Effects of Neuromuscular Electrical Stimulation on Glucose Variability in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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In patients with type 2 diabetes mellitus (T2DM) chronic hyperglycemia is the main cause of complications, promoting several micro and macrovascular damages. In order to understand other mechanisms that could have an impact on the development of these diabetic complications, the assessment of glycemic variability have been widely used. Glucose control can be achieved with multiple interventions, including exercise training. Some individuals, however, especially those with autonomic neuropathy, can have exercise intolerance. In this context, physical therapy proposes neuromuscular electrical stimulation (NMES) as a therapeutic that has been applied in research and clinical practice as an alternative to the training of patients who cannot perform conventional exercise. In patients with T2DM, NMES was shown to improve glycemic control and insulin sensitivity, but quality of these trials is poor. In addition, the effects of NMES on glycemic variability of T2DM patients have not yet been reported. The aim of this study is to evaluate the effects of NMES on glucose levels and glucose variability in patients with T2DM.

Detailed Description
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Patients with T2DM will be recruited from outpatient clinic of the Hospital de Clinicas de Porto Alegre. Patients will be randomized to NMES session, with maximal intensity tolerance by to induce visible contractions or to NMES-placebo, with minimal intensity to provide a sensory stimulus, but insufficient to elicit a tetanic muscular contraction. Subjects will attend to research facility four times. On the first visit clinical, physical examination and autonomic evaluation (Ewing test) will be performed and a blood sample will be collected. On the second visit CGMS will be placed for glycemic variability evaluation. On the third visit NMES or NMES-placebo will be performed in a randomized way. On the fourth visit the CGMS will be removed. Blood pressure and heart rate will be evaluated during the protocol each 5 minutes and oxygenation tissue will be evaluated before, during and immediately after the protocol, through NIRS.

Official Title
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Effects of Neuromuscular Electrical Stimulation on Glucose Levels and Glucose Variability in Patients With Type 2 Diabetes: a Randomized Clinical Trial

Conditions
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Type2 Diabetes Mellitus

Intervention / Treatment
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* Device: NMES
* Device: NMES-placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes; HbA1c from 7,5 to 10%; Fasting plasma glucose lower to 250 mg/dL Drug therapy maintained for at least one month before inclusion in the study. Exclusion Criteria: Insulin use; Pregnancy; Documented arrhythmia; Unstable angina; Chronic renal failure (GFR lower than 15 ml/min); Varicose vein problems; Clinical musculoskeletal disease.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NMES group<br>NMES will be placed at the knee extensors, with maximal intensity tolerance evaluated by to induce visible contractions. | Device: NMES<br>* NMES will be placed at the knee extensors. Stimulation frequency will be 20 Hz. Pulse width will be 0.5 milliseconds and the contraction time will be 10 seconds (TON: 10s) with a 5-second rest interval (TOFF: 5s). Total time application will be 60 minutes. Intensity will be adjusted individually, taking into account the patient's ability to promote the full knee extension and comfort during contractions.<br>|
| Placebo Comparator: NMES-placebo group<br>NMES-placebo will be placed at the knee extensors, with minimal intensity to provide a sensory stimulus, but insufficient to elicit a tetanic muscular contraction. | Device: NMES-placebo<br>* NMES-placebo will be placed at the knee extensors. Stimulation frequency will be 20 Hz. Pulse width will be 0.5 milliseconds and the contraction time will be 10 seconds (TON: 10s) with a 5-second rest interval (TOFF: 5s). Total time of application will be 60 minutes. Intensity will be adjusted with minimal intensity, utilized to provide a sensory stimulus, but insufficient to elicit a tetanic muscular contraction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose levels | Glucose levels will be assessed through continuous glucose monitoring (CGMS) | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose variability | Glucose variability will be assessed by CGMS 24 hours before, during the protocol and 24 hours after protocol. | 48 hours | 
| Blood pressure | Will be evaluated through non-invasive oscillometric device. | Each 5 minutes during intervention which will last 60 minutes. | 
| Heart Rate | Will be evaluated through non-invasive oscillometric device. | Each 5 minutes during intervention which will last 60 minutes. | 
| Oxygenation tissue | Will be evaluated through near infrared spectroscopy (NIRS). | Before, during and immediately after the intervention which will last 60 minutes. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases