The effects of exercise training on type 2 adult diabetic patients

The Effect of Exercise Training on Type 2 Adult Diabetic Patients

By: Adaugo Iwuala

Written Thesis Submitted in partial fulfillment of the requirements for the degree of Bachelor of Science from the Department of Kinesiology

University of Maryland

May 2, 2017

I pledge on my honor that I have not given or received any unauthorized assistance on this assignment.

Introduction

Type 2 diabetes mellitus (also known as non-insulin dependent diabetes mellitus) has become a widespread epidemic in the United States, with an estimated 24 million individuals with the disease in 2007, 6 million of which are undiagnosed (Colberg et al, 2010). About 60 million individuals were also estimated to have prediabetes, which is characterized by hyperglycemia, putting them at risk for developing type 2 diabetes (Colberg et al, 2010). Hyperglycemia in those who are diabetic is caused by defects in insulin resistance and insulin action, and are closely associated with obesity and physical inactivity (Snowling & Hopkins, 2006). Type 2 diabetes stems from a combination of genetic and environmental factors, such as physical inactivity and poor diet (Stanford & Goodyear, 2014). However, obesity plays a significant role in the vast majority of type 2 diabetic cases (Stanford & Goodyear, 2014). As an individual becomes more obese, their insulin resistance worsens, which leads to impaired glucose tolerance and the beginning of type 2 diabetes (Stanford & Goodyear, 2014).

Diabetes mellitus is a disease in which the body is unable to adequately regulate the amount of glucose in the blood (Siddiqui et al, 2013). In the body, glucose travels through the blood stream to cells to provide energy (Siddiqui et al, 2013). When food is ingested, the liver converts it to glucose, which is then released into the blood stream (Siddiqui et al, 2013).

In a healthy individual, glucose is regulated by insulin, as well as other hormones (Siddiqui et al, 2013). The pancreas is the organ responsible for the release of insulin when glucose is present in the blood stream (Siddiqui et al, 2013). Insulin acts a transporter that allows glucose to leave the blood stream and enter cells throughout the body (Siddiqui et al, 2013). For individuals suffering from diabetes, glucose is unable to move from the blood to the cells properly (Siddiqui et al, 2013). This leads to high blood sugar levels, starves the cells of necessary energy, and damages tissues that are exposed to the high blood glucose level (Siddiqui et al, 2013).

For those at risk of type 2 diabetes, pancreatic β-cells are no longer able to secrete enough insulin to overcome the insulin resistance induced by overweight and obesity (Siddiqui et al, 2013). Excess body weight contributes to the development of the disease due to hormone imbalances (ex. leptin, adiponectin, and glucagon) (Siddiqui et al, 2013). Obesity also results in an increased concentration of cytokines, suppression of cytokine signaling, and other inflammatory signals, all of which lead to insulin resistance (Siddiqui et al, 2013). With the change in insulin activity and change in β-cell function, the body secretes excess amounts of insulin to compensate[dm1] for the lack of glucose excursion (Siddiqui et al, 2013). When this influx of insulin no longer works, the individual becomes diabetic (Siddiqui et al, 2013).

Macrovascular disease is an important cause of mortality in type 2 diabetic patients, and is more prevalent in this population than in non-diabetic populations (Laakso, 1999). Mortality from type 2 diabetes is normally caused by macrovascular complications, leading to a narrowing of arterial walls (Maiorana et al, 2001). This affects blood flow and puts the patient at risk for heart attacks, strokes, and other forms of heart failure [MD2] (Maiorana et al., 2001). This, along with other vascular complications, results in cardiovascular disease, blindness, kidney and nerve disease, amputations, and death (Colberg et al., 2010). When treating type 2 diabetes, the goal is to normalize blood glucose, lipid, and blood pressure levels to prevent or delay the onset of the complications listed above (Colberg et al., 2010).

Skeletal muscle comprises approximately 33% of total body weight in most humans, and are heavily involved in energy metabolism (Cheng & Kujala, 2012). The work conducted by skeletal muscle during exercise is mediated through many different signaling pathways (Cheng & Kujala, 2012). Skeletal muscle is also the most important site of peripheral insulin resistance (Perseghin et al, 1996). During exercise, insulin-dependent glucose transport (GLUT4) activity is increased (Cheng & Kujala, 2012). GLUT4 is the predominant glucose transporter in muscle, which is stimulated by insulin and exercise (Stanford & Goodyear, 2014). Insulin signaling involves quick phosphorylation of the insulin receptor and insulin receptor substrate-1/2 tyrosine residues, followed by the activation of phosphatidylinositol 3-kinase (Stanford & Goodyear, 2014).

Also, endurance training induces the translocation of GLUT4 through AMP-activated protein kinase (AMPK) signaling pathways [dm3] (Cheng & Kujala, 2012). AMPK is a protein consisting of a catalytic α-subunit, as well as regulatory β- and γ-subunits (Stanford & Goodyear, 2014). This protein, activated by phosphorylation by other kinases, leads to GLUT4 action in muscle cells (Stanford & Goodyear, 2014). Although it is unclear whether AMPK is necessary for glucose uptake stimulated by exercise, research has shown that it is a key component in the regulation of exercise-induced glucose uptake (Stanford & Goodyear ,2014). There are potentially many different mechanisms involved in exercise-stimulate glucose uptake in skeletal muscle, some of which involves AMPK (Stanford & Goodyear, 2014).

Exercise also has long-lasting effects that occur even after an acute bout of endurance exercise is over (Cheng & Kujala, 2012). Individuals with type 2 diabetes tend to have smaller, dysfunctional, or damaged mitochondria and decreased expression of mitochondrial biogenesis markers (Stanford & Goodyear, 2014). Insulin resistance and type 2 diabetes are also associated with skeletal muscle mitochondrial dysfunction (Stanford & Goodyear, 2014). After exercise, there is an increase in mitochondrial biogenesis, as well as adenine triphosphate synthesis (Cheng & Kujala, 2012). These changes present in skeletal muscle increase muscular insulin sensitivity in the post-exercise time frame (Cheng & Kujala, 2012). Also, another proposed mechanism is that there is an increase in membrane permeability and microvascular perfusion after exercise that may contribute to an increase in glucose uptake (Cheng & Kujala, 2012).

The cellular mechanisms for glucose activity in resistance exercise training are less clear (Cheng & Kujala, 2012). This is most likely due to the lack of research surrounding resistance training and type 2 diabetes (Cauza et al, 2005). However, the increase in muscle mass over time is believed to be the source of the increase of glycemic control and ability to dispose of excess glucose (Cheng & Kujala, 2012). A study conducted in 2012 showed that one bout of strength exercise resulted in a reduction of hyperglycemia by 36% after 24 hours (Cheng & Kujala, 2012). This was attributed to the direct and immediate improvements of insulin-dependent and insulin-independent glucose uptake, resembling the aftereffects of endurance training on glucose activity (Cheng & Kujala, 2012). However, there is a lack of research surrounding the longevity of these effects, as well as if these results are similar at different resistance training intensities (Cheng & Kujala, 2012).

Typically, endurance exercise training, coupled with an improved diet, is prescribed by clinicians to treat diabetes, primarily because of its ability to decrease glucose levels, reduce body fat, and improve cardiovascular fitness (Cauza et al., 2005). In addition, endurance training can improve insulin resistance (Cauza et al, 2005). There is strong support for endurance training as a means of treating type 2 diabetes, however, studies surrounding resistance training are limited (Castaneda et al, 2002). Also, it was suggested by Castaneda and colleagues (2002) that elderly patients may struggle to complete moderate-intensity, high-volume resistance exercise programs, making this a potentially ineffective treatment plan[MD4] . Exercise training has been generally accepted as beneficial for type 2 diabetic patients, however, there has not been a consensus on the best type of exercise to prescribe to diabetic patients (aerobic vs. resistance) (Church et al., 2010). The purpose of this thesis is to examine how different forms of exercise training affect type 2 diabetic patients of different age groups. This will aid in determining whether clinicians should prescribe aerobic exercise, resistance exercise, or both, to treat the disease.

Effects of Endurance Training on Type 2 Diabetic Patients

Diabetes, characterized by hyperglycemia due to defects in insulin resistance, can be treated with acute exercise (Reitman et al, 1984). Exercise lowers plasma glucose levels by enhancing the effect of insulin on glucose entry into muscle (Reitman et al, 1984). The problems that are associated with type 2 diabetes (glucose intolerance, insulin resistance abnormal plasma insulin response to rises in glucose levels, and increased fasting insulin levels) are also observed in obese patients (Reitman et al, 1984). Because exercise has been shown to improve glucose disposal in obese patients, Reitman and colleagues (1984) designed a study to observe the effects of regular aerobic physical activity on regulation of plasma glucose.

Six obese American Indians participated in the study (Reitman et al, 1984). They were required to exercise 5-6 days a week, for 20-40 minutes (Reitman et al, 1984). During exercise, they needed to reach 60-90% VO_2max (Reitman et al, 1984), and this study lasted 10 weeks. Reitman and colleagues (1984) measured plasma glucose levels, insulin-induced glucose disposal, glucose tolerance, and insulin secretion in the participants. Reitman and colleagues (1984) found that exercise capacity and VO_2max increased in almost every subject, in addition to a loss in body weight. After training, fasting plasma glucose levels decreased in every subject, and oral glucose tolerance improved in 5 out of the 6 participants (Reitman et al, 1984). They also found that there was an overall improvement in glucose homeostasis (Reitman et al, 1984). This study concluded that regular aerobic exercise can reduce glucose concentration and improve glucose tolerance and insulin secretion in obese type 2 diabetic patients. They also concluded that endurance exercise therapy can be as effective as other modes of treating early type 2 diabetes (Reitman et al, 1984). This study, although interesting, utilized a small sample size (Reitman et al, 1984), and studied only one population.

Diabetes dramatically increases the likelihood of developing coronary heart disease, and more than 50% the cases of death in diabetic patients is due to this (Lehmann et al, 1995). The complications of type 2 diabetes leading to coronary heart disease include changes in insulin resistance, obesity, dyslipidemia, and hypertension (Lehmann et al, 1995).[MD5] However, the physical benefits of aerobic exercise training have been studied and understood for many years (Lehmann et al, 1995). As a result, aerobic exercise has been prescribed by physicians to type 2 diabetic patients (Cauza et al, 2005). Glycemic control, although an effective means of treating type 2 diabetes, is often insufficient in controlling the risk factors that lead to cardiovascular disease (Lehmann et al, 1995). Therefore, Lehmann, Vokac, Niedermann and colleagues (1995) conducted an experiment that evaluated the effects of endurance training on glycemic control, plasma lipids, blood pressure, weight, and abdominal fat.

They studied 16 type-2 diabetic patients (9 women, 12 men) from ages 42-73 (Lehmann et al, 1995). BMI, blood pressure, waist and hip circumference, blood glucose, plasma insulin levels, as well as various cholesterol and protein levels were measured before the beginning of the study (Lehmann et al, 1995). In addition to measuring plasma glucose levels, clinicians also measure HbA_1c, which is a measure of glycemic control over the previous 4-12 weeks (Siddiqui et al, 2013). This is measured to determine the presence of hyperglycemia (Cauza et al, 2005). [MD6] All subjects were required to follow a diet consisting of 50% carbohydrates, 35% fat and 15% protein content, along with moderated alcohol, fiber, and cholesterol intake (Lehmann et al, 1995). Individuals in the control group continued their regular exercise regimen. The individuals in the experimental group engaged in aerobic exercise (exercise bike, walking, jogging, etc.) for 30-45 min at 50-70% of maximal heart rate, 3 times/week. They were also monitored during exercise by a physician or physical therapist [MD7] once a week. Lehmann and colleagues (1995) conducted this experiment for 3 months.

Lehmann and colleagues (1995) found that plasma lipids significantly improved, and there was an overall decrease in triglyceride levels in the experimental group. There was an increase in high density lipoproteins, as well as a significant reduction in systolic and diastolic blood pressure (Lehmann et al, 1995). Resting heart rate also decreased, as well as waist circumference and body fat (Lehmann et al, 1995). This study showed that aerobic exercise training effectively reduces the risk of coronary heart disease in type 2 diabetic patients (Lehmann et al, 1995). [MD8]

Aerobic physical activity is usually recommended for the management and treatment of diabetes (Ligtenberg et al, 1997). Many of the sources supporting this claim were studies that observed the effects of aerobic activity on young and middle-aged diabetic men (Ligtenberg et al, 1997). Because of this, the feasibility of elderly type 2 diabetic patients complying with these recommendations was under question (Ligtenberg et al, 1997). Because of this, Ligtenberg and colleagues developed a study to observe the effects of aerobic physical training on elderly patients with advanced type 2 diabetes (Ligtenberg et al, 1997).

Ligtenberg and colleagues (1997) randomly assigned 58 participants into two groups: control and physical training group. The control group was assigned a concise education program, but were not given any instruction about exercise (Ligtenberg et al, 1997). The physical training group exercised for a total of 26 weeks, 3 times a week, under the supervision of a physical therapist and a physician (Ligtenberg et al, 1997). HbA_1C, fasting glucose, various forms of cholesterol, and VO_2max were measured before the study (Ligtenberg et al, 1997). These, along with other measurements, were also measured periodically throughout the study (Ligtenberg et al, 1997). Physical training participants engaged in aerobic exercise training (such as biking, swimming and rowing) at 60-80% VO_2max (Ligtenberg et al, 1997).

Fasting blood glucose levels remained the same in both groups, and changes in HbA_1C levels did not differ significantly between the groups (Ligtenberg et al, 1997). However, the training group tended to have lower HbA_1C levels after the 26 weeks of exercise in comparison to the control group (Ligtenberg et al, 1997). Ligtenberg and colleagues (1997) did not observe any short-term improvements in the fitness, insulin sensitivity, or glucose tolerance in the elderly participants. The small difference in HbA_1C levels between the control group and the experimental group was not statistically significant (Ligtenberg et al, 1997). The reason for the relatively unaltered HbA_1C levels in the training group could have been because the intensive training period was only 6 weeks (Ligtenberg et al, 1997). After the first 6 weeks of monitored training, patients could go home to continue the intensive training, 3 times a week. However, majority of the participants only exercised once or twice a week, and this may have changed their HbA_1C levels (Ligtenberg et al, 1997).

Ligtenberg and colleagues (1997) concluded that aerobic training does not significantly change glycemic control in the short-term. However, they believe that endurance training is still beneficial for the elderly population in the prevention of cardiovascular disease, a widespread problem in diabetics (Ligtenberg et al, 1997). Therefore, they recommended that endurance exercise training be prescribed to elderly patients with caution (Ligtenberg et al, 1997). This study is interesting because it contradicts the notion that endurance training is an effective means for treating type 2 diabetes in all populations (Cauza et al, 2005). It also conflicts with the findings of Reitman and colleagues (1984), who found that there was an improvement in glucose tolerance and insulin sensitivity after endurance exercise. However, Reitman and colleagues (1984) studied a small sample size, which may have skewed results and may not be representative for larger populations. [dm9]

Exercise interventions that emphasize regular exercise and healthy dietary changes are generally effective at treating type 2 diabetes, and moderate-to-high intensity activity is recommended by the American Diabetes Association (Baldi & Snowling, 2003). It has been shown to reduce HbA_1C levels, increase insulin sensitivity, improve cardiovascular fitness and reduce fat mass in type 2 diabetic patients (Hansen et al, 2009). There are, however, no guidelines on the preferred mode of exercise to maximize these clinical benefits (Hansen et al, 2009). There is also no clinical distinction between exercise intensity and their corresponding benefits (Hansen et al, 2009). This is potentially a very important distinction that should be made when determining the type of care necessary for a type 2 diabetic patient (Hansen et al, 2009). For this reason, Hansen and colleagues (2009) studied the clinical benefits of continuous low-to moderate (LI) versus moderate-to-high (HI) intensity aerobic exercise training in obese type 2 diabetic patients.

Hansen and colleagues (2009) selected fifty sedentary male obese type 2 diabetic patients, of whom were all taking oral blood-glucose-lowering medication. Before the beginning of the program, plasma glucose, plasma insulin, blood hemoglobin content, oral glucose tolerance, plasma lipid and other metabolic and cardiovascular levels were measured (Hansen et al, 2009). These measurements were also taken 4 days, 8 days, 2 months and 6 months into the intervention (Hansen et al, 2009). All participants engaged in individually supervised, continuous endurance exercise 3 days/week for 6 months (Hansen et al, 2009). For the group participating in LI exercise, each session consisted of 55 min of exercise at exactly 50% VO_2max (Hansen et al, 2009). For the group engaging in HI exercise, each session was 40 min long, at 75% VO_2max (Hansen et al, 2009).

It was found that in both groups, there was a decrease in HbA_1C levels, but there was no interaction between exercise intensity and decrease in HbA_1C levels (Hansen et al, 2009). Plasma glucose, plasma insulin, and glucose tolerance levels did not change significantly in both groups after 6 months of exercise (Hansen et al, 2009). VO_2max increased more in the HI group than in the LI group after 2 months of training, and both groups experienced significant weight loss (Hansen et al, 2009). Therefore, Hansen and colleagues (2009) concluded that there is no significant difference between the clinical benefits of low-to-moderate intensity aerobic exercise vs. moderate-to-high intensity aerobic exercise.

When treating type 2 diabetes, glycemic control is the main focus (Mikus et al, 2012). There is an association between HbA_1C levels and the risk of developing diabetes-related complications such as macrovascular diseases and mortality (Mikus et al, 2012). HbA_1C, although a strong predictor diabetes-related complications, does not provide information about hypoglycemia or changes in glycemic variability (Mikus et al, 2012). Hypoglycemia is associated with the many of the same complications as hyperglycemia (Dandona et al, 2010). Also, large fluctuations in blood glucose trigger the events that lead to micro- and macrovascular complication that accompany type 2 diabetes (Mikus et al, 2012). For these reasons, fluctuations between hyperglycemia and hypoglycemia should be monitored (Mikus et al, 2012). Also, a study done in 2000 suggests that postprandial glucose (PPG) may be a better predictor of cardiovascular disease risk and mortality in comparison to fasting blood glucose or HbA_1C (Temelkova-Kurktschiev et al, 2000). Because of this, Mikus and colleagues (2012) studied the effects of a week of aerobic exercise on PPG and glycemic variability in type 2 diabetic patients.

Thirteen sedentary overweight/obese middle aged type 2 diabetics were used for this study (Mikus et al, 2012). Glycemic control was measured at baseline and during the final 3 days of the program (Mikus et al, 2012). The exercise intervention consisted of one hour of supervised aerobic exercise for 7 consecutive days at 60-70% HR_max (Mikus et al, 2012). Diet was strictly standardized, PPG was measured at 30-minute post meal intervals, and oral glucose tolerance tests (OGTT) were performed 12-24 hours post-exercise (Mikus et al, 2012). Mikus and colleagues (2012) found that there was a decrease in PPG levels, as well as the amount, frequency and duration of glycemic excursions. Also, average 24-hour blood glucose did not change over the duration of the intervention (Mikus et al, 2012). Glucose, insulin, and C-peptide responses to OGTT did not change (Mikus et al, 2012). Mikus and colleagues (2012) could conclude that one week of aerobic exercise reduces PPG and glycemic variability in individuals with type 2 diabetes, but does not change results of OGTT. These findings are similar to Ligtenberg and colleagues (1997), who also found that aerobic exercise caused no significant changes in glycemic control in the short-term.

Overall, endurance exercise is effective in reducing the risk of micro- and macrovascular complications resulting from cardiovascular disease in diabetic patients, which is one of the main causes of mortality in this population (Colberg et al., 2010). Glucose variability and glucose tolerance is also positively altered by endurance training (Reitman et al, 1984) (Lehmann et al, 1995).

Effects of Resistance Training on Type 2 Diabetic Patients

Resistance training is a form of exercise that has not been extensively studied within the context of type 2 diabetes treatment (Cauza et al, 2005). As stated earlier, skeletal muscle is responsible for at least 80% of insulin-stimulated glucose uptake [dm10] (Tabata et al, 1999). Aerobic exercise training is considered a suitable practice for treating type 2 diabetes, and moderate-to-high intensity activity is recommended by the American Diabetes Association (Baldi & Snowling, 2003). However, many studies that cite aerobic exercise as a means of improving glycemic control employ vigorous aerobic programs, and moderate intensity aerobic training may not have the same effects (Baldi & Snowling, 2003). This is a problem for obese patients, who are less inclined to engage in vigorous exercise training (Baldi & Snowling, 2003). For those with severe obesity, arthritis, or physical complications from type 2 diabetes (such as cardiovascular disease), aerobic exercise may be uncomfortable or painful to complete (Eves & Plotnikoff, 2006). Resistance training offers an alternative to traditional aerobic exercise plans that may appeal to those who have trouble moving (Baldi & Snowling, 2003). Therefore Baldi & Snowling (2003) proposed that resistance training should be investigated as an option for obese patients, who are at higher risk of developing type 2 diabetes. Baldi & Snowling (2003) investigated the effects of 10 weeks of resistance training on glycemic control in obese type 2 diabetic men.[MD11]

Eighteen sedentary men with type 2 diabetes and no cardiovascular disease participated in the study (Baldi & Snowling, 2003). The participants were randomly divided into 2 groups: resistance training group (RT) and control (C) group (Baldi & Snowling, 2003). The RT group exercised 3 days a week, for 10 weeks, with increasing intensity (Baldi & Snowling, 2003). Body mass, isokinetic strength, HbA_1C levels, plasma glucose levels, and insulin sensitivity were measured and assessed before and after the 10-week trial (Baldi & Snowling, 2003). Fasting glucose and insulin decreased, and decrease in HbA_1C levels approached significance (Baldi & Snowling, 2003). Although percent body fat did not change, muscular strength increased (Baldi & Snowling, 2003). Baldi & Snowling (2003) concluded [MD12] that resistance training is effective at improving glycemic control and lowering fasting insulin levels in type 2 diabetic patients.

For the treatment of type 2 diabetes, endurance training has been considered the most beneficial form of exercise, with many benefits to overall health [MD13] (Cauza et al, 2005). These benefits include improvements in lipid profile, reduction in body fat, and decreased blood glucose levels (Cauza et al, 2005). Endurance training has also been found to decrease insulin resistance in patients with type 2 diabetes, as well as obese patients without the disease (Cauza et al, 2005). However, conclusions on the effects of strength training on type 2 diabetes have been limited (Cauza et al, 2005). Cauza and colleagues (2005) proposed that any positive effects that resistance training has on insulin resistance may be due to the increase in glucose transporter (GLUT4) proteins. Tabata and colleagues (1999) reported an increase in GLUT4 proteins after strength training. Also, an increase in muscle mass results in an increase in glucose uptake (Cauza et al, 2005). Cauza and colleagues (2005) hypothesized that an increase in muscle mass may induce a decrease in insulin resistance in type 2 diabetes patients.

In this study, 23 men and 21 women, aged 50-70 years old, with type 2 diabetes and no complications were randomized into two groups: strength training (ST) and endurance training (ET) (Cauza et al, 2005). Each group trained 3 days a week, for 4 months (Cauza et al, 2005). Maximum strength, VO_2max, body mass, BMI, HbA_1C levels, insulin resistance, and blood pressure were assessed (Cauza et al, 2005).

In the ST group, HbA_1C levels declined significantly; this did not happen in the ET group (Cauza et al, 2005). Their findings were different from those in study by Church and colleagues (2010). Church and colleagues (2010) report a slight decline in HbA_1C levels in their resistance group, however it was not significant in comparison to their control group. Blood glucose levels and insulin resistance also improved in the ST group, and not significantly in the ET group (Cauza et al, 2005). Therefore, the authors concluded that strength training was more effective in improving glycemic control[MD14] than endurance training, and may play a crucial role in the treatment of type 2 diabetes (Cauza et al, 2005). This finding is consistent with Baldi and Snowling (2003), in which strength training was found to be an effective means of improving glycemic control as well.

Exercise training is effective in treating the effects of type 2 diabetes, and has been studied extensively in middle-aged populations (Dunstan et al., 2002). However, little is known about the effects of physical activity on older type 2 diabetic patients (Dunstan et al., 2002). Endurance training is often prescribed to older patients with the disease, and is also associated with weight loss, increased fitness, and improved glucose tolerance (Dunstan et al., 2002). Resistance training has also been recommended to older patients in addition to endurance training, to produce a well-rounded exercise program for them (Dunstan et al., 2002). The positive effects of both aerobic and resistance training in middle-aged patients was discussed in the study by Church and colleagues (2010) stating that a combination of both is the most effective in treating type 2 diabetes (Church et al., 2010). However, the impact of progressive resistance training on older type 2 diabetic patients has not been extensively studied [MD15] (Dunstan et al., 2002). Because aging is associated with a decline in muscle mass, strength, and control, resistance training may be an effective solution for treating the illness in the older population (Dunstan et al., 2002). In addition, high-intensity progressive resistance training has not been studied extensively in this population (Dunstan et al., 2002).

Sedentary, overweight, type 2 diabetic men and women between the ages of 60-80 were used for this study (Dunstan et al., 2002). The participants were randomized into two groups: high-intensity progressive resistance training + moderate weight loss (RT & WL), and moderate weight loss + control program (WL) (Dunstan et al., 2002). All participants were given a healthy eating plan to follow throughout the study, and the RT & WL group participated in progressive resistance training with high intensity (50-60% of max resistance, with the goal of reaching 75-85% by the end of the study) (Dunstan et al., 2002). Glucose, insulin, and HbA_1C levels were measured and analyzed (Dunstan et al, 2002).

HbA_1C levels decreased significantly in the RT & WL group in comparison to the WL group (Dunstan et al., 2002). Lean body mass increased in the RT & WL group as well (Dunstan et al, 2002). Dunstan and colleagues (2002) concluded [MD16] that high intensity progressive resistance training, accompanied by healthy eating, was an effective way of improving glycemic control in older diabetic patients (Dunstan et al., 2002). This finding is comparable with that of Baldi & Snowling (2003), who also concluded that resistance training was effective in improving glycemic control in type 2 diabetic patients. Strength training seems to be effective for both middle aged and older diabetic populations (Dunstan et al, 2002) (Baldi & Snowling, 2003). [MD17]

Over 18% of the US population over the age of 65 suffers from diabetes (Castaneda et al, 2002). Unfortunately, it is also becoming increasingly more prevalent and undertreated [MD18] (Castaneda et al, 2002). Additionally, the rate of type 2 diabetes in the Latino population is double than that of Caucasians (Castaneda et al, 2002). Some of the studies focusing on resistance training use moderate-intensity, high-volume exercise programs that may have an aerobic component that is difficult for the elderly population to facilitate (Castaneda et al, 2002). However, high-intensity, low-volume progressive resistance training (PRT) may be more bearable for elderly patients, and will also lead to an increase in muscle mass (Castaneda et al, 2002). The study done by Castaneda and colleagues (2002) evaluated the effectiveness of high-intensity, low-volume PRT on improving glycemic control in older Latino diabetic patients.

In this study, 62 Latino men and women over the age of 55 with type 2 diabetes were randomized into two groups: standard care (control group) and standard care plus PRT (Castaneda et al, 2002). The duration of the study was 16 weeks, and all participants were sedentary before beginning the study (Castaneda et al, 2002). The PRT group exercised 3 times a week, ~45 min/session, progressing from 60-80% of maximum resistance to 70-80% of maximum resistance. Both groups continued normal treatment of type 2 diabetes prescribed by healthcare providers (Castaneda et al, 2002). Plasma HbA_1C levels, glycogen levels, body weight, cholesterol and muscle biopsies were obtained and assessed before and after the study.

There was an increase in glycogen stores, a decrease in HbA_1C levels, and a decrease in the amount of medication necessary to treat the illness (Castaneda et al, 2002). The PRT group also increased in lean mass, reduced systolic blood pressure, and decreased trunk fat mass (Castaneda et al, 2002). There was no change in glycogen and hemoglobin levels in the control group, and there was a 42% increase in the amount of medication needed to treat the illness (Castaneda et al, 2002). These results are consistent with that of the study conducted by Dunstan and colleagues (2002), as HbA_1C levels also decreased for elderly individuals participating in high-intensity resistance training (Dunstan et al., 2002). Castaneda and colleagues (2002) concluded [MD19] that progressive resistance training, along with standard care of type 2 diabetes is an effective means of improving glycemic control in the elderly Latino population.[dm20]

Within the scope of resistance training, there are different modes of resistance training. Hypertrophy resistance training (HRT) induces muscle hypertrophy, strength, and muscle mass, and is more pronounced through heavy weights and few repetitions until fatigue (Egger et al, 2012). In this form of resistance training, blood glucose levels and insulin sensitivity improve (Klimcakova et al, 2006). For this reason, hypertrophic resistance training is recommended by the American College of Sports Medicine for adults to remain healthy (Ratamess et al, 2009). However, this is difficult for some patients due to orthopedic problems or preference for lighter weight-lifting (Egger et al, 2012). Another alternative form of strength training would be endurance resistance training (ERT), which is more commonly used by athletes (Egger et al, 2012). ERT is understudied, even though cycle ergometer training (a type of ERT) has been shown to decrease fasting blood glucose levels, HbA_1C and body fat (Hambrecht et al, 1995). Therefore, Egger and colleagues (2012) studied whether combining aerobic exercise training with either HRT or ERT would result in different effects on body composition, glycemic control, and muscle mass and strength (Egger et al, 2012).

The study randomized 32 patients between either HRT or ERT training groups, both with an equal combination of aerobic exercise training (Egger et al, 2012). Body composition measurements were taken, as well as HbA1C, fasting glucose, frucosamine, and lipid profile (Egger et al, 2012). Each group engaged in 8 weeks of aerobic training on cycle ergometers, followed by the resistance training assigned to them. The HRT group did 10-12 repetitions for each major muscle group, with 3-5 minutes of rest and 70% of their 1-Repetition maximum (Egger et al, 2012). The ERT group completed the same exercises, but with weight set at 40% of their 1-Reptition maximum, for 20-30 repetitions (Egger et al, 2012). It was found that there was a significant improvement in glycemic control, weight, waist circumference, muscle mass and work capacity in both groups, as well as a greater increase in muscle strength in the HRT group than ERT group (Egger et al, 2012). For this reason, Egger and colleagues (2012) concluded that there are no inherent benefits in one type of resistance training vs. another, and can be prescribed to patients according to their own preferences (Egger et al, 2012).

From the existing research, resistance training is effective at improving glucose tolerance, as well as improving muscle mass and reducing body fat mass (Egger et al, 2012).

Effects of Combined Endurance and Resistance Training on Type 2 Diabetic Patients

The benefits of both aerobic and resistance training has been examined, and both lead to benefits in glucose tolerance, insulin action, and insulin sensitivity. However, less is known about the effects of combined aerobic and resistance training exercises.

Tessier and colleagues (2002) evaluated the effects of aerobic and resistance exercise in elderly type 2 diabetes mellitus (DM) patients. [MD21] In middle aged diabetic subjects, aerobic exercise has been shown to improve expression of the glucose transporter GLUT4, which results in an increase in insulin sensitivity (Tessier et al, 2000). However, there is limited data studying the effects of aerobic exercise training on the elderly diabetic population (Tessier et al., 2000). Elderly diabetics suffer from insulin resistance in the same way that middle-aged diabetic patients experience, but have been studied much less [MD22] (Tessier et al, 2000). Personal-model beliefs and social-environmental barriers have also been found to play an important role in patients’ self-management of type 2 diabetes (Tessier et al, 2000). A study conducted in 1997 utilized a support group to encourage physical activity in elderly type 2 diabetic patients (Tessier et al, 2000). However, there was no change in the amount of physical activity reported by the elderly patients, showing that their attitude towards DM and physical activity was relatively negative (Tessier et al, 2000). Individuals who score low on the assessment of quality of life (QOL) tend to have lower rates of physical activity (Tessier et al, 2000). Because of this, Tessier and colleagues (2000) conducted a study to determine the effects of physical activity on glucose excursion, physical performance, QOL and attitudes in type 2 diabetic elderly patients.

There were 39 Caucasian ambulatory outpatients over the age of 65 that participated in this study (Tessier et al., 2000). Participants were given a 3-hour oral glucose tolerance test, HbA_1c test, fructosamine test, Balke-Naughton treadmill test, as well as a survey on quality of life and attitude towards type 2 diabetes (Tessier et al, 2000). They were then randomized into control (C) and active physical training program (E) groups (Tessier et al, 2000). The active physical training program had a 16-week exercise regimen consisting of warm up, stretching, rapid walking for 20 minutes, followed by a strength component activating major muscle groups for 20 minutes, followed by stretching and cooldown (Tessier et al, 2000). Participants were required to exercise at 35-59% max HR, then up to 60-79% max HR (approximately 50-74% VO_2max) by week 4 (Tessier et al, 2000).

Tessier and colleagues (2000) found that there was a significant decrease in glucose excursion and an increase in total time on the treadmill during the treadmill test, with no increase in the percentage of maximal heart rate achieved. Interestingly, there was no significant change in HbA_1C levels, fasting glycaemia, weight, and BMI (Tessier et al, 2000). However, there was an improvement in attitudes towards diabetes and physical activity [MD23] in the experimental group (Tessier et al, 2000). This suggests that aerobic and resistance exercise training has a significant effect on exercise tolerance and glucose excursion in elderly type 2 diabetic patients (Tessier et al, 2000).

Exercise has been shown to reduce glycated hemoglobin (HbA_1C) levels (Church et al., 2010). A study conducted in 2007 showed that participants that were assigned a combination of both aerobic and resistance training had a larger reduction in HbA_1C levels when compared to groups who did just aerobic training or just resistance training (Sigal et al, 2007). However, because the combination group exercised longer than those in the other groups, it is unclear whether the type of exercise training had more effect than the amount of time spent exercising (Sigal et al, 2007). Because of this, Church and colleagues (2010) designed an experiment observing the effects of aerobic and resistance training on the treatment of type 2 diabetes, ensuring equal amounts of exercise training time (Church et al, 2010).

The study by Church and colleagues (2010) consisted of 262 sedentary participants with type 2 diabetes and HbA_1C levels over 6.5%. The participants were divided into four groups: aerobic training only, resistance training only, combination of aerobic and resistance training, and nonexercise (Church et al., 2010). Training lasted for 9 months, participants were weighed weekly, while HbA_1C levels were measured monthly (Church et al., 2010). Church and colleagues standardized exercise training programs to body weight, and determined that each participant should exercise 150 min/week (Church et al, 2010). Exercise intensity was 50-80% VO_2max, and HbA1C levels were measured monthly (Church et al, 2010).

Individuals in the combination group experienced improvements in VO_2max in comparison to the control and resistance groups (Church et al, 2010). Every group, apart from the control group, exhibited improved time on the treadmill, as well as a decrease in body weight (Church et al, 2010). HbA_1C levels were reduced by 0.34% in the combination group in comparison to the control group (Church et al, 2010). Changes in HbA_1C levels were not significant in either resistance training or aerobic training groups in comparison to the control group (Church et al., 2010). These findings contradict the findings of Tessier and colleagues (2000), who observed no significant change in body weight, BMI, or fasting glycemia. However, the study conducted by Church and colleagues lasted longer, which may have played a factor in the difference of findings (Church et al, 2010). Church and colleagues (2010) concluded that a combination of aerobic and resistance exercise training was a successful means of improving HbA_1C levels in type 2 diabetes patients, in addition to reducing body weight and improving cardiovascular fitness (Church et al, 2010).

Exercise training in any form or capacity is associated with lowered risk of cardiovascular disease and mortality rates (Balducci et al, 2012). It is recommended by the American College of Sports Medicine and American Diabetes Association that individuals with type 2 diabetes perform at least 150 min/week of moderate-to-vigorous aerobic exercise, followed by moderate-to-vigorous resistance training at least 2-3 days/week (Balducci et al, 2012). However, there is no evidence that moderate-to-high intensity (HI) training is more beneficial than low-to-moderate intensity (LI) exercise on the symptoms of type 2 diabetes (Balducci et al, 2012). Many studies, such as Hansen and colleagues, suggest that there is no difference in effectiveness between moderate-to-high intensity exercise and low-to-moderate intensity training (Hansen et al, 2009). Balducci and colleagues (2012) conducted a study similar to Hansen and colleagues (2009), with supervised combined aerobic and resistance exercise. This was in order to test the hypothesis that training at HI is more effective than LI in improving cardiovascular disease risk factors in type 2 diabetic patients (Balducci et al, 2012).

There were 606 sedentary Caucasian type 2 diabetic patients in this study (Balducci et al, 2012). Of this group of participants, 303 were randomly assigned to a control (CON) group consisting of exercise counseling alone, and 303 were assigned to the supervised training AND exercise counseling group (EXE) (Balducci et al, 2012). Participants in the EXE group were further split into LI and HI groups (Balducci et al, 2012). The EXE program consisted of supervised sessions of combined aerobic and resistance exercise twice a week (Balducci et al, 2012). Individuals in the LI group engaged in aerobic training at 55% VO_2max and resistance training at 60% of 1-Repetition maximum (Balducci et al, 2012). The HI group performed endurance training at 70% of VO2max and resistance training at 60% of 1-Repetition maximum (Balducci et al, 2012). Both the control and experimental groups received individualized counseling every 3 months that was aimed at encouraging participants to reach the recommended amount of physical activity in their daily lives (Balducci et al, 2012). HbA_1C levels, fasting blood glucose levels, serum insulin, as well as body composition measurements were taken before and after the study (Balducci et al, 2012).

In the HI training group, there was a slight, but statistically significant improvement in HbA_1C levels, triglycerides, and total cholesterol levels in comparison to the LI training group (Balducci et al, 2012). However, there were no significant difference in improvements in other metabolic and cardiovascular components, such as systolic and diastolic blood pressure, fasting glucose, and insulin levels (Balducci et al, 2012). Therefore, Balducci and colleagues (2012) concluded that, for sedentary subjects with type 2 diabetes, increasing exercise intensity to moderate or high levels is not harmful, but does not provide any additional benefits when considering cardiovascular risk factors. This finding is similar the findings of Hansen and colleagues (2009), who concluded that HI exercise training is not inherently more beneficial than LI exercise training.

Although much is known about the effects of endurance and resistance training on type 2 diabetic patients, there is little data on the disadvantages of detraining in these patients (Tokmakidis et al, 2014). A study done in 1996 showed that just 6 days of inactivity reduces insulin action in highly active endurance-trained runners (Vukovich et al, 1996). This may be caused by a reduction in muscle GLUT4 transporter levels as a result of inactivity (Vukovich et al, 1996). Illness, injury, travel, or vacation may cause brief detraining moments, which could affect treatment of the disease (Tokmakidis et al, 2014). Knowing the effects of detraining in type 2 diabetic patients is important, since this is a commonly prescribed therapy method (Tokomakidis et la, 2014). Tokmakidis and colleagues (2014) designed a study to examine the training, detraining, and retraining effects of a combined endurance and resistance training regimen on the management of type 2 diabetes.

For this study, 13 middle aged women were participants (Tokmakidis et al, 2014). They maintained their usual medicine, diet and activity plan throughout this study (Tokmakidis et al, 2014). They followed a supervised exercise regimen consisting of aerobic and strength training for 9 months (training) (Tokmakidis et al, 2014). They stopped training for 3 months (detraining), then resumed exercise training for another 9 months (retraining). Each training session took place 4 times/week: 3 sessions consisted of combined aerobic and strength training, while the 4^th session was just aerobic training (Tokmakidis et al, 2014). Fasting plasma glucose levels, HbA_1c levels, muscular strength, aerobic performance, and body weight measurements were collected during each stage (Tokmakidis et al, 2014). Tokmakidis and colleagues (2014) found that training lead to a decrease in BMI, fasting plasma glucose, and HbA1C. Detraining reversed these initial gains, but retraining regained the losses experienced in the previous stage, with an even greater loss in BMI, fasting glucose levels, and muscular strength (Tokmakidis et al, 2014). They were, therefore, able to conclude that detraining brings about negative changes in type 2 diabetic symptoms, and retraining restores what was lost and improves them even more (Tokmakidis et al, 2014). However, because detraining resulted in a reversal of the therapeutic effects of combined exercise training, Tokmakidis and colleagues (2014) recommend that type 2 diabetic patients follow a regular, uninterrupted exercise program.

Conclusion

Type 2 diabetes patients suffer from a decrease in insulin sensitivity and defects in insulin action (Snowling & Hopkins, 2006). Physicians often prescribe a change in diet, as well as exercise training, to individuals with the disease to treat the symptoms and ultimately reverse the disease (Snowling & Hopkins, 2006). Aerobic exercise is usually encouraged, but there is less research surrounding the effects of resistance training on diabetic patients (Castaneda et al, 2002). There is also limited research on the effects of exercise training on elderly populations with diabetes. (Castaneda et al, 2002).

Aerobic exercise is effective in treating cardiovascular complications that arise from having the disease, such as hypertension and dyslipidemia (Tessier et al, 2000). It also increases cardiovascular fitness and reduces body fat percentage, which improves the overall health of the individual (Cauza et al, 2005). However, these treatment plans may be difficult for type 2 diabetics to commit to, because of the effects of obesity on their body (Baldi & Snowling, 2003).

Obesity can lead to many cardiovascular complications, as well as physical pain and discomfort when exercising (Eves & Plotnikoff, 2006). Also, sedentary elderly patients may have difficulty participating in strenuous aerobic activity (Castaneda et al, 2002). [MD24] Resistance training offers an alternative to developing skeletal muscle, which will, in turn, improve insulin resistance (Tabata, 1999). Studies have shown that resistance training does improve glycemic control (Castaneda et al, 2002) and lower fasting insulin levels (Baldi & Snowling, 2003). It was also found that, along with a change in diet, a combination of endurance and resistance training can reduce HbA_1C levels, indicating that a combination of both is better than simply endurance training or resistance training (Church et al, 2010).

These studies, along with more research, indicate that it is beneficial and essential for type 2 diabetic patients to exercise to treat the illness, and that a combination of both resistance and endurance training can potentially have additive effects in the battle against type 2 diabetes (Sigal et al, 2007). [dm25] Clinicians should stress the importance of exercise in treating the illness to their diabetic patients, and should prescribe a combination of endurance and resistance training, altered to the needs of their patients.

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