Type 1 diabetes mellitus (T1DM) has a prevalence of 0.2% in the American adolescent population . T1DM represents a chronic metabolic disease characterized by a relative or absolute insulin deficiency. The disorder begins when an autoimmune response due to an unknown environmental trigger destroys the insulin-producing islet cells in the pancreas . Typically, this is a gradual process occurring over months that accounts for the gradual onset of symptoms, including easy fatigability, muscle soreness, polydipsia, and polyuria . As the insulin deficiency in T1DM develops, exogenous insulin is required as a mainstay of therapy in order to avoid the complications of hyperglycemia, ketoacidosis, and death [1,2].
T1DM in the athlete poses numerous challenges to both the patient and sports physician. With proper management, diabetic athletes compete at all levels of sports, from recreational to professional, including endurance events. This review focuses on the benefits and risks of exercise for the type 1 diabetic and will aid the sports medicine physician in understanding the body's metabolic response to exercise, the physiologic effects of exercise in those with the disease, and management strategies to prevent both hypo- and hyperglycemia.
Metabolic Response to Exercise
Before discussing glucose regulation during exercise in T1DM, an understanding of normal glucose metabolism during exercise is necessary. The body undergoes numerous physiologic changes when exercising in order to respond to rising energy needs. One specific change involves balancing the glucose utilization by muscle and the mobilization of fuel sources from other tissues. The primary fuel sources during exercise are divided into those present in muscle, including glycogen and triglycerides, and extramuscular sources such as glucose, released into the blood stream from stored glycogen in the liver (glycogenolysis), and fatty acids, mobilized from adipose tissue . The fuel source used varies with the intensity and duration of exercise.
The initial energy source during exercise is muscle stores of ATP and phosphocreatine. These initial stores can supply sufficient energy for muscles during short-term, high-intensity exercise bouts lasting from approximately 2 to 30 seconds . ATP is initially replenished by the anaerobic breakdown of muscle glycogen to form lactate. As exercise duration increases, aerobic metabolism predominates with an increase in gluconeogenesis by the liver from rising muscle lactate and release of free fatty acids (FFAs) from adipose tissue.
With prolonged exercise, muscle becomes more dependent on plasma (or blood-borne) glucose and FFA levels. Exercise duration of 60 to 90 minutes necessitates usage of FFAs as the main energy source. Endurance athletes adapt to use FFAs for energy preferentially over glycogen stores. This use of FFAs helps lower the production of lactate . Further, this adaptation is beneficial in fitness training, reducing glycogen depletion in muscle. The level of muscle glycogen has been shown to correlate with the timing of exhaustion during exercise .
During exercise, muscle glucose requirements are mediated by complex hormonal and autonomic responses, the effect of which increases liver glycogenolysis and gluconeogenesis, as well as the mobilization of FFAs from adipose tissue. During exercise, the body responds by lowering plasma insulin levels due to elevated sympathetic tone and conversely increasing the secretion of glucagon, cortisol, and growth hormone. These processes, coupled with the increased sensitivity of muscle to insulin, lead to a rise in glucose transport into muscle (Fig. 1) .
Glucose uptake into skeletal muscle is facilitated by the transporter protein, GLUT4. In contracting muscles, GLUT4 protein is recruited to the mitochondrial membrane in conjunction with, but independently from, insulin [6•]. The physiologic hormonal and autonomic changes satisfy the glucose requirements of exercising muscle and help to avoid hypoglycemia.
Exercise in the Type 1 Diabetic
For the patient with T1DM, the normal variations in insulin and regulatory hormone levels during exercise cannot occur endogenously. Glucose homeostasis requires exogenous insulin administration; due to the need of exogenous insulin, there are ongoing challenges to balancing glucose levels and insulin availability. Proper adjustments in insulin dosing are needed prior to exercise but adequate carbohydrate replacement during and after exercise appear to have the most profound effect on preventing hypoglycemia [7••]. The consequences of improper insulin injections can lead to excessive or inadequate insulin levels. When a hyperinsulinemic state occurs, hepatic glucose production is suppressed. This often occurs in conjunction with deficient glucagon and other regulatory hormone secretion [7••]. Furthermore, exercising muscle increases its insulin-independent uptake of glucose. As a result, with hyperinsulinemic states and inadequate caloric intake adjustments, hypoglycemia may occur during, immediately after, or several hours after exercise. When an athlete has an episode of hypoglycemia, that athlete is at an increased risk of further episodes of hypoglycemia due to depletion of counter regulatory hormones [8••]. Each athlete is different in his or her response to exercise, and individualization of insulin dosage and nutrition before, during, and after exercise is critical to prevent hypoglycemia.
Postexercise hypoglycemia has been documented in the type 1 diabetic occurring 6 to 24 hours after activity, often termed late-onset hypoglycemia [2,9•]. In the hours following exercise, muscle and hepatic glycogen levels are restored by using circulating plasma glucose. Postexercise resting muscle has an increased insulin sensitivity with a resultant enhancement in glucose uptake. When these physiologic processes occur, they lead to late-onset (and often nocturnal) hypoglycemia. Late-onset hypoglycemia seems to occur most often with an increase in exercise intensity or duration such as occurs when an athlete increases level of competition (eg, high school to college) or with two a day practices at the beginning of the sport's season.
In contrast to excess insulin leading to hypoglycemia, the exercising diabetic also faces the risk of hyperglycemia. In response to exercise in the normal athlete, plasma glucose levels rise due to a suppression of insulin release, an elevation in glucagon, and activation of the sympathetic nervous system. Plasma glucose levels fall to normal levels after exercise when insulin is secreted and regulatory hormones such as glucagon and epinephrine decline. In T1DM, plasma glucose remains elevated after exercise due to the absence of elevation in postexercise insulin level. This typically occurs after intense exercise in the poorly controlled diabetic in whom pre-exercise glucose levels are elevated. In the hypoinsulinemic state, glucose uptake is impaired while hepatic glucose production, lipolysis, and ketogenesis are all elevated . This may result not only in hyperglycemia but also hyperlipidemia, and in the more severe cases, ketoacidosis and coma.
Benefits and Risks of Exercise
In contrast to the well-known exercise benefits for type 2 diabetes, no such obvious benefit has been found concerning prevention of T1DM and direct lowering of hemoglobin A1c (HbA1C) . Nevertheless, exercise is beneficial for persons with T1DM by preventing other complications commonly found with diabetes [9•]. Athletic participation by those with T1DM should be encouraged so they may achieve the same cardiovascular health benefits as other exercising individuals. People with type 1 DM are at increased risk for macrovascular disease compared with the general population, but exercise has been shown to be beneficial in decreasing blood pressure, total cholesterol , and low-density lipoprotein cholesterol , and increasing high-density lipoprotein cholesterol. Exercise increases insulin sensitivity in T1DM and lowers insulin requirements . Promotion of exercise and participation in athletics in this patient population helps maintain ideal body weight, improves self confidence, and is an important part of high-quality care.
In addition to the risks of hypoglycemia and hyperglycemia documented earlier, other precautions, linked to complications from the disease, need to be noted. In people with longstanding diabetes, cardiovascular manifestations such as atherosclerosis increase the risk for angina, myocardial infarction and arrhythmias. During exercise, resultant hypertension may lead to retinal and vitreous hemorrhages. Peripheral neuropathy may lead to loss of sensation in the feet, making diabetic ulcers and traumatic injury more likely. Autonomic neuropathy may cause orthostatic hypotension and inadequate elevation of heart rate during exercise. Patients with autonomic neuropathy are less capable of performing strenuous exercise due to this inability to reach a maximal heart rate. Blunted autonomic response may also lead to poor vasoconstriction making exercise in the cold more difficult. Therefore, a thorough physical examination and proper screening for diabetic complications are needed prior to the start of an exercise program in athletes with T1DM. In the younger, well-controlled diabetic, the benefits of exercise far surpass the risks. With the presence of diabetic complications, the athlete and physician must work together to ensure safe and prudent participation.
When evaluating an athlete with T1DM, the physician must focus on the patient's knowledge of the disease and initiation of habitual monitoring of blood glucose. The preparticipation evaluation of the diabetic athlete is outlined in Table 1 . Commitment to a program that establishes adequate metabolic control is critical for safe athletic participation. Self-monitoring of blood glucose four times each day is advisable, as well as measuring urinary ketones prior to exercise. During any prolonged sporting event, blood glucose should be monitored before, during, and after exercise.
Education on the possibility of hypoglycemia and it's symptoms should be reviewed in detail. The physician should ask about the frequency of hypoglycemic episodes, if any, and the patient's ability to detect them. Further, the patient should understand the strategies for treatment of early, mild hypoglycemia. All athletes with diabetes should wear a medic-alert bracelet and should keep subcutaneous or intramuscular glucagons available in the event of severe hypoglycemia.
Lastly, the physician should investigate carefully for the presence of existing diabetic complications. Diabetic patients require a focused cardiovascular and musculoskeletal examination due to the higher incidence of coronary artery disease and peripheral neuropathy. Screening for hypertension, neurologic dysfunction, joint mobility, retinal function, and skin integrity is required during every physical examination. Laboratory screening should include a fasting lipid profile, especially if family history suggests premature coronary artery disease or stroke. Urine screening for proteinuria should be performed to monitor for presence of diabetic nephropathy, and yearly ophthalmology examinations are required to evaluate for diabetic retinopathy.
There are times when exercising worsens metabolic control or increases complications from diabetes. When metabolic control is poor (HgbA1C > 9), the athlete should obtain adequate control prior to initiation of moderate to severe exercise. An elevated HgbA1C is indicative of poor long-term glucose control, and if blood glucose is persistently high, the athlete is at risk for hyperglycemia and diabetic ketoacidosis (DKA). A graded exercise test may be recommended if a patient, about to embark on a moderate- to high-intensity exercise program, is at high risk for coronary artery disease, or has had T1DM for more than 10 years. Running, prolonged walking, step aerobics, or any similar activities that may cause foot trauma should not be performed by people with significant peripheral neuropathy. Swimming, rowing, and cycling represent appropriate alternatives for these patients. Athletes with diabetes with retinopathy should not participate in activities that cause increased ocular pressure, such as high-impact aerobics, due to the risk of retinal or vitreous hemorrhages. Valsalva maneuvers during weight lifting may also increase this risk. Clearly, not all sports are beneficial or prudent for all athletes with T1DM. By attaining ideal body weight, avoiding hypertension, and exercising wisely, long-term diabetic complications can be prevented. The activities that emphasize endurance training, aerobic conditioning, muscle tone, and that have the potential for lifelong participation have a higher likelihood of contributing to the achievement of a healthy lifestyle.
The hallmark for managing any athlete with T1DM is prevention of hypo- and hyperglycemia. Educating each athlete about the disease and how best to manage glucose levels will aid in avoidance of complications. The diabetic athlete must have excellent metabolic control prior to undertaking exercise or activities, and as stated previously, a documented HgbA1C that demonstrates glycemic control is essential. It is advisable that they begin a consistent daily routine of insulin administration and caloric intake, as well as frequent home blood glucose recordings on a glucometer that stores finger stick values. Once adequate glucose control is established, a gradual daily exercise plan should be instituted while maintaining vigilant glucose recordings. Exercising daily will lead to a more reliable understanding of an athlete's insulin and carbohydrate needs. Each athlete is unique and will require individualization of insulin adjustments and carbohydrate intake. In new-onset diabetes, the person might be naïve to insulin; this “honeymoon period” of small need for insulin might be prolonged in athletes. Once past, an increase in insulin dosage will be needed.
The intensity and duration of exercise determines specific modifications in the insulin regimen. These include eating a meal 1 to 3 hours before exercise, exercising after the peak action of subcutaneous insulin injection, and delaying exercise until glucose and ketones are under control . Prior to exercise, and depending on the predicted intensity, athletes should modify insulin dosage accordingly. Typically, this reduction ranges from 20% to 50%. A recent table was proposed in order to better adjust carbohydrate intake and insulin dosing (Table 2) [7••]. Taking into account the peak action of each insulin, it has been advised to decrease the dose of the specific insulin that would peak during an upcoming sporting event. For a morning workout, the morning dose of short-acting insulin (regular insulin; onset 1–2 hours, peak 2–4 hours) should be reduced, whereas an afternoon activity requires reduction of the morning dose of intermediate-acting insulin (NPH or lente insulin; onset 1–3 hours, peak 4–10 hours). The physician must understand that some trial and error occurs to meet each individual athlete's insulin and carbohydrate modifications. If hyperglycemia (blood glucose > 250 mg/dL) and ketonuria exist prior to exercise, athletic activity should be postponed until adequate glycemic control is achieved .
During exercise athletes with diabetes do not have the endogenous insulin feedback mechanism that decreases insulin levels in response to exercise. This needs to be accounted for when timing insulin injections. When administering exogenous insulin, the insulin level may remain elevated during exercise leading to inhibition of both glycogenolysis and gluconeogenesis. To avoid the resultant hypoglycemia, adequate calorie intake and vigilant blood glucose monitoring is critical. During prolonged exercise (> 1 hour), blood glucose monitoring should take place every 30 minutes. The athlete needs to replace fluid losses adequately. The contact or collision athlete with diabetes, who is unable to use his or her insulin pump during exercise, will initially experience a drop in glucose levels. As insulin levels begin to decrease, about 1 hour after removal of the insulin pump, frequent monitoring is necessary to assess subsequent glucose elevation to avoid hyperglycemia. Because it is important for the athlete to replenish glycogen stores during and immediately after exercise, they should ingest 30 to 40 g of carbohydrate for every 30 minutes of intensive exercise.
Following exercise, the athlete with diabetes should anticipate late-onset hypoglycemia and recognize the precursor symptoms in order to adequately prevent it. If the exercise intensity was unusually high, blood glucose monitoring should occur frequently in the hours following activity, even throughout the night. Any sense of exhaustion or weakness or increase in appetite hours after exercise may warn the athlete of possible hypoglycemia. Prevention requires upward adjustments of caloric intake, lowering of longer-acting insulin dosage that typically would peak overnight, and frequent blood glucose checks.
For the athlete with diabetes using multiple injections, the site of injection and rate of absorption is important. Insulin absorption is more rapid and less predictable when injected into the leg prior to exercise . Care should be taken to avoid accidental intramuscular injection. The most common site used by athletes for injection is the abdomen given its ease of access during meals and more predictable insulin absorption time .
As the size of insulin pumps has decreased, their popularity has risen. Insulin pumps infuse short-acting insulin via a catheter that is replaced every 3 to 4 days. The insulin pump (also known as continuous subcutaneous insulin infusion [CSII]) is most frequently used in athletes with T1DM and has some clear advantage over multiple subcutaneous injections, especially for athletes. The CSII method allows more flexibility for skipped meals, sleeping late, and spontaneous exercise. The subcutaneous insulin delivery with the pump allows for precise dosing; even incremental doses as small as 0.05 units are possible. Appropriate basal rates can be set for each individual, and adjusted according to periods of rest and exercise. The pump can be used to administer boluses of insulin for premeal insulin coverage. In order to reduce hypoglycemia, the athlete should precede intense exercise by reducing the action of the pump by 50% about 1 hour prior to activity . For exercise of lower intensity or shorter duration, the standard basal rate can be maintained and a simple reduction in the premeal bolus is sufficient.
Insulin pumps can malfunction during exercise. The athlete must be mindful of displacement of the infusion set, which can lead to a hypoinsulinemic state and DKA in a short period of time. Continuing to exercise unaware of a displaced catheter results in lower insulin levels than expected and can easily quicken the progression to DKA.
Sweating can displace the pump and liquid skin preparations can be used to prevent displacement. The use of antiperspirants around the infusion site has helped reduce sweating around the infusion set. The environment can affect the overall effectiveness of an insulin pump. Insulin is heat sensitive and overheating can occur when exercising in the heat with the pump next to the body. If unexplainable hyperglycemia occurs, the infusion catheter and insulin cartridge should be replaced. Proper care and monitoring of the equipment is essential to successful use of the pump during exercise.
If removal of the pump is needed during contact and collision sports, it should be stopped 30 minutes prior to short-duration exercise (< 1 hour) due to the persistent action of insulin after pump removal. Care should be taken in order to ensure protection of the catheter that will remain in the athlete. Small boluses during exercise may be needed for longer activities (> 1 hour) in order to prevent hypoinsulinemic states in activities such as marathons and soccer matches. These boluses should be given every hour and the amount of insulin given should represent about 50% of the usual hourly basal rate .
The athlete with diabetes should be aware of the warning signs of hypoglycemia. They tend to be reproducible for each individual. Symptoms typically involve headache, hunger, and dizziness, which indicate mild hypoglycemia (blood glucose levels between 50 and 70 mg/dL). Both the practitioner and athlete should be prepared to treat acute hypoglycemia with glucose-containing liquids, hard candy, or oral glucose tablets. More severe hypoglycemia occurs when glucose levels drop below 40 mg/dL and the athlete may be unconscious, combative, or severely obtunded. If the level of consciousness does not allow for protection of the airway, glucose by the oral route should be avoided. In these cases, intravenous glucose administration is indicated. It is always preferable to have confirmation of hypoglycemia by finger stick; however, this should not delay glucose therapy. In those experiencing severe hypoglycemia, glucagon (1 mg subcutaneously or intramuscularly) should be given to produce a rapid release of liver glycogen. This is ineffective if all liver glycogen stores have been depleted after prolonged, intense exercise. Given that glucagon is relatively short acting, once mental status has improved, oral carbohydrate supplements should be given to avoid rebound hypoglycemia.
Athletes with T1DM may participate in any athletic event if they carefully monitor insulin administration and carbohydrate intake. Even extreme sports such as scuba diving and mountain climbing should no longer be considered absolute contraindications for people with T1DM [21,22]. The patient and physician should work together to create an individualized plan of treatment depending on the sport and extent of disease. It is crucial that the diabetic athlete achieve adequate metabolic control and be well educated about the disease before beginning any exercise regimen. With strict attention to prevention of hyperglycemia and hypoglycemia, both before and after exercise, most complications of diabetes can be avoided.
We would like to thank Dr. Diana Heiman for her assistance in proofreading the manuscript. We would also like to thank Laura Vastbinder for her development of the figure.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
1. Sperling MA: Diabetes in adolescence
. Adolesc Med
2. Hough DO: Diabetes mellitus in sports
. Med Clin North Am
3. Williams MH, Branch JD: Creatine supplementation and exercise performance: an update
. J Am Coll Nutr
4. Horton E: Exercise and diabetes mellitus
. Med Clin North Am
5. Hermanson L, Hultman R, Saltin B: Muscle glycogen during prolonged severe exercise
. Acta Physiol Scand
6.• Goodyear LJ: Exercise, glucose transport, and insulin sensitivity
. Annu Rev Med
The article reviews numerous beneficial adaptations in skeletal muscles from exercise training in humans, including an increase in GLUT4 expression. The increase in muscle GLUT4 in trained individuals contributes to an increase in the responsiveness of muscle glucose uptake to insulin.
7.•• Grimm JJ, Ybarra J, Berne C, et al.
: A new table for prevention of hypoglycemia during physical activity in type 1 diabetic patients
. Diabetes Metab
This study proposes guidelines for adjusting carbohydrate intake and insulin dosage during different levels of exercise duration and intensity. It is the most extensive study on the effects of various levels of exercise on glucose.
8.•• Ertl AC, Davis SN: Evidence for a vicious cycle of exercise and hypoglycemia in type 1 diabetes mellitus
. Diabetes Metab Res Rev
This review covers the studies that investigate the effects of counter regulatory hormones in men and women with T1DM.
9.• Peirce NS: Diabetes and exercise
. Br J Sports Med
A thorough review article that covers the physiology, risks, and benefits and possible complications of exercise in both type 1 and type 2 diabetics.
10. Wasserman DH, Zinman B: Exercise in individuals with IDDM
. Diabetes Care
11. Stratton R, Wilson DP, Endres RK: Acute glycemic effects of exercise in adolescents with insulin-dependent diabetes mellitus
. Phys Sportsmed
12. Costill D, Cleary P, Fink W, et al.
: Training adaptations in skeletal muscle of juvenile diabetes
13. Campaigne B, Gilliam T, Spencer M, et al.
: Effects of a physical activity program on metabolic control and cardiovascular fitness in children with insulin-dependent diabetes mellitus
. Diabetes Care
14. Stratton R, Wilson D, Endres R, et al.
: Improved glycemic control after a supervised eight week exercise program in insulin-dependent diabetic adolescents
. Diabetes Care
15. Landry GL, Allen DA: Diabetes mellitus and exercise
. Clin Sports Med
16. Horton ES: Role and management of exercise in diabetes mellitus
. Diabetes Care
17. Koivisto VA, Felig P: Effects of leg exercise on insulin absorption in diabetic patients
. N Engl J Med
18. Frid A, Ostman J, Linde B: Hypoglycemia risk during exercise after intramuscular injection of insulin in the thigh of IDDM
. Diabetes Care
19. Sonnenberg GE, Kemmer FW, Berger M: Exercise in type 1 diabetic patients treated with continuous subcutaneous insulin infusion. Prevention of exercise induced hypoglycemia
20. Schiffrin A, Parikh S: Accommodating planned exercise in type 1 diabetic patients on intensive treatment
. Diabetes Care
21. Moore K, Thompson C, Hayes R: Diabetes and extreme altitude mountaineering
. Br J Sports Med
22. Dear Gde L, Pollock NW, Uguccioni DM, et al.
: Plasma glucose responses in recreational divers with insulin-requiring diabetes
. Undersea Hyperb Med