Diabetes Mellitus (DM) is perhaps on of the most interesting diseases from an epidemiological standpoint. In 2013, 382 million people had DM, a number that has more than doubled in the last 30 years (12, 21). This figure represents around 7% of the world population, signifying that it is not just a problem in the United States, but a global one (2, 12). Furthermore, 90% of patients with DM have Type II Diabetes Mellitus (T2DM) (2, 32). Perhaps one of the reasons this figure is so large is due to the fact that T2DM, previously referred to as “Adult-Onset”, and pre-diabetes are now being developed in early childhood (12).
Genetic Contribution to Type II Diabetes Mellitus
Since pre-diabetes is developing so early in life, the genetic contribution of T2DM must be considered. The range of heritability of T2DM can vary from 20%-80%, depending on if one or both parents pass on the genetic predisposition (4). For example, if one parent has T2DM a child has a 40% chance of developing T2DM, the percentage is slightly increased if it the mother that is affected; this risk jumps to a staggering 70% if both parents are affected (2, 4). It should be noted that these risk values exist without the environmental contributions, such as obesity as defined by body mass index (BMI >30 kg/m2), sedentary lifestyle, and abnormal birth weight (2, 4).
Pathology of Type II Diabetes Mellitus
T2DM is characterized by the inability of pancreatic islet β-cells to produce adequate insulin to maintain blood glucose levels (4, 34). This can be due to the ever-increasing insulin insensitivity of target tissues such as muscle, hepatic, and adipose tissues or simply a physiological discrepancy within the pancreatic islet β-cells themselves that leads to reduce production and secretion of insulin (4, 34). Pathologically the cause does not matter as both conditions result in elevated fasting blood glucose levels (34).
The following information contained in this thesis will explore the various components of the prevention and treatment of T2DM. Areas assessed will include the diagnostic criteria as well as the metabolic processes contained within the disease. Furthermore, this thesis will aim to determine the optimal diet and exercise prescription for patients at risk of developing T2DM and patients with existing diagnoses.
SIGNIFICANCE OF THE PROBLEM
Incorporation of an exercise routine that has maximal positive effects on blood glucose and insulin levels
Exercise training, both aerobic and resistance, is notorious for its ability to regulate blood glucose levels. In fact, the positive effects of even a brief bout of high intensity exercise can be seen up to three days post exercise in patients with T2DM (1). Exercise not only regulates insulin secretion, but it also significantly increases insulin sensitivity (1, 23, 29).
Adherence to a well-balanced diet specifically tailored to Type II Diabetes Mellitus
Another key component of blood glucose regulation is diet. Foods high in carbohydrates often result a state of hyperglycemia (36). Furthermore, carbohydrates combined with fat result in decreased insulin sensitivity, increasing the risk if T2DM (4, 34, 36). This is often referred to as the glycemic index of foods; the higher on the glycemic index a food is the faster it is likely to spike blood glucose levels (6, 36, 39).
Combination lifestyle incorporating exercise and diet modification
With both diet and exercise training being factors in blood glucose and insulin levels, it can be inferred that the combination of a balanced diet and consistent exercise training will result in the highest overall benefits. Though exercise alone will help balance blood glucose and insulin levels, the dietary regulation is needed for the metabolic boost that will result in greater physiological changes towards a healthier individual (6, 23, 29, 36, 39). This combined approach will lead to a longer-lasting effect on insulin sensitivity (4, 34, 36).
REVIEW OF LITERATURE
Exercise and HbA1c levels
The modern diagnostic test for T2DM consists of an assessment of the levels of glycated hemoglobin, also known as HbA1c (19). It has nearly replaced the conventional method of the glucose tolerance test due its ability to depict a trend over the previous 120 days, the length of time a red blood cell lives within the human body, as well as the future clinical outcome (18, 19). The diagnostic threshold for T2DM is an HbA1c reading of 48mmol/mol (6.5%) or greater (19, 24).
Alkatan et al. (5) found that aerobic exercise training, specifically swimming and cycling, reduce HbA1c levels. These reductions are not only significant, but they are also long-term, provided the exercise program is consistent (5, 48). Yavari and colleagues (48) witnessed decreases up to 1.4% of HbA1c after the completion of a 16-week aerobic exercise-training program, which is incredibly significant considering the diagnostic value is 6.5% (19, 24). The simple program of three, thirty-minute days at 50-80% VO2max also yielded decreases in fasting blood glucose (~25 mmol/L) and body mass index (1kg/m2), leading to increased insulin sensitivity and decreased adverse affects of T2DM (1, 4, 34). The measured decrease in HbA1c is consistent with an increase in control of glycaemia and was directly related to exercise intensity and duration (4, 34, 48).
More rigorous than the Yavari study (48), Mavros and colleagues (33) found that after a 12-month progressive resistance training program of a higher intensity resulted in decreased HbA1c. Furthermore, Yardley et al. (47) found that resistance training, specifically weight lifting, had a much more pronounced lowering affect on HbA1c than any other aerobic training programs.
A person’s HbA1c level is frequently used as an indicator of insulin resistance. The resistance training model demonstrated that though aerobic training is effective at reducing body fat and, ultimately, insulin insensitivity, resistance training can be used as a tool for targeting insulin sensitivity alone (33, 48). Due to the fact that the methods of increased insulin sensitivity are different for different modes of exercise training, it can be inferred that the ideal exercise program would be a combination of both resistance and endurance training (33, 48). By combining endurance training and resistance training, the overall reduction in HbA1c values will be far greater than a training program of only one type. In fact, the addition of a mere 150 minutes of combined physical activity per week can lower a person’s HbA1c from above 8% to well below the highest acceptable value (38).
In studies utilizing animal models, specifically Wistar rats, it has been found that HbA1c cannot be lowered by diet alone, but must also have an exercise component. Furthermore, it was concluded that even in the presence of a high monosaturated fat diet, which is often known for its blood glucose lowering actions, HbA1c had no change until a treadmill exercise component was added according to a twice daily schedule five days per week (31, 42, 43). Based upon Sénéchal and colleagues’ (41) nine-month exercise training program, this could be attributed to the fact that an increase in fitness and the subsequent reduction of central obesity are the two prominent components of reducing a person’s HbA1c over a long period of time (42).
Exercise and Insulin Sensitivity
Insulin is one of the body’s most vital hormones as it allows the utilization of blood glucose within the tissues (49). Since most patients presenting with T2DM experience at least a minimally decreased level of insulin sensitivity, it is imperative to target improving insulin sensitivity in early care plans (1, 4, 23, 28, 29, 34). Furthermore, the general characteristic of the disease is a sedentary lifestyle leading to insulin resistance caused by subsequent obesity that then turns into pre-diabetes and progresses to the point of full-blown T2DM (8, 49). Simply adding a brief bout of light intensity walking after a meal can increase insulin sensitivity and lower the total amount of insulin secreted postprandial (8, 15, 49). For example, Vandanmagsar and colleagues (43) did a one-year intensive lifestyle intervention on ten obese males and found that this pathway is due to a chronic inflammation when the body, specifically the lrp3 inflammasome, senses that the person is obese, with a particularly high mass of abdominal adipose tissue. When the body senses this obesity, it activates the inflammatory response in an effort to rid the body of this toxin, this holds true in animal models as well (16, 43, 49). Unfortunately this inflammation is not enough to cure a person from obesity, thus the inflammation becomes chronic and does more harm than good in terms of the activation of insulin resistance (16, 43, 49). If this condition progresses without intervention, T2DM becomes more severe and eventually life threatening (14, 16, 28, 43). Insulin sensitivity will be optimally increased with a combined diet and exercise approach; however, it can surely be raised through exercise alone (14, 28). Interestingly Lee and colleagues (28) found in obese adolescent boys that resistance exercise alone is highly successful in improving insulin sensitivity by up to 27% while aerobic exercise does little to improve it. This finding can be attributed to the fact that resistance training increases skeletal muscle mass and, consequently, insulin use (8, 28, 40). One cannot forgo the consideration of the inflammation-reducing effects of exercise in this increased insulin sensitivity mechanism (16, 28). It is, however, important to realize that both aerobic and resistance training programs are beneficial to patients with T2DM (14, 16, 28, 43).
As mentioned previously, it is unfortunate for patients living with or at risk of developing T2DM, that the disease is often coupled with obesity and other mobility-limiting syndromes (8, 38). A sedentary lifestyle results in a dangerously low level of fitness, as measured by maximum exercise VO¬2, which is inversely proportional to incidence of T2DM development (8, 38). With the increase in insulin sensitivity from exercise alone, Reusch and colleagues (38) found that an at-risk person’s risk of developing T2DM can decreases as much as 58% over the course of three years (28). Dubé and colleagues (14) would actually argue that exercise alone is the one true controllable lifestyle factor that has a major, direct impact on the prevention and treatment of T2DM due to its insulin sensitivity reducing effects. Similar to Yuvari and colleagues (47), Dubé (14) implemented a sixteen-week program for previously sedentary adults and found that there are no age or gender restrictions for the insulin sensitivity increasing effects of exercise. It is, however, interesting to note that, unlike Lee and colleagues (28), Dubé (14) found that it is endurance exercise that improves a patient’s insulin sensitivity, based upon intensity level. One can infer that this is perhaps because the resistance training in Lee’s study (28) was quite intense in modality as a program of ten whole-body exercises for one hour three times weekly and so it is intensity that ultimately dictates the improvement of insulin resistance in patients with insulin sensitivity or T2DM (14, 38).
As some cases of limited mobility are low fitness levels are severe, practitioners will oftentimes resort to a pharmacological approach to increase insulin sensitivity and decrease obesity. Kanat and colleagues (25) determined that a combined pharmacotherapy and exercise regimen is effective lowering blood glucose values and, ultimately, insulin sensitivity. However, without the exercise component, a pharmacotherapy regimen alone is not successful at reducing obesity (25, 26).
As with all other medical diagnoses, there is no sense in waiting until a patient has reached a severe status of T2DM and mobility-limiting obesity to begin a preventative exercise program. It is worth mentioning that the T2DM preventative effects of exercise are not only obtainable when a patient receives a negative blood panel reading. In fact, Carter and colleagues (11) found promising evidence in animal models that maternal exercise can improve insulin sensitivity in the offspring through their lifespan. This is quite an important educational point to include in prenatal care as mothers can ultimately set their child on a pre-determined path towards T2DM or a disease-free life.
Glycemic Index Diet and Blood Glucose Levels
As briefly mentioned before, the Glycemic Index is simply a tool used by healthcare professionals to describe how quickly a food is broken down into its simple sugar, glucose, within the body (6, 36, 39). It is based upon the glycemic response to food in terms of blood glucose and insulin levels in regards to blood glucose levels within two hours of eating a food comparing 50g of its carbohydrate content to 50g of pure glucose (6, 30, 36, 39). For example, the way that it is normal for both blood glucose levels, due to the consumption of food, and blood insulin levels, due to the increase of blood glucose, to briefly rise and then regulate after a meal (30). It is interesting to note that though two food compounds may be nearly identical in carbohydrate content, they can widely differ in the amount in which they raise a person’s blood glucose, and, quite frankly, it isn’t really understood why that is (39). Furthermore, Sacks and colleagues (39) questioned whether or not the Glycemic Index is even a useful tool for tailoring a diet aiming to improve insulin sensitivity due to the fact that their study showed little to no improvement in insulin resistance when combining high and low levels are carbohydrates with high or low level foods as measured by the Glycemic Index. In fact, many people, not just healthcare professionals, disregard the viability of the Glycemic Index. However, Sacks (39) did find that a high carbohydrate dietary intake worsened insulin resistance by up to 20% even when the carbohydrates were low on the Glycemic Index furthering the assumption that there is a direct link between carbohydrate consumption and insulin resistance (6, 30, 36). Sacks and colleagues (39) did go on to reason that the Glycemic Index of a given food is only one of many nutritional attributes of foods high in carbohydrates. Furthermore, the Glycemic Index rating of a particular food could be heavily influenced by the other components such as fiber, potassium, or any other health benefiting components (39). This is particularly interesting when considering the benefits of whole grain foods, especially those with additional fiber content.
A study by Cho and colleagues (13) assessed the benefits of the addition of whole grain cereals, some with added bran as a fiber supplement, to the diets of people at increased genetic and lifestyle risk for T2DM. It was determined that the addition or increase, within recommended amounts, of whole grains and fiber into the diet of a patient with T2DM will not only be beneficial, but it is actually necessary for the proper regulation of the disease (13). Furthermore, the aforementioned nutrients are successful aids in decreasing a person’s chances for developing T2DM, regardless of risk level (13, 39).
A food high on the Glycemic Index will measure at about 65% on the glucose scale, with a food measuring around 40% being on the low end of the Index (39). However, many healthcare professionals agree that Glycemic Load, which is just a simply calculation of the percentage and the number of carbohydrates consumed, is more important to assess than Glycemic Index alone (39, 45). Historically foods with a lower Glycemic Index and Glycemic Load have coincided with a lower risk of developing T2DM, which is understandable considering it is simply a lower intake of glucose at any given time (20, 39, 45). This can also be examined in conjunction with the decreased abdominal adiposity that comes with decreased simple sugars, for example those carbohydrates that quickly digest and are higher on the Glycemic Index. Perhaps this also ties into the dietary benefits of whole grains and their ability to decrease abdominal fat (13).
It should be noted that unlike a mother’s ability to influence her child’s insulin sensitivity in-utero, an infant’s adiposity within the first year and beyond is not influenced by a mother’s Glycemic Index choices (11, 27). If the pregnant mother is at high risk for developing gestational diabetes or T2DM, a fetus’ birth weight may be affected (27). However, there seemed to be no correlation between a mother’s Glycemic Index consumption and her child’s future adiposity or weight (27).
Carbohydrates and Blood Glucose Levels
In order to reference the Glycemic Index, one must go further to define the role of carbohydrates in terms of blood glucose levels. As carbohydrates are digested, they undergo enzymatic hydrolysis, yielding the simplest form of organic sugar: glucose (22). The glucose is directly absorbed into the blood stream (39, 45). As blood glucose is raised, endogenous insulin secretion is increased to allow the uptake of glucose into working muscles (40). The higher a patient’s insulin resistance is, the greater the needed amount of endogenous insulin (8, 49). Unfortunately, for patients consuming a high amount of carbohydrates, which is greater than 45%, this creates an even bigger problem on their rapidly increasing insulin resistance (8, 17, 49).
With the direct increase of blood glucose levels, carbohydrate monitoring in patients with T2DM seems to be the perfect solution to the ever-growing epidemic. However, healthcare practitioners must consider the many things that can result in skewed data. From human error to a simple misunderstanding of varying dietary components, there are many things that can cause inaccuracies in estimating blood glucose based upon carbohydrate content alone.
For example, most patients who record and report their carbohydrate intake frequently make mistakes when counting carbohydrate content of meals (10). Though one might assume that the mistakes could balance out, for example a patient thinking one food item had less carbohydrate content than it actually did yet another food having more than it actually did, Brazeau and colleagues (10) found that patients made such significant mistakes that it resulted in a consistently higher blood glucose level throughout the management of their disease.
Dr. Wolpert, et al. (46) noted another possible error. It was found that dietary fat, completely independent of levels of carbohydrate consumption, has the potential to raise blood glucose levels (46). Consequently, insulin requirements were also increased resulting in a problem for patients trying to improve their insulin sensitivity (46). Interestingly when studying animal models such as the blunt snout bream, Li and colleagues (31) found that even a high carbohydrate diet was not responsible for inducing hyperglycemia when consumed in accordance with an optimum carbohydrate to lipid ratio. For patients desiring to adhere to appropriate carbohydrate guidelines, it is important that they also have a solid understanding of the importance of fat intake regulation as well.
It is imperative that practitioners consider these data sets and others when creating a specialized diet for patients with T2DM. If they were to put a patient on a very low- (ketogenic) to low-carbohydrate, with total energy levels coming from carbohydrate sources being no higher than 26%, yet high in fats, a patient could not only underestimate the amount of carbohydrates they are truly consuming, but they could be replacing their carbohydrate-laden foods with healthy fats that result in a higher than ever blood glucose level, and they would not understand why due to strict adherence to a specialized diet (10, 17, 31, 46).
Though carbohydrate tracking alone has been determined to be an invalid source of blood glucose measurement, the importance of a low-carbohydrate diet, which is 10%-26% of total daily energy intake, in lowering blood glucose levels and insulin resistance cannot be overlooked (3, 17). Ajala and colleagues (3) stress the benefits of reducing blood glucose concentrations with the simple reduction of carbohydrate consumption. It was found that a low carbohydrate diet led to a .12% reduction in HbA1c¬, a 0.69kg weight loss, and an increase in test subjects’ HDL (3).
Protein and Type II Diabetes Mellitus
Protein acts as an invaluable tool in the management and prevention of T2DM. With increased protein consumption, provided it is within a reasonable range of around 0.8 g/kg daily, can lead to increased satiety and resting energy expenditure (9, 25, 37, 44). It is important to note that Bray and colleagues found that protein consumption straying far from this value results in a “metabolically inefficient” diet (9). One of the great things about protein is that there are so many different types. For example, Whey protein can be found in milk or thousands of different supplements. Plant-based soy protein can both increase satiety and fiber content (44). Though animal protein has received mixed reviews regarding the health impacts, both positive and negative, it yields; one must recognize the widely popular reputation it still holds and the fact that it is perhaps one of the easiest sources of protein to obtain and consume at higher levels.
Though animal muscle protein is quite popular, whey protein is beginning to gain momentum in regards to health benefits, both long and short term. Jakubowicz and Froy (25) determined that dietary whey protein possesses a promising potential for the prevention and treatment of T2DM. One benefit of whey protein consumption is its food intake controlling properties (25). Increased satiety in subjects consuming a higher amount of whey protein resulted in decreased obesity and over-eating behaviors (25). This portion control property alone is substantial due to the fact that T2DM is often the result of obesity, which is easily connected to over eating (6, 23, 25, 29, 36, 39). Furthermore, whey protein has been shown to lower blood glucose levels in both T2DM patients and healthy subjects (25). Jakubowicz and Froy (25) believe these effects to be induced through specific bioactive proteins generated during digestion of the consumed whey protein. The extensive pathways that result from the digestion of whey protein have been known to lead to increased insulin regulation and, in turn, insulin sensitivity (4, 25, 34).
It is worth noting that Badr (7) also found interesting pathways in regards to whey protein consumption and T2DM. It was discovered that supplementation with undenatrued whey protein resulted in a more efficient healing and closure of wounds associated with T2DM, including in patients with chronic wounds facing amputation (7). This improvement led to decreased inflammation, one of the major causes of T2DM (7, 16, 43, 49). With the simple reduction in inflammation and diabetic wounds, patients can be expected to have a higher willingness to exercise and improve existing diagnoses.
Nielen and colleagues (35) examined various postmenopausal women presenting with upper levels of abdominal obesity, progressing towards metabolic syndrome. Going off of the belief that increased protein consumption yields preventative health benefits, the effects of soy and animal proteins were compared (9, 25, 35, 37, 44). At the conclusion of the four-week study, test subjects were observed to have significantly lower, 12mU/L, insulin sensitivity (35). If these values are indeed accurate, and Nielen and colleagues (35) seem to believe that they are, the implementation of soy protein in the diets of at-risk patients can significantly lower the possibility of developing T2DM or allowing a current diagnosis to progress beyond a level of relatively simple control. Insulin resistance is one of the leading characteristics of T2DM and this can be easily improved by a simple switch in protein source (1, 4, 23, 28, 29, 34, 35). Furthermore, the soy protein consumption appeared to yield a lower adiposity across both groups of test subjects (35). Lower adiposity, thus decreased abdominal obesity, is widely accepted as a decreased risk for developing T2DM (35, 41, 42).
SUMMARY AND CONCLUSION
Exercise Has Positive Effects On The Maintenance of Type II Diabetes Mellitus
Exercise offers significant health benefits to every person, but the benefits are profound in patients with T2DM. When engaging in a long-term, consistent program, patients can expect to reap the benefits of exercise for days after exercise has ceased (1, 5, 48). With HbA1c levels being the current diagnostic assessment for T2DM, the fact that exercise directly reduces these values provides patients with a means to easily become proactive in lessening their diagnosis and receiving a more customized plan of action (5, 19, 24). Though a short bout of intermediate intensity exercise can yield three days worth of benefits, the exercise must be consistent to yield HbA1c improvements, allowing healthcare providers to get a genuine look at a patient’s lifestyle changes (1, 5, 19, 24, 48).
Exercise also yields decreased obesity resulting in increased insulin sensitivity (1, 4, 8, 23, 28, 29, 34, 49). By decreasing obesity-induced inflammation, the body will better revert to needing normal levels of insulin for day-to-day operations (43). It is important, however, to remember that many patients with T2DM also suffer from inflammation and obesity-induced limited mobility, and thus require specialized programs to slowly integrate an exercise regime (8, 38, 43).
Diet Modification has Positive Effects on the Maintenance of Type II Diabetes Mellitus
As there are many dietary contributors for obesity and subsequent T2DM such as imbalanced nutrients, decreased satiety, and metabolic factors, it is imperative that healthcare providers adequately educate their patients on the importance of dietary control. For example, simply regulating the number of carbohydrates a person consumes will have a direct lowering effect on their blood glucose levels (3, 6, 30, 36, 39). Though there are mixed reviews on utilizing the Glycemic Index as a tool for monitoring carbohydrate content, one must argue the benefit of using it in conjunction with other tools to assess the value of carbohydrates consumed (6, 30, 36, 39). As noted by Cho and colleagues (13), though whole grain cereals and bran-based fiber supplements are carbohydrates, they offer preventative abilities for patients with pre-diabetes and assist with the disease regulation for patients with existing diagnoses.
Another great regulatory nutrient for patients suffering from T2DM is protein. Provided that consumption remains within the recommended range, patients can expect to see a more efficient metabolism and increased satiety (9, 25, 37, 44). It is important, however, to remind patients that the consumption of red meat, one of the most commonly consumed forms of protein, can result in the over-consumption of fat that can ultimately lead to increased insulin resistance, blood glucose levels, and abdominal obesity (4, 25, 34, 36, 46).
A Combination Lifestyle Has the Greatest Positive Effects on the Maintenance of Type II Diabetes Mellitus
Though the benefits of both exercise and diet regulation are independently valuable for patients with T2DM, the two lifestyle factors must be combined for maximal benefits (4, 6, 23, 29, 34, 36, 39). The metabolic benefits from diet modification will help increase the benefits gained from regular exercise resulting in a more stable blood profile in terms of insulin and glucose levels (6, 23, 29, 36, 39). Both dietary regulation and incorporation of an exercise program will yield mobility benefits that will allow the patient to continuously increase their exercise intensity and, as a result, continuously increase their level of health (3, 6, 8, 30, 36, 38, 39, 43). With diet and exercise being the most important controllable factors in the development and progression of T2DM, healthcare providers must strive to educate their patients on the importance of these lifestyle characteristics. Unfortunately it remains unclear what the optimal combination lifestyle actually is. Though we know how valuable both diet and exercise is in the lives of patients at risk of developing T2DM or worsening their diagnoses, it remains apparent that the exact combination is unique to each individual (3, 4, 6, 8, 23, 29, 30, 34, 36, 38, 39, 43).
Weaning From Medication to Control Type II Diabetes Mellitus by the Careful Maintenance of A Balanced Lifestyle
As the management benefits of combined exercise and diet modification were previously outlined, one must eventually hypothesize that a diligent adherence to a balanced lifestyle can ultimately lead to such an improvement that pharmaceuticals are no longer needed to regulate insulin secretion. As exercise and proper diet both result in decreased obesity and blood glucose, over a possibly lengthy period of time there is no reason that a patient would need medication to assist in the regulation of these levels.
Optimal Exercise Methods for the Control of Type II Diabetes Mellitus
With the hopes of medication weaning, it would be detrimental to determine the optimal exercise prescription for patients hoping to regulate their T2DM with lifestyle changes alone. Perhaps a balance between resistance and endurance training yields maximal benefits. However, without future research on type, intensity, and duration, it would be incredibly difficult to offer a standardized exercise prescription for the management of T2DM.
Optimal Dietary Practices for the Control of Type II Diabetes Mellitus
As with exercise methods, the ideal dietary practices remain undetermined. Speculation results in the expectation that patients will need a more customized dietary plan to follow than a simple research study could yield. However, deeper research on the direct effects of all nutrients on blood glucose, insulin levels, and obesity factors could result in a more efficient tool for diet modification. With a tailored plan, patients could be expected to follow a diet more closely.
Demographic Considerations and Type II Diabetes Mellitus
Many of the current research populations are very specific. For example, all subjects are the same biological sex or within the same age range. It would be beneficial to compare populations to hopefully detect a commonality between patients suffering from T2DM. Furthermore, it would be interesting to assess the benefits that carry over from childhood to adulthood in regards to the development of T2DM in obese children.
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