Exercise, Gut Microbiota and Type 2 Diabetes

NCT06562842 | Recruiting

• 1 other identifier: Ex-GM-T2D study
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (55)

• Changes in gut microbiota composition

  Gut microbiota composition will be assessed in feces via Next generation sequencing

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

• Changes in butyrate

  Butyrate will be assessed in feces via HPLC/MS

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

• Changes in propionate

  Propionate will be assessed in feces via HPLC/MS

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

• Changes in acetate

  Acetate will be assessed in feces via HPLC/MS

  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

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

• Changes in Lymphocytes (LYM)

  LYM will be assessed in whole blood via hematological analyzer

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

• Changes in Monocytes (MON)

  MON will be assessed in whole blood via hematological analyzer

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

• Changes in Granulocytes (GRA)

  GRA will be assessed in whole blood via hematological analyzer

  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

  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

  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

  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

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

• Changes in Hemoglobin (HGB)

  HGB will be assessed in whole blood via hematological analyzer

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

• Changes in Hematocrit (HCT)

  HCT will be assessed in whole blood via hematological analyzer

  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

  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

  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

  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

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

• Changes in Platelets (PLT)

  PLT will be assessed in whole blood via hematological analyzer

  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

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

• Changes in Plateletcrit (PCT)

  PCT will be assessed in whole blood via hematological analyzer

  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

  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

  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

  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

  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

  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

  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

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

• Changes in malondialdehyde (MDA) concentration

  MDA concentration will be assessed in plasma via HPLC

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

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

• Changes in triglycerides (TG)

  TG will be assessed via a biochemical analyzer

  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

  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

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

• Changes in handgrip strength

  Handgrip strength will be assessed via a handgrip dynamometer

  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

  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

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

• Changes in resting metabolic rate (RMR)

  RMR will be assessed via indirect calorimetry

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

• Changes in body mass (BM)

  BM will be assessed via a stadiometer-Beam balance

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

• Changes in body height

  Body height will be assessed via a stadiometer-Beam balance

  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

  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

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

Study Arms (6)

NGT - Exercise

EXPERIMENTAL

Regular exercise for 12 weeks and detraining for 4 weeks

Other: Regular exercise

NGT - Control comparator

ACTIVE COMPARATOR

Sedentary behavior for 16 weeks

Other: Control comparator

Pre-D - Exercise

EXPERIMENTAL

Regular exercise for 12 weeks and detraining for 4 weeks

Other: Regular exercise

Pre-D - Control comparator

ACTIVE COMPARATOR

Sedentary behavior for 16 weeks

Other: Control comparator

T2D - Exercise

EXPERIMENTAL

Regular exercise for 12 weeks and detraining for 4 weeks

Other: Regular exercise

T2D - Control comparator

ACTIVE COMPARATOR

Sedentary behavior for 16 weeks

Other: Control comparator

Interventions

Regular exercise OTHER

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

NGT - Exercise; Pre-D - Exercise; T2D - Exercise

Control comparator OTHER

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

NGT - Control comparator; Pre-D - Control comparator; T2D - Control comparator

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Thessaly: lead

Study Sites (1)

Department of Physical Education and Sport Science, Uninersity of Thessaly

Trikala, 42100, Greece

RECRUITING

Related Publications (4)

• 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.

  PMID: 29219149 BACKGROUND

• Gurung 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.

  PMID: 31901868 BACKGROUND

• Pasini 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.

  PMID: 30667205 BACKGROUND

• Torquati 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.

  PMID: 35107058 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Chariklia K. Deli, PhD

  University of Thessaly

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chariklia K. Deli, PhD

CONTACT

+302431047011; delixar@pe.uth.gr

Athanasios Z Jamurtas, PhD

CONTACT

ajamurt@pe.uth.gr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 10, 2024
• First Posted: August 20, 2024
• Study Start: March 10, 2025
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)