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NCT Number: NCT06562842

Exercise, Gut Microbiota and 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.

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Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

45 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Physical Education and Sport Science, Uninersity of Thessaly

Trikala, 42100, Greece

Location status: Recruiting

Location contact

Chariklia K. Deli, Phd

CONTACT

[email protected]

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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)

Treatment and study plan

Regular Exercise

Other

Participants will perform regular exercise training for 12 weeks, followed by 4 weeks of detraining.

Control comparator

Other

Participants will remain sedentary throughout the 16-weeks intervention period.

Primary outcomes

  1. 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

  2. Changes in butyrate

    Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)

    Butyrate will be assessed in feces via HPLC/MS

  3. Changes in propionate

    Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)

    Propionate will be assessed in feces via HPLC/MS

  4. Changes in acetate

    Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)

    Acetate will be assessed in feces via HPLC/MS

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. Changes in triglycerides (TG)

    Time frame: Baseline (pre), 12 weeks post-training, 16 weeks (post-detraining)

    TG will be assessed via a biochemical analyzer

  46. 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

  47. 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

  48. 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

  49. 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

  50. 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

  51. 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

  52. 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

  53. 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

  54. 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

  55. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Athanasios Z Jamurtas, PhD

CONTACT

[email protected]

Chariklia K. Deli, PhD

CONTACT

[email protected]

+302431047011

Sponsors and collaborators

Lead sponsor

University of Thessaly

Other

Registry information

Official study title

The Effects of Regular Exercise on Gut Microbiota Composition in Individuals with Type 2 Diabetes

Acronym: Ex-GM-T2D

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Aug 20, 2024
Registry last updated
Mar 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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