It’s not enough to tell patients to exercise. The exercise regimen needs to be “SMART.”
John P. Kirwan, PhD
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic; Department of Physiology and Biophysics, Case Western Reserve University; Metabolic Translational Research Center, Endocrinology & Metabolism Institute, Cleveland Clinic, Cleveland, OH
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic; Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH
Correspondence: John P. Kirwan, PhD, Department of Pathobiology, Lerner Research Institute, NE40, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; email@example.com
Dr. Kirwan reported research grant support from NIH R01DK108089, NIH R01HD088061, NIH U34DK107917, NIH R21AR067477, and Metagenics Inc. Jessica Sacks and Stephan Nieuwoudt reported no financial interests or relationships that pose a potential conflict of interest with this article.
Exercise is typically one of the first management strategies advised for patients newly diagnosed with type 2 diabetes. Together with diet and behavior modification, exercise is an essential component of all diabetes and obesity prevention and lifestyle intervention programs. Exercise training, whether aerobic or resistance training or a combination, facilitates improved glucose regulation. High-intensity interval training is also effective and has the added benefit of being very time-efficient. While the efficacy, scalability, and affordability of exercise for the prevention and management of type 2 diabetes are well established, sustainability of exercise recommendations for patients remains elusive.
Type 2 diabetes has emerged as a major public health and economic burden of the 21st century. Recent statistics from the Centers for Disease Control and Prevention suggest that diabetes affects 29.1 million people in the United States,1 and the International Diabetes Federation estimates diabetes effects 366 million people worldwide.2
As these shocking numbers continue to increase, the cost of caring for patients with diabetes is placing enormous strain on the economies of the US and other countries. In order to manage and treat a disease on the scale of diabetes, the approaches need to be efficacious, sustainable, scalable, and affordable.
Of all the treatment options available, including multiple new medications and bariatric surgery (for patients who meet the criteria, discussed elsewhere in this supplement),3–5 exercise as part of a lifestyle approach6 is a strategy that meets the majority of these criteria.
The health benefits of exercise have a long and storied history. Hippocrates, the father of scientific medicine, was the first physician on record to recognize the value of exercise for a patient with “consumption.”7 Today, exercise is recommended as one of the first management strategies for patients newly diagnosed with type 2 diabetes and, together with diet and behavior modification, is a central component of all type 2 diabetes and obesity prevention programs.
The evidence base for the efficacy, scalability, and affordability of exercise includes multiple large randomized controlled trials; and these data were used to create the recently updated exercise guidelines for the prevention and treatment of type 2 diabetes, published by the American Diabetes Association (ADA), American College of Sports Medicine (ACSM), and other national organizations.8–10
Herein, we highlight the literature surrounding the metabolic effects and clinical outcomes in patients with type 2 diabetes following exercise intervention, and point to future directions for translational research in the field of exercise and diabetes.
It is known that adults who maintain a physically active lifestyle can reduce their risk of developing impaired glucose tolerance, insulin resistance, and type 2 diabetes.8 It has also been established that low cardiovascular fitness is a strong and independent predictor of all-cause mortality in patients with type 2 diabetes.11,12 Indeed, patients with diabetes are 2 to 4 times more likely than healthy individuals to suffer from cardiovascular disease, due to the metabolic complexity and underlying comorbidities of type 2 diabetes including obesity, insulin resistance, dyslipidemia, hyperglycemia, and hypertension.13,14
Additionally, elevated hemoglobin A1c (HbA1c) levels are predictive of vascular complications in patients with diabetes, and regular exercise has been shown to reduce HbA1c levels, both alone and in conjunction with dietary intervention. In a meta-analysis of 9 randomized trials comprising 266 adults with type 2 diabetes, patients randomized to 20 weeks of regular exercise at 50% to 75% of their maximal aerobic capacity (VO2max) demonstrated marked improvements in HbA1c and cardiorespiratory fitness.11 Importantly, larger reductions in HbA1c were observed with more intense exercise, reflecting greater improvements in blood glucose control with increasing exercise intensity.
In addition to greater energy expenditure, which aids in reversing obesity-associated type 2 diabetes, exercise also boosts insulin action through short-term effects, mainly via insulin-independent glucose transport. For example, our laboratory and others have shown that as little as 7 days of vigorous aerobic exercise training in adults with type 2 diabetes results in improved glycemic control, without any effect on body weight.15,16 Specifically, we observed decreased fasting plasma insulin, a 45% increase in insulin-stimulated glucose disposal, and suppressed hepatic glucose production (HGP) during carefully controlled euglycemic hyperinsulinemic clamps.15
Although the metabolic benefits of exercise are striking, the effects are short-lived and begin to fade within 48 to 96 hours.17 Therefore, an ongoing exercise program is required to maintain the favorable metabolic milieu that can be derived through exercise.
Notably, aerobic exercise is a well-established way to improve HbA1c, and strong evidence exists with regard to the effects of aerobic activity on weight loss and the enhanced regulation of lipid and lipoprotein metabolism.8 For example, in a 2007 report, 6 months of aerobic exercise training in 60 adults with type 2 diabetes led to reductions in HbA1c (−0.63% ± 0.41 vs 0.31% ± 0.10, P < .001), fasting plasma glucose (−18.6 mg/dL ± 4.4 vs 4.28 mg/dL ± 2.57, P < .001), insulin resistance (−1.52 ± 0.6 vs 0.56 ± 0.44, P = .023; as measured by homeostatic model assessment), fasting insulin (−2.91 mU/L ± 0.4 vs 0.94 mU/L ± 0.21, P = .031), and systolic blood pressure (−6.9 mm Hg ± 5.19 vs 1.22 mm Hg ± 1.09, P = .010) compared with the control group.14
Furthermore, meta-analyses reviewing the benefits of aerobic activity for patients with type 2 diabetes have repeatedly confirmed that compared with patients in sedentary control groups, aerobic exercise improves glycemic control, insulin sensitivity, oxidative capacity, and important related metabolic parameters.11 Taken together, there is ample evidence that aerobic exercise is a tried-and-true exercise modality for managing and preventing type 2 diabetes.
During the last 2 decades, resistance training has gained considerable recognition as a viable exercise training option for patients with type 2 diabetes. Synonymous with strength training, resistance exercise involves movements utilizing free weights, weight machines, body weight exercises, or elastic resistance bands.
Primary outcomes in studies evaluating the effects of resistance training in type 2 diabetes have found improvements that range from 10% to 15% in strength, bone mineral density, blood pressure, lipid profiles, cardiovascular health, insulin sensitivity, and muscle mass.18,20 Furthermore, because of the increased prevalence of type 2 diabetes with aging, coupled with age-related decline in muscle mass, known as sarcopenia,21 resistance training can provide additional health benefits in older adults.
Dunstan et al21 reported a threefold greater reduction in HbA1c in patients with type 2 diabetes ages 60 to 80 compared with nonexercising patients in a control group. They also noted an increase in lean body mass in the resistance-training group, while those in the nonexercising control group lost lean mass after 6 months. In a shorter, 8-week circuit weight training study performed by the same research group, patients with type 2 diabetes had improved glucose and insulin responses during an oral glucose tolerance test.22
These findings support the use of resistance training as part of a diabetes management plan. In addition, key opinion leaders advocate that the resistance-training-induced increase in skeletal muscle mass and the associated reductions in HbA1c may indicate that skeletal muscle is a “sink” for glucose; thus, the improved glycemic control in response to resistance training may be at least in part the result of enhanced muscle glycogen storage.21,23
Based on increasing evidence supporting the role of resistance training in glycemic control, the ADA and ACSM recently updated their exercise guidelines for treatment and prevention of type 2 diabetes to include resistance training.9
It’s not enough to tell patients to exercise. The exercise regimen needs to be “SMART.”