Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Exercise in adults with type 1 diabetes mellitus

Abstract

Regular physical activity improves cardiometabolic and musculoskeletal health, helps with weight management, improves cognitive and psychosocial functioning, and is associated with reduced mortality related to cancer and diabetes mellitus. However, turnover rates of glucose in the blood increase dramatically during exercise, which often results in either hypoglycaemia or hyperglycaemia as well as increased glycaemic variability in individuals with type 1 diabetes mellitus (T1DM). A complex neuroendocrine response to an acute exercise session helps to maintain circulating levels of glucose in a fairly tight range in healthy individuals, while several abnormal physiological processes and limitations of insulin therapy limit the capacity of people with T1DM to exercise in a normoglycaemic state. Knowledge of the acute and chronic effects of exercise and regular physical activity is critical for the formulation of clinical strategies for the management of insulin and nutrition for active patients with T1DM. Emerging diabetes-related technologies, such as continuous glucose monitors, automated insulin delivery systems and the administration of solubilized glucagon, are demonstrating efficacy for preserving glucose homeostasis during and after exercise in this population of patients. This Review highlights the beneficial effects of regular exercise and details the complex endocrine and metabolic responses to different types of exercise for adults with T1DM. An overview of basic clinical strategies for the preservation of glucose homeostasis using emerging technologies is also provided.

Key points

  • Type 1 diabetes mellitus is associated with marginal impairments in skeletal muscle health and cardiorespiratory fitness; however, these impairments can be offset with good glycaemic control and exercise training.

  • In general, endurance exercise activities reduce glycaemia and explosive activities raise glycaemia, while high-intensity interval training and resistance training activities can have a moderating effect.

  • Reductions in basal and/or bolus insulin delivery are typically required for endurance activities, along with supplemental carbohydrate feeding for performance reasons or if glucose level falls below ~7.0 mmol/l (126 mg/dl) during the activity.

  • Increases in insulin delivery after explosive exercise, resistance exercise and/or high-intensity interval training might be required if hyperglycaemia develops; however, the risk of post-exercise hypoglycaemia is heightened in the 12–24 h after exercise so frequent glucose monitoring is required.

  • Automated insulin delivery systems and continuous glucose monitoring technologies have the potential to improve glucose control around most forms of exercise.

  • However, several user-initiated actions are still required for endurance-type activities to help raise the pre-exercise glycaemic target, minimize insulin on board and maintain glycaemia on target (5–10 mmol/l; 90–180 mg/dl) during the activity when using automated insulin delivery and continuous glucose monitoring.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Change in relative maximal strength over time in adult men and women with and without T1DM.
Fig. 2: General trends in glycaemia in response to different forms of exercise in T1DM.
Fig. 3: Factors thought to influence the glucose response to exercise in T1DM.

References

  1. Tipton, C. M. Susruta of India, an unrecognized contributor to the history of exercise physiology. J. Appl. Physiol. 104, 1553–1556 (2008).

    Article  Google Scholar 

  2. Joslin, E. P. The treatment of diabetes mellitus. Can. Med. Assoc. J. 6, 673–684 (1916).

    CAS  Google Scholar 

  3. Lawrence, R. D. The effect of exercise on insulin action in diabetes. Br. Med. J. 1, 648–650 (1926).

    Article  CAS  Google Scholar 

  4. MacDonald, M. J. Postexercise late-onset hypoglycemia in insulin-dependent diabetic patients. Diabetes Care 10, 584–588 (1987).

    Article  CAS  Google Scholar 

  5. Berger, M. et al. Metabolic and hormonal effects of muscular exercise in juvenile type diabetics. Diabetologia 13, 355–365 (1977).

    Article  CAS  Google Scholar 

  6. Sigal, R. J. et al. Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects. J. Clin. Endocrinol. Metab. 79, 1049–1057 (1994).

    CAS  Google Scholar 

  7. Sherwin, R. S. & Koivisto, V. Keeping in step: does exercise benefit the diabetic? Diabetologia 20, 84–86 (1981).

    Article  CAS  Google Scholar 

  8. Ploug, T., Galbo, H. & Richter, E. A. Increased muscle glucose uptake during contractions: no need for insulin. Am. J. Physiol. 247, E726–E731 (1984).

    CAS  Google Scholar 

  9. Dela, F., Mikines, K. J., von Linstow, M., Secher, N. H. & Galbo, H. Effect of training on insulin-mediated glucose uptake in human muscle. Am. J. Physiol. 263, E1134–E1143 (1992).

    CAS  Google Scholar 

  10. Klip, A., McGraw, T. E. & James, D. E. Thirty sweet years of GLUT4. J. Biol. Chem. 294, 11369–11381 (2019).

    Article  CAS  Google Scholar 

  11. Colberg, S. R. et al. Physical activity/exercise and diabetes: a position statement of the American Diabetes Association. Diabetes Care 39, 2065–2079 (2016).

    Article  Google Scholar 

  12. Hartvig Jensen, T., Darre, E., Holmich, P. & Jahnsen, F. Insulin-dependent diabetes mellitus and marathon running. Br. J. Sports Med. 21, 51–52 (1987).

    Article  CAS  Google Scholar 

  13. Sane, T., Helve, E., Pelkonen, R. & Koivisto, V. A. The adjustment of diet and insulin dose during long-term endurance exercise in type 1 (insulin-dependent) diabetic men. Diabetologia 31, 35–40 (1988).

    Article  CAS  Google Scholar 

  14. Riddell, M. C. et al. The competitive athlete with type 1 diabetes. Diabetologia 63, 1475–1490 (2020).

    Article  CAS  Google Scholar 

  15. Silva Daniel, N. V. et al. Nutritional strategies of an athlete with type 1 diabetes mellitus during a 217-km ultramarathon. Wilderness Environ. Med. 33, 128–133 (2022).

    Article  Google Scholar 

  16. Lespagnol, E. et al. In amateur athletes with type 1 diabetes, a 9-day period of cycling at moderate-to-vigorous intensity unexpectedly increased the time spent in hyperglycemia, which was associated with impairment in heart rate variability. Diabetes Care 43, 2564–2573 (2020).

    Article  Google Scholar 

  17. Moser, O., Dietrich, M., McCarthy, O., Bracken, R. M. & Eckstein, M. L. Bolus insulin dose depends on previous-day race intensity during 5 days of professional road-cycle racing in athletes with type 1 diabetes: a prospective observational study. Diabetes Obes. Metab. 22, 1714–1721 (2020).

    Article  CAS  Google Scholar 

  18. Braune, K., May, A. & Thurm, U. Safe and Successful completion of a half marathon by an adult with type 1 diabetes using a personalized open source artificial pancreas system. J. Diabetes Sci. Technol. 14, 1137–1138 (2020).

    Article  Google Scholar 

  19. Nolan, J., Rush, A. & Kaye, J. Glycaemic stability of a cyclist with type 1 diabetes: 4011 km in 20 days on a ketogenic diet. Diabet. Med. 36, 1503–1507 (2019).

    Article  CAS  Google Scholar 

  20. Bach, C. W., Baur, D. A., Hyder, W. S. & Ormsbee, M. J. Blood glucose kinetics and physiological changes in a type 1 diabetic finisher of the Ultraman triathlon: a case study. Eur. J. Appl. Physiol. 117, 913–919 (2017).

    Article  CAS  Google Scholar 

  21. Khodaee, M., Riederer, M., VanBaak, K. & Hill, J. C. Ultraendurance athletes with type 1 diabetes: Leadville 100 experience. Wilderness Environ. Med. 26, 273–275 (2015).

    Article  Google Scholar 

  22. Thuillier, P. et al. Prevention of exercise-induced hypoglycemia in 12 patients with type 1 diabetes running the Paris Marathon using continuous glucose monitoring: a prospective, single-center observational study. Diabetes Metab. 48, 101321 (2022).

    Article  CAS  Google Scholar 

  23. Scott, S. N. et al. Evaluation of factors related to glycemic management in professional cyclists with type 1 diabetes over a 7-day stage race. Diabetes Care 43, 1142–1145 (2020).

    Article  CAS  Google Scholar 

  24. McCarthy, O. et al. Glycemic responses to strenuous training in male professional cyclists with type 1 diabetes: a prospective observational study. BMJ Open Diabetes Res. Care 8, e001245 (2020).

    Article  Google Scholar 

  25. Pinsker, J. E. et al. Techniques for exercise preparation and management in adults with type 1 diabetes. Can. J. Diabetes 40, 503–508 (2016).

    Article  Google Scholar 

  26. Prévost, M. S. et al. Gender differences in strategies to prevent physical activity-related hypoglycemia in patients with type 1 diabetes: a BETTER study. Diabetes Care 45, e51–e53 (2022).

    Article  Google Scholar 

  27. Colberg, S. R., Kannane, J. & Diawara, N. Physical activity, dietary patterns, and glycemic management in active individuals with type 1 diabetes: an online survey. Int. J. Environ. Res. Public Health 18, 9332 (2021).

    Article  CAS  Google Scholar 

  28. Deichmann, J., Bachmann, S., Burckhardt, M.-A., Szinnai, G. & Kaltenbach, H.-M. Simulation-based evaluation of treatment adjustment to exercise in type 1 diabetes. Front. Endocrinol. 12, 723812 (2021).

    Article  Google Scholar 

  29. Riddell, M. C. et al. Exercise management in type 1 diabetes: a consensus statement. Lancet Diabetes Endocrinol. 5, 377–390 (2017).

    Article  Google Scholar 

  30. Kimball, S. R., Farrell, P. A. & Jefferson, L. S. 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).

    Article  CAS  Google Scholar 

  31. Monaco, C. M. F., Gingrich, M. A. & Hawke, T. J. Considering type 1 diabetes as a form of accelerated muscle aging. Exerc. Sport Sci. Rev. 47, 98–107 (2019).

    Article  Google Scholar 

  32. James, H. A., O’Neill, B. T. & Nair, K. S. Insulin regulation of proteostasis and clinical implications. Cell Metab. 26, 310–323 (2017).

    Article  CAS  Google Scholar 

  33. Cree-Green, M. et al. Youth with type 1 diabetes have adipose, hepatic, and peripheral insulin resistance. J. Clin. Endocrinol. Metab. 103, 3647–3657 (2018).

    Article  Google Scholar 

  34. Coleman, S. K., Rebalka, I. A., D’Souza, D. M. & Hawke, T. J. Skeletal muscle as a therapeutic target for delaying type 1 diabetic complications. World J. Diabetes 6, 1323–1336 (2015).

    Article  Google Scholar 

  35. Baron, A. D., Brechtel, G., Wallace, P. & Edelman, S. V. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am. J. Physiol. 255, E769–E774 (1988).

    CAS  Google Scholar 

  36. Wolfe, R. R. The underappreciated role of muscle in health and disease. Am. J. Clin. Nutr. 84, 475–482 (2006).

    Article  CAS  Google Scholar 

  37. Jakobsen, J. & Reske-Nielsen, E. Diffuse muscle fiber atrophy in newly diagnosed diabetes. Clin. Neuropathol. 5, 73–77 (1986).

    CAS  Google Scholar 

  38. Kalaitzoglou, E., Fowlkes, J. L., Popescu, I. & Thrailkill, K. M. Diabetes pharmacotherapy and effects on the musculoskeletal system. Diabetes Metab. Res. Rev. 35, e3100 (2019).

    Article  Google Scholar 

  39. Monaco, C. M. F., Perry, C. G. R. & Hawke, T. J. Diabetic myopathy: current molecular understanding of this novel neuromuscular disorder. Curr. Opin. Neurol. 30, 545–552 (2017).

    Article  CAS  Google Scholar 

  40. Napoli, N. et al. Mechanisms of diabetes mellitus-induced bone fragility. Nat. Rev. Endocrinol. 13, 208–219 (2017).

    Article  CAS  Google Scholar 

  41. Dial, A. G. et al. Impaired Function and altered morphology in the skeletal muscles of adult men and women with type 1 diabetes. J. Clin. Endocrinol. Metab. 106, 2405–2422 (2021).

    Article  Google Scholar 

  42. Dial, A. G. et al. Alterations in skeletal muscle repair in young adults with type 1 diabetes mellitus. Am. J. Physiol. Cell Physiol. 321, C876–C883 (2021).

    Article  CAS  Google Scholar 

  43. D’Souza, D. M. et al. Decreased satellite cell number and function in humans and mice with type 1 diabetes is the result of altered notch signaling. Diabetes 65, 3053–3061 (2016).

    Article  Google Scholar 

  44. Fritzsche, K. et al. 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).

    Article  CAS  Google Scholar 

  45. Monaco, C. M. F. et al. Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes. Diabetologia 61, 1411–1423 (2018).

    Article  CAS  Google Scholar 

  46. Monaco, C. M. F. et al. Normal to enhanced intrinsic mitochondrial respiration in skeletal muscle of middle- to older-aged women and men with uncomplicated type 1 diabetes. Diabetologia 64, 2517–2533 (2021).

    Article  CAS  Google Scholar 

  47. Lee, H. C., Yin, P. H., Lu, C. Y., Chi, C. W. & Wei, Y. H. Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells. Biochem. J. 348, 425–432 (2000).

    Article  CAS  Google Scholar 

  48. Boirie, Y., Short, K. R., Ahlman, B., Charlton, M. & Nair, K. S. Tissue-specific regulation of mitochondrial and cytoplasmic protein synthesis rates by insulin. Diabetes 50, 2652–2658 (2001).

    Article  CAS  Google Scholar 

  49. Nair, K. S., Garrow, J. S., Ford, C., Mahler, R. F. & Halliday, D. Effect of poor diabetic control and obesity on whole body protein metabolism in man. Diabetologia 25, 400–403 (1983).

    Article  CAS  Google Scholar 

  50. Sinha, A. et al. Effects of insulin on body composition in patients with insulin-dependent and non-insulin-dependent diabetes. Diabet. Med. 13, 40–46 (1996).

    Article  CAS  Google Scholar 

  51. Rosenfalck, A. M., Almdal, T., Hilsted, J. & Madsbad, S. Body composition in adults with type 1 diabetes at onset and during the first year of insulin therapy. Diabet. Med. 19, 417–423 (2002).

    Article  CAS  Google Scholar 

  52. O’Neill, B. T. et al. FoxO transcription factors are critical regulators of diabetes-related muscle atrophy. Diabetes 68, 556–570 (2019).

    Article  Google Scholar 

  53. Charlton, M. & Nair, K. S. Protein metabolism in insulin-dependent diabetes mellitus. J. Nutr. 128, 323S–327S (1998).

    Article  CAS  Google Scholar 

  54. Minnock, D. et al. Effects of acute aerobic, resistance and combined exercises on 24-h glucose variability and skeletal muscle signalling responses in type 1 diabetics. Eur. J. Appl. Physiol. 120, 2677–2691 (2020).

    Article  CAS  Google Scholar 

  55. Minnock, D. et al. Altered muscle mitochondrial, inflammatory and trophic markers, and reduced exercise training adaptations in type 1 diabetes. J. Physiol. 600, 1405–1418 (2022).

    Article  CAS  Google Scholar 

  56. Nguyen, T. et al. Fitness and physical activity in youth with type 1 diabetes mellitus in good or poor glycemic control. Pediatr. Diabetes 16, 48–57 (2015).

    Article  CAS  Google Scholar 

  57. Donga, E., Dekkers, O. M., Corssmit, E. P. M. & Romijn, J. A. Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis. Eur. J. Endocrinol. 173, 101–109 (2015).

    Article  CAS  Google Scholar 

  58. Lespagnol, E. et al. Early endothelial dysfunction in type 1 diabetes is accompanied by an impairment of vascular smooth muscle function: a meta-analysis. Front. Endocrinol. 11, 203 (2020).

    Article  Google Scholar 

  59. Cree-Green, M. et al. Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance. Diabetes 64, 383–392 (2015).

    Article  CAS  Google Scholar 

  60. Ruegsegger, G. N., Creo, A. L., Cortes, T. M., Dasari, S. & Nair, K. S. Altered mitochondrial function in insulin-deficient and insulin-resistant states. J. Clin. Invest. 128, 3671–3681 (2018).

    Article  Google Scholar 

  61. Eckstein, M. L. et al. Differences in physiological responses to cardiopulmonary exercise testing in adults with and without type 1 diabetes: a pooled analysis. Diabetes Care 44, 240–247 (2021).

    Article  Google Scholar 

  62. Heyman, E. et al. Muscle oxygen supply and use in type 1 diabetes, from ambient air to the mitochondrial respiratory chain: is there a limiting step? Diabetes Care 43, 209–218 (2020).

    Article  CAS  Google Scholar 

  63. Yardley, J. E., Hay, J., Abou-Setta, A. M., Marks, S. D. & McGavock, J. A systematic review and meta-analysis of exercise interventions in adults with type 1 diabetes. Diabetes Res. Clin. Pract. 106, 393–400 (2014).

    Article  Google Scholar 

  64. Riddell, M. C. & Burr, J. Evidence-based risk assessment and recommendations for physical activity clearance: diabetes mellitus and related comorbidities. Appl. Physiol. Nutr. Metab. 36 (Suppl. 1), S154–S189 (2011).

    Article  Google Scholar 

  65. Armstrong, M. J. et al. Clinical utility of pre-exercise stress testing in people with diabetes. Can. J. Cardiol. 35, 185–192 (2019).

    Article  Google Scholar 

  66. American Diabetes Association Professional Practice Committee et al.5. Facilitating behavior change and well-being to improve health outcomes: standards of medical care in diabetes-2022. Diabetes Care 45 (Suppl. 1), S60–S82 (2022).

    Article  Google Scholar 

  67. Sluik, D. et al. Physical activity and mortality in individuals with diabetes mellitus: a prospective study and meta-analysis. Arch. Intern. Med. 172, 1285–1295 (2012).

    Article  Google Scholar 

  68. Bohn, B. et al. Impact of physical activity on glycemic control and prevalence of cardiovascular risk factors in adults with type 1 diabetes: a cross-sectional multicenter study of 18,028 patients. Diabetes Care 38, 1536–1543 (2015).

    Article  Google Scholar 

  69. Tikkanen-Dolenc, H. et al. Physical activity reduces risk of premature mortality in patients with type 1 diabetes with and without kidney disease. Diabetes Care 40, 1727–1732 (2017).

    Article  Google Scholar 

  70. Buoite Stella, A., Yardley, J., Francescato, M. P. & Morrison, S. A. Fluid intake habits in type 1 diabetes individuals during typical training bouts. Ann. Nutr. Metab. 73, 10–18 (2018).

    Article  CAS  Google Scholar 

  71. Ostman, C., Jewiss, D., King, N. & Smart, N. A. Clinical outcomes to exercise training in type 1 diabetes: a systematic review and meta-analysis. Diabetes Res. Clin. Pract. 139, 380–391 (2018).

    Article  CAS  Google Scholar 

  72. Keshawarz, A. et al. Lower objectively measured physical activity is linked with perceived risk of hypoglycemia in type 1 diabetes. J. Diabetes Complications 32, 975–981 (2018).

    Article  Google Scholar 

  73. McCarthy, M. M., Whittemore, R. & Grey, M. Physical activity in adults with type 1 diabetes. Diabetes Educ. 42, 108–115 (2016).

    Article  Google Scholar 

  74. Plotnikoff, R. C. et al. Factors associated with physical activity in Canadian adults with diabetes. Med. Sci. Sports Exerc. 38, 1526–1534 (2006).

    Article  Google Scholar 

  75. Orchard, T. J. et al. Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care 26, 1374–1379 (2003).

    Article  Google Scholar 

  76. Brazeau, A.-S., Rabasa-Lhoret, R., Strychar, I. & Mircescu, H. Barriers to physical activity among patients with type 1 diabetes. Diabetes Care 31, 2108–2109 (2008).

    Article  Google Scholar 

  77. Kennedy, A. et al. Attitudes and barriers to exercise in adults with a recent diagnosis of type 1 diabetes: a qualitative study of participants in the Exercise for Type 1 Diabetes (EXTOD) study. BMJ Open 8, e017813 (2018).

    Article  Google Scholar 

  78. Oser, T. K. et al. Using social media to broaden understanding of the barriers and facilitators to exercise in adults with type 1 diabetes. J. Diabetes Sci. Technol. 13, 457–465 (2019).

    Article  Google Scholar 

  79. Lascar, N. et al. Attitudes and barriers to exercise in adults with type 1 diabetes (T1DM) and how best to address them: a qualitative study. PLoS ONE 9, e108019 (2014).

    Article  Google Scholar 

  80. Brennan, M. C., Brown, J. A., Ntoumanis, N. & Leslie, G. D. Barriers and facilitators of physical activity participation in adults living with type 1 diabetes: a systematic scoping review. Appl. Physiol. Nutr. Metab. 46, 95–107 (2021).

    Article  Google Scholar 

  81. Alarcón-Gómez, J., Chulvi-Medrano, I., Martin-Rivera, F. & Calatayud, J. Effect of high-intensity interval training on quality of life, sleep quality, exercise motivation and enjoyment in sedentary people with type 1 diabetes mellitus. Int. J. Environ. Res. Public Health 18, 12612 (2021).

    Article  Google Scholar 

  82. Alarcón-Gómez, J., Calatayud, J., Chulvi-Medrano, I. & Martín-Rivera, F. Effects of a HIIT protocol on cardiovascular risk factors in a type 1 diabetes mellitus population. Int. J. Environ. Res. Public Health 18, 1262 (2021).

    Article  Google Scholar 

  83. Scott, S. N., Shepherd, S. O., Strauss, J. A., Wagenmakers, A. J. M. & Cocks, M. Home-based high-intensity interval training reduces barriers to exercise in people with type 1 diabetes. Exp. Physiol. 105, 571–578 (2020).

    Article  Google Scholar 

  84. Scott, S. N. et al. A multidisciplinary evaluation of a virtually supervised home-based high-intensity interval training intervention in people with type 1 diabetes. Diabetes Care 42, 2330–2333 (2019).

    Article  Google Scholar 

  85. Riddell, M. C. et al. Reproducibility in the cardiometabolic responses to high-intensity interval exercise in adults with type 1 diabetes. Diabetes Res. Clin. Pract. 148, 137–143 (2019).

    Article  Google Scholar 

  86. Maran, A. et al. Continuous glucose monitoring reveals delayed nocturnal hypoglycemia after intermittent high-intensity exercise in nontrained patients with type 1 diabetes. Diabetes Technol. Ther. 12, 763–768 (2010).

    Article  Google Scholar 

  87. Aronson, R., Brown, R. E., Li, A. & Riddell, M. C. Optimal Insulin correction factor in post-high-intensity exercise hyperglycemia in adults with type 1 diabetes: the FIT study. Diabetes Care 42, 10–16 (2019).

    Article  CAS  Google Scholar 

  88. Potashner, D., Brown, R. E., Li, A., Riddell, M. C. & Aronson, R. Paradoxical rise in hypoglycemia symptoms with development of hyperglycemia during high-intensity interval training in type 1 diabetes. Diabetes Care 42, 2011–2014 (2019).

    Article  Google Scholar 

  89. Farrell, C. M. et al. A randomised controlled study of high intensity exercise as a dishabituating stimulus to improve hypoglycaemia awareness in people with type 1 diabetes: a proof-of-concept study. Diabetologia 63, 853–863 (2020).

    Article  CAS  Google Scholar 

  90. Rooijackers, H. M. et al. A single bout of high-intensity interval training reduces awareness of subsequent hypoglycemia in patients with type 1 diabetes. Diabetes 66, 1990–1998 (2017).

    Article  CAS  Google Scholar 

  91. Yardley, J. E. et al. Resistance versus aerobic exercise: acute effects on glycemia in type 1 diabetes. Diabetes Care 36, 537–542 (2013).

    Article  CAS  Google Scholar 

  92. Reddy, R. et al. Effect of aerobic and resistance exercise on glycemic control in adults with type 1 diabetes. Can. J. Diabetes 43, 406–414.e1 (2019).

    Article  Google Scholar 

  93. Riddell, M. C. et al. More time in glucose range during exercise days than sedentary days in adults living with type 1 diabetes. Diabetes Technol. Ther. 23, 376–383 (2021).

    Article  CAS  Google Scholar 

  94. Gal, J. J., Li, Z., Willi, S. M. & Riddell, M. C. Association between high levels of physical activity and improved glucose control on active days in youth with type 1 diabetes. Pediatr. Diabetes 23, 1057–1063 (2022).

    Article  CAS  Google Scholar 

  95. Röhling, M., Herder, C., Roden, M., Stemper, T. & Müssig, K. Effects of long-term exercise interventions on glycaemic control in type 1 and type 2 diabetes: a systematic review. Exp. Clin. Endocrinol. Diabetes 124, 487–494 (2016).

    Article  Google Scholar 

  96. Momeni, Z., Logan, J. E., Sigal, R. J. & Yardley, J. E. Can resistance exercise be a tool for healthy aging in post-menopausal women with type 1 diabetes? Int. J. Environ. Res. Public Health 18, 8716 (2021).

    Article  Google Scholar 

  97. McCarthy, O. et al. Resistance isn’t futile: the physiological basis of the health effects of resistance exercise in individuals with type 1 diabetes. Front. Endocrinol. 10, 507 (2019).

    Article  Google Scholar 

  98. Richter, E. A., Sylow, L. & Hargreaves, M. Interactions between insulin and exercise. Biochem. J. 478, 3827–3846 (2021).

    Article  CAS  Google Scholar 

  99. Chow, L. S. et al. Exerkines in health, resilience and disease. Nat. Rev. Endocrinol. 18, 273–289 (2022).

    Article  CAS  Google Scholar 

  100. Hargreaves, M. & Spriet, L. L. Exercise metabolism: fuels for the fire. Cold Spring Harb. Perspect. Med. 8, a029744 (2018).

    Article  Google Scholar 

  101. Spencer, M. R. & Gastin, P. B. Energy system contribution during 200- to 1500-m running in highly trained athletes. Med. Sci. Sports Exerc. 33, 157–162 (2001).

    Article  CAS  Google Scholar 

  102. Riddell, M. C. et al. Individual glucose responses to prolonged moderate intensity aerobic exercise in adolescents with type 1 diabetes: the higher they start, the harder they fall. Pediatr. Diabetes 20, 99–106 (2019).

    CAS  Google Scholar 

  103. Vartak, V., Chepulis, L., Driller, M. & Paul, R. G. Comparing two treatment approaches for patients with type 1 diabetes during aerobic exercise: a randomised, crossover study. Sports Med. Open 7, 29 (2021).

    Article  Google Scholar 

  104. Marliss, E. B. & 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).

    Article  CAS  Google Scholar 

  105. Galassetti, P. et al. Effects of antecedent prolonged exercise on subsequent counterregulatory responses to hypoglycemia. Am. J. Physiol. Endocrinol. Metab. 280, E908–E917 (2001).

    Article  CAS  Google Scholar 

  106. Jaggers, J. R., King, K. M., Watson, S. E. & Wintergerst, K. A. Predicting nocturnal hypoglycemia with measures of physical activity intensity in adolescent athletes with type 1 diabetes. Diabetes Technol. Ther. 21, 406–408 (2019).

    Article  CAS  Google Scholar 

  107. Tsalikian, E. et al. Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus. J. Pediatr. 147, 528–534 (2005).

    Article  Google Scholar 

  108. Paramalingam, N. et al. A 10-second sprint does not blunt hormonal counter-regulation to subsequent hypoglycaemia. Diabet. Med. J. 34, 1440–1446 (2017).

    Article  CAS  Google Scholar 

  109. Fahey, A. J. et al. The effect of a short sprint on postexercise whole-body glucose production and utilization rates in individuals with type 1 diabetes mellitus. J. Clin. Endocrinol. Metab. 97, 4193–4200 (2012).

    Article  CAS  Google Scholar 

  110. Ainsworth, B. E. et al. 2011 Compendium of physical activities: a second update of codes and MET values. Med. Sci. Sports Exerc. 43, 1575–1581 (2011).

    Article  Google Scholar 

  111. Bussau, V. A., Ferreira, L. D., Jones, T. W. & Fournier, P. A. 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).

    Article  CAS  Google Scholar 

  112. Davey, R. J. et al. A 10-s sprint performed after moderate-intensity exercise neither increases nor decreases the glucose requirement to prevent late-onset hypoglycemia in individuals with type 1 diabetes. Diabetes Care 36, 4163–4165 (2013).

    Article  CAS  Google Scholar 

  113. Gibala, M. J. Physiological basis of interval training for performance enhancement. Exp. Physiol. 106, 2324–2327 (2021).

    Article  Google Scholar 

  114. Guelfi, K. J., Jones, T. W. & Fournier, P. A. New insights into managing the risk of hypoglycaemia associated with intermittent high-intensity exercise in individuals with type 1 diabetes mellitus: implications for existing guidelines. Sports Med. 37, 937–946 (2007).

    Article  Google Scholar 

  115. Scott, S. N. et al. High-intensity interval training improves aerobic capacity without a detrimental decline in blood glucose in people with type 1 diabetes. J. Clin. Endocrinol. Metab. 104, 604–612 (2019).

    Article  Google Scholar 

  116. Guelfi, K. J., Jones, T. W. & Fournier, P. A. The decline in blood glucose levels is less with intermittent high-intensity compared with moderate exercise in individuals with type 1 diabetes. Diabetes Care 28, 1289–1294 (2005).

    Article  CAS  Google Scholar 

  117. Lee, A. S. et al. Effect of high-intensity interval training on glycemic control in adults with type 1 diabetes and overweight or obesity: a randomized controlled trial with partial crossover. Diabetes Care 43, 2281–2288 (2020).

    Article  CAS  Google Scholar 

  118. Minnebeck, K. et al. Four weeks of high-intensity interval training (HIIT) improve the cardiometabolic risk profile of overweight patients with type 1 diabetes mellitus (T1DM). Eur. J. Sport Sci. 21, 1193–1203 (2021).

    Article  Google Scholar 

  119. Li, A., Riddell, M. C., Potashner, D., Brown, R. E. & Aronson, R. Time lag and accuracy of continuous glucose monitoring during high intensity interval training in adults with type 1 diabetes. Diabetes Technol. Ther. 21, 286–294 (2019).

    Article  CAS  Google Scholar 

  120. Lee, A. S., Way, K. L., Johnson, N. A. & Twigg, S. M. High-intensity interval exercise and hypoglycaemia minimisation in adults with type 1 diabetes: a randomised cross-over trial. J. Diabetes Complications 34, 107514 (2020).

    Article  Google Scholar 

  121. Turner, D. et al. Algorithm that delivers an individualized rapid-acting insulin dose after morning resistance exercise counters post-exercise hyperglycaemia in people with type 1 diabetes. Diabet. Med. 33, 506–510 (2016).

    Article  CAS  Google Scholar 

  122. Turner, D. et al. Impact of single and multiple sets of resistance exercise in type 1 diabetes. Scand. J. Med. Sci. Sports 25, e99–e109 (2015).

    Article  CAS  Google Scholar 

  123. Toghi-Eshghi, S. R. & Yardley, J. E. Morning (fasting) vs afternoon resistance exercise in individuals with type 1 diabetes: a randomized crossover study. J. Clin. Endocrinol. Metab. 104, 5217–5224 (2019).

    Article  Google Scholar 

  124. Brockman, N. K. et al. Sex-related differences in blood glucose responses to resistance exercise in adults with type 1 diabetes: a secondary data analysis. Can. J. Diabetes 44, 267–273.e1 (2020).

    Article  Google Scholar 

  125. Yardley, J. E. et al. Effects of performing resistance exercise before versus after aerobic exercise on glycemia in type 1 diabetes. Diabetes Care 35, 669–675 (2012).

    Article  CAS  Google Scholar 

  126. Yardley, J. E., Sigal, R. J., Riddell, M. C., Perkins, B. A. & Kenny, G. P. Performing resistance exercise before versus after aerobic exercise influences growth hormone secretion in type 1 diabetes. Appl. Physiol. Nutr. Metab. 39, 262–265 (2014).

    Article  CAS  Google Scholar 

  127. Temple, M. Y., Bar-Or, O. & Riddell, M. C. The reliability and repeatability of the blood glucose response to prolonged exercise in adolescent boys with IDDM. Diabetes Care 18, 326–332 (1995).

    Article  CAS  Google Scholar 

  128. Abraham, M. B. et al. Reproducibility of the plasma glucose response to moderate-intensity exercise in adolescents with type 1 diabetes. Diabet. Med. 34, 1291–1295 (2017).

    Article  CAS  Google Scholar 

  129. Biankin, S. A. et al. Target-seeking behavior of plasma glucose with exercise in type 1 diabetes. Diabetes Care 26, 297–301 (2003).

    Article  CAS  Google Scholar 

  130. Notkin, G. T., Kristensen, P. L., Pedersen-Bjergaard, U., Jensen, A. K. & Molsted, S. Reproducibility of glucose fluctuations induced by moderate intensity cycling exercise in persons with type 1 diabetes. J. Diabetes Res. 2021, 6640600 (2021).

    Article  Google Scholar 

  131. Moser, O. et al. Improved glycaemic variability and basal insulin dose reduction during a running competition in recreationally active adults with type 1 diabetes-A single-centre, prospective, controlled observational study. PLoS ONE 15, e0239091 (2020).

    Article  CAS  Google Scholar 

  132. Yardley, J. E., Brockman, N. K. & Bracken, R. M. Could age, sex and physical fitness affect blood glucose responses to exercise in type 1 diabetes? Front. Endocrinol. 9, 674 (2018).

    Article  Google Scholar 

  133. Taylor, G. S. et al. Capturing the real-world benefit of residual β-cell function during clinically important time-periods in established type 1 diabetes. Diabet. Med. 39, e14814 (2022).

    Article  CAS  Google Scholar 

  134. Jeyam, A. et al. Clinical impact of residual c-peptide secretion in type 1 diabetes on glycemia and microvascular complications. Diabetes Care 44, 390–398 (2021).

    Article  CAS  Google Scholar 

  135. Taylor, G. S. et al. Postexercise glycemic control in type 1 diabetes is associated with residual β-cell function. Diabetes Care 43, 2362–2370 (2020).

    Article  CAS  Google Scholar 

  136. Brooks, G. A. The precious few grams of glucose during exercise. Int. J. Mol. Sci. 21, E5733 (2020).

    Article  Google Scholar 

  137. Rapoport, B. I. Metabolic factors limiting performance in marathon runners. PLoS Comput. Biol. 6, e1000960 (2010).

    Article  Google Scholar 

  138. Mallad, A. et al. Exercise effects on postprandial glucose metabolism in type 1 diabetes: a triple-tracer approach. Am. J. Physiol. Endocrinol. Metab. 308, E1106–E1115 (2015).

    Article  CAS  Google Scholar 

  139. Rabasa-Lhoret, R., Bourque, J., Ducros, F. & Chiasson, J. L. Guidelines for premeal insulin dose reduction for postprandial exercise of different intensities and durations in type 1 diabetic subjects treated intensively with a basal-bolus insulin regimen (ultralente-lispro). Diabetes Care 24, 625–630 (2001).

    Article  CAS  Google Scholar 

  140. Jensen, J., Rustad, P. I., Kolnes, A. J. & Lai, Y.-C. The role of skeletal muscle glycogen breakdown for regulation of insulin sensitivity by exercise. Front. Physiol. 2, 112 (2011).

    Article  Google Scholar 

  141. Metcalf, K. M. et al. Effects of moderate-to-vigorous intensity physical activity on overnight and next-day hypoglycemia in active adolescents with type 1 diabetes. Diabetes Care 37, 1272–1278 (2014).

    Article  Google Scholar 

  142. Morrison, D. et al. Comparable glucose control with fast-acting insulin aspart versus insulin aspart using a second-generation hybrid closed-loop system during exercise. Diabetes Technol. Ther. 24, 93–101 (2022).

    Article  CAS  Google Scholar 

  143. Franc, S. et al. Insulin-based strategies to prevent hypoglycaemia during and after exercise in adult patients with type 1 diabetes on pump therapy: the DIABRASPORT randomized study. Diabetes Obes. Metab. 17, 1150–1157 (2015).

    Article  CAS  Google Scholar 

  144. Wilson, L. M., Jacobs, P. G., Riddell, M. C., Zaharieva, D. P. & Castle, J. R. Opportunities and challenges in closed-loop systems in type 1 diabetes. Lancet Diabetes Endocrinol. 10, 6–8 (2022).

    Article  Google Scholar 

  145. Gomez, A. M. et al. Effects of performing morning versus afternoon exercise on glycemic control and hypoglycemia frequency in type 1 diabetes patients on sensor-augmented insulin pump therapy. J. Diabetes Sci. Technol. 9, 619–624 (2015).

    Article  Google Scholar 

  146. Yardley, J. E. Reassessing the evidence: prandial state dictates glycaemic responses to exercise in individuals with type 1 diabetes to a greater extent than intensity. Diabetologia https://doi.org/10.1007/s00125-022-05781-8 (2022).

    Article  Google Scholar 

  147. Campbell, M. D. et al. Insulin therapy and dietary adjustments to normalize glycemia and prevent nocturnal hypoglycemia after evening exercise in type 1 diabetes: a randomized controlled trial. BMJ Open Diabetes Res. Care 3, e000085 (2015).

    Article  Google Scholar 

  148. Moser, O. et al. Reduction in insulin degludec dosing for multiple exercise sessions improves time spent in euglycaemia in people with type 1 diabetes: a randomized crossover trial. Diabetes Obes. Metab. 21, 349–356 (2019).

    Article  CAS  Google Scholar 

  149. Zaharieva, D. P. et al. Improved open-loop glucose control with basal insulin reduction 90 minutes before aerobic exercise in patients with type 1 diabetes on continuous subcutaneous insulin infusion. Diabetes Care 42, 824–831 (2019).

    Article  CAS  Google Scholar 

  150. McGaugh, S. M. et al. Carbohydrate requirements for prolonged fasted exercise with and without basal rate reductions in adults with type 1 diabetes on continuous subcutaneous insulin infusion. Diabetes Care 44, 610–613 (2021).

    Article  CAS  Google Scholar 

  151. Dovc, K. et al. Faster compared with standard insulin aspart during day-and-night fully closed-loop insulin therapy in type 1 diabetes: a double-blind randomized crossover trial. Diabetes Care 43, 29–36 (2020).

    Article  CAS  Google Scholar 

  152. Paldus, B. et al. A randomized crossover trial comparing glucose control during moderate-intensity, high-intensity, and resistance exercise with hybrid closed-loop insulin delivery while profiling potential additional signals in adults with type 1 diabetes. Diabetes Care 45, 194–203 (2022).

    Article  CAS  Google Scholar 

  153. McCarthy, O. et al. Extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin adjustments in individuals with type 1 diabetes. Nutr. Metab. Cardiovasc. Dis. 31, 227–236 (2021).

    Article  CAS  Google Scholar 

  154. Moser, O. et al. Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA). Diabetologia 63, 2501–2520 (2020).

    Article  CAS  Google Scholar 

  155. Ruegemer, J. J. et al. Differences between prebreakfast and late afternoon glycemic responses to exercise in IDDM patients. Diabetes Care 13, 104–110 (1990).

    Article  CAS  Google Scholar 

  156. Scott, S. N. et al. Fasted high-intensity interval and moderate-intensity exercise do not lead to detrimental 24-hour blood glucose profiles. J. Clin. Endocrinol. Metab. 104, 111–117 (2019).

    Article  Google Scholar 

  157. Sato, S. et al. Atlas of exercise metabolism reveals time-dependent signatures of metabolic homeostasis. Cell Metab. 34, 329–345.e8 (2022).

    Article  CAS  Google Scholar 

  158. Ozaslan, B. et al. Safety and feasibility evaluation of step count informed meal boluses in type 1 diabetes: a pilot study. J. Diabetes Sci. Technol. 16, 670–676 (2021).

    Article  Google Scholar 

  159. Tagougui, S. et al. A single-blind, randomised, crossover study to reduce hypoglycaemia risk during postprandial exercise with closed-loop insulin delivery in adults with type 1 diabetes: announced (with or without bolus reduction) vs unannounced exercise strategies. Diabetologia 63, 2282–2291 (2020).

    Article  CAS  Google Scholar 

  160. Savikj, M. et al. Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes: a randomised crossover trial. Diabetologia 62, 233–237 (2019).

    Article  CAS  Google Scholar 

  161. Moholdt, T. et al. The effect of morning vs evening exercise training on glycaemic control and serum metabolites in overweight/obese men: a randomised trial. Diabetologia 64, 2061–2076 (2021).

    Article  CAS  Google Scholar 

  162. Sato, S. et al. Time of exercise specifies the impact on muscle metabolic pathways and systemic energy homeostasis. Cell Metab. 30, 92–110.e4 (2019).

    Article  CAS  Google Scholar 

  163. Chaix, A. & Panda, S. Timing tweaks exercise. Nat. Rev. Endocrinol. 15, 440–441 (2019).

    Article  Google Scholar 

  164. Al Khalifah, R. A. et al. Association of aerobic fitness level with exercise-induced hypoglycaemia in Type 1 diabetes. Diabet. Med. 33, 1686–1690 (2016).

    Article  CAS  Google Scholar 

  165. Sandoval, D. A., Guy, D. L. A., Richardson, M. A., Ertl, A. C. & Davis, S. N. Effects of low and moderate antecedent exercise on counterregulatory responses to subsequent hypoglycemia in type 1 diabetes. Diabetes 53, 1798–1806 (2004).

    Article  CAS  Google Scholar 

  166. Cade, W. T. et al. Hypoglycemia during moderate intensity exercise reduces counterregulatory responses to subsequent hypoglycemia. Physiol. Rep. 4, e12848 (2016).

    Article  Google Scholar 

  167. Weitgasser, R., Ocenasek, H. & Fallwickl, S. Race across America: first athlete with type 1 diabetes to finish solo with diabetes technology support. Diabetes Spectr. 35, 227–231 (2022).

    Article  Google Scholar 

  168. Adolfsson, P., Mattsson, S. & Jendle, J. Evaluation of glucose control when a new strategy of increased carbohydrate supply is implemented during prolonged physical exercise in type 1 diabetes. Eur. J. Appl. Physiol. 115, 2599–2607 (2015).

    Article  CAS  Google Scholar 

  169. Mattsson, S., Jendle, J. & Adolfsson, P. Carbohydrate loading followed by high carbohydrate intake during prolonged physical exercise and its impact on glucose control in individuals with diabetes type 1-an exploratory study. Front. Endocrinol. 10, 571 (2019).

    Article  Google Scholar 

  170. Scott, S. N. et al. Post-exercise recovery for the endurance athlete with type 1 diabetes: a consensus statement. Lancet Diabetes Endocrinol. 9, 304–317 (2021).

    Article  Google Scholar 

  171. Zaharieva, D. P. et al. Glucose control during physical activity and exercise using closed loop technology in adults and adolescents with type 1 diabetes. Can. J. Diabetes 44, 740–749 (2020).

    Article  Google Scholar 

  172. Turksoy, K. et al. Multivariable artificial pancreas for various exercise types and intensities. Diabetes Technol. Ther. 20, 662–671 (2018).

    Article  Google Scholar 

  173. Rickels, M. R. et al. Mini-dose glucagon as a novel approach to prevent exercise-induced hypoglycemia in type 1 diabetes. Diabetes Care 41, 1909–1916 (2018).

    Article  CAS  Google Scholar 

  174. Jacobs, P. G. et al. Randomized trial of a dual-hormone artificial pancreas with dosing adjustment during exercise compared with no adjustment and sensor-augmented pump therapy. Diabetes Obes. Metab. 18, 1110–1119 (2016).

    Article  CAS  Google Scholar 

  175. Taleb, N. et al. Efficacy of single-hormone and dual-hormone artificial pancreas during continuous and interval exercise in adult patients with type 1 diabetes: randomised controlled crossover trial. Diabetologia 59, 2561–2571 (2016).

    Article  CAS  Google Scholar 

  176. Steineck, I. I. K. et al. Preserved glucose response to low-dose glucagon after exercise in insulin-pump-treated individuals with type 1 diabetes: a randomised crossover study. Diabetologia 62, 582–592 (2019).

    Article  CAS  Google Scholar 

  177. Haymond, M. W. et al. Efficacy and safety of mini-dose glucagon for treatment of nonsevere hypoglycemia in adults with type 1 diabetes. J. Clin. Endocrinol. Metab. 102, 2994–3001 (2017).

    Article  Google Scholar 

  178. Riddell, M. C. & Milliken, J. Preventing exercise-induced hypoglycemia in type 1 diabetes using real-time continuous glucose monitoring and a new carbohydrate intake algorithm: an observational field study. Diabetes Technol. Ther. 13, 819–825 (2011).

    Article  CAS  Google Scholar 

  179. Herzig, D. et al. Effects of aerobic exercise on systemic insulin degludec concentrations in people with type 1 diabetes. J. Diabetes Sci. Technol. https://doi.org/10.1177/19322968211043915 (2021).

    Article  Google Scholar 

  180. Eckstein, M. L. et al. Time in range for closed-loop systems versus standard of care during physical exercise in people with type 1 diabetes: a systematic review and meta-analysis. J. Clin. Med. 10, 2445 (2021).

    Article  Google Scholar 

  181. Franc, S. et al. No more hypoglycaemia on days with physical activity and unrestricted diet when using a closed-loop system for 12 weeks: a post hoc secondary analysis of the multicentre, randomized controlled Diabeloop WP7 trial. Diabetes Obes. Metab. 23, 2170–2176 (2021).

    Article  CAS  Google Scholar 

  182. Paldus, B. et al. Strengths and challenges of closed-loop insulin delivery during exercise in people with type 1 diabetes: potential future directions. J. Diabetes Sci. Technol. https://doi.org/10.1177/19322968221088327 (2022).

    Article  Google Scholar 

  183. Lee, M. H. et al. Glucose and counterregulatory responses to exercise in adults with type 1 diabetes and impaired awareness of hypoglycemia using closed-loop insulin delivery: a randomized crossover study. Diabetes Care 43, 480–483 (2020).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank D. Shakeri from the School of Kinesiology and Health Science at York University, Toronto, Canada, for editorial assistance (managing the references and proofreading) with this manuscript.

Author information

Authors and Affiliations

Authors

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Michael C. Riddell.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Endocrinology thanks Stephen Bain, Kleman Dovc and Daniel West for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Riddell, M.C., Peters, A.L. Exercise in adults with type 1 diabetes mellitus. Nat Rev Endocrinol 19, 98–111 (2023). https://doi.org/10.1038/s41574-022-00756-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41574-022-00756-6

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing