Care of the Athlete With Type 1 Diabetes Mellitus PDF

Int J Endocrinol Metab. 2016 April; 14(2):e36091. doi: 10.5812/ijem.36091. Published online 2016 March 26....

Int J Endocrinol Metab. 2016 April; 14(2):e36091. doi: 10.5812/ijem.36091. Published online 2016 March 26. Review Article Care of the Athlete With Type 1 Diabetes Mellitus: A Clinical Review William B. Horton,1,* and Jose S. Subauste1,2,3 1 Department of Medicine, University of Mississippi Medical Center, Mississippi, United States 2 Division of Endocrinology, University of Mississippi Medical Center, Mississippi, United States 3 Department of Medicine, G.V. Montgomery VA Medical Center, Mississippi, Jackson, United States * Corresponding author: William B. Horton, Department of Medicine, University of Mississippi Medical Center, 2500 N State Street, Jackson, Mississippi 39216, United States. Tel: +1-6019845601, Fax: +1-6019846665, E-mail: [email protected] Received 2016 January 06; Revised 2016 February 24; Accepted 2016 March 01. Abstract Context: Type 1 diabetes mellitus (T1DM) results from a highly specific immune-mediated destruction of pancreatic β cells, resulting in chronic hyperglycemia. For many years, one of the mainstays of therapy for patients with T1DM has been exercise balanced with appropriate medications and medical nutrition. Compared to healthy peers, athletes with T1DM experience nearly all the same health-related benefits from exercise. Despite these benefits, effective management of the T1DM athlete is a constant challenge due to various concerns such as the increased risk of hypoglycemia. This review seeks to summarize the available literature and aid clinicians in clinical decision-making for this patient population. Evidence Acquisition: PubMed searches were conducted for “type 1 diabetes mellitus AND athlete” along with “type 1 diabetes mellitus AND exercise” from database inception through November 2015. All articles identified by this search were reviewed if the article text was available in English and related to management of athletes with type 1 diabetes mellitus. Subsequent reference searches of retrieved articles yielded additional literature included in this review. Results: The majority of current literature available exists as recommendations, review articles, or proposed societal guidelines, with less prospective or higher-order treatment studies available. The available literature is presented objectively with an attempt to describe clinically relevant trends and findings in the management of athletes living with T1DM. Conclusions: Managing T1DM in the context of exercise or athletic competition is a challenging but important skill for athletes living with this disease. A proper understanding of the hormonal milieu during exercise, special nutritional needs, glycemic con- trol, necessary insulin dosing adjustments, and prevention/management strategies for exercise-related complications can lead to successful care plans for these patients. Individualized management strategies should be created with close cooperation between the T1DM athlete and their healthcare team (including a physician and dietitian). Keywords: Type 1 Diabetes Mellitus, Exercise, Hypoglycemia, Hyperglycemia 1. Context malities (9), increased insulin sensitivity, decreased in- sulin requirements, lower hemoglobin A1c (HbA1c) levels Type 1 diabetes mellitus (T1DM) results from a highly (10), improved endothelial function (11), and improvement specific immune-mediated destruction of pancreatic β in cardiorespiratory fitness (12). Despite these benefits, ef- cells, resulting in chronic hyperglycemia (1). Individuals fective management of the T1DM athlete is a constant chal- living with T1DM require chronic injection of exogenous lenge due to various concerns such as the increased risk insulin for survival (2). Today, with the advent of many ad- of hypoglycemia. Recent data demonstrates that the inci- vances in insulin therapy and delivery, along with improve- dence of T1DM is increasing (13). As the number and life ments in blood glucose (BG) monitoring, individuals with expectancy of T1DM patients increases, it is important for T1DM are seeing improvements in life expectancy (3) and clinicians to understand appropriate management strate- participating at the highest levels of competitive athletics gies for patients participating in athletic pursuits. This re- (4-6). view seeks to summarize the available literature and aid For many years, one of the mainstays of therapy for pa- clinicians in clinical decision-making for this patient pop- tients with T1DM has been exercise balanced with appro- ulation. priate medications and medical nutrition (7). Compared to healthy peers, athletes with T1DM experience nearly all the same health-related benefits from exercise (8). These include improvements in health-related quality of life, re- duction in blood pressure, improvement in lipid abnor- Copyright © 2016, Research Institute For Endocrine Sciences and Iran Endocrine Society. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.  Horton WB and Subauste JS 2. Evidence Acquisition free fatty acids (FFA) as fuel (1). Most endurance sports are performed within the moderate-intensity range (i.e. 2.1. Methods long-distance running and cycling) (1). As muscle glyco- PubMed searches were conducted for “type 1 diabetes gen stores are depleted, a balance develops between glu- mellitus AND athlete” along with “type 1 diabetes mellitus cose production (primarily via hepatic glycogenolysis (27)) AND exercise” from database inception through November and glucose uptake by exercising muscle (14). Insulin se- 2015. All articles identified by this search were reviewed if cretion concurrently falls (28, 29) as muscle glucose uptake the article text was available in English and related to man- increases due to exercise stimulating the translocation of agement of athletes with type 1 diabetes mellitus. All titles GLUT-4 receptors to the cell surface (30). A slight increase and abstracts of papers identified by the searches were as- in catecholamines combined with the decrease of insulin sessed for inclusion by one reviewer. Subsequent reference promotes lipolysis in exercise, permitting the use of FFA as searches of retrieved articles yielded additional literature fuel (14), and later gluconeogenesis (31, 32). included in this review. High-intensity exercise (85 to 100% VO2 max or greater than 90% maximal heart rate), sustained for 10 to 30 min- utes or intermittent bouts of 3 to 5 minutes, is common 3. Results in team-oriented sports, such as lacrosse, football, hockey, soccer, track and field, and swimming (1). Exercise to VO2 3.1. Exercise and Glucoregulation max is primarily sustained by aerobic metabolism, includ- Exercise is a metabolic challenge with a synchronized ing oxidative phosphorylation and, to a lesser extent, beta endocrine response (14). Metabolic responses to exer- oxidation (1). High-intensity, supramaximal-effort (> VO2 cise are determined primarily by the intensity, duration, max) activities sustained for only 3 to 30 seconds, such and environmental conditions (i.e. temperature, humid- as sprinting, utilize the anaerobic energy system. In ei- ity, time of day) (1). Skeletal muscle plays a critical role ther scenario, high-intensity exercise is highly dependent in glycemic control and metabolic homeostasis and is on glucose as fuel, derived from either hepatic or muscle the predominant site of glucose disposal under insulin- glycogenolysis (1). Additionally, exercise at high-intensity stimulated conditions (15, 16). Skeletal muscle is also the is characterized by marked lactate accumulation and a largest glycogen storage organ, having an approximate 4- substantial increase in catecholamine concentrations, ap- fold greater glycogen storage capacity than the liver (15). proximately 14- to 18-folds above basal levels (33). AMP-activated protein kinase (AMPK) is a serine/threonine Once exercise stops, insulin levels rapidly increase kinase that serves as a sensor of cellular energy status (15, both in response to high BG levels and removal of circu- 17). AMPK modulates cellular metabolism via phosphory- lating catecholamines (1). As a result, hyperglycemia and lation of metabolic enzymes (18) and transcriptional regu- hyperinsulinemia combine postexercise to provide ideal lation (19, 20). AMPK activation is chiefly regulated by cel- homeostatic metabolic conditions for the replenishment lular energy deficits, which are reflected by increases in of muscle glycogen (14). This promotes rapid recovery and the adenosine monophosphate (AMP)/adenosine triphos- primes the athlete for repeated bouts of high-intensity ex- phate (ATP) and creatine (Cr)/phosphocreatine (PCr) ratios ercise. (21). Given the high rate of ATP turnover during muscle contraction, exercise increases AMPK phosphorylation and 3.2. Nutritional Recommendations for Peak Performance enzymatic activity in an intensity-dependent manner (22, 3.2.1. Daily Macronutrient Needs for Exercise 23). AMPK activation acts to conserve ATP by inhibiting Diabetic athletes have unique nutritional require- biosynthetic and anabolic pathways, while simultaneously ments that should be met to aid in peak performance. stimulating catabolic pathways to restore cellular energy Proper understanding of current recommendations for stores (21). In skeletal muscle, acute AMPK activation sup- caloric and fluid intake before, during, and after exercise presses glycogen (18) and protein synthesis (24), but pro- is necessary for successful BG management and preven- motes glucose transport (25) and lipid metabolism (26). tion of hypo- and hyperglycemia. Energy and macronutri- Muscles use glucose as their primary source of fuel ent needs, especially CHO and fat, must be met to maxi- in the initial stages of exercise (14). During moderate- mize training effects and maintain health (14). The recom- intensity exercise (40% - 59% of maximal oxygen consump- mended balance of these nutrients for athletes does not tion [VO2 max] or 55% - 69% of maximal heart rate), the differ significantly from recommendations for the general fuel for muscular contraction is gained almost exclusively population, though additional calories and fluids may be from aerobic metabolism- by using a mixture of carbohy- required for diabetic athletes and varies based on circum- drate (CHO) from muscle glycogen stores and circulating stances (exercise intensity, total energy expenditure, type 2 Int J Endocrinol Metab. 2016; 14(2):e36091.  Horton WB and Subauste JS of exercise/training program, duration of exercise, gender, Box 1. Recommendations for CHO and Fluid Intake During Exercise in Type 1 Diabetic and environmental factors) (1). Current guidelines recom- Athletesa mend 5 - 12 g of CHO per kilogram of body mass per day (14, 34). Table 1 details daily CHO recommendations for athletes Duration of Event by training load (14, 35). 30-60 minutes Primary goal is fluid replacement Table 1. Guidelines for Daily CHO Intake for Fuel and Recovery in Type 1 Diabetic Begin exercise well-hydrated Athletesa Drink at a rate that is comfortable and practical to replace fluid lost by sweating Training Load CHO Recommendation (g/kg/day) CHO intake is beneficial for the performance of high-intensity exercise Very light training (low intensity 3-5 of about 1 hour duration (37) exercise or skill-based exercise) 1 - 3 hours Moderate intensity exercise for 1 5-7 hour/day Primary goal is fluid replacement + CHO intake Moderate-to-high intensity 7 - 10 30 grams CHO per hour of exercise exercise for 1 - 3 hours/day Drink at a rate that is comfortable and practical to replace fluid lost by Moderate-to-high intensity ≥ 10 - 12 sweating exercise for 4 - 5 hours/day ≥ 3 hours Abbreviation: CHO, carbohydrate. a Primary goal is fluid replacement + CHO + sodium intake Adapted with permission from references (14) and (35). 30 - 60 grams CHO per hour of exercise; when greater than 70 g CHO per hour are required, use a mixture of CHO sources (i.e. 2:1 ratio of A joint position statement by the American Dietetic As- glucose and fructose) sociation, Dietitians for Canada, and the American College Drink at a rate that is comfortable and practical to replace fluid lost by of Sports Medicine recommends the following general en- sweating ergy requirements for competitive athletes (36): Abbreviation: CHO, carbohydrate. 1. CHO consumption range of 6 - 10 g/kg body weight a Adapted with permission from references (14) and (35). per day. 2. Protein consumption range for endurance and strength-trained athletes of 1.2 - 1.7 g/kg body weight per of healthy individuals (40, 41). However, several complica- day. This recommendation can generally be met through tions can be seen with exercise in this patient population. diet alone, without the use of dietary supplements. T1DM athletes frequently experience hypoglycemia during 3. Fat consumption range of 20% - 35% of total energy endurance exercise due to augmented insulin absorption, intake. Consuming ≤ 20% of energy from fat intake does impaired glucagon secretion, and reduced catecholamine not benefit performance. responses (42-45). Exercise also specifically increases the CHO consumption is necessary to maintain BG levels risk of hypoglycemia 6 - 15 hours after exercise is completed during exercise and replace muscle glycogen (1). Protein is (46) due to increased insulin sensitivity resulting from a needed for tissue repair and muscle growth while fat pro- prolonged increase in GLUT-4 transporter translocation to vides needed calories as well as fat-soluble vitamins and the cell surface (47-49). It should also be noted that not all essential fatty acids (36). Box 1 summarizes recommenda- forms of exercise lead to hypoglycemia, as some forms of tions for CHO and fluid intake during exercise (14, 35). intense exercise have been identified as potential causes of hyperglycemia (50). With these factors in mind, it is impor- 3.2.2. Timing of Nutrient and Fluid Intake tant for T1DM athletes to consume appropriate amounts The primary goals for nutrient intake during training of carbohydrates and coordinate food intake with timing and competition are to replace fluid losses and provide of exercise and insulin dosing. This approach is critical CHO for maintenance of BG levels (14). Food and fluid for optimizing glycemic control and exercise performance, choices to be utilized before, during, and after exercise are maintenance of muscle and liver glycogen stores, and pre- influenced by various factors, including intensity and du- vention of fatigue and complications (1). ration of training, environmental conditions, and individ- ual characteristics of the athlete. 3.2.4. Carbohydrate Intake Recommendations for the Diabetic Athlete 3.2.3. Special Considerations for the Diabetic Athlete Intense exercise at the time of peak insulin activity is Uncomplicated T1DM does not reduce physical perfor- associated with glucose disposal into muscle of approxi- mance (38, 39) and exercise capacity is equivalent to that mately 1 g glucose/kg/h of exercise (14, 51). As demonstrated Int J Endocrinol Metab. 2016; 14(2):e36091. 3  Horton WB and Subauste JS in Box 1, general recommendations for CHO intake dur- basal rate adjustments, therefore needs during exercise ing exercise are 30 - 60 g CHO per hour of exercise. A re- are likely to differ (14). cent study by Francescato et al. confirmed the utility of a 2. Timing of exercise relative to insulin bolus: If exer- recently proposed customizable algorithm (Ecres) for es- cise is within 90 - 120 minutes of an insulin bolus, the ath- timating the amount of carbohydrates necessary to pre- lete should be able to adjust the meal insulin bolus and vent glycemic imbalances during moderate-intensity aer- consequently CHO needs during exercise will be reduced, obic physical activity (52). Box 2 summarizes recommen- otherwise exercising within 2 hours of a bolus may require dations for CHO intake before, during, and after exercise taking more CHO than the recommended 30 - 60 g/h (14, in T1DM athletes (1). 51). 3. BG when initiating exercise: If the BG level is below 126 mg/dL (7 mmol/L), a 15 - 30 g CHO snack may be required. Box 2. CHO Intake Recommendations Before, During, and After Exercise in the Ath- lete With Type 1 Diabetes Mellitusa When the BG level is 180 mg/dL (10 mmol/L) or above, CHO intake during exercise should be delayed (14). Recommendations 4. Antecedent hypoglycemia and prolonged moder- Pre-Exercise ate exercise: Both of these factors have been shown to cause similar blunting effects of the counter-regulatory re- Athletes with diabetes who “CHO load” (200 - 350 g per meal) to increase glycogen stores before athletic events should monitor BG sponses during subsequent exercise, thereby making the levels regularly and adjust insulin doses accordingly. athlete more susceptible to hypoglycemia. Davis et al. Recommended pre-event CHO intake is approximately 1 g CHO/kg body (53) demonstrated that nearly three-fold greater exoge- weight one hour before exercise. Low-fat CHO foods, such as crackers, toast, fruit, and/or yogurt instead of sugary sweets are ideal choices. nous glucose infusion rates were needed to preserve eu- glycemia during exercise following a day of antecedent If the exercise is of short duration (< 45 mins), a pre-exercise snack of ~ 15 g CHO eaten 15 to 30 minutes before the event is adequate. hypoglycemia when compared to a day without hypo- During Exercise glycemia (14). 5. Type of exercise: High intensity (i.e. sprinting) During prolonged (> 45 - 60 minutes) or intense exercise (> 80% maximal heart rate), an intake of 30 g CHO for every 60 minutes of and intermittent high intensity (i.e. football) exercise may activity is a safe starting guideline. result in hyperglycemia during and/or after the exercise; Solid or liquid forms of CHO may be consumed. Each form has distinct therefore, CHO intake during these forms of exercise is advantages. Liquids provide fluid for hydration whereas solids may reduce or prevent hunger. For exercise lasting > 60 - 90 minutes, a likely to be problematic. General CHO intake recommen- liquid CHO form is most recommended since it is more practical and dations for athletes should be adapted during these activi- contributes to adequate hydration. ties (14). Refer to Table 1, Boxes 1 and 2 for further details. Post-Exercise Consuming CHO immediately after exercise as opposed to waiting for a 3.3. Management Strategies for the Athlete with Type 1 Diabetes period of time has been shown to replace CHO stores more efficiently. Intake of 1.5 g CHO/kg body weight within 30 minutes after an extended 3.3.1. Education exercise session (> 90 minutes in duration) and intake of an additional 1.5 g CHO/kg body weight one to two hours later will replete glycogen Glycemic control in the diabetic athlete is dependent to pre-exercise levels and reduce risk of post-exercise hypoglycemia. upon both the athlete and healthcare provider having an BG levels should be monitored at 1- or 2-hour intervals to assess appropriate understanding of the pathophysiology of di- response to exercise and make any necessary adjustments in insulin abetes and its nuances with respect to athletic activity. dosing and/or food intake. The cornerstone of management for T1DM athletes is pre- Abbreviations: CHO, carbohydrate; BG, blood glucose. vention of glycemic excursions (both hypo- and hyper- a Created from recommendations found in reference (1). glycemia) while maintaining adequate energy balance for exercise performance (1). All diabetic athletes should be While the above recommendations serve as a useful counseled on the importance of establishing a daily pat- guide for determining CHO needs, many other factors tern of consistency for all aspects of diabetes management. should be considered and advice tailored to individual This pattern of consistency would ideally include a routine needs of the diabetic patient, including: of insulin administration, consistent caloric intake, regi- 1. Form of treatment: Insulin pump therapy, or con- mented exercise program, and frequent monitoring of BG tinuous subcutaneous insulin infusion (CSII), provides the levels (1). Each athlete is unique and will likely require per- athlete a greater degree of flexibility for making basal rate sonalized adjustments until an optimal routine can be es- adjustments before, during, and after exercise. This dif- tablished (1). Education of those working with these ath- fers from multiple daily injection (MDI) and twice daily letes is just as important as educating the athletes them- insulin regimens, which provide little room for on-the-fly selves. For those T1DM athletes who participate in scholas- 4 Int J Endocrinol Metab. 2016; 14(2):e36091.  Horton WB and Subauste JS tic competition or team sports, it is vital to ensure that par- if BG < 100 mg/dL. Monitoring BG levels using a glucome- ents, coaches, teammates, teachers, and other adults un- ter or continuous glucose monitor (CGM) frequently dur- derstand the importance of timed meals, snacks, and ad- ing exercise is essential (1). It is also imperative that ath- equate fluid intake, as well as recognizing the features and letes keep detailed BG records during athletic activity, so management of hypoglycemia (54, 55). they may understand their glycemic response to exercise, learn to make appropriate exercise-related management 3.3.2. Glycemic Control and Target Values in Athletics decisions, and evaluate the effectiveness of these decisions General recommendations suggest that T1DM athletes over time (58). exhibiting poor glycemic control (Hemoglobin A1c > 9%) should refrain from moderate-to-high intensity exercise 3.3.3. Insulin Dosing Adjustments for Athletic Activity until adequate glycemic control has been obtained (1). This The development of highly specialized insulin has al- is advisable because it helps decrease the risk of exacerbat- lowed more physiologic regimens to be used in the treat- ing hyperglycemia and minimizes the risk of progression ment of patients with T1DM (7). Insulin dosing adjust- to frank diabetic ketoacidosis (DKA) (56). ments for exercise are largely dependent upon the insulin In athletes with T1DM, glucose production from the regimen used by the athlete. MDI is a type of intensive in- liver, regardless of prior CHO intake, does not match the sulin therapy which uses a long-acting insulin (such as in- elevated rates of glucose disposal into muscle during exer- sulin glargine [Lantus] or insulin detemir [Levemir]), in- cise and in recovery (57). This leads to an increased fluctua- jected once or twice daily, to provide fairly constant, low- tion in BG levels (58). Adjustments in both dietary intake levels of circulating insulin for basal control (7). The other and insulin dosing are necessary for prevention of these component of MDI therapy includes a mealtime short- BG fluctuations. Waiting 60 to 90 minutes after a meal be- acting insulin (such as insulin analogs lispro [Humalog], fore exercising and monitoring BG levels both during and aspart [Novolog], and glulisine [Apidra]) injected as a bo- after exercise/athletic competition are important baseline lus immediately before eating, preferably matched to the management measures (1). CHO-rich, low-glycemic index number of calories or carbohydrates to be consumed (7). meals should be consumed 1 to 3 hours prior to exercise It is advisable for all T1DM athletes to avoid exercise dur- (59, 60). Immediately before and during athletic activity, ing peak insulin activity times, if possible (1). For athletes consumption of additional CHO (17 g at initiation and 17 utilizing MDI regimens, the dose of short-acting insulin g every 15 minutes for 60 minutes of exercise at 65% VO2 should generally be decreased by 30% to 50% at the meal max) has proven beneficial in maintaining BG levels both preceding exercise (54). For example, if a morning work- during and after exercise in patients with T1DM (61). out or athletic competition is expected, the short-acting Consumption of low-glycemic index diets has been insulin at breakfast should be reduced as above (1). One shown to improve metabolic regulation (62) as these study has demonstrated that near euglycemia is obtain- foods require less insulin for optimal glucose utilization able in T1DM athletes during exercise with short-acting in- (1). These foods give a “low and slow” elevation in glu- sulin dose reductions as high as 70% to 90% (66). It should cose when consumed and include non-starchy vegetables, also be noted that further insulin dose adjustments of 10% fruits, nuts, milk, fructose, and lactated sugars (63). Ex- to 30% may be needed as the athlete becomes more fit (67). amples of high-glycemic index foods that lead to rapid in- Insulin injection sites are also an important factor to be creases in BG include white bread and glucose sugars (63). considered. The abdomen is regarded as the preferred site It should also be noted that as long as the diet contains ade- for athletes due to ease of access at mealtimes and more quate CHO to maintain normal glycogen levels, low-calorie predictable absorption time (68). diets can be used in this patient population without affect- CSII (insulin pump) therapy affords greater flexibility ing exercise tolerance (64). of insulin delivery than is currently available to those ath- The general guidelines for glycemic targets during ex- letes using MDI regimens (14). A recent study among in- ercise are 120 to 180 mg/dL (6.7 to 10 mmol/L), though BG dividuals performing regular moderate-to-heavy intensity goals should always be individualized to meet the specific aerobic exercise demonstrated that use of CSII helped to patient’s needs (58). If pre-exercise BG is 100 - 250 mg/dL, limit post-exercise hyperglycemia compared to MDI ther- it is generally safe to begin exercising (65). The American apy and was not associated with increased risk for post- Diabetes Association has published guidelines (54) for reg- exercise late-onset hypoglycemia (69). T1DM athletes uti- ulating the glycemic response to exercise which include lizing CSII therapy should reduce the action of the pump the following recommendations: avoid exercise if fasting by 50% approximately one hour before high-intensity exer- BG > 250 mg/dL and ketosis is present, use caution if BG > cise is initiated (70). Mealtime bolus doses should also be 300 mg/dL without ketosis present, and ingest extra CHO decreased by 50% if a meal is eaten prior to competition. Int J Endocrinol Metab. 2016; 14(2):e36091. 5  Horton WB and Subauste JS For low-intensity exercise, the standard basal rate may be (7). Table 2 provides a general summary for prevention of maintained with a small reduction in the mealtime bolus exercise-associated hypoglycemia in T1DM athletes. (1). If the athlete participates in a sport with contact or collision, it should be removed approximately 30 minutes Table 2. Strategies for Prevention of Exercise-Associated Hypoglycemia in the T1DM prior to exercise to compensate for the persistent insulin Athlete a effect after pump removal (1). For activity lasting > 1 hour, small boluses may be needed to prevent a hypoinsuline- Strategy Advantages Disadvantages mic state (1). Boluses should be given every hour and the Reducing Reduces CHO Requires proper amount of insulin given should represent about 50% of the pre-exercise bolus requirement; Reduced planning; not helpful (preferably when hypoglycemia during for spontaneous or late usual hourly basal rate (71). exercise is within 90 - exercise; beneficial for postprandial exercise; 120 minutes of a weight management may result in starting bolus) exercise with 3.4. Glycemic Complications in Athletes: Prevention and Man- increased BG agement Adjusting As above Requires proper pre-exercise and planning, as basal rate 3.4.1. Hypoglycemia during exercise basal adjustments should be insulin rate (for made at least 60 Hypoglycemia is a feared complication for T1DM ath- patients on CSII minutes prior to letes and can arise for many reasons in this population. therapy) exercise Common causes include too high a daily dose of insulin, Reducing basal Reduces nocturnal May cause increase in insulin post-exercise hypoglycemia fasting BG errors in dosage, increased activity duration or intensity, (possible with CSII insufficient or delayed food intake, and alcohol intake dur- and MDI therapy) ing or immediately after exercise (1). As glycogen is used CHO feeding during Useful for unplanned Counterproductive if for fuel during athletic competition or exercise, the reduc- exercise or prolonged exercise purpose of exercise is weight tions in hepatic and intramuscular glycogen concentra- reduction/control; not tions lead to increased insulin action (1). While the rate practical with all sports; potential of CHO utilization depends upon the duration and inten- gastrointestinal sity of exercise, training status, and prior diet, as glyco- discomfort gen stores in active muscle and liver are depleted, the risk Pre-exercise or Reduces immediate Effect limited to post-exercise sprint post-exercise shorter or less intense for hypoglycemia correspondingly increases (1, 72). There hypoglycemia exercise; no effect on are known conditions that affect the counter-regulatory re- hypoglycemia during exercise sponse to hypoglycemia that may be encountered in ath- letes with T1DM: antecedent exercise (73), antecedent hypo- Caffeine intake prior Reduced Possible impairments to exercise hypoglycemia during or alterations of fine glycemia (74), and autonomic neuropathy (75). This failed and after exercise; motor control and counter-regulatory mechanism is hypothesized to be the reduced CHO technique; possible requirements interference with result of cortisol stimulation that occurs during a stress recovery and sleep (such as hypoglycemia) and the effect it exerts on the cen- patterns tral nervous system (74). These individuals maintain a Abbreviations: BG, blood glucose; CHO, carbohydrate; CSII, continuous subcu- taneous insulin infusion; MDI, multiple daily injections. higher susceptibility to hypoglycemic episodes in the fu- a Adapted with permission from Reference (14). ture (1). 3.4.2. Pre-Exercise Hypoglycemia Prevention Strategies Adjustments in insulin dosing are necessary prior to 3.4.3. Management of Acute Hypoglycemia During Exercise exercise initiation (and have been covered above), but ap- T1DM athletes who participate in athletic activity propriate CHO replacement during and after exercise ap- should be able to recognize the symptoms of hypo- pears to have the most positive effect on preventing hy- glycemia (BG < 70 mg/dL): dizziness, weakness, sweating, poglycemia (76). If the insulin dosing is not altered prior headache, hunger, pallor, blurred vision, slurred speech, to exercise, a CHO snack must be ingested to minimize confusion, irritability, and poor coordination (1). If hypo- the likelihood of hypoglycemia (77). Individualization of glycemia occurs, exercise should be stopped immediately insulin dosing, timing, and caloric intake before, during, and BG monitored every 15 minutes until it rises above 80 and after exercise is critical to hypoglycemia prevention mg/dL (1). Acute hypoglycemia is best treated immediately (1). Repeated experience with glycemic control during ath- with 15 g CHO (examples include 1/2 cup fruit juice, 4 glu- letic activity by the T1DM athlete should help individualize cose tablets, 6 oz sweetened carbonated beverage, or 8 oz any necessary adaptations to help prevent hypoglycemia low-fat or skim milk) (78). Severe hypoglycemia should be 6 Int J Endocrinol Metab. 2016; 14(2):e36091.  Horton WB and Subauste JS treated with glucagon 1 mg subcutaneously or intramus- 3.5. Future Investigation cularly to produce a rapid release of liver glycogen (1). It Recent technological advancements have provided should also be noted that this therapy is ineffective if liver new ways for patients with T1DM to monitor their BG lev- glycogen stores have been depleted by prolonged, intense els. CGM is now available through several different de- exercise (1). vices (80), and many investigators are working to optimize a “closed-loop” artificial pancreas that links CGM with in- sulin administration through CSII pumps (81). Future stud- 3.4.4. Post-Exercise Hypoglycemia ies should seek to investigate how these devices function The risk of hypoglycemia in T1DM athletes persists even during exercise in T1DM patients. after athletic competition or exercise is completed. Late- Recent studies have also explored the effects of en- onset post-exercise hypoglycemia (LOPEH) has been seen durance (45) and ultra-endurance (82) athletic competi- in T1DM patients as long as 6 to 24 hours after activity tion on T1DM athletes, and results suggest individualized (79). The mechanism of LOPEH contains two main com- adaptation of therapy during training and competition is ponents: after exercise is completed, muscle and hepatic most effective. Future studies could examine these topics glycogen stores are filled by utilizing circulating plasma further and help create effective management strategies glucose. This coupled with increased insulin sensitivity for these scenarios. and glucose uptake by peripheral tissues and a blunting of the glucoregulatory response to insulin-induced hypo- glycemia is believed to cause LOPEH, which is often noc- 4. Conclusions turnal (56). LOPEH most commonly occurs with increases Managing T1DM in the context of exercise or athletic in training level or during “two-a-day” preseason practices competition is a challenging but important skill for ath- (commonly seen in football), although it may occur at any letes living with this disease. While regular exercise is an time (1). important aspect of T1DM management, the demands of One study has shown that regardless of post-exercise athletic activity can predispose T1DM athletes to dangerous supplementation, glucose concentrations fell after 22 complications such as hypo- and hyperglycemia. A proper hours, and pre-bedtime snacks were an important compo- understanding of the hormonal milieu during exercise, nent of prevention or correction of nocturnal LOPEH (77). special nutritional needs, glycemic control, necessary in- Consumption of nearly any commercially-available sports sulin dosing adjustments, and prevention/management drink has proven to be effective in prevention and/or treat- strategies for exercise-related complications can lead to ment of LOPEH; however, sports drinks with a mix of successful care plans for these patients. Individualized CHO, fat, and protein were associated with sustained hy- management strategies should be created with close co- perglycemia (and lack of hypoglycemia) during the post- operation between the T1DM athlete and their healthcare exercise period (77). Whole milk (77) and slowly absorbed team (including a physician and dietitian). snacks (such as chips, chocolate, and fruit) (1) have also demonstrated effectiveness in preventing LOPEH. Footnotes 3.4.5. Hyperglycemia Authors’ Contribution: William B. Horton contributed Hyperglycemia in T1DM athletes (BG > 250 mg/dL) gen- the study design, acquisition and analysis/interpretation erally occurs as a result of low circulating insulin lev- of data, drafting and critical revision of the manuscript. els (commonly secondary to inadequate insulin adminis- Jose S. Subauste contributed the drafting and critical revi- tration), excessive food intake, physical inactivity, illness, sion of the manuscript along with study supervision. stress, or injury (1). If pre-exercise BG is > 250 mg/dL, ath- Financial Disclosure: Neither William B. Horton nor Jose letes should check for urinary ketones (54). If ketonuria is S. Subauste have any financial disclosures to list. moderate-to-high, exercise should be avoided until BG im- proves and ketosis resolves (1, 42) Aggressive BG lowering References is important, as it may prevent progression to frank DKA (1, 56). It should also be noted that T1DM athletes with BG 250 - 1. Macknight JM, Mistry DJ, Pastors JG, Holmes V, Rynders CA. The 300 mg/dL and without ketosis may exercise or participate daily management of athletes with diabetes. Clin Sports Med. 2009;28(3):479–95. doi: 10.1016/j.csm.2009.02.005. [PubMed: in athletic competition provided they monitor their BG ev- 19505628]. ery 15 minutes and demonstrate that BG values are falling 2. Unger J. Management of type 1 diabetes. Prim Care. 2007;34(4):791– appropriately (65). 808. doi: 10.1016/j.pop.2007.07.002. [PubMed: 18061818] vi-vii. Int J Endocrinol Metab. 2016; 14(2):e36091. 7  Horton WB and Subauste JS 3. Miller RG, Secrest AM, Sharma RK, Songer TJ, Orchard TJ. 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