A HIIT to Improve Metabolic Health in Obese Adults With Insulin Resistance

Significance The obesity epidemic is a worldwide public health problem. Recent data indicate that over 650 million adults around the world (~13%) are considered obese. Obesity is one of the major risk factors for type 2 diabetes mellitus (T2D) and 90% of T2D cases are attributable to excess fat mass. The connection between obesity and T2D is believed to be intrinsically related to insulin resistance (IR). IR is characterized by a blunted effect of insulin on decreasing circulating blood glucose at the whole-body level and/or a lower response of certain tissues to the action of insulin. For example, skeletal muscle is responsible for ~70% of insulin-stimulated postprandial glucose uptake and plays a key role in the maintenance of whole-body insulin sensitivity and glycemic homeostasis. Additionally, IR is one of the earliest detectable defects preceding hyperglycemia, present up to 10 years before diabetes is diagnosed.

Although the cause of obesity-induced IR is complex and multifactorial, the beneficial effects of exercise training in preventing and treating IR are well established. In individuals with IR, an improvement in insulin action on skeletal muscle glucose metabolism is one of the main effects induced by exercise training. For example, previous research demonstrated that a single session of exercise reduced cellular stress, which may contribute to exercise-induced increases in insulin sensitivity. Despite the efficacy of exercise training on IR, the majority of individuals do not achieve the minimum recommended levels of physical activity: 30 minutes or more of moderate intensity physical activity at least 5 days a week, or 20 minutes of vigorous physical activity at least 3 days a week, or a combination thereof, in addition to activities of daily living. Of note, lack of time and difficulty in accessing facilities for exercise are commonly cited as barriers to physical activity.

In this context, the high-intensity interval training (HIIT), which consists of short periods of intense exercise (≥ 80% of maximal heart rate) alternated with periods of active recovery or rest, is a relatively time-efficient training strategy to improve metabolic health and has been considered more enjoyable than moderate-to-vigorous intensity continuous training. HIIT increases skeletal muscle oxidative capacity and induces physiological remodeling like the changes promoted by continuous moderate-intensity aerobic training. HIIT appears effective in improving insulin sensitivity, particularly in those at risk of, or with, T2D. A previous study using 10 x of 60-seconds of cycling intervals (∼90% of maximal heart rate) interspersed with 60-seconds of active recovery, three times per week over a period of two weeks, reduced hyperglycemia and increased skeletal muscle oxidative capacity in patients with T2D. Recently published data has shown that an 8-week HIIT program resulted in lower IR in individuals with obesity and also promoted greater expression of proteins related to oxidative metabolism in skeletal muscle. Although HIIT may be an efficient option to improve insulin sensitivity and glycemic control in individuals at risk of T2D, most HIIT studies have been conducted primarily in traditional laboratory setting and may not be practical for the general population.

Innovation The common approach to study the effects of exercise are either using treadmills or cycle ergometers. These approaches have limited translation to a "real word" scenario. Among the barriers generally reported for a regular physical activity program are lack of time, difficulty in accessing facilities for exercise, and low motivation. The goal of the proposed study is to investigate the effects of a HIIT program using a suitable exercise alternative (stair climbing) on IR in individuals with obesity and at risk of T2D. Stair climbing can be considered an activity of daily living and is easily accessible. Previous studies have shown that one short bout of stair climbing (<6 min) acutely increased postprandial glucose uptake in middle-aged men with impaired glucose tolerance and older T2D subjects. Another study showed 6 weeks of a brief high intense intermittent stair climbing program was effective improving cardiorespiratory fitness in healthy individuals but did not improve IR. More recently, a preliminary study examined the effect of 6 weeks of brief intermittent stair climbing exercise on glycemic control in people with T2D. The authors reported that the protocol (3 x 1-minute bouts of repeatedly ascending and descending a single flight of stairs) was insufficient to induce improvements in glucose control. In this context, the volume was too low (approximately 50 stairs) and there was no progression of training volume over time. Additionally, the authors counted for the time descending the stairs as part of the 1-minute bout which may have reduced even more the time spent ascending the stairs. To address these limitations, the proposed study will implement a more prolonged protocol with progressive increase in exercise volume and will only count the time spent ascending the stairs. To the best of the author's knowledge, no study has tested this approach using HIIT in individuals with obesity and a risk of T2D. Findings from this study will help to translate research-based evidence to clinical practice and contribute to prevent or treat individuals at risk of T2D with a nonpharmacological and low-cost approach. This topic is within the "Cell and Organism" New Mexico - Idea Network of Biomedical Research Excellence (NM-INBRE) focus area to advance the understanding of human health.

Approach The study is an 8-wk within-subject intervention design where participants will be tested pre and post intervention. 20 participants (10 males and 10 females) will be recruited from the local community through poster advertisement and one-to-one interaction. Before agreeing to participate in the study, the participants will given written informed consent, which will be approved by the institutional review board of the local institution. Inclusion criteria include body mass index (BMI) ≥ 30 kg/m2; homeostasis model assessment for insulin resistance (HOMA-IR) ≥ 2.71; no fear of being totally submerged underwater; freedom from orthopedic injuries, diagnoses of T2D or glucose intolerance, known acute or chronic diseases, and current use of anti-inflammatory, hypoglycemic or other drugs known to affect metabolism. Subjects that meet the initial requirements will have a fasting blood draw. Individuals with altered glucose metabolism (fasting plasma glucose >126 mg/dL) will be excluded. The researchers will ensure the inclusion of males and females from differing ethnic background. The required sample size was calculated a priori based on changes in the HOMA-IR using an alpha level of 0.05 and power of 80%. Prior to exercise training, participants undergo: a fasting blood draw for blood glucose and insulin measurements, anthropometrics and body composition analysis, and a maximal graded exercise test.