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Type 2 diabetes mellitus (T2DM) is a complex, chronic metabolic disease that carries with it a high prevalence of comorbid conditions, making T2DM one of the leading causes of death in the U.S. Traditional lifestyle interventions (e.g., diet, exercise) can counter some adverse effects of T2DM, however, participation in these activities is low with reasons ranging from physical discomfort to lack of time. Thus, there is a critical need to develop novel management strategies that effectively reduce cardiometabolic disease risk and address barriers to adherence. High-resistance inspiratory muscle strength training (IMST) is a time-efficient and simple breathing exercise that significantly reduces systolic and diastolic BP and improves vascular endothelial function in adults with abovenormal blood pressure. Herein we describe the study protocol for a randomized clinical trial to determine the effects of a 6-week IMST regimen on glycemic control and insulin sensitivity in adults with T2DM. Our primary outcome measures include fasting plasma glucose, fasting serum insulin, and insulin resistance utilizing homeostatic model assessment for insulin resistance (HOMA-IR). Secondary outcome measures include resting systolic BP and endothelium-dependent dilation. Further, we will collect plasma for exploratory proteomic analyses. This trial seeks to establish the cardiometabolic effects of 6 weeks of high-resistance IMST in patients with T2DM. [ABSTRACT FROM AUTHOR]

Above-normal blood pressure (BP) is a primary risk factor for cardiovascular diseases. In a retrospective analysis of five pilot trials, we assessed the BP-lowering effects of high-resistance inspiratory muscle strength training (IMST) in adults aged 18–82 years and the impact of IMST on maximal inspiratory pressure (PIMAX), a gauge of inspiratory muscle strength and independent disease risk factor. Participants were randomized to high-resistance IMST (75% PIMAX) or low-resistance sham (15% PIMAX) training (30 breaths/day, 5–7 days/wk, 6 wk). IMST (n = 67) reduced systolic BP (SBP) by 9 ± 6 mmHg (P < 0.01) and diastolic BP (DBP) by 4 ± 4 mmHg (P < 0.01). IMST-related reductions in SBP and DBP emerged by week 2 of training (−4 ± 8 mmHg and −3 ± 6 mmHg; P ≤ 0.01, respectively) and continued across the 6-wk intervention. SBP and DBP were unchanged with sham training (n = 61, all P > 0.05). Select subject characteristics slightly modified the impact of IMST on BP. Greater reductions in SBP were associated with older age (β = −0.07 ± 0.03; P = 0.04) and greater reductions in DBP associated with medication-naïve BP (β = −3 ± 1; P = 0.02) and higher initial DBP (β = −0.12 ± 0.05; P = 0.04). PIMAX increased with high-resistance IMST and low-resistance sham training, with a greater increase from high-resistance IMST (+20 ± 17 vs. +6 ± 14 cmH2O; P < 0.01). Gains in PIMAX had a modest inverse relation with age (β = −0.20 ± 0.09; P = 0.03) and baseline PIMAX (β = −0.15 ± 0.07; P = 0.04) but not to reductions in SBP or DBP. These compiled findings from multiple independent trials provide the strongest evidence to date that high-resistance IMST evokes clinically significant reductions in SBP and DBP, and increases in PIMAX, in adult men and women. NEW & NOTEWORTHY In young-to-older adult men and women, 6 wk of high-resistance inspiratory muscle strength training lowers casual systolic and diastolic blood pressure by 9 mmHg and 4 mmHg, respectively, with initial reductions observed by week 2 of training. Given blood pressure outcomes with the intervention were only slightly altered by subject baseline characteristics (i.e., age, blood pressure medication, and health status), inspiratory muscle strength training is effective in lowering blood pressure in a broad range of adults. [ABSTRACT FROM AUTHOR]

In awake humans, breathing depends on automatic brainstem pattern generators. It is also heavily influenced by cortical networks. For example, functional magnetic resonance imaging and electroencephalographic data show that the supplementary motor area becomes active when breathing is made difficult by inspiratory mechanical loads like resistances or threshold valves, which is associated with perceived respiratory discomfort. We hypothesized that manipulating the excitability of the supplementary motor area with repetitive transcranial magnetic stimulation would modify the breathing pattern response to an experimental inspiratory load and possibly respiratory discomfort. Seven subjects (three men, age 25 ± 4) were studied. Breathing pattern and respiratory discomfort during inspiratory loading were described before and after conditioning the supplementary motor area with repetitive stimulation, using an excitatory paradigm (5 Hz stimulation), an inhibitory paradigm, or sham stimulation. No significant change in breathing pattern during loading was observed after sham conditioning. Excitatory conditioning shortened inspiratory time (p = 0.001), decreased tidal volume (p = 0.016), and decreased ventilation (p = 0.003), as corroborated by an increased end-tidal expired carbon dioxide (p = 0.013). Inhibitory conditioning did not affect ventilation, but lengthened expiratory time (p = 0.031). Respiratory discomfort was mild under baseline conditions, and unchanged after conditioning of the supplementary motor area. This is the first study to show that repetitive transcranial magnetic stimulation conditioning of the cerebral cortex can alter breathing pattern. A 5 Hz conditioning protocol, known to enhance corticophrenic excitability, can reduce the amount of hyperventilation induced by inspiratory threshold loading. Further studies are needed to determine whether and under what circumstances rTMS can have an effect on dyspnoea. [ABSTRACT FROM AUTHOR]