Type 2 Diabetes MellitusDOSE-EXNCT03769883
Exercise Volume and Beta-cell Function in T2D The DOSE-EX Randomized Trial
A study testing Exercise and diet and Diet in people with Type 2 Diabetes Mellitus and Type2 Diabetes, run by Mathias Ried-Larsen at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Type 2 Diabetes Mellitus, Type2 Diabetes, Diabetes Mellitus, Type 2
- What is being tested?
- Exercise and diet and Diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteDenmark
- Study dates
- 12 Dec 2018to 28 Oct 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 26Show fewer
- 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
- No current treatment with anti-inflammatory medication
- No weight loss of > 5kg within the last 6 months
- No diagnose of depression or treatment with anti-depressive medication, ongoing or within the last three months before enrolment
- No diagnose of psychiatric disorder or treatment with anti-psychotic medication
- No history of suicidal behavior or ideations within the last three months before enrolment
- No previous surgical treatment for obesity (excluding liposuction > 1 year prior to enrolment)
- Not pregnant/considering pregnancy
- No functional impairments that prevents the performance of intensive exercise
- Accept of medical regulation by the U-TURN endocrinologist
- Inactivity, defined as < 1,5 hours of structured physical activity pr. week at moderate intensity and cycling < 30 minutes/5 km pr. day at moderate intensity (moderate intensity = out of breath but able to speak)
- No participation in other research intervention studies
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Physical Activity Research, Copenhagen University Hospital
Copenhagen, 2100
About this study
Official title: The Effects of Different Doses of Exercise on Pancreatic ß-cell Function in Patients With Newly Diagnosed Type 2 Diabetes (DOSE-EX): A Randomized Clinical Trial
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.
Read the detailed description
A 4-armed, 16-week, parallel-group, assessor-blinded, randomized, clinical trial. Participants will be randomly allocated (1:1:1:1), stratified by sex
Interventions:
The lifestyle interventions will consist of two main components; 1) increased physical activity and structured exercise and/or 2) a dietary intervention aiming at a weight loss. Whereas there will be no differences in the dietary intervention between the lifestyle groups, the volume of physical activity and structured exercise will vary according to the frequencies of the structured exercise sessions.
The study groups are prescribed:
- Control group (CON): No intervention
- Dietary control (DCON): Dietary intervention (see below)
- Moderate Exercise Dose (MED): 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 (described below)
- High Exercise Dose (HED): 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 (described below)
Detailed description of the intervention components. Exercise: The training protocol will be adapted based on a previous study where the T2D participants were prescribed 6 weekly sessions of aerobic training alone or combined aerobic and resistance training (averaging 360-420 min of exercise per week). As previous analyses suggest that there may be an inverse dose-response relationship between reductions in HbA1c and aerobic exercise volume, this parameter will be used to adapt the training protocol. As the effect of exercise on HbA1c is closer related to the number of training sessions rather than intensity15, we will reduce the number of sessions by 50%, to three sessions/week in the moderate exercise dose group and maintain the original session frequency in the high dose exercise group (six sessions/week).Training will be supervised and monitored to ensure intensity and compliance.
Dietary intervention and intended weight loss (DCON, MED and HED: The dietary intervention will be based on the recommendations from the American Diabetes Association (ADA) with increased focus on macronutrient quality. The macronutrient 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 45-60 energy% carbohydrate, 15-20 energy% protein and 20-35 energy% fat. Thus, the dietary intervention emphasis will be on low glycemic index and low glycemic load in shape of non-processed foods and will aim at reducing saturated fat intake <7 energy%.
- Conditions
- Type 2 Diabetes Mellitus, Type2 Diabetes, Diabetes Mellitus, Type 2, Type2 Diabetes Mellitus
- Being tested
- Exercise and diet, Diet
- Keywords
- Exercise, Physical Activity, Type 2 diabetes, Pancreatic beta-cell function, Insulin sensitivity, Dose finding, lifestyle
- Medical subject headings
- Diabetes Mellitus, Type 2, Motor Activity, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise and dietBehavioural
The participants will undergo diet or combined diet and exercise. The exercise will be provided at different volumes
DietBehavioural
Dietary intervention
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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) Receives: 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) Receives: Behavioral: Exercise and diet |
| Control | No intervention | No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Secondary outcomes (50)
Pancreatic beta-cell function (Intention to treat)
As for per protocol
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Glucagon like peptide 1 sensitivity (c-peptide)
Change in Glucagon like peptide 1 stimulated C-peptide secretion
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Glucagon like peptide 1 sensitivity (glucagon)
Change in Glucagon like peptide 1 stimulated glucagon secretion
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Glucagon like peptide 1 sensitivity (insulin)
Change in Glucagon like peptide 1 stimulated insulin secretion
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Arginine sensitivity (insulin)
Change in Arginine stimulated insulin secretion
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Arginine sensitivity (c-peptide)
Change in Arginine stimulated C-peptide secretion
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Arginine sensitivity (glucagon)
Change in Arginine stimulated glucagon secretion
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Early phase disposition index (c-peptide)
Change in 1st phase C-peptide secretion defined as the peak concentration during the initial 10 minutes of the hyperglycaemic clamp
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Early phase disposition index (insulin)
Change in 1st phase insulin secretion defined as the peak concentration during the initial 10 minutes of the hyperglycaemic clamp
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Glucose clearance
Change in Rate of glucose clearance (stable isotope infusion) during steady state hyperglycemia
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Glucose appearance
Change in Rate of glucose appearance (stable isotope infusion) during steady state hyperglycemia
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Insulin sensitivity
Change in mean Glucose infusion rate over last 30 min of clamp phase/(mean insulin×glucose
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Mean amplitude of glycemic excursions
Change in Mean amplitude of glycemic excursions (MAGE - calculated based on min 3 days sensor glucose profiles)
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Coefficient of glucose variation
Change in Coefficient of variation defined as (mean glucose/the standard deviation (SD)) of min 3 days sensor glucose profiles
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Mean glucose levels
Change in the mean glucose levels (calculated based on min 3 days sensor glucose profiles)
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Time in hyperglycemia
Change in time in hyperglycaemia (calculated based on min 3 days sensor glucose profiles)
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Time in hypoglycemia
Change in time in hypoglycaemia from min 3 days sensor glucose profiles
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Pancreatic fat
Change in Pancreatic fat
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Hepatic fat
Change in Hepatic fat
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Visceral fat
Change in visceral fat
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Total fat mass
Change in Total fat mass
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Total fat free mass
Change in Total fat free mass
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Total lean body mass
Change in Total lean body mass
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Android fat mass
Change in Android fat mass
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Gynoid fat mass
Change in gynoid fat mass
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Body weight
Change in body weight
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Body mass index
Change in body mass index
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Systemic oxidative stress (RNA)
Change in 8-oxo-guanosine
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Systemic oxidative stress (DNA)
Change in 8-oxo-deoxoguonase
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Advanced glycation end-products (AGE)
Change in AGE
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
The circulating receptor for advanced glycation end-products (sRAGE)
Change in sRAGE
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Markers of low-grade inflammation
Change in inflammatory markers (e.g. high sensitive C-reactive protein, interferon-ϒ, interleukin-10, interleukin-8, interleukin-6, interleukin-1, TNFα)
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Glycated haemoglobin type 1AC (HbA1c)
Change in HbA1c
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Total cholesterol
Change in total cholesterol
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Total triglyceride
Change in total triglyceride
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Low density lipoprotein (LDL)
Change in LDL
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
High density lipoprotein (HDL)
Change in HDL
Measured: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Systolic blood pressure
Change systolic blood pressures
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Diastolic blood pressure
Change diastolic blood pressure
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Glucose tolerance
Change incremental and total area under the curve (glucose, c-peptide, insulin) during a mixed meal tolerance test
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Gastric emptying (AUC)
Change in the AUC (paracetamol) during a mixed meal tolerance test
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Gastric emptying (Rate of appearance)
Change in rate of appearance of paracetamol during a mixed meal tolerance test
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Physical fitness (VO2max)
Change in physical fitness (VO2) during a progressive maximal bicycle ergometer test
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Muscular 1 repetition max (strength)
Change in 1 repetition max
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Total physical activity
Change in objectively measured physical activity (counts per minute)
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Moderate and vigorous physical activity (MVPA)
Change in time spend on MVPA
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Sedentary time (SED)
Change in time spend on SED
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Physical well being
Change in physical well being (Based on the physical dimension score from short-form 36, range 0-100)
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Mental well being
Change in mental well being (Based on the mental dimension score from Short-form 36) (range 0-100)
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Satiety
Change in self-reported satiety (VAS) during a mixed meal tolerance test (range 0-10)
Measured: From baseline (0 weeks) to follow-up (16 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2018
- Study start12 Dec 2018
- Primary completion28 Oct 2021
- Study completion28 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mathias Ried-Larsen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mathias Ried-Larsen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Mathias Ried-Larsen, PhD, Principal investigator, Centre for Physical Activity Research, Righospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03769883
- Sponsor's protocol ID
- H-18038298
- Acronym
- DOSE-EX
- Status last verified
- May 2024
- First submitted
- 22 Nov 2018
- Last updated
- 10 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: If the data can be fully anonymized the data can be shared.
Publications
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.
PubMed 33794975Legaard 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.
PubMed 37127822Legaard 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.
PubMed 37532066
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Different Doses of Exercise on Pancreatic ß-cell Function in Patients With Newly Diagnosed Type 2 Diabetes (DOSE-EX): A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03769883
- Acronym / sponsor ID
- DOSE-EX / H-18038298
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Mathias Ried-LarsenUniversity, hospital or other
- Study start
- 12 Dec 2018 (actual)
- Primary completion
- 28 Oct 2021 (actual)
- Study completion
- 28 Oct 2021 (actual)
- First posted
- 10 Dec 2018 (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 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.
Detailed description
A 4-armed, 16-week, parallel-group, assessor-blinded, randomized, clinical trial. Participants will be randomly allocated (1:1:1:1), stratified by sex
Interventions:
The lifestyle interventions will consist of two main components; 1) increased physical activity and structured exercise and/or 2) a dietary intervention aiming at a weight loss. Whereas there will be no differences in the dietary intervention between the lifestyle groups, the volume of physical activity and structured exercise will vary according to the frequencies of the structured exercise sessions.
The study groups are prescribed:
- Control group (CON): No intervention
- Dietary control (DCON): Dietary intervention (see below)
- Moderate Exercise Dose (MED): 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 (described below)
- High Exercise Dose (HED): 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 (described below)
Detailed description of the intervention components. Exercise: The training protocol will be adapted based on a previous study where the T2D participants were prescribed 6 weekly sessions of aerobic training alone or combined aerobic and resistance training (averaging 360-420 min of exercise per week). As previous analyses suggest that there may be an inverse dose-response relationship between reductions in HbA1c and aerobic exercise volume, this parameter will be used to adapt the training protocol. As the effect of exercise on HbA1c is closer related to the number of training sessions rather than intensity15, we will reduce the number of sessions by 50%, to three sessions/week in the moderate exercise dose group and maintain the original session frequency in the high dose exercise group (six sessions/week).Training will be supervised and monitored to ensure intensity and compliance.
Dietary intervention and intended weight loss (DCON, MED and HED: The dietary intervention will be based on the recommendations from the American Diabetes Association (ADA) with increased focus on macronutrient quality. The macronutrient 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 45-60 energy% carbohydrate, 15-20 energy% protein and 20-35 energy% fat. Thus, the dietary intervention emphasis will be on low glycemic index and low glycemic load in shape of non-processed foods and will aim at reducing saturated fat intake <7 energy%.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dietary control (DCON) | Experimental | Behavioral: DietThe 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 |
| Moderate Exercise Dose (MED) | Experimental | Behavioral: Exercise and dietTwo 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) |
| High Exercise Dose (HED) | Experimental | Behavioral: Exercise and dietFour 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) |
| Control | No intervention | –No intervention |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| Exercise and dietThe participants will undergo diet or combined diet and exercise. The exercise will be provided at different volumes | Behavioural | High Exercise Dose (HED), Moderate Exercise Dose (MED) |
| DietDietary intervention | Behavioural | Dietary control (DCON) |
Primary outcome
Pancreatic beta-cell function (Per protocol)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
The change in the late-phase disposition index (DI) during the final 30 minutes of hyperglycemic phase of the hyperglycemic clamp.
50 secondary outcomes
Pancreatic beta-cell function (Intention to treat)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Glucagon like peptide 1 sensitivity (c-peptide)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Glucagon like peptide 1 sensitivity (glucagon)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Glucagon like peptide 1 sensitivity (insulin)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Arginine sensitivity (insulin)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Arginine sensitivity (c-peptide)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Arginine sensitivity (glucagon)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Early phase disposition index (c-peptide)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Early phase disposition index (insulin)
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Glucose clearance
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Glucose appearance
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Insulin sensitivity
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Mean amplitude of glycemic excursions
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Coefficient of glucose variation
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Mean glucose levels
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Time in hyperglycemia
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Time in hypoglycemia
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Pancreatic fat
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Hepatic fat
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Visceral fat
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Total fat mass
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Total fat free mass
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Total lean body mass
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Android fat mass
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Gynoid fat mass
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Body weight
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Body mass index
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Systemic oxidative stress (RNA)
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Systemic oxidative stress (DNA)
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Advanced glycation end-products (AGE)
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
The circulating receptor for advanced glycation end-products (sRAGE)
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Markers of low-grade inflammation
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Glycated haemoglobin type 1AC (HbA1c)
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Total cholesterol
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Total triglyceride
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Low density lipoprotein (LDL)
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
High density lipoprotein (HDL)
Time frame: From baseline (0 weeks) to follow-up (4, 12 and 16 weeks)
Systolic blood pressure
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Diastolic blood pressure
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Glucose tolerance
Time frame: From baseline (0 weeks) to follow-up (16 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
- Background: PubMed 33794975Lyngbaek 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.
- Results publication: PubMed 37127822Legaard 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.
- Results publication: PubMed 37532066Legaard 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.
- Individual participant dataSharing planned: No. If the data can be fully anonymized the data can be shared.
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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. This study is not recruiting at the moment.
Mathias Ried-Larsen, PhD principal investigator
Centre for Physical Activity Research, Righospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise and diet and Diet in people with Type 2 Diabetes Mellitus and Type2 Diabetes, run by Mathias Ried-Larsen at 1 site in Denmark.
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 26 inclusion and 11 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: finished, as of the sponsor's last update on 10 May 2024. 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 Denmark. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pancreatic beta-cell function (Per protocol) (time frame: From baseline (0 weeks) to follow-up (16 weeks)). 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 NCT03769883, which also lists 3 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 10 May 2024.