Resistance Exercise in Already-Active Diabetic Individuals (READI): Study rationale, design and methods for a randomized controlled trial of resistance and aerobic exercise in type 1 diabetes
Introduction
Type 1 diabetes mellitus (T1DM) is characterized by the absence or near-absence of insulin secretion. Long-term complication risk is comparable to similarly-aged individuals with type 2 diabetes mellitus (T2DM) [1], [2], even though those with T1DM usually have fewer additional cardiovascular risk factors. Hemoglobin A1c (HbA1c) reflects average glucose concentrations over the previous 2–3 months. A 1% higher HbA1c is associated with a 37% higher risk of developing advanced diabetes microvascular complications [3]. While aerobic exercise clearly improves glycemic (blood glucose) control in T2DM [4], [5], aerobic exercise interventions in T1DM have generally not found significant effects on HbA1c [6], [7], despite reduced insulin requirements [8], [9], [10], and improved insulin sensitivity [11], [12]. In a cross-sectional study of 1030 people with T1DM, physical activity explained none of the HbA1c variance in men, and less than 2% in women [13]. This may be because those with T1DM are at higher risk of hypoglycemia and tend to overcompensate with carbohydrate intake (and reduced insulin administration) to avoid exercise-induced drops in glucose, negating potential benefits on HbA1c. It may also be that aerobic training has little impact on HbA1c in T1DM, and HbA1c is impacted primarily by other factors (diet, insulin regimen and other behavioral/physiological processes).
Resistance exercise produces slower glucose declines than aerobic exercise [14], and might offer other exercise-related metabolic benefits with less hypoglycemia risk. Acutely, there is less glucose instability after a bout of resistance exercise versus aerobic exercise [14]. Small studies suggested resistance training reduced HbA1c in T1DM. Durak et al. [15] studied eight males using a crossover design, and found that HbA1c averaged 6.9% following rest and 5.8% following resistance training (3–4 sets of 14 exercises three days/week). Mosher et al. [16] found that a 12-week combined aerobic and resistance exercise program decreased HbA1c (7.72% to 6.76%, n = 10). Similarly, Ramalho et al. [17] found a non-statistically significant decline in HbA1c (8.2 ± 2.9% to 7.6 ± 1.6%) after a 12-week resistance exercise program (three times/week, n = 13).
Earlier studies could not capitalize on recent advances in T1DM care. Rapid-acting insulin analogues have decreased the risk of hypoglycemia and consequently the need for excessive exercise-related carbohydrate consumption. Small, light-weight, rapid-acting glucose meters have made capillary glucose testing more convenient. Few published exercise intervention studies incorporated background diabetes care that would meet current guidelines [18], and none possessed the methodological rigor currently expected in clinical trials [19].
New research examining the effects of resistance exercise on glycemic control in the context of modern diabetes care is necessary. Most previous exercise trials enrolled only previously inactive subjects [6], [7]. However, people who already perform aerobic exercise regularly may be more likely than sedentary individuals to begin, and maintain, resistance exercise. We therefore undertook the Resistance Exercise in Already-active Diabetic Individuals (READI) clinical trial to evaluate the impact of resistance exercise on metabolic control in people with T1DM who were already aerobically active. Herein we describe the READI trial methods; trial results will be submitted for publication separately.
Section snippets
Design
READI was a four-center randomized parallel-group controlled trial in individuals with T1DM already performing aerobic activity regularly. Prior to randomization, participants entered a five-week stabilization/run-in period, including assessment and optimization of participant diet and insulin therapy and, starting in the second week, low-volume moderate-intensity resistance exercise. Those previously on only two insulin injections per day were encouraged to switch to a basal–bolus regimen
Measurements
All measurements and the timing of their collection are listed in Table 2. All participants (exercise and control) met with the diabetes nurse-educator and the dietitian at baseline, one month (immediately pre-randomization), three months and six months. Participants were questioned about the following at each visit: episodes of hypoglycemia, smoking, blood glucose monitoring, medication changes and major medical events.
Sample size calculation
In the controlled trial of resistance exercise in individuals with type 1 diabetes by Durak [15], the absolute HbA1c difference between resistance exercise and control was 1.1% with SD 0.9%. We polled 10 academic endocrinologists and 10 diabetes educators, and they unanimously felt that a HbA1c difference as low as 0.5% would be clinically significant, given the strong relationship between HbA1c and the risks of both microvascular [37] and macrovascular disease [38], [39]. This difference would
Discussion
READI is the first randomized clinical trial to examine the incremental effects of resistance exercise in individuals with type 1 diabetes who already habitually perform aerobic exercise. Most previous trials have either not considered participant activity levels at study entry, or have only involved previously sedentary participants. It is also one of very few exercise studies where background diabetes care meets modern clinical standards. READI trial participation required a significant time
Acknowledgements
The READI trial was supported by the Canadian Institutes of Health Research (CIHR) grant MCT-154710. Dr. Sigal is supported by a Health Senior Scholar award from Alberta Innovates-Health Solutions (grant 200800688), and was supported by a Research Chair from the Ottawa Hospital Research Institute (OHRI) during part of this trial. Dr. Yardley was supported by a Doctoral Student Research Award (grant DS-3-05-1769_JY) from the Canadian Diabetes Association, and funds from CIHR grants MCT-15470 and
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