calulated via the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in insulin resistance - Oral glucose tolerance test (OGTT)
OGTT will be assessed via the estimation of 2-h plasma glucose following oral glucose consumption
Measured: Pre, 30 minutes post-, 60 minutes post-, 90 minutes post-,120 minutes post-glucose consumption
Changes in total cholesterol (CHOL-T)
CHOL-T will be assessed via a biochemical analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in low-density lipoprotein cholesterol (LDL-C)
LDL-C will be assessed via a biochemical analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in high-density lipoprotein cholesterol (HDL-C)
HDL-C will be assessed via a biochemical analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in triglycerides (TG)
TG will be assessed via a biochemical analyzer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in countermovement jump height (CMJ)
CMJ height will be measured via an optical system
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in isokinetic strength of knee extensors and knee flexors
Isometric, concentric and eccentric peak torque of the knee extensors and knee flexors of both limbs will be assessed via an isokinetic dynamometer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in handgrip strength
Handgrip strength will be assessed via a handgrip dynamometer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in resting heart rate (HR)
Resting HR will be assessed via a HR monitor
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in resting systolic (SBP) and diastolic blood pressure (DBP)
Resting SBP and DBP will be assessed via a manual sphygmomanometer
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in resting metabolic rate (RMR)
RMR will be assessed via indirect calorimetry
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in body mass (BM)
BM will be assessed via a stadiometer-Beam balance
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in body height
Body height will be assessed via a stadiometer-Beam balance
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in body mass index (BMI)
BMI will be calculated by dividing body mass by the square of body height
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in maximal oxygen uptake (VO2max)
Changes in maximal oxygen uptake (VO2peak) will be assesed via a submaximal test on a treadmill
Measured: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2024
- Study start10 Mar 2025
- Primary completion30 May 2026 (estimated)
- Study completion30 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University of ThessalyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Thessaly
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chariklia K. Deli, University of Thessaly
- Investigators
- Chariklia K. Deli, PhD, Principal investigator, University of Thessaly
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06562842
- Sponsor's protocol ID
- Ex-GM-T2D study
- Acronym
- Ex-GM-T2D
- Status last verified
- Mar 2025
- First submitted
- 10 Aug 2024
- Last updated
- 28 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018 Feb;14(2):88-98. doi: 10.1038/nrendo.2017.151. Epub 2017 Dec 8.
PubMed 29219149Gurung M, Li Z, You H, Rodrigues R, Jump DB, Morgun A, Shulzhenko N. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020 Jan;51:102590. doi: 10.1016/j.ebiom.2019.11.051. Epub 2020 Jan 3.
PubMed 31901868Pasini E, Corsetti G, Assanelli D, Testa C, Romano C, Dioguardi FS, Aquilani R. Effects of chronic exercise on gut microbiota and intestinal barrier in human with type 2 diabetes. Minerva Med. 2019 Feb;110(1):3-11. doi: 10.23736/S0026-4806.18.05589-1.
PubMed 30667205Torquati L, Gajanand T, Cox ER, Willis CRG, Zaugg J, Keating SE, Coombes JS. Effects of exercise intensity on gut microbiome composition and function in people with type 2 diabetes. Eur J Sport Sci. 2023 Apr;23(4):530-541. doi: 10.1080/17461391.2022.2035436. Epub 2022 Mar 23.
PubMed 35107058
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Regular Exercise on Gut Microbiota Composition in Individuals with Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT06562842
- Acronym / sponsor ID
- Ex-GM-T2D / Ex-GM-T2D study
- Conditions
- Type 2 Diabetes
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of ThessalyUniversity, hospital or other
- Study start
- 10 Mar 2025 (actual)
- Primary completion
- 30 May 2026 (estimated)
- Study completion
- 30 May 2026 (estimated)
- First posted
- 20 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized, parallel, controlled study, will investigate the effect of regular exercise on GM composition, inflammatory status, and insulin sensitivity, in the progression from normal glucose tolerance (NGT), to prediabetes (pre-D), to type 2 diabetes (T2D). Following baseline assessment of glucose tolerance, the participants will be randomly assigned to either a 12-week, thrice-weekly exercise training program followed by 4 weeks of detraining, or will remain sedentary for the 16-week intervention. Thus, the six study groups will be: 1) NGT group (NGT), NGT individuals - no exercise, 2) NGT exercise group (NGT+Ex), NGT individuals that will participate in training and detraining, 3) pre-D group (pre-D), pre-D individuals - no exercise, 4) pre-D exercise group (Pre-D+Ex), pre-D individuals that will participate in training and detraining, 5) T2D group (T2D), T2D individuals - no exercise, and 6) T2D exercise group (T2D+Ex), T2D individuals that will participate in training and detraining. Assessment of physiological measures, anthropometric characteristics, body composition, glucose tolerance, insulin sensitivity, complete blood count, lipidemic profile, GM composition, inflammatory status, oxidative stress, and muscle performance, will be conducted before and following 12 weeks of the exercise training intervention and following 4 weeks of detraining for all participants.
Detailed description
Type 2 diabetes is a global metabolic epidemic and a major global health threat. In 2021, 537 million adults aged 20-79 years worldwide had diabetes. T2D, is related with life threatening microvascular and macrovascular health complications that contribute tremendously to the burden of mortality and disability worldwide. T2D is defined by fasting hyperglycemia which is largely secondary to inadequate action of insulin. T2D is usually preceded by a state of intermediate hyperglycemia or Pre-D, which is characterized by impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both, and greatly increases the risk for T2D. In T2D, although insulin levels are normal or high, tissues such as liver, skeletal muscle, and adipose tissue become resistant to insulin resulting in high levels of blood glucose. T2D is associated with a systemic inflammatory response which seems to be an independent risk factor for the development of T2D. Additionally, individuals with T2D tend to have a more oxidative internal environment than healthy subjects. Hyperglycemia-induced oxidative stress has been found to affect the insulin signaling cascade and decrease GLUT4 gene transcription and also alter mitochondrial activity. T2D pathophysiology has also been associated with GM composition. Dysbiosis of GM is suggested to have a central role in the pathogenesis of insulin resistance and T2D through several mechanisms.
The important role of regular exercise for the prevention and treatment of T2D has been established. Most benefits of exercise on T2D management and prevention are realized through the adaptations to skeletal muscle which in turn induce acute and chronic improvements in insulin action. Exercise also exerts anti-inflammatory effects. Emerged evidence suggests that exercise may also favorably affect T2D by improving GM composition. The most promising effect of regular exercise is the alteration of GM towards a healthier microbial composition by producing a more diverse GM, decreasing pathogenic bacterial communities and increasing SCFAs-producing bacteria. However, the impact of exercise on the GM structure and function of T2D individuals is poorly understood, as only a limited number of studies exist in this area, so far.
According to a preliminary power analysis (a probability error of 0.05 and a statistical power of 80%), a sample size of 8-10 participants/group was considered appropriate to detect statistically meaningful changes between trials. Thus, ≥60 middle-aged individuals will be assessed for eligibility to participate in the study. The study will be conducted in a parallel, randomized, controlled design. The participants, will be primarily informed of the study procedures, as well as the benefits and possible risks, and they will also sign an informed consent form for participation in the study. All eligible individuals will provide blood samples for the determination of fasting blood glucose, glycosylated hemoglobin (HbA1c), and fasting plasma insulin, and will take an oral glucose tolerance test (OGTT) to determine their glycemic profile, according to which, they will be characterized as normal glucose tolerance (NGT) individuals, or pre-diabetes (pre-D) individuals, or type 2 diabetes (T2D) individuals. Physical activity levels will also be assessed through the International Physical Activity Questionnaire (IPAQ). Afterwards, the participants of each glucose tolerance stage will be randomly assigned to either the 12 weeks of regular combined aerobic and resistance exercise according to the guidelines for pre-D and T2D individuals, or remain sedentary for 12 weeks. Thus, six intervention groups will be as follows: i) NGT group (NGTG), NGT individuals - no exercise, ii) NGT exercise group (NGTG+Ex), NGT individuals that will participate in training and detraining, iii) pre-D group (pre-DG), pre-D individuals - no exercise, iv) pre-D exercise group (Pre-DG+Ex), pre-D individuals that will participate in training and detraining, v) T2D group (T2DG), T2D individuals - no exercise, and vi) T2D exercise group (T2DG+Ex), T2D individuals that will participate in training and detraining. Randomization of the conditions will be done by a software generating random integers available on the internet (Random.org).
Baseline measurements will take place at the Laboratory of Biochemistry, Physiology and Nutrition of Exercise (SmArT Lab), Department of Physical Education and Sports, University of Thessaly: physiological measures (resting heart rate, resting systolic and diastolic blood pressure, resting metabolic rate), anthropometric characteristics (body height, body mass, body mass index), body composition (amount of body fat, lean body mass, fat mass, bone density), muscle performance [aerobic capacity (VO2max), isokinetic strength of the lower extremities (isometric, concentric and eccentric torque of the knee extensors and knee flexors), handgrip strength, muscle power (countermovement jump)]. Additionally, the participants will provide feces for the determination of GM composition and GM metabolites [short chain fatty acids (SCFAs)], as well as blood samples for the determination of complete blood count (CBC), systemic inflammation [tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-reactive protein (CRP), zonulin, lipopolysaccharides-binding protein (LBP)], blood redox status [total antioxidant capacity (TAC), catalase (CAT), protein carbonyls (PC), reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, malondialdehyde (MDA), uric acid, bilirubin], and lipid profile [total cholesterol (CHO-T), low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG)]. In addition, the participants will record their diet via a 7-days recall before their participation in the first experimental condition, and dietary data will be analyzed. All of the above measurements will be repeated following the 12-weeks of exercise intervention, as well as following the 4-weeks of detraining period. The participants that will be allocated into the regular exercise, except for VO2max, they will further undergo estimation of maximal strength of the main muscle groups for the determination of intensity of each participant's exercise program; aerobic capacity and muscle strength determination will also be repeated after four weeks of the regular exercise for the necessary intensity adjustments of the exercise program.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| NGT - Exercise | Experimental | Other: Regular exerciseRegular exercise for 12 weeks and detraining for 4 weeks |
| NGT - Control comparator | Active comparator | Other: Control comparatorSedentary behavior for 16 weeks |
| Pre-D - Exercise | Experimental | Other: Regular exerciseRegular exercise for 12 weeks and detraining for 4 weeks |
| Pre-D - Control comparator | Active comparator | Other: Control comparatorSedentary behavior for 16 weeks |
| T2D - Exercise | Experimental | Other: Regular exerciseRegular exercise for 12 weeks and detraining for 4 weeks |
| T2D - Control comparator | Active comparator | Other: Control comparatorSedentary behavior for 16 weeks |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age between 45 and 65 years old
- Sedentary lifestyle or insufficient daily physical activity according to guidelines for T2D
- Abstinence of anti-inflammatory drugs and/or antibiotics and/or dietary supplements that could affect GM composition before the study (>3 months)
- No other chronic diseases and/or musculoskeletal injuries (>6 months)
Key exclusion criteria (4 listed)
- Age <45 years or >65 years
- Physically active individuals
- Consumption of anti-inflammatory drugs and/or antibiotics and/or dietary supplements that could affect GM composition before the study (<3 months)
- Other chronic diseases ot recent history of musculoskeletal injury (<6 months)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Regular exerciseParticipants will perform regular exercise training for 12 weeks, followed by 4 weeks of detraining. | Other | NGT - Exercise, Pre-D - Exercise, T2D - Exercise |
| Control comparatorParticipants will remain sedentary throughout the 16-weeks intervention period. | Other | NGT - Control comparator, Pre-D - Control comparator, T2D - Control comparator |
Primary outcome
Changes in gut microbiota composition
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Gut microbiota composition will be assessed in feces via Next generation sequencing
Changes in butyrate
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Butyrate will be assessed in feces via HPLC/MS
Changes in propionate
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Propionate will be assessed in feces via HPLC/MS
Changes in acetate
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Acetate will be assessed in feces via HPLC/MS
Changes in White blood cells (WBC)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
WBC will be assessed in whole blood via hematological analyzer
Changes in Lymphocytes (LYM)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
LYM will be assessed in whole blood via hematological analyzer
Changes in Monocytes (MON)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
MON will be assessed in whole blood via hematological analyzer
Changes in Granulocytes (GRA)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
GRA will be assessed in whole blood via hematological analyzer
Changes in percent Lymphocytes (LYM%)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
LYM% will be assessed in whole blood via hematological analyzer
Changes in percent Monocytes (MON%)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
MON% will be assessed in whole blood via hematological analyzer
Changes in percent Granulocytes (GRA%)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
GRA% will be assessed in whole blood via hematological analyzer
Changes in Red blood cells (RBC)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
RBC will be assessed in whole blood via hematological analyzer
Changes in Hemoglobin (HGB)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
HGB will be assessed in whole blood via hematological analyzer
Changes in Hematocrit (HCT)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
HCT will be assessed in whole blood via hematological analyzer
Changes in Mean corpuscular volume (MCV)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
MCV will be assessed in whole blood via hematological analyzer
Changes in Mean corpuscular hemoglobin (MCH)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
MCH will be assessed in whole blood via hematological analyzer
Changes in Mean corpuscular hemoglobin concentration (MCHC)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
MCHC will be assessed in whole blood via hematological analyzer
Changes in Red cell distribution width (RDW)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
RDW will be assessed in whole blood via hematological analyzer
Changes in Platelets (PLT)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
PLT will be assessed in whole blood via hematological analyzer
Changes in Mean platelets volume (MPV)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
MPV will be assessed in whole blood via hematological analyzer
Changes in Plateletcrit (PCT)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
PCT will be assessed in whole blood via hematological analyzer
Changes in Plateletcrit distribution width (PDW)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
PDW will be assessed in whole blood via hematological analyzer
Changes in TNF-α concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
TNF-α concentration will be assessed in serum via ELISA
Changes in IL-6 concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
IL-6 concentration will be assessed in serum via ELISA
Changes in high-sensitivity C-reactive protein concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
C-reactive protein concentration will be assessed in serum via ELISA
Changes in lipopolysacharides-binding protein (LBP) concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
LBP concentration will be assessed in serum via ELISA
Changes in zonulin concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Zonulin concentration will be assessed in serum and in feces via ELISA
Changes in protein carbonyls (PC) concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
PC concentration will be assessed in plasma via a spectrophotometer
Changes in malondialdehyde (MDA) concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
MDA concentration will be assessed in plasma via HPLC
Changes in reduced glutathione (GSH) concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
GSH concentration will be assessed in red blood cells lycate via a spectrophotometer
Changes in oxidized glutathione (GSSG) concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
GSSG concentration will be assessed in red blood cells lycate via a spectrophotometer
Changes in GSH/GSSG ratio
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
GSH/GSSG ratio will be calculated by dividing GSH concentration with GSSG concentration
Changes in catalase concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Catalase concentration will be assessed in red blood cells lycate via a spectrophotometer
Changes in total antioxidant capacity (TAC)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
TAC will be assessed in red blood cells lycate via a spectrophotometer
Changes in uric acid concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Uric acid concentration will be assessed in serum via a biochemical analyzer
Changes in bilirubin concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Bilirubin concentration will be assessed in serum via a biochemical analyzer
Changes in glycosylated hemoblobin (HbA1c) concentration
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
HbA1c concentration will be assessed in whole blood via a HbA1c analyzer
Changes in fasting plasma glucose
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Fasting plasma glucose will be assessed in plasma via a biochemical analyzer
Changes in fasting plasma insulin
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Fasting plasma insulin will be assessed in plasma via a biochemical analyzer
Changes in insulin resistance
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Insulin resistance will be calulated via the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index
Changes in insulin resistance - Oral glucose tolerance test (OGTT)
Time frame: Pre, 30 minutes post-, 60 minutes post-, 90 minutes post-,120 minutes post-glucose consumption
OGTT will be assessed via the estimation of 2-h plasma glucose following oral glucose consumption
Changes in total cholesterol (CHOL-T)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
CHOL-T will be assessed via a biochemical analyzer
Changes in low-density lipoprotein cholesterol (LDL-C)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
LDL-C will be assessed via a biochemical analyzer
Changes in high-density lipoprotein cholesterol (HDL-C)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
HDL-C will be assessed via a biochemical analyzer
Changes in triglycerides (TG)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
TG will be assessed via a biochemical analyzer
Changes in countermovement jump height (CMJ)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
CMJ height will be measured via an optical system
Changes in isokinetic strength of knee extensors and knee flexors
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Isometric, concentric and eccentric peak torque of the knee extensors and knee flexors of both limbs will be assessed via an isokinetic dynamometer
Changes in handgrip strength
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Handgrip strength will be assessed via a handgrip dynamometer
Changes in resting heart rate (HR)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Resting HR will be assessed via a HR monitor
Changes in resting systolic (SBP) and diastolic blood pressure (DBP)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Resting SBP and DBP will be assessed via a manual sphygmomanometer
Changes in resting metabolic rate (RMR)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
RMR will be assessed via indirect calorimetry
Changes in body mass (BM)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
BM will be assessed via a stadiometer-Beam balance
Changes in body height
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Body height will be assessed via a stadiometer-Beam balance
Changes in body mass index (BMI)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
BMI will be calculated by dividing body mass by the square of body height
Changes in maximal oxygen uptake (VO2max)
Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)
Changes in maximal oxygen uptake (VO2peak) will be assesed via a submaximal test on a treadmill
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- Background: PubMed 29219149Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018 Feb;14(2):88-98. doi: 10.1038/nrendo.2017.151. Epub 2017 Dec 8.
- Background: PubMed 31901868Gurung M, Li Z, You H, Rodrigues R, Jump DB, Morgun A, Shulzhenko N. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020 Jan;51:102590. doi: 10.1016/j.ebiom.2019.11.051. Epub 2020 Jan 3.
- Background: PubMed 30667205Pasini E, Corsetti G, Assanelli D, Testa C, Romano C, Dioguardi FS, Aquilani R. Effects of chronic exercise on gut microbiota and intestinal barrier in human with type 2 diabetes. Minerva Med. 2019 Feb;110(1):3-11. doi: 10.23736/S0026-4806.18.05589-1.
- Background: PubMed 35107058Torquati L, Gajanand T, Cox ER, Willis CRG, Zaugg J, Keating SE, Coombes JS. Effects of exercise intensity on gut microbiome composition and function in people with type 2 diabetes. Eur J Sport Sci. 2023 Apr;23(4):530-541. doi: 10.1080/17461391.2022.2035436. Epub 2022 Mar 23.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Athanasios Z Jamurtas, PhD contact
Chariklia K. Deli, PhD principal investigator
University of Thessaly
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Regular exercise in people with Type 2 Diabetes, run by University of Thessaly at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chariklia K. Deli, PhD (+302431047011, delixar@pe.uth.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in gut microbiota composition (time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)). The study lists 55 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06562842, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2025.