Exercise Volume and Beta-cell Function in T2D The DOSE-EX Randomized Trial

NCT03769883 | Completed

• 1 other identifier: H-18038298
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

This project will provide an exercise-based lifestyle intervention with the potential to reduce complications for patients with short standing type 2 diabetes (T2D). While exercise is widely accepted as a component of T2D management, little is known about the additive effect of exercise when combined with a diet on T2D pathophysiology and mechanisms believed to lead to micro- and macrovascular complications. Moreover, the necessary dose of exercise to revert the progression of T2D and the related complications has not been investigated. A large-scale randomized controlled trial (RCT) will be essential to document the effectiveness on reducing the risk of T2D complications. However, prior to conducting a large-scale RCT, we need to specify the exercise dose that efficiently compliments the diet. In a 4-armed randomized, clinical trial (N=80 T2D patients, T2D duration \< than 7 years) we aim to investigate 1) the potential additive role of exercise on pancreatic β-cell function in patients with T2D when combined with a diet, 2) the causal relationship between lifestyle-induced reductions in glycaemic variability, oxidative stress and low-grade inflammation and, 3) the role of exercise in rescuing dysregulated muscle progenitor cells. The participants will be randomly allocated to either a) control, b) diet, c) diet and exercise 3 times/week or d) diet and exercise 6 times/week for 16 weeks. Prior to, during and following the interventions, all participants will undergo extensive testing.

Conditions

Type 2 Diabetes Mellitus; Type2 Diabetes; Diabetes Mellitus, Type 2; Type2 Diabetes Mellitus

Keywords

Exercise; Physical Activity; Type 2 diabetes; Pancreatic beta-cell function; Insulin sensitivity; Dose finding; lifestyle

Outcome Measures

Primary Outcomes (1)

• Pancreatic beta-cell function (Per protocol)

  The change in the late-phase disposition index (DI) during the final 30 minutes of hyperglycemic phase of the hyperglycemic clamp.

  From baseline (0 weeks) to follow-up (16 weeks)

Secondary Outcomes (50)

• Pancreatic beta-cell function (Intention to treat)

  From baseline (0 weeks) to follow-up (16 weeks)

• Glucagon like peptide 1 sensitivity (c-peptide)

  From baseline (0 weeks) to follow-up (16 weeks)

• Glucagon like peptide 1 sensitivity (glucagon)

  From baseline (0 weeks) to follow-up (16 weeks)

• Glucagon like peptide 1 sensitivity (insulin)

  From baseline (0 weeks) to follow-up (16 weeks)

• Arginine sensitivity (insulin)

  From baseline (0 weeks) to follow-up (16 weeks)

Other Outcomes (2)

• Muscular metabolic function

  From baseline (0 weeks) to follow-up (16 weeks)

• Fat tissue metabolic function

  From baseline (0 weeks) to follow-up (16 weeks)

Study Arms (4)

Dietary control (DCON)

EXPERIMENTAL

The macro-nutrient distributions are in line with the current guidelines from the national Diabetes Association and Canadian guidelines, where individualization in macronutrient distribution should lie within the range of 45-60E% carbohydrate, 15-20E% protein and 20-35E% fat. The dietary plan will aim at reducing saturated fat intake \<7E% aiming at a caloric deficit of 500 kilo calories/day

Behavioral: Diet

Moderate Exercise Dose (MED)

EXPERIMENTAL

Two aerobic training sessions per week of 45-60 min duration and one session per week with combined aerobic (30-35 min) and resistance (30 min) training and a dietary intervention (as above)

Behavioral: Exercise and diet

High Exercise Dose (HED)

EXPERIMENTAL

Four aerobic training sessions per week of 45-60 min duration and two sessions per week with combined aerobic (30-35 min) and resistance (30 min) training and a dietary intervention (as above)

Behavioral: Exercise and diet

Control

NO INTERVENTION

No intervention

Interventions

Exercise and diet BEHAVIORAL

The participants will undergo diet or combined diet and exercise. The exercise will be provided at different volumes

High Exercise Dose (HED); Moderate Exercise Dose (MED)

Diet BEHAVIORAL

Dietary intervention

Dietary control (DCON)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with diabetes type 2 and/or HbA1c ≥ 48 mmol/mol if no treatment with anti-diabetic medication and/or use of antidiabetic medication
• Caucasian
• No diagnose of Type 1 diabetes, mature onset diabetes of the young, Latent autoimmune diabetes of adults
• T2D 0-6 years of duration
• No treatment with insulin
• Body Mass Index (BMI) \>27 kg/m2 and \<40 kg/m2
• No known or signs of intermediate or severe microvascular complications to diabetes (retino-, neuro- or nephropathy)
• No known cancer
• No Known lung disease
• No known cardiovascular disease
• No known thyroid disease
• No known liver disease
• No known autoimmune disease
• No other endocrine disorder causing obesity
• No current treatment with anti-obesity medication

You may not qualify if:

• HbA1c: \>=75 mmol/mol with no glucose lowering medications
• HbA1c: \>=64 mmol/mol with mono glucose lowering therapy (if compliant with the prescription)
• HbA1c: \>=57 mmol/mol with \>=dual glucose lowering therapy (if compliant with the prescription)
• estimated glomerular filtration rate\<60 mL/min
• Protein or glucose in the urine at pre-screening
• No biochemical sign of other major diseases
• Presence of circulating glutamate-decarboxylase anti body (GAD) 65
• Objective findings that contraindicates participation in intensive exercise
• Anamnestic findings that contraindicates participation in the study
• Unable to allocate the needed time to fulfill the intervention
• Language barrier, mental incapacity, unwillingness or inability to understand and be able to complete the interventions

Sponsors & Collaborators

• Mathias Ried-Larsen: lead

Study Sites (1)

Center for Physical Activity Research, Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

Related Publications (3)

• Lyngbaek MPP, Legaard GE, Bennetsen SL, Feineis CS, Rasmussen V, Moegelberg N, Brinklov CF, Nielsen AB, Kofoed KS, Lauridsen CA, Ewertsen C, Poulsen HE, Christensen R, Van Hall G, Karstoft K, Solomon TPJ, Ellingsgaard H, Almdal TP, Pedersen BK, Ried-Larsen M. The effects of different doses of exercise on pancreatic beta-cell function in patients with newly diagnosed type 2 diabetes: study protocol for and rationale behind the "DOSE-EX" multi-arm parallel-group randomised clinical trial. Trials. 2021 Apr 1;22(1):244. doi: 10.1186/s13063-021-05207-7.

  PMID: 33794975 BACKGROUND

• Legaard GE, Lyngbaek MPP, Almdal TP, Karstoft K, Bennetsen SL, Feineis CS, Nielsen NS, Durrer CG, Liebetrau B, Nystrup U, Ostergaard M, Thomsen K, Trinh B, Solomon TPJ, Van Hall G, Brond JC, Holst JJ, Hartmann B, Christensen R, Pedersen BK, Ried-Larsen M. Effects of different doses of exercise and diet-induced weight loss on beta-cell function in type 2 diabetes (DOSE-EX): a randomized clinical trial. Nat Metab. 2023 May;5(5):880-895. doi: 10.1038/s42255-023-00799-7. Epub 2023 May 1.

  PMID: 37127822 RESULT

• Legaard GE, Lyngbaek MPP, Almdal TP, Durrer CG, Nystrup U, Larsen EL, Poulsen HE, Karstoft K, Pedersen BK, Ried-Larsen M. Effects of different doses of exercise in adjunct to diet-induced weight loss on the AGE-RAGE axis in patients with short standing type 2 diabetes: Secondary analysis of the DOSE-EX multi-arm, parallel-group, randomised trial. Free Radic Biol Med. 2023 Nov 1;208:52-61. doi: 10.1016/j.freeradbiomed.2023.07.031. Epub 2023 Jul 31.

  PMID: 37532066 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Motor Activity; Insulin Resistance

Interventions

Exercise; Diet

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Mathias Ried-Larsen, PhD

  Centre for Physical Activity Research, Righospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Upon completion of the study and prior to breaking the allocation code, a data-collection form is generated by a statistician and the principal investigator. The data-analyst breaks the allocation code and labels the participants according to the assigned treatment and analyzes the outcomes. Following the analyses, group allocation will be concealed in all data outputs and the N per group and present the data to the writing committee in a blinded fashion. Then the writing committee will provide their blinded interpretations.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: November 22, 2018
• First Posted: December 10, 2018
• Study Start: December 12, 2018
• Primary Completion: October 28, 2021
• Study Completion: October 28, 2021
• Last Updated: May 10, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)