RESIST! Blood-flow Restriction Resistance Training for Improving Insulin Sensitivity in Type 2 Diabetes

NCT ID: NCT04222231

Last Updated: 2023-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-28

Study Completion Date

2024-03-01

Brief Summary

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The study aims to investigate the metabolic and cardiovascular effects of classical resistance training with high loads and blood-flow restricted training (BFRT) with low loads in individuals with type 2 diabetes over 12 weeks.

Detailed Description

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Type 2 diabetes (T2D) is characterized by an increasing insensitivity of muscle, fat and liver cells to the hormone insulin. About 9% of the global population is affected by this condition and mortality risk is twice as high in individuals with diabetes compared to similar-aged people without diabetes.

Muscle is of particular importance for glucose homeostasis, since in healthy people it accounts for 80-90% of postprandial insulin-stimulated glucose disposal. After cellular uptake of glucose by the specialized glucose transporter 4 (GLUT4), glucose is phosphorylated and stored as glycogen. In individuals with obesity or T2D, the capacity for insulin to facilitate glucose uptake and glycogen synthesis is impaired. This reduced response of a given insulin concentration to exert its biological effect is termed insulin resistance. Subsequent diminished insulin secretion due to β-cell failure results in fasting hyperglycemia and overt diabetes. Importantly, muscle insulin resistance is the initial defect occurring in the development of T2D and precedes the clinical development of the disease by up to 20 years.

Thus, the preservation of skeletal muscle function is essential for people with T2D who have an increased risk of sarcopenia. On the one hand high intensity resistance training (HIT) with 80 % one-repetition maximum (%1-RM) is a well-recognized strategy to improve muscle strength and glycemic control for individuals with T2D, on the other hand elderly or obese people may not be able to tolerate these high loads. Blood flow restriction training (BFRT) with low loads (20-30% 1-RM) has consistently demonstrated comparable effects to HIT and seems to be a promising alternative to increase muscle function.

During the BFRT the muscle becomes hypoxic due to a brief occlusion of venous blood flow using a tourniquet while exercising. Consequently metabolites like lactate, growth hormone (GH) and insulin like growth factor (IGF-1) are released and result in muscle hypertrophy through activating the collagen synthesis and the recruitment of satellite cells. Furthermore cell swelling based on venous blood pooling, reactive hyperemia and metabolite accumulation has been shown to increase protein synthesis by activating the mammalian Target of Rapamycin Complex 1 (mTORC1) pathway. Also, BFRT increases the level of reactive oxygen species (ROS) which may lead to higher glucose uptake during exercise. Last but not least higher threshold motor units (fast twitch fibers) are recruited due to hypoxia and metabolite accumulation.

Although there is a significant inverse relationship between muscle strength and the risk of cardiovascular mortality, cardiovascular adaptations to resistance training are under-explored and poorly understood.

The study therefore aims to investigate the metabolic and cardiovascular effects of BFRT with low loads in individuals with T2D.

Conditions

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Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Blood-flow restriction resistance training

Resistance training with low loads (15-30% RM) in combination with a brief occlusion of venous blood flow using a tourniquet while exercising.

Group Type EXPERIMENTAL

Blood-flow restriction resistance training

Intervention Type OTHER

Training program: After 10 minutes of warm-up the participant performs three exercises with BFRT for the lower extremities. The intensity is about 15-30% of 1-RM.

Classical resistance training

Resistance training with high loads (60-80% RM).

Group Type EXPERIMENTAL

Classical resistance training

Intervention Type OTHER

Training program: After warm-up the participant performs three exercises for lower body. The intensity is about 60-80% of 1-RM.

Interventions

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Blood-flow restriction resistance training

Training program: After 10 minutes of warm-up the participant performs three exercises with BFRT for the lower extremities. The intensity is about 15-30% of 1-RM.

Intervention Type OTHER

Classical resistance training

Training program: After warm-up the participant performs three exercises for lower body. The intensity is about 60-80% of 1-RM.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Male and female, age between ≥ 30 and ≤ 69 years
* Individuals with type 2 diabetes
* BMI: 19-40 kg/m²

Exclusion Criteria

* Acute infections in the last 2 weeks
* Weight fluctuations (\> 10% in the last 6 month)
* Therapy with Glitazone, Beta blocker, Insulin
* Malignant cancer
* Heart diseases (angina pectoris, myocardial infarction, acute myocarditis or pericarditis, cardiac wall aneurysms/ stenose, untreated hypotension or hypertension, aortic stenosis, stroke, cardiac insufficiency, NYHA-class ≥II, heart arrhythmia, disturbances of blood circulation in extremities, venous insufficiency, varicose veins)
* Diabetic neuropathy
* Respiratory disease (COPD, Gold grade ≥II)
* Serious heart, kidney or liver disease: - New York Heart Association-Classification (NYHA) stage ≥ II - creatinine ≥ 1.6 mg / dl - Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥ two-fold upper reference value
* Anemia (Hb \<12g / l), blood donation in the last 3 month
* Disease of the immune system (leucocytes \<5000/μl)
* Application of immunomodulatory agents (Glucocorticoids, Antihistamine, Acetylsalicylic acid)
* Application of antithrombotic agents (Anticoagulant)
* Blood clotting disorders (abnormally levels of thrombocytes \[\<150.000, \>450.000 ± 50 \], Partial thromboplastin time (PTT) \[26-36 s ± 5 s\], Quick \[70-120% ± 10%\]) or wound healing
* Thyroid disease (untreated hypothyroidism or hyperthyroidism, treatment with thiamazol)
* Epilepsy
* Application of drugs which can manipulate the thermoregulation (Antipsychotic)
* Rosacea
* Vitamine supplement (with the las 4 weeks)
* Cigarettes (or non-smokers \<1 year) alcohol consumption (men\> 30 g / d, women\> 20 g / d), drug abuse
* Severe psychiatric illness or addiction
* Risk for/ or HIV or Hepatitis B or C
* Shift work or anormal circadian rhythm
* Muscle diseases, orthopedic restrictions
* Hypersensitivity to local anaesthetic
* Pregnancy, lactation
* Metallic and magnetic implants (for example, mechanical heart valves, joint prostheses, clip after vascular surgery, middle and inner ear implants or fresh dental implants)
* Claustrophobia
* Hypohidrosis
* Participation in another intervention study within the last 3 month
Minimum Eligible Age

30 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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German Diabetes Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Roden, Prof., MD

Role: STUDY_DIRECTOR

German Diabetes Center

Locations

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German Diabetes Center

Düsseldorf, North Rhine-Westphalia, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Michael Roden, Prof., MD

Role: CONTACT

00492113382 ext. 201

Nina Saatmann, M.Sc.

Role: CONTACT

00492113382 ext. 514

Facility Contacts

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Michael Roden, Prof., MD

Role: primary

00492113382 ext. 201

Nina Saatmann, M.Sc.

Role: backup

00492113382 ext. 514

References

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Christiansen D, Eibye KH, Hostrup M, Bangsbo J. Blood flow-restricted training enhances thigh glucose uptake during exercise and muscle antioxidant function in humans. Metabolism. 2019 Sep;98:1-15. doi: 10.1016/j.metabol.2019.06.003. Epub 2019 Jun 12.

Reference Type BACKGROUND
PMID: 31199953 (View on PubMed)

Loenneke JP, Fahs CA, Rossow LM, Abe T, Bemben MG. The anabolic benefits of venous blood flow restriction training may be induced by muscle cell swelling. Med Hypotheses. 2012 Jan;78(1):151-4. doi: 10.1016/j.mehy.2011.10.014. Epub 2011 Nov 1.

Reference Type BACKGROUND
PMID: 22051111 (View on PubMed)

Abe T, Fujita S, Nakajima T, Sakamaki M, Ozaki H, Ogasawara R, Sugaya M, Kudo M, Kurano M, Yasuda T, Sato Y, Ohshima H, Mukai C, Ishii N. Effects of Low-Intensity Cycle Training with Restricted Leg Blood Flow on Thigh Muscle Volume and VO2MAX in Young Men. J Sports Sci Med. 2010 Sep 1;9(3):452-8. eCollection 2010.

Reference Type BACKGROUND
PMID: 24149640 (View on PubMed)

Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N. Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans. J Appl Physiol (1985). 2000 Jun;88(6):2097-106. doi: 10.1152/jappl.2000.88.6.2097.

Reference Type BACKGROUND
PMID: 10846023 (View on PubMed)

Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N. Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol (1985). 2000 Jan;88(1):61-5. doi: 10.1152/jappl.2000.88.1.61.

Reference Type BACKGROUND
PMID: 10642363 (View on PubMed)

Hughes L, Paton B, Rosenblatt B, Gissane C, Patterson SD. Blood flow restriction training in clinical musculoskeletal rehabilitation: a systematic review and meta-analysis. Br J Sports Med. 2017 Jul;51(13):1003-1011. doi: 10.1136/bjsports-2016-097071. Epub 2017 Mar 4.

Reference Type BACKGROUND
PMID: 28259850 (View on PubMed)

Mattocks KT, Jessee MB, Mouser JG, Dankel SJ, Buckner SL, Bell ZW, Owens JG, Abe T, Loenneke JP. The Application of Blood Flow Restriction: Lessons From the Laboratory. Curr Sports Med Rep. 2018 Apr;17(4):129-134. doi: 10.1249/JSR.0000000000000473.

Reference Type BACKGROUND
PMID: 29629973 (View on PubMed)

Harreiter J, Roden M. [Diabetes mellitus-Definition, classification, diagnosis, screening and prevention (Update 2019)]. Wien Klin Wochenschr. 2019 May;131(Suppl 1):6-15. doi: 10.1007/s00508-019-1450-4. German.

Reference Type BACKGROUND
PMID: 30980151 (View on PubMed)

Pesta DH, Goncalves RLS, Madiraju AK, Strasser B, Sparks LM. Resistance training to improve type 2 diabetes: working toward a prescription for the future. Nutr Metab (Lond). 2017 Mar 2;14:24. doi: 10.1186/s12986-017-0173-7. eCollection 2017.

Reference Type BACKGROUND
PMID: 28270856 (View on PubMed)

Centner C, Wiegel P, Gollhofer A, Konig D. Effects of Blood Flow Restriction Training on Muscular Strength and Hypertrophy in Older Individuals: A Systematic Review and Meta-Analysis. Sports Med. 2019 Jan;49(1):95-108. doi: 10.1007/s40279-018-0994-1.

Reference Type BACKGROUND
PMID: 30306467 (View on PubMed)

Related Links

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Other Identifiers

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DDZ_Resist

Identifier Type: -

Identifier Source: org_study_id

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