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Exercise and Type 1 Diabetes (T1DM)

Pietro Galassetti, Michael C. Riddell

10.1002/cphy.c110040

Source: Volume 3, Issue 3, July 2013

Published online: July 2013

Full Article on Wiley Online Library



Abstract

Physical exercise is firmly incorporated in the management of type 1 diabetes (T1DM), due to multiple recognized beneficial health effects (cardiovascular disease prevention being preeminent). When glycemic values are not excessively low or high at the time of exercise, few absolute contraindications exist; practical guidelines regarding amount, type, and duration of age‐appropriate exercise are regularly updated by entities such as the American Diabetes Association and the International Society for Pediatric and Adolescent Diabetes. Practical implementation of exercise regimens, however, may at times be problematic. In the poorly controlled patient, specific structural changes may occur within skeletal muscle fiber, which is considered by some to be a disease‐specific myopathy. Further, even in well‐controlled patients, several homeostatic mechanisms regulating carbohydrate metabolism often become impaired, causing hypo‐ or hyperglycemia during and/or after exercise. Some altered responses may be related to inappropriate exogenous insulin administration, but are often also partly caused by the “metabolic memory” of prior glycemic events. In this context, prior hyperglycemia correlates with increased inflammatory and oxidative stress responses, possibly modulating key exercise‐associated cardio‐protective pathways. Similarly, prior hypoglycemia correlates with impaired glucose counterregulation, resulting in greater likelihood of further hypoglycemia to develop. Additional exercise responses that may be altered in T1DM include growth factor release, which may be especially important in children and adolescents. These multiple alterations in the exercise response should not discourage physical activity in patients with T1DM, but rather should stimulate the quest for the identification of the exercise formats that maximize beneficial health effects. © 2013 American Physiological Society. Compr Physiol 3:1309‐1336, 2013.

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Figure 1. Figure 1.

Various blood glucose responses to exercise. Euglycemia occurs when there is a decrease in the insulin/counterregulatory hormone ratio (glucagon, catecholamines, etc.) that permits increased glucose production that matches the increase in glucose disposal into working muscle (top panel). Hypoglycemia occurs if insulin levels are not lowered at the onset of exercise in patients with T1DM (middle panel). Hyperglycemia occurs when the exercise intensity is very vigorous (>80% VO2max), if insulin administration is withheld, or if competition stress exists (bottom panel).
Figure 2. Figure 2.

Schematic of sequence of homeostatic events affecting carbohydrate metabolism during moderate, constant‐load exercise in healthy and T1DM subjects, showing the possible causes of exercise‐associated hypoglycemia in T1DM.
Figure 3. Figure 3.

Schematic of sequence of homeostatic events affecting carbohydrate metabolism during and immediately after intense exercise (above the anaerobic threshold, AT) in healthy and T1DM subjects, showing the possible causes of postexercise hyperglycemia in T1DM.
Figure 4. Figure 4.

Theoretical effects of blood glucose control on exercise performance in T1DM. A number of possible mechanisms exist that may explain deteriorated exercise performance during both hypoglycemia and hyperglycemia in individuals with T1DM.
Figure 5. Figure 5.

Increased inflammatory response to exercise in subjects with T1DM with worse glycemic control over the previous 3 days (264). In 47 young adults with T1DM, the exercise‐induced increase in interleukin‐6 (IL‐6), a proinflammatory cytokine was progressively greater in subjects who had experienced higher mean average glycemic values over the prior 3 days (A). When the same IL‐6 responses were analyzed based only on morning hyperglycemia on the day of the exercise challenge, the half of the subject with higher morning glycemia had a greater IL‐6 response that the lower half (B), but within each half a close dose response was not observed. When the half with the highest morning hyperglycemia, however, was resubdivided in two quarters based on prior 3‐day glycemia, again a dose response with magnitude of prior hyperglycemia became evident (C). Our data indicate that a hierarchical proinflammatory effect is induced by prior hyperglycemia occurred at different times in the past: recent hyperglycemia seems to have the strongest effect, but among subject with similar recent hyperglycemia, hyperglycemia occurred at an earlier time seems to exert an additional proinflammatory reinforcement.
Figure 6. Figure 6.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (111). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.
Figure 7. Figure 7.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (111). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.
Figure 8. Figure 8.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (111). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.
Figure 9. Figure 9.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (111). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.


Figure 1.

Various blood glucose responses to exercise. Euglycemia occurs when there is a decrease in the insulin/counterregulatory hormone ratio (glucagon, catecholamines, etc.) that permits increased glucose production that matches the increase in glucose disposal into working muscle (top panel). Hypoglycemia occurs if insulin levels are not lowered at the onset of exercise in patients with T1DM (middle panel). Hyperglycemia occurs when the exercise intensity is very vigorous (>80% VO2max), if insulin administration is withheld, or if competition stress exists (bottom panel).



Figure 2.

Schematic of sequence of homeostatic events affecting carbohydrate metabolism during moderate, constant‐load exercise in healthy and T1DM subjects, showing the possible causes of exercise‐associated hypoglycemia in T1DM.



Figure 3.

Schematic of sequence of homeostatic events affecting carbohydrate metabolism during and immediately after intense exercise (above the anaerobic threshold, AT) in healthy and T1DM subjects, showing the possible causes of postexercise hyperglycemia in T1DM.



Figure 4.

Theoretical effects of blood glucose control on exercise performance in T1DM. A number of possible mechanisms exist that may explain deteriorated exercise performance during both hypoglycemia and hyperglycemia in individuals with T1DM.



Figure 5.

Increased inflammatory response to exercise in subjects with T1DM with worse glycemic control over the previous 3 days (264). In 47 young adults with T1DM, the exercise‐induced increase in interleukin‐6 (IL‐6), a proinflammatory cytokine was progressively greater in subjects who had experienced higher mean average glycemic values over the prior 3 days (A). When the same IL‐6 responses were analyzed based only on morning hyperglycemia on the day of the exercise challenge, the half of the subject with higher morning glycemia had a greater IL‐6 response that the lower half (B), but within each half a close dose response was not observed. When the half with the highest morning hyperglycemia, however, was resubdivided in two quarters based on prior 3‐day glycemia, again a dose response with magnitude of prior hyperglycemia became evident (C). Our data indicate that a hierarchical proinflammatory effect is induced by prior hyperglycemia occurred at different times in the past: recent hyperglycemia seems to have the strongest effect, but among subject with similar recent hyperglycemia, hyperglycemia occurred at an earlier time seems to exert an additional proinflammatory reinforcement.



Figure 6.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (111). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.



Figure 7.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (111). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.



Figure 8.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (111). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.



Figure 9.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (111). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.

References
 1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 30(Suppl 1): S42‐S47, 2007.
 2. Diabetes Research in Children Network (DirecNet) Study Group. Impaired overnight counterregulatory hormone responses to spontaneous hypoglycemia in children with type 1 diabetes. Pediatr Diabetes 8: 199‐205, 2007.
 3. American College of Sports Medicine. ACSM Guidelines for Exercise Testing and Prescription. Lippincott, Williams & Wilkins, 2005.
 4. Mohammed Q, Gillies MC, Wong TY. A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Sorbinil Retinopathy Trial Research Group. Arch Ophthalmol 108: 1234‐1244, 1990.
 5. U.S. Department of Health and Human Services. Physical Activity Guidelines Advisory Committee report, 2008. To the Secretary of Health and Human Services. Part A: Executive summary. Nutr Rev 67: 114‐120, 2009.
 6. Abordo EA, Westwood ME, Thornalley PJ. Synthesis and secretion of macrophage colony stimulating factor by mature human monocytes and human monocytic THP‐1 cells induced by human serum albumin derivatives modified with methylglyoxal and glucose‐derived advanced glycation endproducts. Immunol Lett 53: 7‐13, 1996.
 7. Ahmad I, Zaldivar F, Iwanaga K, Koeppel R, Grochow D, Nemet D, Waffarn F, Eliakim A, Leu SY, Cooper DM. Inflammatory and growth mediators in growing preterm infants. J Pediatr Endocrinol Metab 20: 387‐396, 2007.
 8. Akerstrom T, Steensberg A, Keller P, Keller C, Penkowa M, Pedersen BK. Exercise induces interleukin‐8 expression in human skeletal muscle. J Physiol 563: 507‐516, 2005.
 9. Alikhani Z, Alikhani M, Boyd CM, Nagao K, Trackman PC, Graves DT. Advanced glycation end products enhance expression of pro‐apoptotic genes and stimulate fibroblast apoptosis through cytoplasmic and mitochondrial pathways. J Biol Chem 280: 12087‐12095, 2005.
 10. Almeida S, Riddell MC, Cafarelli E. Slower conduction velocity and motor unit discharge frequency are associated with muscle fatigue during isometric exercise in type 1 diabetes mellitus. Muscle Nerve 37: 231‐240, 2008.
 11. Andersen H. Muscular endurance in long‐term IDDM patients. Diabetes Care 21: 604‐609, 1998.
 12. Andersen H, Gadeberg PC, Brock B, Jakobsen J. Muscular atrophy in diabetic neuropathy: A stereological magnetic resonance imaging study. Diabetologia 40: 1062‐1069, 1997.
 13. Andersen H, Gjerstad MD, Jakobsen J. Atrophy of foot muscles: A measure of diabetic neuropathy. Diabetes Care 27: 2382‐2385, 2004.
 14. Andersen H, Poulsen PL, Mogensen CE, Jakobsen J. Isokinetic muscle strength in long‐term IDDM patients in relation to diabetic complications. Diabetes 45: 440‐445, 1996.
 15. Andersen H, Schmitz O, Nielsen S. Decreased isometric muscle strength after acute hyperglycaemia in Type 1 diabetic patients. Diabet Med 22: 1401‐1407, 2005.
 16. Andersen H, Stalberg E, Gjerstad MD, Jakobsen J. Association of muscle strength and electrophysiological measures of reinnervation in diabetic neuropathy. Muscle Nerve 21: 1647‐1654, 1998.
 17. Andreassen CS, Jakobsen J, Andersen H. Muscle weakness: A progressive late complication in diabetic distal symmetric polyneuropathy. Diabetes 55: 806‐812, 2006.
 18. Andreassen CS, Jakobsen J, Flyvbjerg A, Andersen H. Expression of neurotrophic factors in diabetic muscle–relation to neuropathy and muscle strength. Brain 132: 2724‐2733, 2009.
 19. Andreassen CS, Jakobsen J, Ringgaard S, Ejskjaer N, Andersen H. Accelerated atrophy of lower leg and foot muscles–a follow‐up study of long‐term diabetic polyneuropathy using magnetic resonance imaging (MRI). Diabetologia 52: 1182‐1191, 2009.
 20. Armstrong RB, Gollnick PD, Ianuzzo CD. Histochemical properties of skeletal muscle fibers in streptozotocin‐diabetic rats. Cell Tissue Res 162: 387‐394, 1975.
 21. Armstrong RB, Ianuzzo CD. Compensatory hypertrophy of skeletal muscle fibers in streptozotocin‐diabetic rats. Cell Tissue Res 181: 255‐266, 1977.
 22. Atalay M, Laaksonen DE, Khanna S, Kaliste‐Korhonen E, Hanninen O, Sen CK. Vitamin E regulates changes in tissue antioxidants induced by fish oil and acute exercise. Med Sci Sports Exerc 32: 601‐607, 2000.
 23. Banarer S, McGregor VP, Cryer, PE. A decrease in β−cell insulin secretion is a signal to increased α−cell glucagon secretion. Diabetes 50(Suppl 2), A140, 2001.
 24. Banarer S, McGregor VP, Cryer PE. Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response. Diabetes 51: 958‐965, 2002.
 25. Baraldi E, Monciotti C, Filippone M, Santuz P, Magagnin G, Zanconato S, Zacchello F. Gas exchange during exercise in diabetic children. Pediatr Pulmonol 13: 155‐160, 1992.
 26. Berger M, Berchtold P, Cuppers HJ, Drost H, Kley HK, Muller WA, Wiegelmann W, Zimmermann‐Telschow H, Gries FA, Kruskemper HL, Zimmermann H. Metabolic and hormonal effects of muscular exercise in juvenile type diabetics. Diabetologia 13: 355‐365, 1977.
 27. Berger M, Halban PA, Assal JP, Offord RE, Vranic M, Renold AE. Pharmacokinetics of subcutaneously injected tritiated insulin: Effects of exercise. Diabetes 28(Suppl 1): 53‐57, 1979.
 28. Berger M, Halban PA, Muller WA, Offord RE, Renold AE, Vranic M. Mobilization of subcutaneously injected tritiated insulin in rats: Effects of muscular exercise. Diabetologia 15: 133‐140, 1978.
 29. Bernardini AL, Vanelli M, Chiari G, Iovane B, Gelmetti C, Vitale R, Errico MK. Adherence to physical activity in young people with type 1 diabetes. Acta Biomed 75: 153‐157, 2004.
 30. Binder CJ, Chang MK, Shaw PX, Miller YI, Hartvigsen K, Dewan A, Witztum JL. Innate and acquired immunity in atherogenesis. Nat Med 8: 1218‐1226, 2002.
 31. Bjorkman O, Miles P, Wasserman D, Lickley L, Vranic M. Regulation of glucose turnover during exercise in pancreatectomized, totally insulin‐deficient dogs. Effects of beta‐adrenergic blockade. J Clin Invest 81: 1759‐1767, 1988.
 32. Bliss M. Resurrections in Toronto: The emergence of insulin. Horm Res 64(Suppl 2): 98‐102, 2005.
 33. Boehncke S, Poettgen K, Maser‐Gluth C, Reusch J, Boehncke WH, Badenhoop K. Endurance capabilities of triathlon competitors with type 1 diabetes mellitus. Dtsch Med Wochenschr 134: 677‐682, 2009.
 34. Boirie Y, Short KR, Ahlman B, Charlton M, Nair KS. Tissue‐specific regulation of mitochondrial and cytoplasmic protein synthesis rates by insulin. Diabetes 50: 2652‐2658, 2001.
 35. Borghouts LB, Keizer HA. Exercise and insulin sensitivity: A review. Int J Sports Med 20: 1‐12, 2000.
 36. Bosch AN, Kirkman MC. Maintenance of hyperglycaemia doe snot improve performance in a 100 km cycling time trial. South African Journal of Sports Medicine 19: 94‐98, 2007.
 37. Bottini P, Boschetti E, Pampanelli S, Ciofetta M, Del Sindaco P, Scionti L, Brunetti P, Bolli GB. Contribution of autonomic neuropathy to reduce plasma adrenaline responses to hypoglycemia in IDDM. Diabetes 46: 814‐823, 1997.
 38. Boveris A. Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria. Methods Enzymol 105: 429‐435, 1984.
 39. Brazeau AS, Rabasa‐Lhoret R, Strychar I, Mircescu H. Barriers to physical activity among patients with type 1 diabetes. Diabetes Care 31: 2108‐2109, 2008.
 40. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 414: 813‐820, 2001.
 41. Burr JF, Rowan CP, Jamnik VK, Riddell MC. The role of physical activity in type 2 diabetes prevention: Physiological and practical perspectives. Physician Sports Med 38: 72‐82, 2010.
 42. Bussau VA, Ferreira LD, Jones TW, Fournier PA. A 10‐s sprint performed prior to moderate‐intensity exercise prevents early post‐exercise fall in glycaemia in individuals with type 1 diabetes. Diabetologia 50: 1815‐1818, 2007.
 43. Cahill GF Jr, Aoki TT, Marliss EB. Insulin and muscle protein. In: Steiner DF, Freinkel N, editors. Handbook of Physiology. Section 7: Endocrinology. Baltimore, Maryland: Williams and Wilkins. 1972, pp. 563‐577.
 44. Camacho RC, Galassetti P, Davis SN, Wasserman DH. Glucoregulation during and after exercise in health and insulin‐dependent diabetes. Exerc Sport Sci Rev 33: 17‐23, 2005.
 45. Cappon JP, Ipp E, Brasel JA, Cooper DM. Acute effects of high fat and high glucose meals on the growth hormone response to exercise. J Clin Endocrinol Metab 76: 1428‐1422, 1993.
 46. Carnethon MR, Gidding SS, Nehgme R, Sidney S, Jacobs DR, Jr, Liu K. Cardiorespiratory fitness in young adulthood and the development of cardiovascular disease risk factors. JAMA 290: 3092‐3100, 2003.
 47. Caspersen CJ. Physical activity, exercise, and physical fitness: Definitions and distinctions for health‐related research. Public Health Rep 100: 126‐131, 1985.
 48. Chase HP, Lockspeiser T, Peery B, Shepherd M, Mackenzie T, Anderson J, Garg SK. The impact of the diabetes control and complications trial and humalog insulin on glycohemoglobin levels and severe hypoglycemia in type 1 diabetes. Diabetes Care 24: 430‐434, 2001.
 49. Chow LS, Albright RC, Bigelow ML, Toffolo G, Cobelli C, Nair KS. Mechanism of insulin's anabolic effect on muscle: Measurements of muscle protein synthesis and breakdown using aminoacyl‐tRNA and other surrogate measures. Am J Physiol Endocrinol Metab 291: E729‐E736, 2006.
 50. Clarke WL, Cox DJ, Gonder‐Frederick LA, Julian D, Schlundt D, Polonsky W. The relationship between nonroutine use of insulin, food, and exercise and the occurrence of hypoglycemia in adults with IDDM and varying degrees of hypoglycemia awareness and metabolic control. Diabetes Educ 23: 55‐58, 1997.
 51. Coggan A, Raguso CA, Gastaldelli A, Willams BD, Wolfe RR. Regulation of glucose production during exercise at 80% VO2peak in untrained humans. Am J Physiol 273: E348‐E354, 1997.
 52. Cooper DM, Nemet D, Galassetti P. Exercise, stress, and inflammation in the growing child: From the bench to the playground. Curr Opin Pediatr 16: 286‐292, 2004.
 53. Cooper DM, Radom‐Aizik S, Schwindt C, Zaldivar F. A minireview: Dangerous exercise‐lessons learned from dysregulated inflammatory responses to physical activity. J Appl Physiol Aug;103(2): 700‐709, 2007.
 54. Cotter M, Cameron NE, Lean DR, Robertson S. Effects of long‐term streptozotocin diabetes on the contractile and histochemical properties of rat muscles. Q J Exp Physiol 74: 65‐74, 1989.
 55. Crowther GJ, Milstein JM, Jubrias SA, Kushmerick MJ, Gronka RK, Conley KE. Altered energetic properties in skeletal muscle of men with well‐controlled insulin‐dependent (type 1) diabetes. Am J Physiol Endocrinol Metab 284: E655‐E662, 2003.
 56. Crozier SJ, Anthony JC, Schworer CM, Reiter AK, Anthony TG, Kimball SR, Jefferson LS. Tissue‐specific regulation of protein synthesis by insulin and free fatty acids. Am J Physiol Endocrinol Metab 285: E754‐E762, 2003.
 57. Cryer PE. Glucose counterregulation in man. Diabetes 30: 261‐264, 1981.
 58. Cryer PE. Hypoglycemia‐associated autonomic failure in diabetes. Am J Physiol Endocrinol Metab 281: E1115‐E1121, 2001.
 59. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care 26: 1902‐1912, 2003.
 60. D'hooge R, Hellinckx T, Van LC, Stegen S, De SJ, Van AS, Dewolf D, Calders P. Influence of combined aerobic and resistance training on metabolic control, cardiovascular fitness and quality of life in adolescents with type 1 diabetes: A randomized controlled trial. Clin Rehabil 25: 349‐359, 2011.
 61. Davis SN, Galassetti P, Wasserman DH, Tate D. Effects of antecedent hypoglycemia on subsequent counterregulatory responses to exercise. Diabetes 49: 73‐81, 2000.
 62. Davison GW, George L, Jackson SK, Young IS, Davies B, Bailey DM, Peters JR, Ashton T. Exercise, free radicals, and lipid peroxidation in type 1 diabetes mellitus. Free Radic Biol Med 33: 1543‐1551, 2002.
 63. De BF, Alonzi T, Moretta A, Lazzaro D, Costa P, Poli V, Martini A, Ciliberto G, Fattori E. Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin‐like growth factor‐I. A model for stunted growth in children with chronic inflammation. J Clin Invest 99: 643‐650, 1997.
 64. Decsi T, Molnar D. Insulin resistance syndrome in children : Pathophysiology and potential management strategies. Paediatr Drugs 5: 291‐299, 2003.
 65. DeFeo P, Perriello G, De Cosmo S, Ventura MM, Campbell PJ, Brunetti P, Gerich JE, Bolli GB. Comparison of glucose counterregulation during short‐term and prolonged hypoglycemia in normal humans. Diabetes 35: 563‐569, 1986.
 66. DeFeo P, Perriello G, Torlone E, Fanelli C, Ventura MM, Santeusanio F, Brunetti P, Gerich JE, Bolli GB. Contribution of adrenergic mechanisms to glucose counterreguation in humans. Am J Physiol 261: E725‐E736, 1991.
 67. DeFeo P, Perriello G, Torlone E, Ventura M, Santeusanio F. Demonstration of a role for growth hormone in glucose counterregulation. Am J Physiol 256: E835‐E843, 1989.
 68. DeFeo P, Perriello G, Torlone E, Ventura MM, Fanelli C, Santeusanio F, Brunetti P, Gerich JE, Bolli GB. Contribution of cortisol to glucose counterregulation in humans. Am J Physiol 257: E35‐E42, 1989.
 69. Devaraj S, Glaser N, Griffen S, Wang‐Polagruto J, Miguelino E, Jialal I. Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 55: 774‐779, 2006.
 70. Devlin J, Ruderman NB. Handbook of Exercise and Diabetes. Alexandria, VA: American Diabetes Association. 2002.
 71. Di Marzio D, Mohn A, Mokini ZH, Giannini C, Chiarelli F. Macroangiopathy in adults and children with diabetes: From molecular mechanisms to vascular damage (part 1). Horm Metab Res 38: 691‐705, 2006.
 72. Dillard CJ, Litov RE, Savin WM, Dumelin EE, Tappel AL. Effects of exercise, vitamin E, and ozone on pulmonary function and lipid peroxidation. J Appl Physiol 45: 927‐932, 1978.
 73. Ditzel J, Standl E. The problem of tissue oxygenation in diabetes mellitus. Acta Med Scand Suppl 578: 59‐68, 1975.
 74. Doi T, Vlassara H, Kirstein M, Yamada Y, Striker GE, Striker LJ. Receptor‐specific increase in extracellular matrix production in mouse mesangial cells by advanced glycosylation end products is mediated via platelet‐derived growth factor. Proc Natl Acad Sci U S A 89: 2873‐2877, 1992.
 75. Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M. Hyperglycemia‐induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor‐1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci U S A 97: 12222‐12226, 2000.
 76. Durak EP, Jovanovic‐Peterson L, Peterson CM. Randomized crossover study of effect of resistance training on glycemic control, muscular strength, and cholesterol in type I diabetic men. Diabetes Care 13: 1039‐1043, 1990.
 77. Ebeling P, Tuominen JA, Bourey R, Koranyi L, Koivisto VA. Athletes with IDDM exhibit impaired metabolic control and increased lipid utilization with no increase in insulin sensitivity. Diabetes 44: 471‐477, 1995.
 78. El‐Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med 205: 2409‐2417, 2008.
 79. Eliakim A, Scheett TP, Newcomb R, Mohan S, Cooper DM. Fitness, training, and the growth hormone–>insulin‐like growth factor I axis in prepubertal girls. J Clin Endocrinol Metab 86: 2797‐2802, 2001.
 80. Elosua R, Moliona L, Fito' M, Arquer A, Sanchez‐Quesada JL, Covas M‐I, Ordonez‐Llanos J, Marrugat J. Response of oxidative stress biomarkers to a 16‐week aerobic physical activity program, and to acute physical activity, in healthy young men and women. Atherosclerosis 167: 334, 2003.
 81. Engerman RL, Kern TS, Larson ME. Nerve conduction and aldose reductase inhibition during 5 years of diabetes or galactosaemia in dogs. Diabetologia 37: 141‐144, 1994.
 82. Erbagci AB, Tarakcioglu M, Coskun Y, Sivasli E, Sibel NE. Mediators of inflammation in children with type I diabetes mellitus: Cytokines in type I diabetic children. Clin Biochem 34: 645‐650, 2001.
 83. Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: Role of oxidative stress. Circulation 106: 2067‐2072, 2002.
 84. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress‐acitvated signaling pathways: A unifying hypothesis of Type 2 Diabetes. Endocr Rev 23: 599‐622, 2002.
 85. Evelo CT, Palmen NG, Artur Y, Janssen GM. Changes in blood glutathione concentrations, and in erythrocyte glutathione reductase and glutathione S‐transferase activity after running training and after participation in contests. Eur J Appl Physiol 64: 354‐358, 1992.
 86. Fan J, Wojnar MM, Theodorakis M, Lang CH. Regulation of insulin‐like growth factor (IGF)‐I mRNA and peptide and IGF‐binding proteins by interleukin‐1. Am J Physiol 270: R621‐R629, 1996.
 87. Farrell PA, Fedele MJ, Hernandez J, Fluckey JD, Miller JL, III, Lang CH, Vary TC, Kimball SR, Jefferson LS. Hypertrophy of skeletal muscle in diabetic rats in response to chronic resistance exercise. J Appl Physiol 87: 1075‐1082, 1999.
 88. Farrell PA, Fedele MJ, Vary TC, Kimball SR, Jefferson LS. Effects of intensity of acute‐resistance exercise on rates of protein synthesis in moderately diabetic rats. J Appl Physiol 85: 2291‐2297, 1998.
 89. Farrell PA, Fedele MJ, Vary TC, Kimball SR, Lang CH, Jefferson LS. Regulation of protein synthesis after acute resistance exercise in diabetic rats. Am J Physiol 276: E721‐E727, 1999.
 90. Farrell PA, Garthwaite TL, Gustafson AB. Plasma adrenocorticotropin and cortisol responses to submaximal and exhaustive exercise. J Appl Physiol 55: 1441‐1444, 1983.
 91. Febbraio MA, Steensberg A, Keller C, Starkie RL, Nielsen HB, Krustrup P, Ott P, Secher NH, Pedersen BK. Glucose ingestion attenuates interleukin‐6 release from contracting skeletal muscle in humans. J Physiol 549: 607‐612, 2003.
 92. Fedele MJ, Hernandez JM, Lang CH, Vary TC, Kimball SR, Jefferson LS, Farrell PA. Severe diabetes prohibits elevations in muscle protein synthesis after acute resistance exercise in rats. J Appl Physiol 88: 102‐108, 2000.
 93. Fehrenbach E. Multifarious microarray‐based gene expression patterns in response to exercise. J Appl Physiol 102: 7‐8, 2007.
 94. Felig P, Cherif A, Minageref A, Wahren J. Hypoglycemia during prolonged exercise in man. N Engl J Med 306: 895‐900, 1982.
 95. Felsing NE, Brasel JA, Cooper DM. Effect of low and high intensity exercise on circulating growth hormone in men. J Clin Endocrinol Metab 75: 157‐162, 1992.
 96. Fenster CP, Weinsier RL, Darley‐Usmar VM, Patel RP. Obesity, aerobic exercise, and vascular disease: The role of oxidant stress. Obes Res 10: 964‐968, 2002.
 97. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 31: 289‐294, 2008.
 98. Foley L, Maddison R, Olds T, Ridley K. Self‐report use‐of‐time tools for the assessment of physical activity and sedentary behaviour in young people: Systematic review. Obes Rev 13: 711‐722, 2012.
 99. Ford ES, Mokdad AH, Giles WH, Brown DW. The metabolic syndrome and antioxidant concentrations: Findings from the third national health and nutrition examination survey. Diabetes 52: 2346‐2352, 2003.
 100. Fredrickson DS, Ono K. CO2 trapping: A new cunning trick. J Lab Clin Med 41: 147‐151, 1958.
 101. Frid A, Ostman J, Linde B. Hypoglycemia risk during exercise after intramuscular injection of insulin in thigh in IDDM. Diabetes Care 13: 473‐477, 1990.
 102. Fritzsche K, Bluher M, Schering S, Buchwalow IB, Kern M, Linke A, Oberbach A, Adams V, Punkt K. Metabolic profile and nitric oxide synthase expression of skeletal muscle fibers are altered in patients with type 1 diabetes. Exp Clin Endocrinol Diabetes 116: 606‐613, 2008.
 103. Frohnauer M, Lui K, Devlin J. Adjustment of basal Lispro insulin in CSII to minimize glycemic fluctuations caused by exercise. Diabetes Res ClinPract 50(suppl 1): S80, 2000.
 104. Galassetti P, Larson J, Iwanaga K, Salsberg SL, Eliakim A, Pontello A. Effect of a high‐fat meal on the growth hormone response to exercise in children. J Pediatr Endocrinol Metab 19: 777‐786, 2006.
 105. Galassetti P, Mann S, Tate D, Neill RA, Wasserman DH, Davis SN. Effect of morning exercise on counterregulatory responses to subsequent, afternoon exercise. J Appl Physiol 91: 91‐99, 2001.
 106. Galassetti P, Tate D, Neill RA, Morrey S, Wasserman DH, Davis SN. Effect of antecedent hypoglycemia on counterregulatory responses to subsequent euglycemic exercise in Type 1 Diabetes. Diabetes 52: 1761‐1769, 2003.
 107. Galassetti P, Tate D, Neill RA, Morrey S, Wasserman DH, Davis SN. Effect of sex on counterregulatory responses to exercise after antecedent hypoglycemia in type 1 diabetes. Am J Physiol Endocrinol Metab 287: E16‐E24, 2004.
 108. Galassetti P, Tate D, Neill RA, Richardson MA, Davis SN. Effect of differing antecedent hypoglycemia on counterregulatory responses to subsequent exercise in Type 1 diabetes. Diabetes 52: A349, 2003.
 109. Galassetti P, Tate D, Neill RA, Richardson A, Leu SY, Davis SN. Effect of differing antecedent hypoglycemia on counterregulatory responses to exercise in type 1 diabetes. Am J Physiol Endocrinol Metab 290: E1109‐E1117, 2006.
 110. Galassetti PR, Iwanaga K, Crisostomo M, Zaldivar FP, Larson J, Pescatello A. Inflammatory cytokine, growth factor and counterregulatory responses to exercise in children with type 1 diabetes and healthy controls. Pediatr Diabetes 7: 16‐24, 2006.
 111. Galassetti PR, Iwanaga K, Pontello AM, Zaldivar FP, Flores RL, Larson JK. Effect of prior hyperglycemia on IL‐6 responses to exercise in children with type 1 diabetes. Am J Physiol Endocrinol Metab 290: E833‐E839, 2006.
 112. Galbo H. The hormonal response to exercise. Diabetes Metab Rev 1: 385‐408, 1986.
 113. Garcia SF, Virag L, Jagtap P, Szabo E, Mabley JG, Liaudet L, Marton A, Hoyt DG, Murthy KG, Salzman AL, Southan GJ, Szabo C. Diabetic endothelial dysfunction: The role of poly(ADP‐ribose) polymerase activation. Nat Med 7: 108‐113, 2001.
 114. Gerich JE, Langlois M, Noacco C, Karam J, Forsham PH. Lack of a glucagon response to hypoglycemia in diabetes: Evidence for an intrinsic pancreatic alpha‐cell defect. Science 182: 171‐173, 1973.
 115. Gibney J, Healy ML, Sonksen PH. The growth hormone/insulin‐like growth factor‐I axis in exercise and sport. Endocr Rev 28: 603‐624, 2007.
 116. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 19: 257‐267, 1996.
 117. Goldberg AL. Protein synthesis in tonic and phasic skeletal muscles. Nature 216: 1219‐1220, 1967.
 118. Goldberg AL. Protein synthesis during work‐induced growth of skeletal muscle. J Cell Biol 36: 653‐658, 1968.
 119. Goldberg AL. Role of insulin in work‐induced growth of skeletal muscle. Endocrinology 83: 1071‐1073, 1968.
 120. Goldfarb AH, McIntosh MK, Boyer BT. Vitamin E attenuates myocardial oxidative stress induced by DHEA in rested and exercised rats. J Appl Physiol 80: 486‐490, 1996.
 121. Goldfine AB, Fonseca V, Shoelson SE. Therapeutic approaches to target inflammation in type 2 diabetes. Clin Chem 57: 162‐167, 2011.
 122. Goldfine AB, Silver R, Aldhahi W, Cai D, Tatro E, Lee J, Shoelson SE. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin Transl Sci 1: 36‐43, 2008.
 123. Gonder‐Frederick LA, Zrebiec JF, Bauchowitz AU, Ritterband LM, Magee JC, Cox DJ, Clarke WL. Cognitive function is disrupted by both hypo‐ and hyperglycemia in school‐aged children with type 1 diabetes: A field study. Diabetes Care 32: 1001‐1006, 2009.
 124. Gordin D, Forsblom C, Rönnback M, Parkkonen M, Wadén J, Hietala K, Groop PH. Acute hyperglycaemia induces an inflammatory response in young patients with type 1 diabetes. Ann Med 40: 627‐633, 2008.
 125. Gordon CS, Serino AS, Krause MP, Campbell JE, Cafarelli E, Adegoke OA, Hawke TJ, Riddell MC. Impaired growth and force production in skeletal muscles of young partially pancreatectomized rats: A model of adolescent type 1 diabetic myopathy? PLoS One 5: e14032, 2010.
 126. Gray AB, Telford RD, Weidemann MJ. Endocrine response to intense interval exercise. Eur J Appl Physiol Occup Physiol 66: 366‐371, 1993.
 127. Greene DA, Arezzo JC, Brown MB. Effect of aldose reductase inhibition on nerve conduction and morphometry in diabetic neuropathy. Zenarestat Study Group. Neurology 53: 580‐591, 1999.
 128. Grimm JJ, Ybarra J, Berne C, Muchnick S, Golay A. A new table for prevention of hypoglycaemia during physical activity in type 1 diabetic patients. Diabetes Metab 30: 465‐470, 2004.
 129. Guelfi KJ, Ratnam N, Smythe GA, Jones TW, Fournier PA. Effect of intermittent high‐intensity compared with continuous moderate exercise on glucose production and utilization in individuals with type 1 diabetes. Am J Physiol Endocrinol Metab 292: E865‐E870, 2007.
 130. Gusso S, Hofman P, Lalande S, Cutfield W, Robinson E, Baldi JC. Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus. Diabetologia 51: 1317‐1320, 2008.
 131. Hagberg JM, Seals DR, Yerg JE, Gavin J, Gingerich R, Premachandra B, Holloszy JO. Metabolic responses to exercise in young and older athletes and sedentary men. J Appl Physiol 65: 900‐908, 1988.
 132. Hajduch E, Alessi DR, Hemmings BA, Hundal HS. Constitutive activation of protein kinase B alpha by membrane targeting promotes glucose and system A amino acid transport, protein synthesis, and inactivation of glycogen synthase kinase 3 in L6 muscle cells. Diabetes 47: 1006‐1013, 1998.
 133. Hakkinen K, Pakarinen A. Acute hormonal responses to two different fatiguing heavy‐resistance protocols in male athletes. J Appl Physiol 74: 882‐887, 1993.
 134. Hakkinen K, Pakarinen A, Alen M, Kauhanen H, Komi PV. Neuromuscular and hormonal responses in elite athletes to two successive strength training sessions in one day. Eur J Appl Physiol Occup Physiol 57: 133‐139, 1988.
 135. Hamilton J, Daneman D. Deteriorating diabetes control during adolescence: Physiological or psychosocial? J Pediatr Endocrinol Metab 15: 115‐126, 2002.
 136. Hargreaves M, Angus D, Howlett K, Conus NM, Febbraio M. Effect of heat stress on glucose kinetics during exercise. J Appl Physiol 81: 1594‐1597, 1996.
 137. Harmer AR, Chisholm DJ, McKenna MJ, Hunter SK, Ruell PA, Naylor JM, Maxwell LJ, Flack JR. Sprint training increases muscle oxidative metabolism during high‐intensity exercise in patients with type 1 diabetes. Diabetes Care 31: 2097‐2102, 2008.
 138. Harrell JS, McMurray RG, Baggett CD, Pennell ML, Pearce PF, Bangdiwala SI. Energy costs of physical activities in children and adolescents. Med Sci Sports Exerc 37: 329‐336, 2005.
 139. Hartley LH, Mason JW, Hogan RP, Jones LG, Kotchen TA, Mougey EH, Wherry FE, Pennington LL, Ricketts PT. Multiple hormonal responses to prolonged exercise in relation to physical training. J Appl Physiol 33: 607‐610, 1972.
 140. Hawkins M, Barzilai N, Liu R, Hu M, Chen W, Rossetti L. Role of the glucosamine pathway in fat‐induced insulin resistance. J Clin Invest 99: 2173‐2182, 1997.
 141. Hayashi T, Wojtaszewski JF, Goodyear LJ. Exercise regulation of glucose transport in skeletal muscle. Am J Physiol 273: E1039‐E1051, 1997.
 142. Hebert SL, Nair KS. Protein and energy metabolism in type 1 diabetes. Clin Nutr 29: 13‐17, 2010.
 143. Heller SR, Cryer PE. Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after one episode of hypoglycemia in nondiabetic humans. Diabetes 40: 223‐226, 1991.
 144. Herbst A, Kordonouri O, Schwab KO, Schmidt F, Holl RW. Impact of physical activity on cardiovascular risk factors in children with type 1 diabetes: A multicenter study of 23,251 patients. Diabetes Care 30: 2098‐2100, 2007.
 145. Heyman E, Briard D, Dekerdanet M, Gratas‐Delamarche A, Delamarche P. Accuracy of physical working capacity 170 to estimate aerobic fitness in prepubertal diabetic boys and in 2 insulin dose conditions. J Sports Med Phys Fitness 46: 315‐321, 2006.
 146. Hirsh IB, Marker JC, Smith LJ, Spina RJ, Parvin CA, Holloszy J, Cryer PE. Insulin and glucagon in prevention of hypoglycemia during exercise in humans. Am J Physiol 260: E695‐E704, 2001.
 147. Hoelzer DR, Dalsky GP, Clutter WE, Shah SD, Holloszy JO, Cryer PE. Glucoregulation during exercise: Hypoglycemia is prevented by redundant glucoregulatory systems, sympathochromaffin activation, and changes in islet hormone secretion. J Clin Invest 77: 212‐221, 1986.
 148. Hoffman RP, Singer‐Granick C, Drash AL, Becker DJ. Plasma catecholamine responses to hypoglycemia in children and adolescents with IDDM. Diabetes Care 14: 81‐88, 1991.
 149. Holt RI, Simpson HL, Sonksen PH. The role of the growth hormone‐insulin‐like growth factor axis in glucose homeostasis. Diabet Med 20: 3‐15, 2003.
 150. Holt RI, Webb E, Pentecost C, Sonksen PH. Aging and physical fitness are more important than obesity in determining exercise‐induced generation of GH. J Clin Endocrinol Metab 86: 5715‐5720, 2001.
 151. Howlett K, Febbraio M, Hargreaves M. Glucose production during strenuous exercise in man: Role of epinephrine. Am J Physiol 276: E1130‐E1135, 1999.
 152. Hubner‐Wozniak E, Panczenko‐Kresowka B, Lerczak K, Posnik J. Effects of graded treadmill exercise on the activity of blood antioxidant enzymes, lipid peroxides and nonenzymatic anti‐oxidants in long‐distance skiers. Biol Sport 11: 217‐226, 1994.
 153. Hughes BC, White RD. Exercise Testing for Primary Care and Sports Medicine. New York: Springer‐Verlag, 2005, pp. 55‐77.
 154. Husain K, Somani SM, Boley TM, Hazelrigg SR. Interaction of physical training and chronic nytroglycerin treatment on blood pressure and plasma oxidant/antioxidant systems in rats. Mol Cell Biochem 247: 37‐44, 2003.
 155. Huttunen NP, Kaar ML, Knip M, Mustonen A, Puukka R, Akerblom HK. Physical fitness of children and adolescents with insulin‐dependent diabetes mellitus. Ann Clin Res 16: 1‐5, 1984.
 156. Iscoe KE, Campbell JE, Jamnik V, Perkins BA, Riddell MC. Efficacy of continuous real‐time blood glucose monitoring during and after prolonged high‐intensity cycling exercise: Spinning with a continuous glucose monitoring system. Diabetes Technol Ther 8: 627‐635, 2006.
 157. Iscoe KE, Corcoran M, Riddell MC. High rates of nocturnal hypoglyemia in a unique sports camp for athletes with type 1 diabetes: Lessons learned from continuous glucose monitoring. Can J Diabet 32: 182‐189, 2008.
 158. Iscoe KE, Riddell MC. Continuous moderate‐intensity exercise with or without intermittent high‐intensity work: Effects on acute and late glycaemia in athletes with Type 1 diabetes mellitus. Diabet Med 28: 824‐832, 2011.
 159. Jackson MJ. Muscle damage during exercise: Possible role of free radicals and protective effect of vitamin E. Proc Nutr Soc 46: 77‐80, 1987.
 160. Jakobsen J, Reske‐Nielsen E. Diffuse muscle fiber atrophy in newly diagnosed diabetes. Clin Neuropathol 5: 73‐77, 1986.
 161. Jenni S, Oetliker C, Allemann S, Ith M, Tappy L, Wuerth S, Egger A, Boesch C, Schneiter P, Diem P, Christ E, Stettler C. Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus–a prospective single‐blinded randomised crossover trial. Diabetologia 51: 1457‐1465, 2008.
 162. Jenni S, Wueest S, Konrad D, Stettler C. Response of interleukin‐6 during euglycaemic and hyperglycaemic exercise in patients with type 1 diabetes mellitus. Diabetes Res Clin Pract 89: e27‐e29, 2010.
 163. Jimenez CC, Corcoran MH, Crawley JT, Guyton HW, Peer KS, Philbin RD, Riddell MC. National athletic trainers' association position statement: Management of the athlete with type 1 diabetes mellitus. J Athl Train 42: 536‐545, 2007.
 164. Kaji H, Asanuma Y, Ide H, Saito N, Hisamura M, Murao M, Yoshida T, Takahashi K. The auto‐brewery syndrome–the repeated attacks of alcoholic intoxication due to the overgrowth of Candida (albicans) in the gastrointestinal tract. Mater Med Pol 8: 429‐435, 1976.
 165. Kanaley JA, Weatherup‐Dentes MM, Jaynes EB, Hartman ML. Obesity attenuates the growth hormone response to exercise. J Clin Endocrinol Metab 84: 3156‐3161, 1999.
 166. Kanaley JA, Weltman JY, Pieper KS, Weltman A, Hartman ML. Cortisol and growth hormone responses to exercise at different times of day. J Clin Endocrinol Metab 86: 2881‐2889, 2001.
 167. Karagiorgos A, Garcia JF, Brooks GA. Growth hormone response to continuous and intermittent exercise. Med Sci Sports 11: 302‐307, 1979.
 168. Kasama T, Miwa Y, Isozaki T, Odai T, Adachi M, Kunkel SL. Neutrophil‐derived cytokines: Potential therapeutic targets in inflammation. Curr Drug Targets Inflamm Allergy 4: 273‐279, 2005.
 169. Kaufman FR. The role of the contonuous glucose monitoring system in pediatric pateints. Diabetes Technol Ther 2: S49‐S52, 2000.
 170. Kaufman FR, Austin J, Neinstein A, Jeng L, Halvorson M, Devoe DJ, Pitukcheewanont P. Nocturnal hypoglycemia detected with the Continuous Glucose Monitoring System in pediatric patients with type 1 diabetes. J Pediatr 141: 625‐630, 2002.
 171. Kelly D, Hamilton JK, Riddell MC. Blood glucose levels and performance in a sports camp for adolescents with type 1 diabetes mellitus: A field study. Int J Pediatr 1‐8, 2010.
 172. Kim JK, Fillmore JJ, Sunshine MJ, Albrecht B, Higashimori T, Kim DW, Liu ZX, Soos TJ, Cline GW, O'Brien WR, Littman DR, Shulman GI. PKC‐theta knockout mice are protected from fat‐induced insulin resistance. J Clin Invest 114: 823‐827, 2004.
 173. Kimball SR, Farrell PA, Jefferson LS. Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise. J Appl Physiol 93: 1168‐1180, 2002.
 174. Kirstein M, Aston C, Hintz R, Vlassara H. Receptor‐specific induction of insulin‐like growth factor I in human monocytes by advanced glycosylation end product‐modified proteins. J Clin Invest 90: 439‐446, 1992.
 175. Kivela R, Silvennoinen M, Touvra AM, Lehti TM, Kainulainen H, Vihko V. Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle. FASEB J 20: 1570‐1572, 2006.
 176. Klueber KM, Feczko JD. Ultrastructural, histochemical, and morphometric analysis of skeletal muscle in a murine model of type I diabetes. Anat Rec 239: 18‐34, 1994.
 177. Kolm‐Litty V, Sauer U, Nerlich A, Lehmann R, Schleicher ED. High glucose‐induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest 101: 160‐169, 1998.
 178. Komatsu WR, Barros Neto TL, Chacra AR, Dib SA. Aerobic exercise capacity and pulmonary function in athletes with and without type 1 diabetes. Diabetes Care 33: 2555‐2557, 2010.
 179. Komatsu WR, Gabbay MA, Castro ML, Saraiva GL, Chacra AR, de Barros Neto TL, Dib SA. Aerobic exercise capacity in normal adolescents and those with type 1 diabetes mellitus. Pediatr Diabetes 6: 145‐149, 2005.
 180. Kraemer WJ, Fleck SJ, Dziados JE, Harman EA, Marchitelli LJ, Gordon SE, Mello R, Frykman PN, Koziris LP, Triplett NT. Changes in hormonal concentrations after different heavy‐resistance exercise protocols in women. J Appl Physiol 75: 594‐604, 1993.
 181. Kraemer WJ, Gordon SE, Fleck SJ, Marchitelli LJ, Mello R, Dziados JE, Friedl K, Harman E, Maresh C, Fry AC. Endogenous anabolic hormonal and growth factor responses to heavy resistance exercise in males and females. Int J Sports Med 12: 228‐235, 1991.
 182. Kraemer WJ, Marchitelli L, Gordon SE, Harman E, Dziados JE, Mello R, Frykman P, McCurry D, Fleck SJ. Hormonal and growth factor responses to heavy resistance exercise protocols. J Appl Physiol 69: 1442‐1450, 1990.
 183. Krause MP, Riddell MC, Gordon CS, Imam SA, Cafarelli E, Hawke TJ. Diabetic myopathy differs between Ins2Akita+/‐ and streptozotocin‐induced Type 1 diabetic models. J Appl Physiol 106: 1650‐1659, 2009.
 184. Krause MP, Riddell MC, Hawke TJ. Effects of Type 1 Diabetes Mellitus on Skeletal Muscle: Clinical Observations and Physiological Mechanisms. Pediatr Diabetes 2010.
 185. Larsen S, Brynjolf I, Birch K, Munck O, Sestoft L. The effect of continuous subcutaneous insulin infusion on cardiac performance during exercise in insulin‐dependent diabetics. Scand J Clin Lab Invest 44: 683‐691, 1984.
 186. Larsson Y, Persson B, Sterky G, Thoren C. Functional adaptation to rigorous training and exercise in diabetic and nondiabetic adolescents. J Appl Physiol 19: 629‐635, 1964.
 187. Larsson YA, Sterky GC, Ekengren ke, Moller TG. Physical fitness and the influence of training in diabetic adolescent girls. Diabetes March‐April;11: 109‐117, 1962.
 188. Lassarre C, Girard F, Durand J, Raynaud J. Kinetics of human growth hormone during submaximal exercise. J Appl Physiol 37: 826‐830, 1974.
 189. Lee AY, Chung SS. Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J 13: 23‐30, 1999.
 190. Lehmann R, Kaplan V, Bingisser R, Bloch KE, Spinas GA. Impact of physical activity on cardiovascular risk factors in IDDM. Diabetes Care 20: 1603‐1611, 1997.
 191. Locard E, David L, Ruitton A, de Chabanolle F, Francois R. Studies of growth hormone secretion in juvenile diabetes. Horm Res 11: 29‐40, 1979.
 192. Luger A, Watschinger B, Deuster P, Svoboda T, Clodi M, Chrousos GP. Plasma growth hormone and prolactin responses to graded levels of acute exercise and to a lactate infusion. Neuroendocrinology 56: 112‐117, 1992.
 193. Lumb AN, Gallen IW. Diabetes management for intense exercise. Curr Opin Endocrinol Diabetes Obes 16: 150‐155, 2009.
 194. Luzi L, Castellino P, Simonson DC, Petrides AS, DeFronzo RA. Leucine metabolism in IDDM. Role of insulin and substrate availability. Diabetes 39: 38‐48, 1990.
 195. Magee MF, Bhatt BA. Management of decompensated diabetes. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. Crit Care Clin 17: 75‐106, 2001.
 196. Marliss EB, Vranic M. Intense exercise has unique effects on both insulin release and its roles in glucoregulation: Implications for diabetes. Diabetes 51(Suppl 1): S271‐S283, 2002.
 197. Marshall S, Bacote V, Traxinger RR. Discovery of a metabolic pathway mediating glucose‐induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 266: 4706‐4712, 1991.
 198. Marzban L, Bhanot S, McNeill JH. In vivo effects of insulin and bis(maltolato)oxovanadium (IV) on PKB activity in the skeletal muscle and liver of diabetic rats. Mol Cell Biochem 223: 147‐157, 2001.
 199. McCrimmon RJ, Evans ML, Jacob RJ, Fan X, Zhu Y, Shulman GI, Sherwin RS. AICAR and phlorizin reverse the hypoglycemia‐specific defect in glucagon secretion in the diabetic BB rat. Am J Physiol Endocrinol Metab 283: E1076‐E1083, 2002.
 200. McKewen MW, Rehrer NJ, Cox C, Mann J. Glycaemic control, muscle glycogen and exercise performance in IDDM athletes on diets of varying carbohydrate content. Int J Sports Med 20: 349‐353, 1999.
 201. McMahon SK, Ferreira LD, Ratnam N, Davey RJ, Youngs LM, Davis EA, Fournier PA, Jones TW. Glucose requirements to maintain euglycemia after moderate‐intensity afternoon exercise in adolescents with type 1 diabetes are increased in a biphasic manner. J Clin Endocrinol Metab 92: 963‐968, 2007.
 202. Mena P, Maynar M, Gutierrez JM, Maynar J, Timon J, Campillo JE. Erythrocyte free radical scavenger enzymes in bicycle professional racers. Adaptation to training. Int J Sports Med 12: 563‐566, 1991.
 203. Mitchell TH, Abraham G, Schiffrin A, Leiter LA, Marliss EB. Hyperglycemia after intense exercise in IDDM subjects during continuous subcutaneous insulin infusion. Diabetes Care 11: 311‐317, 1988.
 204. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators. N Engl J Med 329: 1677‐1683, 1993.
 205. Miyazaki H, Oh‐ishi S, Ookawara T, Kizaki T, Toshinai K, Ha S, Haga S, Ji LL, Ohno H. Strenuous endurance training in humans reduces oxidative stress following exhausting exercise. Eur J Appl Physiol 84: 1‐6, 2001.
 206. Mohamed‐Ali V, Armstrong L, Clarke D, Bolton CH, Pinkney JH. Evidence for the regulation of levels of plasma adhesion molecules by proinflammatory cytokines and their soluble receptors in type 1 diabetes. J Intern Med 250: 415‐421, 2001.
 207. Moore K, Vizzard N, Coleman C, McMahon J, Hayes R, Thompson CJ. Extreme altitude mountaineering and Type 1 diabetes; the Diabetes Federation of Ireland Kilimanjaro Expedition. Diabet Med 18: 749‐755, 2001.
 208. Mora S, Gilsanz V. Establishment of peak bone mass. Endocrinol Metab Clin North Am 32: 39‐63, 2003.
 209. Moy CS, Songer TJ, LaPorte RE, Dorman JS, Kriska AM, Orchard TJ, Becker DJ, Drash AL. Insulin‐dependent diabetes mellitus, physical activity, and death. Am J Epidemiol 137: 74‐81, 1993.
 210. Mylona‐Karayanni C, Gourgiotis D, Bossios A, Kamper EF. Oxidative stress and adhesion molecules in children with type 1 diabetes mellitus: A possible link. Pediatr Diabetes 7: 51‐59, 2006.
 211. Nair KS, Ford GC, Ekberg K, Fernqvist‐Forbes E, Wahren J. Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients. J Clin Invest 95: 2926‐2937, 1995.
 212. Nair KS, Ford GC, Halliday D. Effect of intravenous insulin treatment on in vivo whole body leucine kinetics and oxygen consumption in insulin‐deprived type I diabetic patients. Metabolism 36: 491‐495, 1987.
 213. Nair KS, Garrow JS, Ford C, Mahler RF, Halliday D. Effect of poor diabetic control and obesity on whole body protein metabolism in man. Diabetologia 25: 400‐403, 1983.
 214. Nair KS, Halliday D, Matthews DE, Welle SL. Hyperglucagonemia during insulin deficiency accelerates protein catabolism. Am J Physiol 253: E208‐E213, 1987.
 215. Nareika A, Im YB, Game BA, Slate EH, Sanders JJ, London SD, Lopes‐Virella MF, Huang Y. High glucose enhances lipopolysaccharide‐stimulated CD14 expression in U937 mononuclear cells by increasing nuclear factor kappaB and AP‐1 activities. J Endocrinol 196: 45‐55, 2008.
 216. Naveri H. Blood hormone and metabolite levels during graded cycle ergometer exercise. Scand J Clin Lab Invest 45: 599‐603, 1985.
 217. Naveri H, Kuoppasalmi K, Harkonen M. Metabolic and hormonal changes in moderate and intense long‐term running exercises. Int J Sports Med 6: 276‐281, 1985.
 218. Nemet D, Hong S, Mills PJ, Ziegler MG, Hill M, Cooper DM. Sysemic vs. local cytokine and leukocyte responses to unilateral wrist flexion exercise. J Appl Physiol 93: 546‐554, 2002.
 219. Nemet D, Oh Y, Kim H‐S, Hill MA, Cooper DM. The effect of intense exercise on inflammatory cytokines and growth mediators in adolescent boys. Pediatrics 110: 681‐689, 2002.
 220. Nicolls MR, Haskins K, Flores SC. Oxidant stress, immune dysregulation, and vascular function in type I diabetes. Antiox Redox Sign 9: 879‐889, 2007.
 221. Nieman DC, Miller AR, Henson DA, Warren BJ, Gusewitch G, Johnson RL, Davis JM, Butterworth DE, Herring JL, Nehlsen‐Cannarella SL. Effect of high‐ versus moderate‐intensity exercise on lymphocyte subpopulations and proliferative response. Int J Sports Med 15: 199‐206, 1994.
 222. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404: 787‐790, 2000.
 223. Nugent A‐M, Steele IC, Al‐Modaris F, Vallely S, Moore A, Campbell NPS, Bell PM, Buchanan KD, Trimble ER, Nicholls DP. Exercise responses in patients with IDDM. Diabetes Care 20: 1814‐1821, 1997.
 224. Orchard TJ, Costacou T. When are type 1 diabetic patients at risk for cardiovascular disease? Curr Diab Rep 10: 48‐54, 2010.
 225. Pain VM, Albertse EC, Garlick PJ. Protein metabolism in skeletal muscle, diaphragm, and heart of diabetic rats. Am J Physiol 245: E604‐E610, 1983.
 226. Pain VM, Garlick PJ. Effect of streptozotocin diabetes and insulin treatment on the rate of protein synthesis in tissues of the rat in vivo. J Biol Chem 249: 4510‐4514, 1974.
 227. Pavan P, Sarto P, Merlo L, Casara D, Ponchia A, Biasin R, Noventa D, Avogaro A. Metabolic and cardiovascular parameters in type 1 diabetes at extreme altitude. Med Sci Sports Exerc 36: 1283‐1289, 2004.
 228. Pavan P, Sarto P, Merlo L, Casara D, Ponchia A, Biasin R, Noventa D, Avogaro A. Extreme altitude mountaineering and type 1 diabetes: The Cho Oyu alpinisti in Alta Quota expedition. Diabetes Care 26: 3196‐3197, 2003.
 229. Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, Febbraio M, Saltin B. Searching for the exercise factor: Is IL‐6 a candidate? J Muscle Res Cell Motil 24: 113‐119, 2003.
 230. Perez CJ, Nemet D, Mills PJ, Scheet TP, Ziegler MG, Cooper DM. Effects of laboratory versus field exercise on leukocyte subsets and cell adhesion molecule expression in children. Eur J Appl Physiol 86: 34‐39, 2001.
 231. Petersen AM, Pedersen BK. The anti‐inflammatory effect of exercise. J Appl Physiol 98: 1154‐1162, 2005.
 232. Petersen KF, Price TB, Bergeron R. Regulation of net hepatic glycogenolysis and gluconeogenesis during exercise: Impact of type 1 diabetes. J Clin Endocrinol Metab 89: 4656‐4664, 2004.
 233. Pieper GM, Riaz uH. Activation of nuclear factor‐kappaB in cultured endothelial cells by increased glucose concentration: Prevention by calphostin C. J Cardiovasc Pharmacol 30: 528‐532, 1997.
 234. Poehlman ET, Copeland KC. Influence of physical activity on insulin‐like growth factor‐I in healthy younger and older men. J Clin Endocrinol Metab 71: 1468‐1473, 1990.
 235. Poortmans JR, Saerens P, Edelman R, Vertongen F, Dorchy H. Influence of the degree of metabolic control on physical fitness in type I diabetic adolescents. Int J Sports Med 7: 232‐235, 1986.
 236. Pritzlaff CJ, Wideman L, Weltman JY, Abbott RD, Gutgesell ME, Hartman ML, Veldhuis JD, Weltman A. Impact of acute exercise intensity on pulsatile growth hormone release in men. J Appl Physiol 87: 498‐504, 1999.
 237. Pyke S, Lew H, Quintanilha A. Severe depletion in liver glutathione during physical exercise. Biochem Biophys Res Commun 139: 926‐931, 1986.
 238. Rabinovich A. An update on cytokines in the pathogenesis of insulin‐dependent diabetes mellitus. Diabetes Metab Rev 14: 129‐151, 1998.
 239. Radom‐Aizik S, Zaldivar F, Jr., Leu SY, Galassetti P, Cooper DM. Effects of 30 min of aerobic exercise on gene expression in human neutrophils. J Appl Physiol 104: 236‐243, 2008.
 240. Radom‐Aizik S, Zaldivar F, Leu SY, Cooper DM. Brief bout of exercise alters gene expression in peripheral blood mononuclear cells of early‐ and late‐pubertal males. Pediatr Res Apr;65(4): 447‐452, 2009.
 241. Ramalho AC, de Lourdes LM, Nunes F, Cambui Z, Barbosa C, Andrade A, Viana A, Martins M, Abrantes V, Aragao C, Temistocles M. The effect of resistance versus aerobic training on metabolic control in patients with type‐1 diabetes mellitus. Diabetes Res Clin Pract 72: 271‐276, 2006.
 242. Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM. Advanced glycation end products and RAGE: A common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15: 16R‐28R, 2005.
 243. Ramires PR, Forjaz CL, Silva ME. Exercise tolerance is lower in type 1 diabetics compared with normal young men. Metabolism 42: 191‐195, 1993.
 244. Rask‐Madsen C, King GL. Proatherosclerotic mechanisms involving protein kinase C in diabetes and insulin resistance. Arterioscler Thromb Vasc Biol 25: 487‐496, 2005.
 245. Raynaud J, Capderou A, Martineaud JP, Bordachar J, Durand J. Intersubject viability in growth hormone time course during different types of work. J Appl Physiol 55: 1682‐1687, 1983.
 246. Raynaud J, Drouet L, Martineaud JP, Bordachar J, Coudert J, Durand J. Time course of plasma growth hormone during exercise in humans at altitude. J Appl Physiol 50: 229‐233, 1981.
 247. Reddigan JI, Riddell MC, Kuk JL. The joint association of physical activity and glycaemic control in predicting cardiovascular death and all‐cause mortality in the US population. Diabetologia 55: 632‐635, 2012.
 248. Reske‐Nielsen E, Harmsen A, Vorre P. Ultrastructure of muscle biopsies in recent, short‐term and long‐term juvenile diabetes. Acta Neurol Scand 55: 345‐362, 1977.
 249. Richter EA. Glucose utilization. In: Rowell LB, Shepherd JT, editors. Handbook of Physiology. Oxford, UK: Oxford University Press, 1996, pp. 912‐951.
 250. Riddell MC, Perkins BA. Type 1 diabetes and exercise‐part I: Applications of exercise physiology to patient management during vigorous activity. Can J Diabet 30: 63‐71, 2006.
 251. Riddell M, Perkins BA. Exercise and glucose metabolism in persons with diabetes mellitus: Perspectives on the role for continuous glucose monitoring. J Diabetes Sci Technol 3: 914‐923, 2009.
 252. Riddell MC, Bar‐Or O, Ayub BV, Calvert RE, Heil BV. Glucose ingestion matched with total carbohydrate utilization attenuates hypoglycemia during exercise in adolescents with IDDM. Int J Sports Nutr 9: 24‐34, 1999.
 253. Riddell MC, Bar‐Or O, Gerstein HC, Heigenhauser GJ. Perceived exertion with glucose ingestion in adolescent males with IDDM. Med Sci Sports Exerc 32: 167‐173, 2000.
 254. Riddell MC, Burr J. Evidence‐based risk assessment and recommendations for physical activity clearance: Diabetes mellitus and related comorbidities. This paper is one of a selection of papers published in this Special Issue, entitled Evidence‐based risk assessment and recommendations for physical activity clearance, and has undergone the Journal's usual peer review process. Appl Physiol Nutr Metab 36(Suppl 1): S154‐S189, 2011.
 255. Riddell MC, Iscoe KE. Physical activity, sport, and pediatric diabetes. Pediatr Diabetes 7: 60‐70, 2006.
 256. Riddell M, Ruderman NB, Berger M, Vranic M. Exercise Physiology and Diabetes: From Antiquity to the Age of Exercise Sciences. In: Ruderman NB, Devlin JT, Schneider S, Kriska A, editors. Handbook of Exercise and Diabetes. Alexander, VA: American Diabetes Association. 2002, pp. 3‐15.
 257. Rizza RA, Cryer PE, Gerich JE. Role of glucagon, catecholamines, and growth hormone in human glucose counterregulation. J Clin Invest 64: 62‐71, 1979.
 258. Roberts L, Jones TW, Fournier PA. Exercise training and glycemic control in adolescents with poorly controlled type 1 diabetes mellitus. J Pediatr Endocrinol Metab 15: 621‐627, 2002.
 259. Robertson K, Adolfsson P, Scheiner G, Hanas R, Riddell MC. Exercise in children and adolescents with diabetes. Pediatr Diabetes 10: 154‐168, 2009.
 260. Robitaille M, Dube MC, Weisnagel SJ, Prud'homme D, Massicotte D, Peronnet F, Lavoie C. Substrate source utilization during moderate intensity exercise with glucose ingestion in Type 1 diabetic patients. J Appl Physiol 103: 119‐124, 2007.
 261. Rosa JS, Flores RL, Oliver SR, Pontello AM, Zaldivar FP, Galassetti PR. Resting and exercise‐induced IL‐6 levels in children with Type 1 diabetes reflect hyperglycemic profiles during the previous 3 days. J Appl Physiol 108: 334‐342, 2010.
 262. Rosa JS, Flores RL, Oliver SR, Pontello AM, Zaldivar FP, Galassetti PR. Sustained IL‐1alpha, IL‐4, and IL‐6 elevations following correction of hyperglycemia in children with type 1 diabetes mellitus. Pediatr Diabetes 9: 9‐16, 2008.
 263. Rosa JS, Oliver SR, Flores RL, Graf SC, Pontello AM, Lbardolaza M, Zaldivar FP, Galassetti PR. Kinetic profiles of 18 systemic pro‐ and anti‐inflammatory mediators during and following exercise in children. J Pediatr Endocrinol Metab 20: 1293‐1305, 2007.
 264. Rosa JS, Oliver SR, Mitsuhashi M, Flores RL, Pontello AM, Zaldivar FP, Galassetti PR. Altered kinetics of interleukin‐6 and other inflammatory mediators during exercise in children with type 1 diabetes. J Investig Med 56: 701‐713, 2008.
 265. Rosen P, Nawroth PP, King G, Moller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: A summary of a Congress Series sponsored by UNESCO‐MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 17: 189‐212, 2001.
 266. Ross LA, Warren RE, Kelnar CJ, Frier BM. Pubertal stage and hypoglycaemia counterregulation in type 1 diabetes. Arch Dis Child 90: 190‐194, 2005.
 267. Roth J, Glick SM, Yalow RS and Berson SA. Secretion of human growth hormone: Physiologic and experimental modification. Metabolism 12: 577‐579, 1963.
 268. Roubenoff R. Sarcopenia: Effects on body composition and function. J Gerontol A Biol Sci Med Sci 58: 1012‐1017, 2003.
 269. Sampson MJ, Gopaul N, Davies IR, Hughues DA, Carrier MJ. Plasma F2‐isoprostanes ‐ direct evidence of increased free radical damage during acute hyperglycemia in type 2 diabetes. Diabetes Care 25: 537‐541, 2002.
 270. Sandoval DA, Guy DL, Richardson MA, Ertl AC, Davis SN. Effects of low and moderate antecedent exercise on counterregulatory responses to subsequent hypoglycemia in type 1 diabetes. Diabetes 53: 1798‐1806, 2004.
 271. Sane T, Helve E, Pelkonen R, Koivisto VA. The adjustment of diet and insulin dose during long‐term endurance exercise in type 1 (insulin‐dependent) diabetic men. Diabetologia 31: 35‐40, 1988.
 272. Schmidt AM, Hori O, Chen JX, Li JF, Crandall J, Zhang J, Cao R, Yan SD, Brett J, Stern D. Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule‐1 (VCAM‐1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. J Clin Invest 96: 1395‐1403, 1995.
 273. Schwindt CD, Zaldivar F, Wilson L, Leu SY, Wang‐Rodriguez J, Mills PJ, Cooper DM. Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma? Br J Sports Med 41: 34‐40, 2007.
 274. Segel SA, Fanelli CG, Dence CS, Markham J, Videen TO, Paramore DS, Powers WJ, Cryer PE. Blood‐to‐brain glucose transport, cerebral glucose metabolism, and cerebral blood flow are not increased after hypoglycemia. Diabetes 50: 1911‐1917, 2001.
 275. Sen CK. Oxidants and antioxidants in exercise. J Appl Physiol 79: 675‐686, 1995.
 276. Sen CK, Packer L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 72: 653S‐669S, 2000.
 277. Serino AS, Adegoke OA, Zargar S, Gordon CS, Szigiato AA, Hawke TJ, Riddell MC. Voluntary physical activity and leucine correct impairments in muscle protein synthesis in partially pancreatectomised rats. Diabetologia 54: 3111‐3120, 2011.
 278. Severinsen K, Obel A, Jakobsen J, Andersen H. Atrophy of foot muscles in diabetic patients can be detected with ultrasonography. Diabetes Care 30: 3053‐3057, 2007.
 279. Shen WH, Boyle DW, Wisniowski P, Bade A, Liechty EA. Insulin and IGF‐I stimulate the formation of the eukaryotic initiation factor 4F complex and protein synthesis in C2C12 myotubes independent of availability of external amino acids. J Endocrinol 185: 275‐289, 2005.
 280. Shephard RJ. Cytokine responses to physical activity, with particular reference to IL‐6: Sources, actions, and clinical implications. Crit Rev Immunol 22: 165‐182, 2002.
 281. Sigal R, Kenny G, Oh P, Perkins BA, Plotnikoff RC, Prud'homme D, Riddell MC. Physical activity and diabetes. Canadian diabetes clinical practice guidelines expert committee. Canadian diabetes association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabet 32: S37‐S39, 2008.
 282. Sigal RJ, Fisher S, Halter JB, Vranic M, Marliss EB. The roles of catecholamies in glucoregulation in intense exercise as defined by the islet clamp technique. Diabetes 45: 148‐156, 1996.
 283. Sigal RJ, Fisher SJ, Manzon A, Morais JA, Halter JB, Vranic M, Marliss EB. Glucoregulation during and after antense exercise: Affects of α‐adrenergic blockade. Metab Clin Exp 49: 386‐394, 2000.
 284. Sigal RJ, Purdon C, Fisher SJ, Halter JB, Vranic M, Marliss EB. Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin‐dependent diabetic subjects. J Clin Endocrinol Metab 79: 1049‐1057, 1994.
 285. Simsek M, Naziroglu M, Erdinc A. Moderate exercise with a dietary vitamin C and e combination protects against streptozotocin‐induced oxidative damage to the kidney and lens in pregnant rats. Exp Clin Endocrinol Diabetes 113: 53‐59, 2005.
 286. Skatrud‐Mickelson M, Benson J, Hannon JC, Askew EW. A comparison of subjective and objective measures of physical exertion. J Sports Sci 29: 1635‐1644, 2011.
 287. Skolnik EY, Yang Z, Makita Z, Radoff S, Kirstein M, Vlassara H. Human and rat mesangial cell receptors for glucose‐modified proteins: Potential role in kidney tissue remodelling and diabetic nephropathy. J Exp Med 174: 931‐939, 1991.
 288. Snegovskaya V, Viru A. Elevation of cortisol and growth hormone levels in the course of further improvement of performance capacity in trained rowers. Int J Sports Med 14: 202‐206, 1993.
 289. Somwar R, Sumitani S, Taha C, Sweeney G, Klip A. Temporal activation of p70 S6 kinase and Akt1 by insulin: PI 3‐kinase‐dependent and ‐independent mechanisms. Am J Physiol 275: E618‐E625, 1998.
 290. Somwar R, Sweeney G, Ramlal T, Klip A. Stimulation of glucose and amino acid transport and activation of the insulin signaling pathways by insulin lispro in L6 skeletal muscle cells. Clin Ther 20: 125‐140, 1998.
 291. Stettler C, Jenni S, Allemann S, Steiner R, Hoppeler H, Trepp R, Christ ER, Zwahlen M, Diem P. Exercise capacity in subjects with type 1 diabetes mellitus in eu‐ and hyperglycaemia. Diabetes Metab Res Rev 22: 300‐306, 2006.
 292. Stitt AW, He C, Friedman S, Scher L, Rossi P, Ong L, Founds H, Li YM, Bucala R, Vlassara H. Elevated AGE‐modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis: Relationship to tissue AGEs. Mol Med 3: 617‐627, 1997.
 293. Surridge DH, Erdahl DL, Lawson JS, Donald MW, Monga TN, Bird CE, Letemendia FJ. Psychiatric aspects of diabetes mellitus. Br J Psychiatry 145: 269‐276, 1984.
 294. Sutton J, Lazarus L. Growth hormone in exercise: Comparison of physiological and pharmacological stimuli. J Appl Physiol 41: 523‐527, 1976.
 295. Sutton JR. Hormonal and metabolic responses to exercise in subject of high and low work capacities. Med Sci Sports 10: 1‐6, 1978.
 296. Tansey MJ, Tsalikian E, Beck RW, Mauras N, Buckingham BA, Weinzimer SA, Janz KF, Kollman C, Xing D, Ruedy KJ, Steffes MW, Borland TM, Singh RJ, Tamborlane WV. The effects of aerobic exercise on glucose and counterregulatory hormone concentrations in children with type 1 diabetes. Diabetes Care 29: 20‐25, 2006.
 297. Tapanainen P, Kaar ML, Leppaluoto J, Huttunen NP, Knip M. Normal stimulated growth hormone secretion but low peripheral levels of insulin‐like growth factor I in prepubertal children with insulin‐dependent diabetes mellitus. Acta Paediatr 84: 646‐650, 1995.
 298. Targher G, Zenari L, Bertolini L, Muggeo M, Zoppini G. Elevated levels of interleukin‐6 in young adults with type 1 diabetes without clinical evidence of microvascular and macrovascular complications. Diabetes Care 24: 956‐957, 2001.
 299. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long‐term complications in insulin‐dependent diabetes mellitus. N Engl J Med 329: 977‐986, 1993.
 300. Thirunavukkarasu V, Balakrishnan SD, Ravichandran MK, Anuradha CV. Influence of 6‐week exercise training on erythrocyte and liver antioxidant defense in hyperinsulinemic rats. Comp Biochem Physiol Part C 135: 31‐37, 2003.
 301. Tiidus PM, Pushkarenko J, Houston ME. Lack of antioxidant adaptation to short‐term aerobic training in human muscle. Am J Physiol 271: R832‐R836, 1996.
 302. Tirakitsoontorn P, Nussbaum E, Moser C, Hill M, Cooper DM. Fitness, acute exercise, and anabolic and catabolic mediators in cystic fibrosis. Am J Resp Crit Care Med 164: 1432‐1437, 2001.
 303. Tsalikian E, Mauras N, Beck RW, Tamborlane WV, Janz KF, Chase HP, Wysocki T, Weinzimer SA, Buckingham BA, Kollman C, Xing D, Ruedy KJ. Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus. J Pediatr 147: 528‐534, 2005.
 304. Tuominen JA, Karonen SL, Melamies L, Bolli G, Koivisto VA. Exercise‐induced hypoglycaemia in IDDM patients treated with a short‐acting insulin analogue. Diabetologia 38: 106‐111, 1995.
 305. Umpleby AM, Boroujerdi MA, Brown PM, Carson ER, Sonksen PH. The effect of metabolic control on leucine metabolism in type 1 (insulin‐dependent) diabetic patients. Diabetologia 29: 131‐141, 1986.
 306. Valerio G, Spagnuolo MI, Lombardi F, Spadaro R, Siano M, Franzese A. Physical activity and sports participation in children and adolescents with type 1 diabetes mellitus. Nutr Metab Cardiovasc Dis 17: 376‐382, 2007.
 307. Van der Does FE, De Neeling JN, Snoek FJ, Kostense PJ, Grootenhuis PA, Bouter LM, Heine RJ. Symptoms and well‐being in relation to glycemic control in type II diabetes. Diabetes Care 19: 204‐210, 1996.
 308. VanHelder WP, Casey K, Goode RC, Radomski WM. Growth hormone regulation in two types of aerobic exercise of equal oxygen uptake. Eur J Appl Physiol Occup Physiol 55: 236‐239, 1986.
 309. Veldhuis JD, Iranmanesh A, Ho KK, Waters MJ, Johnson ML, Lizarralde G. Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J Clin Endocrinol Metab 72: 51‐59, 1991.
 310. Veldhuis JD, Liem AY, South S, Weltman A, Weltman J, Clemmons DA, Abbott R, Mulligan T, Johnson ML, Pincus S. Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay. J Clin Endocrinol Metab 80: 3209‐3222, 1995.
 311. Veves A, Saouaf R, Donaghue VM, Mullooly CA, Kistler JA, Giurini JM, Horton ES, Fielding RA. Aerobic exercise capacity remains normal despite impaired endothelial function in the micro‐ and macrocirculation of physically active IDDM patients. Diabetes 46: 1846‐1852, 1997.
 312. Villa‐Caballero L, Nava‐Ocampo AA, Frati‐Munari A, Ponce‐Monter H. Oxidative stress, acute and regular exercise: Are they really harmful in the diabetic patient? Med Hypotheses 55: 43‐46, 2000.
 313. Vina J, Gimeno A, Sastre J, Desco C, Asensi M, Pallardo FV, Cuesta A, Ferrero JA, Terada LS, Repine JE. Mechanism of free radical production in exhaustive exercise in humans and rats; role of xanthine oxidase and protection by allopurinol. IUBMB Life 49: 539‐544, 2000.
 314. Vina J, Gomez‐Cabrera MC, Lloret A, Marquez R, Minana JB, Pallardo FV, Sastre J. Free radical in exhaustive physical exercise: Mechanism of production. IUMBM Life 50: 271‐277, 2000.
 315. Vina J, Sanchis‐Gomar F, Martinez‐Bello V, Gomez‐Cabrera MC. Exercise acts as a drug; the pharmacological benefits of exercise. Br J Pharmacol 167: 1‐12, 2012.
 316. Viru A, Karelson K, Smirnova T. Stability and variability in hormonal responses to prolonged exercise. Int J Sports Med 13: 230‐235, 1992.
 317. Vlassara H, Brownlee M, Manogue KR, Dinarello CA, Pasagian A. Cachectin/TNF and IL‐1 induced by glucose‐modified proteins: Role in normal tissue remodeling. Science 240: 1546‐1548, 1988.
 318. Waden J, Tikkanen H, Forsblom C, Fagerudd J, Pettersson‐Fernholm K, Lakka T, Riska M, Groop PH. Leisure time physical activity is associated with poor glycemic control in type 1 diabetic women: The FinnDiane study. Diabetes Care 28: 777‐782, 2005.
 319. Wallberg‐Henriksson H, Gunnarsson R, Henriksson J, DeFronzo R, Felig P, Ostman J, Wahren J. Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training. Diabetes 31: 1044‐1050, 1982.
 320. Wallymahmed ME, Morgan C, Gill GV, MacFarlane IA. Aerobic fitness and hand grip strength in Type 1 diabetes: Relationship to glycaemic control and body composition. Diabet Med 24: 1296‐1299, 2007.
 321. Wang MY, Chen L, Clark GO, Lee Y, Stevens RD, Ilkayeva OR, Wenner BR, Bain JR, Charron MJ, Newgard CB, Unger RH. Leptin therapy in insulin‐deficient type I diabetes. Proc Natl Acad Sci U S A 107: 4813‐4819, 2010.
 322. Wanke T, Auinger M, Formanek D, Merkle M, Lahrmann H, Ogris E, Zwick H, Irsigler K. Defective endogenous opioid response to exercise in type I diabetic patients. Metabolism 45: 137‐142, 1996.
 323. Wasserman DH. Four grams of glucose. Am J Physiol Endocrinol Metab 296: E11‐E21, 2009.
 324. Wasserman DH, Cherrington AD. Hepatic fuel metabolism during muscular work: Role and regulation. Am J Physiol 260: E811‐E824, 1991.
 325. Wasserman DH, Zinman B. Exercise in individuals with IDDM. Diabetes Care 17: 924‐937, 1994.
 326. Weltman NY, Saliba SA, Barrett EJ, Weltman A. The use of exercise in the management of type 1 and type 2 diabetes. Clin Sports Med 28: 423‐439, 2009.
 327. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: A meta‐analysis of randomized, controlled trials. Ann Intern Med 136: 493‐503, 2002.
 328. Wideman L, Consitt L, Patrie J, Swearingin B, Bloomer R, Davis P, Weltman A. The impact of sex and exercise duration on growth hormone secretion. J Appl Physiol 101: 1641‐1647, 2006.
 329. Williams B, Gallacher B, Patel H, Orme C. Glucose‐induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro. Diabetes 46: 1497‐1503, 1997.
 330. Yardley JE, Iscoe KE, Sigal RJ, Kenny GP, Perkins BA, Riddell MC. Insulin pump therapy is associated with less post‐exercise hyperglycemia than multiple daily injections: An observational study of physically active type 1 diabetes patients. Diabetes Technol Ther 15: 84‐88, 2013.
 331. Yerneni KK, Bai W, Khan BV, Medford RM, Natarajan R. Hyperglycemia‐induced activation of nuclear transcription factor kappaB in vascular smooth muscle cells. Diabetes 48: 855‐864, 1999.
 332. Yu X, Park BH, Wang MY, Wang ZV, Unger RH. Making insulin‐deficient type 1 diabetic rodents thrive without insulin. Proc Natl Acad Sci U S A 105: 14070‐14075, 2008.
 333. Zaccaria M, Varnier M, Piazza P, Noventa D, Ermolao A. Blunted growth hormone response to maximal exercise in middle‐aged versus young subjects and no effect of endurance training. J Clin Endocrinol Metab 84: 2303‐2307, 1999.
 334. Zaldivar F, Eliakim A, Radom‐Aizik S, Cooper DM. The effect of brief exercise on circulating CD34+ stem cells in early and late pubertal boys. Ped Res Apr;61(4):491‐495, 2007.
 335. Zoppini G, Carlini M, Muggeo M. Self‐reported exercise and quality of life in young type 1 diabetic subjects. Diabetes Nutr Metab 16: 77‐80, 2003.

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Article Title: Exercise and Type 1 Diabetes (T1DM)
 

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Pietro Galassetti, Michael C. Riddell. Exercise and Type 1 Diabetes (T1DM). Compr Physiol 2013, 3: 1309-1336. doi: 10.1002/cphy.c110040