Inspiratory Muscle Strength Training in Adults With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
This clinical research study will investigate the effects of 6 weeks of inspiratory muscle strength training on metabolic and cardiovascular outcomes in adults with recent-onset type 2 diabetes.

Detailed Description
-----------------
Type 2 diabetes mellitus (T2DM) is at epidemic proportions in the United States and worldwide. It is a chronic obesity-associated metabolic disorder characterized by glucose dysregulation combined with insulin resistance and beta-cell defects. First-line T2DM treatments include lifestyle remedies, such as dietary modifications and exercise. Exercise, whether aerobic and/or resistance training, increases whole-body insulin sensitivity and stimulates muscle glucose uptake independent of insulin. The acute effects of exercise on muscle in patients with abnormal glucose regulation produce immediate improvements in blood glucose levels. In addition, when exercise is repeated over time, adaptations occur that include more long-lasting increases in insulin sensitivity. The effects of traditional exercise on glycemic control and insulin sensitivity in patients with T2DM are well established. However, adherence to traditional exercise programs is low, in part, due to lack of time and physical discomfort, and new regimens for T2DM treatment are needed. Recently, a novel time-efficient respiratory exercise called Inspiratory Muscle Strength Training (IMST) was developed. IMST is distinct from other traditional forms of exercise as it is only 5 minutes per session and performed on a hand-held device during stationary sitting or standing. Typically, IMST comprises 5 sets of 6 inspiratory maneuvers with 1-minute rests between sets. Previous studies demonstrate that 6 weeks of IMST improve systolic blood pressure (SBP), sympathetic nervous system activity, and endothelial function in healthy individuals, middle-aged and older people, and adults with obstructive sleep apnea. These BP-lowering effects of IMST are significant for reducing the risks of cardiovascular disease (CVD), the number one cause of death in people living with diabetes. IMST is safe and tolerable, with adherence rates >90% in diverse populations, and presents a manageable program for improving metabolic health in T2DM patients who have difficulty maintaining a traditional exercise program requiring a large amount of time and physical exertion. It is unknown if IMST, a highly-abbreviated respiratory exercise that is not physically demanding, has beneficial effects on glycemic control and insulin sensitivity, in combination with its improvements on BP measures, in patients with T2DM. The potential for IMST to exert metabolic benefits in diabetic patients warrants assessment

Official Title
-----------------
Effects of Inspiratory Muscle Strength Training on Metabolic and Cardiovascular Health in Adults With Type 2 Diabetes

Conditions
-----------------
Diabetes Mellitus, Type 2, Hypertension

Intervention / Treatment
-----------------
* Behavioral: Inspiratory muscle strength training (IMST)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: diagnosed with type 2 diabetes by physician fasting plasma glucose levels ≥126 mg/dl and ≤240 mg/dl systolic blood pressure between 120-169 mmHg stable dose of medication (three months on the same dose) weight stable in the prior 3 months (<3.0 kg weight change) and willing to remain weight stable throughout the study absence of unstable clinical disease as determined by medical history Exclusion Criteria: current smoker (including tobacco products, vaping devices, THC, etc…) have an uncontrolled medical condition (e.g., cancer) myocardial infarction or stroke within the previous 12 months performs regular aerobic exercise (>4 bouts/week) BMI ≥ 40 kg/m2 systolic blood pressure <120 or ≥170 mmHg diastolic blood pressure >100 or <60 mmHg Cheyne-Stokes respiration history of perforated eardrum history of glaucoma or retinopathy history of collapsed lung diagnosed with asthma pregnant, breastfeeding, or trying to become pregnant (self-reported) medications that, in the opinion of the study physician or nurse practitioner, may impact the outcomes of the study (e.g., steroids)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly allocated using a 1:1 ratio to A) High-Intensity Training Group (75 % maximal inspiratory pressure) or B)Low-Intensity Training Group (15% maximal inspiratory pressure)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-resistance IMST<br>30 breaths/day (5 sets of 6 breaths, one minute of rest between sets), 5 days/week, 6 weeks | Behavioral: Inspiratory muscle strength training (IMST)<br>* 30 breaths/day, 5 days/week, 6 weeks<br>* Other names: inspiratory muscle training;|
| Active Comparator: Low-resistance IMST<br>30 breaths/day (5 sets of 6 breaths, one minute of rest between sets), 5 days/week, 6 weeks | Behavioral: Inspiratory muscle strength training (IMST)<br>* 30 breaths/day, 5 days/week, 6 weeks<br>* Other names: inspiratory muscle training;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline fasting blood plasma glucose after 6 weeks of IMST | A blood sample will be collected after 12 hours of fasting. Blood and plasma will be separated and plasma glucose levels will be quantified. | Blood plasma collected and analyzed at baseline and after 6 weeks of training | 
| Change from baseline fasting blood plasma Insulin after 6 weeks of IMST | A blood sample will be collected after 12 hours of fasting. Blood and plasma will be separated and plasma insulin levels will be quantified. | Blood plasma collected and analyzed at baseline and after 6 weeks of training | 
| Change from baseline insulin sensitivity after 6 weeks of IMST | A blood sample will be collected after 12 hours of fasting. Insulin sensitivity will be calculated using the homeostatic model assessment of insulin resistance (HOMA-IR): (fasting serum insulin (mU/L) × fasting plasma glucose (mmol/L) × 22.5). | Blood plasma collected and analyzed at baseline and after 6 weeks of training | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline systolic blood pressure after 6 weeks of IMST | Change in systolic blood pressure (SBP) will be measured by both relative and absolute changes from baseline. SBP will be assessed in accordance with American College of Cardiology/American Heart Association guidelines. Measurements will be taken using an automated oscillometric sphygmomanometer and will be performed in triplicate over the brachial artery of the left arm after 5 minutes of quiet rest, with 1 minute of recovery between measures. SBP will be defined as the average of the 3 pressures. | Blood pressure will be assessed at baseline and after 6 weeks of training | 
| Change from baseline Nitric Oxide-mediated Endothelial Dependent Dilation (EDD) | Brachial artery Flow Mediated Dilation (BA-FMD), a well-established measure of NO-mediated endothelial function, will be measured by both relative and absolute changes from baseline. BA-FMD will be determined using high-resolution ultrasonography and analyzed with a commercially available software package. An ultrasound probe will be placed 3-6 cm proximal to the antecubital crease on the right arm and a baseline image of the right brachial artery will be obtained. Following baseline, reactive hyperemia will be produced by inflating a rapid-inflating blood pressure cuff. Brachial artery diameter change will be measured for 2 minutes following 5-min of forearm blood flow occlusion. | EDD will be assessed at baseline and after 6 weeks of training | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
insulin sensitivity, blood pressure, blood glucose, non-pharmacological, inspiratory resistance training