One of my colleagues at the Colorado Mesa University Monfort Family Human Performance lab is Carmine Grieco, PhD, an exercise physiologist. It has been interesting to hear Carmine’s perspective on Exercise is Medicine, as he has been involved at the research level and is very interested in the effects of exercise on Type 2 Diabetes. Carmine and I wrote a four-part series for Personal Training Quarterly (PTQ) discussing the impact of exercise on chronic disease. For that series, we started with the impact of exercise on Type 2 Diabetes and the article is below. Clearly, exercise should play a critical role in the overall treatment plan for patients. (Please note: Patients with diabetes should first discuss a change in exercise levels or habits with their medical provider)
Grieco CR and Reeder MT. (2016) Effects of Exercise on Type 2 Diabetes - Part 1. Personal Training Quarterly, 4(1).
Effects of Exercise on Type 2 Diabetes – Part 1
Carmine Grieco, PhD, CSCS, and Mike Reeder, DO
This article is the first in a four-part series which will explore the impact of exercise on a variety of diseases. Strength and conditioning professionals should have a deep understanding of the positive effect exercise has on health and human performance. Despite the efficacy of exercise as both a preventive measure and treatment for a wide range of diseases and conditions, standard medical interventions, such as pharmaceuticals, remain the “go to” option for most individuals. In fact, recent estimates by the National Center for Health Statistics suggest that nearly 50% of the United States population have used a prescription drug within the last 30 days (18). Therefore, the aim of this article series is to provide a context for understanding the efficacy of exercise as a therapeutic intervention and adjunct therapy, and then compare this to commonly prescribed treatments.
Chronic diseases related to lifestyle (e.g., physical inactivity and poor diet) choices, such as heart disease, hypertension, and type 2 diabetes (T2D), are seemingly becoming the norm. Recent data suggest that half of all adults in the United States have at least one chronic health condition (28). One of the most prevalent chronic diseases is T2D. T2D is a metabolic disease characterized by an inability to properly regulate blood sugar levels and can result in hyperglycemia, an abnormally high level of circulating sugar (i.e., blood glucose). In addition it is closely associated with obesity.
The prevalence of diabetes, particularly T2D, has risen dramatically over the last few decades and parallels the rise in obesity in the United States. In fact, the prevalence rate of diabetes in the United States doubled between 1990 and 2008 (14). Moreover, according to the Centers for Disease Control and Prevention (CDC), 12.3% of adults in the United States have diabetes, with T2D accounting for 90 – 95% of all cases (8). Perhaps even more disturbing, the CDC estimates that an additional 37% of the adult population has prediabetes, a condition characterized by moderate hyperglycemia that falls below the diagnosable threshold of T2D (8).
Diabetes is a significant cause of morbidity and consistently ranks among the leading causes of death in the United States. According to the American Diabetes Association (ADA), adults with diabetes are 1.8 times more likely to have a heart attack and 1.5 times more likely to have a stroke than individuals who are not diagnosed with diabetes (3). Moreover, diabetes is the leading cause of kidney failure, non-traumatic lower-limb amputations, and new cases of blindness in adults (7).
The economic burden of treating diabetes is staggering. At an estimated annual cost of $322 billion, diabetes treatment alone accounts for one out of every five dollars spent on healthcare in the United States (4). If present healthcare trends continue, future healthcare initiatives will need to be reimagined. Therefore, exercise must play a central role in this “new” version of healthcare. Prevention of diabetes and obesity is essential, and increasing physical activity should be at the core of those goals. Currently, only about 20% of adults in the United States meet the minimum recommended aerobic and muscle-strengthening guidelines established by the CDC (19). Nevertheless, exercise is well represented in the scientific literature as both preventive of and a treatment for a wide range of chronic lifestyle-related diseases.
Unfortunately, the importance of physical activity in prevention and treatment of disease is not an essential part of the education of medical providers. More than 50% of medical schools in 2013 lacked formal education on the importance of physical activity as an essential part of healthcare (6). The vast majority of this education is focused on sports medicine or exercise physiology with less attention to behavioral counseling, lifestyle medicine, or preventive medicine.
Treatment of T2D
The fundamental issue associated with T2D is an inability to adequately control blood sugar levels, which results in chronic hyperglycemia. Standard treatment of T2D involves both lifestyle and pharmaceutical interventions targeted at controlling blood glucose levels. However, the majority of individuals with T2D do not meet the physical activity or dietary recommendations, therefore, achieving glycemic control routinely relies on pharmaceutical interventions (20).
Three common methods are used for diagnosing T2D: 1) measuring fasting blood glucose, 2) performing an oral glucose tolerance test, and 3) measuring glycated hemoglobin (HbA1c). HbA1c, which is commonly referred to simply as A1C, represents a long-term measurement of glycemic control. Circulating glucose molecules will frequently bind to the amino acid component of hemoglobin molecules, the oxygen carrying element of red blood cells. When this occurs, it is said that the hemoglobin has become “glycated.” This glycation, which is represented as A1C, occurs in a dose-dependent fashion (i.e., the higher the amount of circulating blood sugar the more likely glycation will occur), with lower scores being indicative of good blood sugar control and higher scores indicating poorer control (1). As a result, A1C provide an estimate of blood sugar control over approximately the previous three months. A1C scores are expressed as a percentage of hemoglobin that has become glycated. A score below 5.7% is considered “normal”, a score of ≥ 5.7% – 6.4% indicates prediabetes, and a score of ≥ 6.5% is the criteria used to diagnose diabetes (1).
The ADA’s Standards of Medical Care identifies the oral hypoglycemic agent metformin as the preferred initial drug therapy (2). Since it is outside the scope of this article to provide a detailed discussion of the effectiveness of each of the oral hypoglycemic drugs, metformin will be used as a representative example of the effectiveness of pharmaceutical intervention for the treatment of hyperglycemia.
Metformin lowers blood glucose levels primarily by down-regulating hepatic (liver) glucose production. Metformin is generally well tolerated and regarded as a safe drug therapy; however, there is still the potential for adverse side effects (2). Several previous meta-analyses have investigated the effectiveness of oral hypoglycemic agents and shown reductions in A1C that commonly range from 0.5% – 1.25%, with metformin performing better than most (23). For example, a more recent meta-analysis found that metformin decreased A1C by 1.12% in individuals with T2D in comparison to a placebo (15).
Achieving optimal glycemic control is the primary goal for the prevention and treatment of T2D, and decreasing A1C levels has demonstrated significant and broad-reaching benefits. In fact, one large-scale study found that a 1% reduction in A1C translated into a 37% reduction in microvascular complications (e.g., neuropathy and retinopathy), as well as a 21% reduction in diabetes-related mortality (25). Moreover, the earlier glycemic control is achieved, the greater the health benefits are over time—a concept which is referred to as the “legacy effect.” To summarize, the effect of drug therapy for hyperglycemia provides a benchmark for comparing the efficacy of exercise.
Effect of Exercise on T2D
T2D is characterized by a diminished production of insulin as well as a decreased efficiency of insulin action (i.e., insulin resistance), which can result in hyperglycemia. Insulin is the hormone responsible for transporting circulating glucose into various bodily tissues (particularly muscle and liver tissues) and plays a pivotal role in glycemic control and the development of diabetes. Exercise influences glycemic control and insulin action through two broad mechanisms:
1. It acutely promotes the rapid uptake of glucose into working muscle tissue independent of insulin action. This unique effect means that the vigorous use of muscle tissue, such as exercise, bypasses the need for insulin to promote glucose uptake. The positive effect of a single bout of exercise on glycemic control can persist for 24 – 72 hr, depending on duration and intensity (10).
2. Chronic exercise training also exerts a beneficial impact on glucose uptake. While the exact mechanisms remain to be fully explained, glycemic control seems to be positively affected by increases in glucose transporters and insulin signaling pathways (10). Moreover, exercise that results in gains of muscle tissue may provide an increased opportunity for glucose disposal as well.
Physical activity is an acknowledged, but clearly underutilized, strategy for preventing and treating T2D. Many healthcare providers seemingly fail to recognize how strong the evidence is for the power of physical activity in the prevention and treatment of T2D. Multiple studies have shown that physical activity has been shown to improve glycemic control and cardiovascular fitness while improving body composition and quality of life (21,26). One of the first studies on this topic, from 1997, simply encouraged an increase in leisure-time physical activity with basic improvements in diet (21). Diabetes incidence significantly decreased over a six-year period in those high-risk patients with prediabetes (21). A similar program in Finland, which consisted of dietary and exercise (both aerobic conditioning and resistance training) interventions, found very comparable results with the risk of developing diabetes reduced by 50% (26).
In patients who are at a high risk of developing T2D (i.e., prediabetes), several studies have reported the impact of exercise and pharmacological interventions on preventing diabetes. The United States Diabetes Prevention Program (DPP) randomized patients who were at high risk for developing T2D and assigned them to either a placebo, metformin, or lifestyle modifications, which included exercise (16). The lifestyle intervention decreased disease incidence by 58% and the metformin decreased incidence by 31%, compared to placebo (16).
Another study looked at exercise plus metformin in decreasing the incidence of T2D (22). The relative risk reduction was 28.5% for lifestyle modification alone, 26.4% for metformin alone, and 28.2% with lifestyle and metformin combined when compared to a control group (22). These results provide strong evidence for prevention of T2D with lifestyle intervention.Furthermore, evidence supports the continued T2D risk reduction with lifestyle intervention. In the 10-year follow up of the DPP study, the cumulative diabetes incidence rate was decreased by 34% in the lifestyle group and 18% in the metformin group, compared to placebo (12). Other studies with lifestyle change and metformin have also resulted in continued prevention or delay of diabetes (21,26). These studies provide evidence that the benefits of lifestyle change for preventing T2D persists in high-risk individuals beyond the initial intensive intervention.
The ADA Position Stand on physical activity for the prevention and treatment of diabetes recommends a minimum of 150 min per week of moderate-to-vigorous intensity aerobic exercise. Additionally, the ADA also recommends 2 – 3 weekly sessions of resistance training and two or more sessions of flexibility and balance training to maintain joint range of motion, muscular strength, and balance (11). Aerobic and resistance exercise both confer a positive impact on glycemic control and a recent meta-analysis provides a context for estimating these effects. A systematic review examined 47 randomized controlled trials (RCT) including 8,538 T2D patients that ranged from a minimum duration of 12 weeks up to a maximum of two years (27). Structured aerobic exercise alone, which represented 18 RCTs, had the greatest impact, decreasing A1C values by 0.73% (27). Resistance training, representing only four RCTs, demonstrated an average reduction in A1C of 0.57%, while combined aerobic and resistance training programs (seven RCTs) reduced A1C by 0.51% (27). Overall, structured exercise programs reduced A1C by 0.67% (27).
It is important to note, however, that individuals with T2D or prediabetes may benefit by performing more than the recommended minimum amount of weekly exercise. For example, a study found that exercise durations that exceeded the recommended 150 min per week resulted in even tighter glycemic control, reducing A1C values by 0.89% (27). Moreover, one study demonstrated a dose-response relationship of exercise on insulin action up to about 2,500 kcals per week (13).
The frequency, type, duration, and intensity of exercise all have the potential to influence glycemic control. Interestingly, combined training may positively impact A1C to a greater extent than aerobic or resistance training alone and the ADA’s Position Stand recognizes this synergistic effect (11). For example, multiple studies found that combined training resulted in greater reductions in A1C than either aerobic or resistance training alone (9,24).
In summary, both aerobic and resistance training have consistently demonstrated an ability to positively impact glycemic control in individuals with T2D, with decreases in A1C averaging about 0.7%. This is similar to, although slightly less than, the effect of metformin, which reduces A1C by about 1%. That is to say, adding exercise as an adjuvant treatment has been shown to reduce A1C an additional0.7%, which would be on top of the effect of Metformin. It is important to note that the vast majority of studies that have attempted to quantify the effect of exercise on T2D do so with patients that are already using pharmaceuticals to improve glycemic control. Therefore, the reported effect of exercise is additive, rather than independent. This represents a significant gap in the scientific literature as it relates to the true effect of exercise on glycemic control for the prevention and treatment of T2D.
Special Concerns with Exercise and the Diabetic Patient
When beginning an exercise program for diabetic patients, it is necessary to consider possible risks associated with exercise. The patient should talk with their physician about the risks and benefits and discuss any specific concerns with exercise. Exercise can cause changes in blood sugar, the most significant changes being hypoglycemia or low blood sugar. This is not very common with T2D, but it can occur in older, poorly controlled patients and those on multiple oral diabetes medications or insulin (5). Extra caution should be used during illness because blood sugar control is often affected. Diabetes is associated with peripheral neuropathy, which decreases sensation of the hands and feet and may affect balance. For low-impact activities, appropriate footwear and careful self-inspection of feet and hands are important.
Hypertension, peripheral vascular disease, and cardiac disease are more common in those who have diabetes. Risk of a cardiac event is associated with exercise, but the overall risk is clearly higher for a diabetic patient who remains inactive. However, it is prudent to consider an initial physician screening for the previously sedentary diabetic patient who is beginning an exercise program (17). The majority of these risks do not preclude exercise, but they may give indications for adjustments of the overall program.
While pharmaceutical treatment is complex, dynamic, and important for optimal glycemic control, exercise clearly plays a critical, but often overlooked, role in the overall treatment plan for patients with T2D or those at risk of developing it. Therefore, the importance of exercise should be emphasized by medical providers, personal trainers, and strength and conditioning professionals. The increase of physical activity in these patients is essential to their health and continued wellbeing.
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