Diabetes mellitus is a disorder of glucose metabolism that affects millions of athletes of all types around the world. It is caused by either an absolute (type 1 diabetes) or relative (type 2 diabetes) deficiency in insulin, the principal hormone that regulates carbohydrate and fat metabolism. Diabetes mellitus is one of the most common chronic medical illnesses to be encountered by sports medicine specialists, coaches, and athletic trainers who work with adolescent and young adult athletes. Two other classifications of diabetes, gestational and overt, are both associated with pregnancy and are also associated with a relative insulin deficiency. In the former, glucose metabolism is normal at the time of conception and early in pregnancy. However, as the pregnancy progresses, glucose intolerance develops as a result of placental hormones that induce insulin resistance in the mother. The latter category is a new classification created by the International Association of Diabetes in Pregnancy Study Groups. In women with overt diabetes, glucose intolerance or frank diabetes exists at the time of conception or early in pregnancy, but it is undetected or undiagnosed. Although women with gestational or overt diabetes may represent only a small fraction of the athletes competing with underlying diabetes, good control of blood glucose is especially important in these women to protect the health of the mother and the fetus.
Exercise and athletic activity, together with medication and diet, have long been cornerstones in the treatment of diabetes and the subsequent prevention of long-term complications that affect the eyes, kidneys, and cardiovascular and nervous systems. However, the alterations in metabolism that occur during athletic activity—specifically those related to the control of blood glucose—can often present a significant challenge for the athlete with diabetes, along with his or her coaches and care providers. Athletic activity, if not properly managed, can increase the risk for the short-term complications of hypoglycemia or significant hyperglycemia, especially in athletes with type 1 diabetes. Both of these metabolic disturbances can have a negative impact on athletic performance. Athletes with diabetes must commit to understanding their illness, and they must expend considerable effort to record and analyze the impact of different activities on their blood glucose levels. In addition, all persons involved in the care of an athlete with diabetes need to have a basic understanding of the metabolic changes that accompany the disorder, how they are influenced by exercise, and methods of testing and treating diabetes so they can promote both good health and ideal performance.
In general, the incidence of diabetes mellitus is increasing worldwide. Recent data published by the American Diabetes Association show an alarming increase in incidence in children and young adults in the United States. In 2011, 25.8 million children and adults, or 8.3% of the total population, were known to have either type 1 or type 2 diabetes. Seven million of these persons were thought to be undiagnosed. Equally concerning is the staggering number of U.S. citizens with “prediabetes,” determined by a fasting glucose or hemoglobin A1c that is elevated but not yet in the range of diabetes. This at-risk group of 79 million people includes both children and adults. The vast majority are at risk for type 2 diabetes and, with lifestyle modifications, can substantially lower their chance of ever developing diabetes.
The prevalence of diabetes in children and adolescents is also alarming; nearly 1 in every 400 has diabetes, or 0.23% of this population. The biggest increase has been in type 2 diabetes. This increase is related to the increasing number of children and adolescents who are overweight or obese and is also likely due to negative factors in nutrition and lifestyle. However, the incidence of children with type 1 diabetes has been increasing rapidly worldwide as well and has been quite striking in certain regions of the United States. Because of the substantial increase in the number of children, adolescents, and young adults with diabetes, it is quite likely that persons involved in the management of sports will encounter athletes who have diabetes with increasing frequency.
Type 1 and Type 2 Diabetes
Most athletes with diabetes are already aware of their disease when they enroll in athletic activity. However, because the incidence in children, adolescents, and young adults is considerable, it is important that coaches and athletic trainers be aware of the symptoms of hyperglycemia. When an athlete experiences a significant (>180 mg/dL) and persistent elevation of blood glucose levels, the resultant osmotic diuresis leads to dehydration and a hyperosmolar state. Symptoms of hyperglycemia include blurry vision, polyuria, nocturia, and polydipsia. Moreover, as the body adapts to a progressive catabolic state, weight loss is common and can be profound. Coaches and athletic trainers associated with the athlete are more likely to first notice subtle signs of hyperglycemia, such as easy fatigability or malaise. A thorough evaluation and the initiation of treatment at that time may help prevent the more serious complications of hyperosmolar coma or diabetic ketoacidosis. Although it would be difficult for an athlete to continue to practice or play regularly in the setting of such a metabolic disturbance, these critical states will eventually develop in the absence of treatment.
In the presence of any of the symptoms of hyperglycemia, a random glucose level of greater than 200 mg/dL is diagnostic of diabetes mellitus. However, in asymptomatic persons, several tests are accepted as diagnostic. First, a fasting plasma glucose of 126 mg/dL or greater (repeated once for confirmation) is diagnostic. A second and more convenient method is the measurement of a hemoglobin A1c level; values of 6.5% or greater are also diagnostic of diabetes. Finally, an oral glucose tolerance test (OGTT) can be performed. However, performing the OGTT is inconvenient for the patient, and thus it has been largely replaced by the measurement of hemoglobin A1c levels as the gold standard in determining the presence of diabetes. The exception is during pregnancy, when the OGTT remains the only accepted diagnostic test. These tests only establish the diagnosis of diabetes and do not distinguish between type 1 and type 2. Although serum testing for autoimmunity (such as anti–glutamic acid decarboxylase or islet cell antibodies) or measurement of endogenous insulin secretion (C-peptide) can be performed to differentiate type 1 from type 2 diabetes, they lack the sensitivity and specificity to justify their widespread use. Instead, the distinction is generally determined by clinical characteristics or response to medications. Patients with type 1 diabetes generally are lean and active and usually have few or no other family members with the disease. They may have or be at risk for other autoimmune disorders. Patients with type 2 diabetes are generally obese, sedentary, have a strong positive family history of diabetes, and are often members of a high-risk ethnic group, such as African American, Asian, Asian American, Latino, or Pacific Islander. In past decades, patients with type 1 diabetes were generally younger at the time of diagnosis and those with type 2 diabetes were generally middle-aged or older, but this distinction has been blurred considerably in recent years. It is now recognized that patients with type 1 diabetes can be diagnosed as older adults. Additionally, in some regions of the United States, a child with newly diagnosed diabetes is more likely to have type 2 than type 1 diabetes.
Both fasting serum glucose values and hemoglobin A1c can be used to detect persons most at risk for the development of frank diabetes. Fasting values between 100 and 125 mg/dL and hemoglobin A1c values between 5.7% and 6.4% are considered abnormal but are not a definitive sign of diabetes. Persons with values in these ranges should be monitored closely. Persons at risk for type 2 diabetes should institute lifestyle modifications to delay or prevent the progression to full-blown disease.
Overt and Gestational Diabetes
Once the gold standard for diagnosing diabetes, the OGTT is now used almost exclusively for the diagnosis of gestational diabetes. The American Diabetes Association and the International Association of Diabetes and Pregnancy Study Groups currently recommend a 2-hour test, with measurements of serum glucose while fasting and at 1 hour and 2 hours after glucose ingestion when the woman is between 24 and 28 weeks of gestation. Any pregnant woman with one or more values greater than the target range is diagnosed with gestational diabetes. Women who are screened earlier in pregnancy and are found to have an abnormal fasting (>126 mg/dL) or random (>200 mg/dL) glucose level or a hemoglobin A1c level greater than 6.5% are assumed to have abnormal glucose metabolism that existed prior to pregnancy and are categorized as having overt diabetes. Exercise is a routine recommendation for pregnant women with any type of diabetes, and thus the guidelines referenced later in this chapter should also be considered for them.
Monitoring After Diagnosis
Monitoring technology has improved dramatically during the past three decades and now allows athletes with diabetes to know the value of their blood glucose levels in real time. The most widely used method employs a handheld device (a glucose meter) that measures capillary glucose, which is obtained by lancing the skin. The meters are thought to be highly accurate except when measuring values in the extreme ranges of hypoglycemia or hyperglycemia. The main disadvantages for athletes is that a single measurement does not show the rate or direction of change of glucose over time and that most athletic activity must be stopped to perform a measurement. A second, newer method used by some athletes involves continuous monitoring of tissue glucose (continuous glucose monitoring; CGM) by a sensor placed under the skin. The results are wirelessly communicated every 10 to 20 minutes to either a separate handheld device or an insulin pump. This method is clearly superior to a traditional glucose meter because the athlete does not have to stop athletic activity for a measurement to be made. Moreover, frequent glucose values plus any rate of change can be observed. However, this system has several disadvantages, including inaccuracy in the range of hypoglycemia, inaccuracy caused by sweating, and the need for the athlete to wear an external device (or potentially two devices if the athlete is also using an insulin pump). The latter issue may be especially challenging for athletes involved in contact sports.
In addition to its use as a diagnostic test, hemoglobin A1c levels can be followed to determine the degree of maintenance of blood glucose levels within target range. In general, a hemoglobin A1c level of 7.0% or less is considered to represent good control, with control becoming increasingly poor as the level increases. When good control is maintained, athletes should be able to exercise or compete safely without concern for sudden deterioration of glucose control or ketone production, which is especially relevant for athletes with type 1 diabetes. Each athlete should consult with his or her health care provider to determine if exercising or competing is safe when glucose values are elevated.
Urine ketone testing is recommended when glucose values are consistently elevated (>250 mg/dL), or before an athletic event of significant intensity or endurance when the production of ketones may be expected. It is carried out with a strip dipped into a fresh urine sample and uses a reaction of alkali and nitroprusside, which provides a semiquantitative measurement of the ketone acetoacetate. Any athlete with ketones present in urine prior to training or intense competition should suspend athletic activity until the ketonuria is resolved.
An in-depth discussion of all the treatment modalities used for persons with diabetes mellitus is beyond the scope of this chapter; however, each person involved in the care or performance of an athlete with diabetes should be familiar with the basic families of medications and the expected actions and potential problems with their use during athletic competition.
Medical Nutrition Therapy
Part of the triad of treatment for patients with type 1 and type 2 diabetes involves careful attention to diet and regular exercise. Patients with diabetes are at risk for cardiovascular disease, and many patients with type 2 diabetes are obese. Therefore medical nutrition therapy is recommended not only to help normalize blood glucose levels but also to help achieve targets for blood pressure and lipids. Patients with type 1 diabetes generally focus on balancing the amount of carbohydrate in meals and snacks with administered insulin, but persons with type 2 diabetes are often prescribed a low-calorie and/or low-fat diet to enhance weight loss. Specific recommendations for carbohydrates include choosing from a wide variety of fruits, vegetables, legumes, and grains and to avoid excess energy intake that might come from foods and beverages that contain sucrose. Saturated fat should be limited to less than 7% of calories, with minimal intake of trans fat and a limit of 200 mg per day of cholesterol. Protein intake should constitute 15% to 20% of caloric intake. Very high protein diets are not recommended because their long-term effect on kidney function has not been established in the setting of diabetes.
Oral Hypoglycemic Agents
Several types of oral hypoglycemic agents (OHAs) are available in the United States. None is useful in the treatment of type 1 diabetes, because some endogenous insulin secretion is necessary for them to be clinically effective in this population.
Sulfonylureas are insulin secretagogues. They increase endogenous insulin levels in the absence of food intake and can cause hypoglycemia, especially if taken prior to exercise. Glucose levels should be carefully monitored during training and competition so the athlete can decide whether reducing or withholding their use is necessary to prevent hypoglycemia.
Metformin is a member of the biguanide family and is an insulin sensitizer. Although it does not lead to an increase in endogenous insulin levels, like sulfonylurea agents, its effect should be carefully monitored in athletes with type 2 diabetes to determine if it should be reduced or withheld during training and competition.
Alpha-glucosidase inhibitors alter the absorption of starch from the gut. This effect leads to a slower and smaller increase in postmeal glucose excursion. Patients have had difficulty tolerating these agents because of the adverse effects of flatulence and diarrhea.
Thiazolidinediones are peroxisome proliferator-activated γ-receptor agonists that enhance insulin sensitivity. Because of a number of adverse effects, their use has been restricted in the United States. The common adverse effects of weight gain and edema makes their use particularly unattractive in athletes with diabetes.
Meglitinides lead to an increase in insulin synthesis within cells. Insulin is then released when it is triggered naturally by food intake. Although the theoretic risk for hypoglycemia is less than that seen with sulfonylureas, the same care should be given to individualize their use in athletes with type 2 diabetes after careful testing has been performed during training.
Dipeptidyl peptase-IV (DPP-4) inhibitors are a relatively new class of oral agents used in the treatment of type 2 diabetes that do not involve the secretion of synthesis of insulin but utilize the incretin pathway to lower blood glucose levels. DPP-4 agents are not believed to cause hypoglycemia, but their use in athletes is limited.
Ideally, as patients with type 2 diabetes lose weight, become better conditioned with exercise, and experience an increase in insulin sensitivity, they can eliminate the need for OHAs from their regimen.
Insulin and Insulin Analogs
Several types of recombinant human insulin and insulin analogs are available in the United States. Many patients with type 2 diabetes use insulin in addition to or in the place of OHAs to control their blood glucose levels, but patients with type 1 diabetes are dependent on exogenous insulin to live. Most regimens use a combination of long-acting (basal) and short-acting (bolus) injected insulin to approximate the secretory patterns found in normal islet call physiology. Continuous insulin infusion (insulin pump therapy) has the capacity to deliver insulin in much smaller increments in either a basal (continuous) pattern or as a bolus designed to cover mealtime excursions in blood glucose. Pumps infuse only short-acting insulin analogs, which might be an issue for athletes who want or need to suspend pump therapy for an extended period. The pharmacokinetics of the various insulins and their durations of action can be found in Table 21-1 .
|Aspart (NovoLog)||5-15 min||45-90 min||3-4 hr|
|Glulisine (Apidra)||5-15 min||45-90 min||3-4 hr|
|Lispro (Humalog)||5-15 min||45-90 min||3-4 hr|
|Regular||30-60 min||2-4 hr||5-6 hr|
|Neutral protamine Hagedorn (NPH)||1-3 hr||4-6 hr||8-12 hr|
|Detemir (Levemir)||1 hr||6-8 hr||12-24 hr|
|Glargine (Lantus)||1 hr||–||24 hr|
Incretin and Islet Amyloid Polypeptide Therapy
Incretins are peptides found in the gastrointestinal tract that act to lower glucose by pathways that are independent of the insulin receptor. The two currently recognized forms are glucagon-like peptide-1 and gastric inhibitory peptide. A commercially available glucagon-like peptide-1 agonist, exenatide, acts to lower blood glucose by delaying gastric emptying, inhibiting glucagon secretion, and increasing insulin secretion after a meal. DPP-4 is an endogenous enzyme that inactivates the incretins. Several oral DPP-4 inhibitors are available as pharmacologic antidiabetes agents (as previously described). These agents act to prolong the activity of endogenous incretins. Little experience has been accrued with either incretins or the DPP-4 inhibitors in the setting of athletic training or competition; however, adverse effects of exenatide include hypoglycemia, and it should be used with caution before or during exercise. Although it is not commercially available in the United States, Islet Amyloid Polypeptide (pramlintide) is a peptide that is normally cosecreted with insulin from the pancreas. Its method of action is very similar to that of incretin therapy, and the risk of hypoglycemia with exercise is also a concern.
Physiologic Changes of Exercise in Healthy Athletes and in Athletes with Diabetes
A comprehensive review of the very complex changes that occur during exercise in healthy persons can be found elsewhere. However, because critical changes occur in glucose metabolism during exercise and recovery, it is important that persons who are managing athletes with diabetes have a basic understanding of what occurs during both aerobic and anaerobic metabolism.
Glucose Regulation During Exercise
Maintenance of a normal plasma glucose level during exercise depends on a precise balance between fuel mobilization and utilization. The exercising muscle fiber can increase its metabolic rate and production of adenosine triphosphate tremendously, with oxidative processes 50 times higher than resting levels and glucose uptake 35 times higher than resting levels. Primary sources of energy include (1) fat and carbohydrate present in muscle and (2) glucose released from the liver as a result of glycogenolysis, that is, the breakdown and mobilization of stored glycogen. The relative contributions of these sources vary with the duration and intensity of exercise. When exercise begins, muscle glucose uptake increases, and muscle glycogen is the primary source of energy. After 20 to 30 minutes of activity, energy is derived from a combination of hepatic-derived glucose and adipose-derived free fatty acids. With prolonged exercise (60 to 90 minutes), free fatty acids become the principal energy source. Glycogen remains an important fuel, with the depletion of muscle glycogen coinciding with the time of exhaustion. Intensity of exercise is measured by the percentage of the individual’s maximum oxygen consumption (V o 2 max ) required for fuel usage. During exercise at a high intensity, oxidation of glucose for energy predominates; with less intense exercise, fat usage is preferred. Physical training enables the athlete to perform the same work at a lower percentage of V o 2 max and to conserve glucose and improve endurance by using a greater proportion of free fatty acids.
Insulin is an important anabolic hormone that regulates carbohydrate and fat metabolism during exercise. Insulin increases the uptake of glucose into muscle and adipose tissue, suppresses the production of glucose by the liver, increases glycogen synthesis, and inhibits fat and protein degradation, encouraging growth and preventing weight loss and tissue breakdown. Decreased levels of insulin lead to an increase in lipolysis or fat breakdown. Thus the appearance of ketones (products of fat breakdown) in the blood or urine of a diabetic patient signifies marked insulin deficiency.
When exercise begins, a number of hormonal responses occur to provide energy to the exercising muscles and maintain blood glucose levels in a normal range. The body decreases its release of insulin and increases its release of glucagon from the pancreas ( Fig. 21-1 ). This decrease in insulin allows for increased hepatic glycogenolysis and facilitates lipolysis and the liberation of free fatty acids and glycerol (used with lactate, pyruvate, and alanine as precursors for gluconeogenesis). The rise in glucagon is required for hepatic glycogenolysis and gluconeogenesis. This suppression of endogenous insulin release and increased secretion of hormones, such as glucagon, that oppose the actions of insulin (counter regulatory hormones) allow hepatic glucose production to increase, satisfying the demands of exercising muscle ( Table 21-2 ). Exercise stimulates insulin-independent glucose uptake and potentiates insulin action. These actions compensate for declining insulin concentrations and facilitate delivery of substrate to exercising tissues. The exact mechanism by which exercise independently stimulates glucose transport into muscle remains incompletely understood. Muscle contraction stimulates muscle glucose uptake in vitro in the absence of insulin. Some evidence also indicates that insulin-independent glucose uptake is related to an increase in plasma membrane glucose transporter number.