Effects of Different Types of Exercise in Type 2 Diabetes (RAED2)

Comparison of Aerobic and Resistance Training Effects on Glycemic Control in Type 2 Diabetes

The purposes of this study are: a) to compare the effects of supervised programs of aerobic training or resistance training on the metabolic control of type 2 diabetes; b) to investigate some potential pathophysiologic and molecular mechanisms underlying these effects; c) to assess whether some changes may persist over time after termination of the supervised programs.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Behavioral: Aerobic Training; Behavioral: Resistance Training

Detailed Description

Meta-analyses of studies which evaluated the effects of interventions based upon structured exercise programs in patients with type 2 diabetes show that regular physical activity may improve glycosylated haemoglobin (HbA1c) by 0.6-0.7%. Most studies assessed the effects of aerobic exercise. However, recent data suggest that resistance training may result in similar effects. It seems likely that these beneficial results are obtained through different molecular mechanisms by aerobic training and resistance training. Consequently, these exercise modalities could be synergistic in improving the metabolic abnormalities in these subjects. On the other hand, comparison data are very limited.

Aims of the protocol are to compare the effects of aerobic training or resistance training on the metabolic control of type 2 diabetes and to investigate some potential pathophysiologic and molecular mechanisms underlying these effects.

The study will be carried out in 40 sedentary type 2 diabetic patients without diabetic complications, aged 40-70 yr, with body mass index (BMI) between 24-36 kg/m2 and HbA1c between 6.5-9.0%. Admitted diabetes treatments will be diet and oral hypoglycemic agents.

Subjects will be assigned, by a randomization schedule weighted by baseline BMI and fitness, to 2 groups of supervised exercise: aerobic training or resistance training. Training programs will have a similar volume and will be scheduled in three 60 min sessions per week for 4 months. During the study subjects will be instructed to follow an isocaloric diet. Before and at the end of the exercise training the following will be assessed: HbA1c (primary outcome), plasma glucose, lipid profile, blood pressure, insulin sensitivity (glucose clamp), body composition (Dual energy X-ray absorptiometry, DEXA), liver and muscle fat content (magnetic resonance imaging), expression in the muscle of some genes involved in ATP production, mitochondrial biogenesis and substrate utilization, markers of inflammation, oxidative stress and early vascular damage, peak oxygen uptake (VO2peak) during a maximal exercise test, other exercise tests, tissue oxygen extraction during exercise (Near-infrared spectroscopy, NIRS), energy expenditure and physical activity in daily life (metabolic Holter and questionnaire). Monitoring of blood glucose will also be carried out over a 48h period, comprising an exercise session (Continuous Glucose Monitoring System).

Metabolic features, exercise tests, body composition, daily physical activity and expression of relevant genes in the muscle will also be assessed 1 yr after completion of the training programs, to establish whether some changes may persist over time.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI between 24-36 kg/m2;
• HbA1c between 6.5-9.0%;
• diabetes diagnosis must have been made at least 1 yr previously;
• admitted diabetes treatments will be diet and oral hypoglycemic agents;
• baseline physical activity, estimated by the IPAQ questionnaire, lower than 1000 MET min per week;
• baseline body weight stable (changes lower than 2 kg in the last 2 months).

Exclusion Criteria:

• moderate-severe somatic or autonomic neuropathy;
• coronary heart disease;
• peripheral or cerebral vascular disease;
• preproliferative or proliferative retinopathy or chronic renal failure (serum creatinine >1.4 mg/dl in females; >1.5 mg/dl in males);
• therapy with beta-blocker drugs;
• smokers;
• acute clinically significant intercurrent diseases;
• inability to perform the scheduled physical activity programs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aerobic Exercise; The aerobic training group will use cardiovascular training devices.	Behavioral: Aerobic Training; The aerobic training group will exercise on cardiovascular training equipment. The workload will be gradually increased up to 60% of the reserve heart rate. Subjects will exercise 3 times per week for 60 min in the Fitness Centre of the Exercise and Sport Science School. Training will be carried out in small groups, under the supervision of personal trainers. During the study subjects will be instructed to follow an isocaloric diet.
EXPERIMENTAL: Resistance Exercise; The resistance training group will perform exercises on weight machines and free weights.	Behavioral: Resistance Training; The resistance training group will perform different exercises on weight machines and free weights to exercise upper and lower extremity muscles. Participants will perform 8-10 different exercises each session, alternating abdominal, upper and lower extremity exercises. Subjects will exercise 3 times per week for 60 min in the Fitness Centre of the Exercise and Sport Science School. Training will be carried out in small groups, under the supervision of personal trainers. During the study subjects will be instructed to follow an isocaloric diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in haemoglobin A1c (HbA1c) levels	The measurement of HbA1c is carried out with a DCCT (Diabetes Control and Complications Trial)-aligned method.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6 minutes walk distance	This test measures the number of meters that can be walked in 6 minutes over a 30 m course. It is a simple field test to assess aerobic functional capacity.	4 months
Change in body weight		4 months
Change in body composition	Assessment by DEXA (Dual energy X-ray absorptiometry)	4 months
Change in fasting plasma glucose levels		4 months
Change in total cholesterol levels		4 months
Change in HDL-cholesterol levels		4 months
Change in LDL-cholesterol levels		4 months
Change in triglycerides levels		4 months
Change in blood pressure		4 months
Change in insulin sensitivity	Measured by euglycemic hyperinsulinemic clamp	4 months
Change in energy expenditure	Measured by indirect calorimetry	4 months
Change in antidiabetic medications	Class and dosage of blood-glucose lowering drugs are recorded before and at the end of the protocol.	4 months
Compliance	Attendance at the scheduled sessions is recorded for each patient.	4 months
Change in beta-cell function	Measured by OGTT (Oral Glucose Tolerance Test)	4 months
Change in energy expenditure through voluntary physical activity	Energy expenditure is estimated through metabolic Holter (Sense Wear Armband) and IPAQ (International physical activity questionnaire).	4 months
Change in peak oxygen uptake	Measured during an incremental exercise test	4 months
Change in tissue oxygen extraction	Measured by NIRS (Near-infrared spectroscopy) during an incremental test exercise	4 months
Change in liver and muscle fat content	Measured by Magnetic Resonance Imaging	4 months
Change in blood glucose during and after exercise	Measured by continuous glucose monitoring system	48 hours
Muscle strength	Measured by 1RM (one-repetition maximum) test	4 months
Change in flexibility	Measured by "sit and reach" test and "back scratch" test	4 months
Changes in expression in the muscle of some genes involved in ATP production, mitochondrial biogenesis and substrate utilization	mRNA analysis with multiplex tandem real-time PCR of fine needle aspirates obtained from the vastus lateralis muscle	4 months

Collaborators and Investigators

• Sponsor: Universita di Verona
• Investigators: Principal Investigator: Paolo Moghetti, MD.,Ph.D., Universita di Verona

Publications and helpful links

General Publications

• Dauriz M, Olioso D, Moghetti P. Response to Comment on Olioso D, et al. "Effect of Aerobic and Resistance Training on Circulating Micro-RNA Expression Profile in Subjects with Type 2 Diabetes". J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgaa068. doi: 10.1210/clinem/dgaa068. No abstract available.
• Olioso D, Dauriz M, Bacchi E, Negri C, Santi L, Bonora E, Moghetti P. Effects of Aerobic and Resistance Training on Circulating Micro-RNA Expression Profile in Subjects With Type 2 Diabetes. J Clin Endocrinol Metab. 2019 Apr 1;104(4):1119-1130. doi: 10.1210/jc.2018-01820.
• Bellavere F, Cacciatori V, Bacchi E, Gemma ML, Raimondo D, Negri C, Thomaseth K, Muggeo M, Bonora E, Moghetti P. Effects of aerobic or resistance exercise training on cardiovascular autonomic function of subjects with type 2 diabetes: A pilot study. Nutr Metab Cardiovasc Dis. 2018 Mar;28(3):226-233. doi: 10.1016/j.numecd.2017.12.008. Epub 2018 Jan 2.
• Bacchi E, Negri C, Trombetta M, Zanolin ME, Lanza M, Bonora E, Moghetti P. Differences in the acute effects of aerobic and resistance exercise in subjects with type 2 diabetes: results from the RAED2 Randomized Trial. PLoS One. 2012;7(12):e49937. doi: 10.1371/journal.pone.0049937. Epub 2012 Dec 5.
• Bacchi E, Negri C, Zanolin ME, Milanese C, Faccioli N, Trombetta M, Zoppini G, Cevese A, Bonadonna RC, Schena F, Bonora E, Lanza M, Moghetti P. Metabolic effects of aerobic training and resistance training in type 2 diabetic subjects: a randomized controlled trial (the RAED2 study). Diabetes Care. 2012 Apr;35(4):676-82. doi: 10.2337/dc11-1655. Epub 2012 Feb 16.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: August 16, 2010
• First Submitted That Met QC Criteria: August 16, 2010
• First Posted (ESTIMATE): August 17, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): August 25, 2011
• Last Update Submitted That Met QC Criteria: August 24, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: type 2 diabetes; therapy; resistance training; aerobic training
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: CE1578