1932

Abstract

Several factors, including genetics, family history, diet, physical activity, obesity, and insulin resistance in puberty, appear to increase the risk of type 2 diabetes in youth. Youth-onset type 2 diabetes is often thought of as a single entity but rather exists as a spectrum of disease with differences in presentation, metabolic characteristics, clinical progression, and complication rates. We review what is currently known regarding the risks associated with developing type 2 diabetes in youth. Additionally, we focus on the spectrum of phenotypes of pediatric type 2 diabetes, discuss the pathogenic underpinnings and potential therapeutic relevance of this heterogeneity, and compare youth-onset type 2 diabetes with type 1 diabetes and adult-onset type 2 diabetes. Finally, we highlight knowledge gaps in prediction and prevention of youth-onset type 2 diabetes.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-042120-012033
2022-01-27
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/med/73/1/annurev-med-042120-012033.html?itemId=/content/journals/10.1146/annurev-med-042120-012033&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Amutha A, Datta M, Unnikrishnan IR et al. 2011. Clinical profile of diabetes in the young seen between 1992 and 2009 at a specialist diabetes centre in south India. Prim. Care Diabetes 5:223–29
    [Google Scholar]
  2. 2. 
    Urakami T, Suzuki J, Mugishima H et al. 2012. Screening and treatment of childhood type 1 and type 2 diabetes mellitus in Japan. Pediatr. Endocrinol. Rev. 10:Suppl. 151–61
    [Google Scholar]
  3. 3. 
    Mayer-Davis EJ, Lawrence JM, Dabelea D et al. 2017. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N. Engl. J. Med. 376:1419–29
    [Google Scholar]
  4. 4. 
    Imperatore G, Boyle JP, Thompson TJ et al. 2012. Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: dynamic modeling of incidence, mortality, and population growth. Diabetes Care 35:2515–20
    [Google Scholar]
  5. 5. 
    Amutha A, Ali MK, Unnikrishnan R et al. 2015. Insulin sensitivity and secretion in youth onset type 2 diabetes with and without visceral adiposity. Diabetes Res. Clin. Pract. 109:32–39
    [Google Scholar]
  6. 6. 
    Newton KP, Hou J, Crimmins NA et al. 2016. Prevalence of prediabetes and type 2 diabetes in children with nonalcoholic fatty liver disease. JAMA Pediatr 170:e161971
    [Google Scholar]
  7. 7. 
    Singer K, Lumeng CN. 2017. The initiation of metabolic inflammation in childhood obesity. J. Clin. Investig. 127:65–73
    [Google Scholar]
  8. 8. 
    Tsalamandris S, Antonopoulos AS, Oikonomou E et al. 2019. The role of inflammation in diabetes: current concepts and future perspectives. Eur. Cardiol. 14:50–59
    [Google Scholar]
  9. 9. 
    Delahanty L, Kriska A, Edelstein S et al. 2013. Self-reported dietary intake of youth with recent onset of type 2 diabetes: results from the TODAY study. J. Acad. Nutr. Diet. 113:431–39
    [Google Scholar]
  10. 10. 
    Mayer-Davis EJ, Nichols M, Liese AD et al. 2006. Dietary intake among youth with diabetes: the SEARCH for Diabetes in Youth study. J. Am. Diet. Assoc. 106:689–97
    [Google Scholar]
  11. 11. 
    Lean ME, Leslie WS, Barnes AC et al. 2018. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet 391:541–51
    [Google Scholar]
  12. 12. 
    Goss AM, Goree LL, Ellis AC et al. 2013. Effects of diet macronutrient composition on body composition and fat distribution during weight maintenance and weight loss. Obesity 21:1139–42
    [Google Scholar]
  13. 13. 
    Gower BA, Chandler-Laney PC, Ovalle F et al. 2013. Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS. Clin. Endocrinol. 79:550–57
    [Google Scholar]
  14. 14. 
    Mayer SB, Jeffreys AS, Olsen MK et al. 2014. Two diets with different haemoglobin A1c and antiglycaemic medication effects despite similar weight loss in type 2 diabetes. Diabetes Obes. Metab. 16:90–93
    [Google Scholar]
  15. 15. 
    Lobelo F, Muth ND, Hanson S, Nemeth BA 2020. Physical activity assessment and counseling in pediatric clinical settings. Pediatrics 145:e20193992
    [Google Scholar]
  16. 16. 
    Kriska A, Delahanty L, Edelstein S et al. 2013. Sedentary behavior and physical activity in youth with recent onset of type 2 diabetes. Pediatrics 131:e850–56
    [Google Scholar]
  17. 17. 
    Klingensmith GJ, Connor CG, Ruedy KJ et al. 2016. Presentation of youth with type 2 diabetes in the Pediatric Diabetes Consortium. Pediatr. Diabetes 17:266–73
    [Google Scholar]
  18. 18. 
    Pettitt DJ, Talton J, Dabelea D et al. 2014. Prevalence of diabetes in U.S. youth in 2009: the SEARCH for Diabetes in Youth study. Diabetes Care 37:402–8
    [Google Scholar]
  19. 19. 
    Beck J, Brandt EN Jr., Blackett P, Copeland K. 2001. Prevention and early detection of type 2 diabetes in children and adolescents. J. Okla. State Med. Assoc. 94:355–61
    [Google Scholar]
  20. 20. 
    Larson-Meyer DE, Newcomer BR, Ravussin E et al. 2011. Intrahepatic and intramyocellular lipids are determinants of insulin resistance in prepubertal children. Diabetologia 54:869–75
    [Google Scholar]
  21. 21. 
    Valaiyapathi B, Gower B, Ashraf AP. 2020. Pathophysiology of type 2 diabetes in children and adolescents. Curr. Diabetes Rev. 16:220–29
    [Google Scholar]
  22. 22. 
    Meigs JB, Shrader P, Sullivan LM et al. 2008. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N. Engl. J. Med. 359:2208–19
    [Google Scholar]
  23. 23. 
    Saxena R, Voight BF, Lyssenko V et al. 2007. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–36
    [Google Scholar]
  24. 24. 
    Zeggini E, Scott LJ, Saxena R et al. 2008. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40:638–45
    [Google Scholar]
  25. 25. 
    Meigs JB, Cupples LA, Wilson PW. 2000. Parental transmission of type 2 diabetes: the Framingham Offspring Study. Diabetes 49:2201–7
    [Google Scholar]
  26. 26. 
    Valaiyapathi B, Gower B, Ashraf AP. 2020. Pathophysiology of type 2 diabetes in children and adolescents. Curr. Diabetes Rev. 16:220–29
    [Google Scholar]
  27. 27. 
    Giannini C, Dalla Man C, Groop L et al. 2014. Co-occurrence of risk alleles in or near genes modulating insulin secretion predisposes obese youth to prediabetes. Diabetes Care 37:475–82
    [Google Scholar]
  28. 28. 
    Srinivasan S, Chen L, Todd J et al. 2021. The first genome-wide association study for type 2 diabetes in youth: the Progress in Diabetes Genetics in Youth (ProDiGY) Consortium. Diabetes 70:996–1005
    [Google Scholar]
  29. 29. 
    Willemsen G, Ward KJ, Bell CG et al. 2015. The concordance and heritability of type 2 diabetes in 34,166 twin pairs from international twin registers: the Discordant Twin (DISCOTWIN) Consortium. Twin Res. Hum. Genet. 18:762–71
    [Google Scholar]
  30. 30. 
    Dyck RF, Jiang Y, Osgood ND. 2014. The long-term risks of end stage renal disease and mortality among First Nations and non–First Nations people with youth-onset diabetes. Can. J. Diabetes 38:237–43
    [Google Scholar]
  31. 31. 
    Corte CD, Ferrari F, Villani A, Nobili V. 2015. Epidemiology and natural history of NAFLD. J. Med. Biochem. 34:13–17
    [Google Scholar]
  32. 32. 
    Hudson OD, Nunez M, Shaibi GQ. 2012. Ethnicity and elevated liver transaminases among newly diagnosed children with type 2 diabetes. BMC Pediatr 12:174
    [Google Scholar]
  33. 33. 
    Dabelea D, Mayer-Davis EJ, Lamichhane AP et al. 2008. Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: the SEARCH Case-Control Study. Diabetes Care 31:1422–26
    [Google Scholar]
  34. 34. 
    Chernausek SD, Arslanian S, Caprio S et al. 2016. Relationship between parental diabetes and presentation of metabolic and glycemic function in youth with type 2 diabetes: baseline findings from the TODAY Trial. Diabetes Care 39:110–17
    [Google Scholar]
  35. 35. 
    Short KR, Teague AM, Fields DA et al. 2015. Lower resting energy expenditure and fat oxidation in Native American and Hispanic infants born to mothers with diabetes. J. Pediatr. 166:884–89
    [Google Scholar]
  36. 36. 
    Mayer-Davis EJ, Dabelea D, Lamichhane AP et al. 2008. Breast-feeding and type 2 diabetes in the youth of three ethnic groups: the SEARCH for Diabetes in Youth Case-Control Study. Diabetes Care 31:470–75
    [Google Scholar]
  37. 37. 
    Crume TL, Ogden LG, Mayer-Davis EJ et al. 2012. The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero: the EPOCH study. Int. J. Obes. 36:529–34
    [Google Scholar]
  38. 38. 
    Lamb MM, Dabelea D, Yin X et al. 2010. Early-life predictors of higher body mass index in healthy children. Ann. Nutr. Metab. 56:16–22
    [Google Scholar]
  39. 39. 
    Copeland KC, Zeitler P, Geffner M et al. 2011. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J. Clin. Endocrinol. Metab. 96:159–67
    [Google Scholar]
  40. 40. 
    Dabelea D, Rewers A, Stafford JM et al. 2014. Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for Diabetes in Youth study. Pediatrics 133:e938–45
    [Google Scholar]
  41. 41. 
    Dabelea D, Bell RA, D'Agostino RB Jr. et al. 2007. Incidence of diabetes in youth in the United States. JAMA 297:2716–24
    [Google Scholar]
  42. 42. 
    Cree-Green M, Wiromrat P, Stuppy JJ et al. 2019. Youth with type 2 diabetes have hepatic, peripheral, and adipose insulin resistance. Am. J. Physiol. Endocrinol. Metab. 316:E186–95
    [Google Scholar]
  43. 43. 
    Bacha F, Pyle L, Nadeau K et al. 2012. Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY Study. Pediatr. Diabetes 13:376–83
    [Google Scholar]
  44. 44. 
    Sam S, Edelstein SL, Arslanian SA et al. 2021. Baseline predictors of glycemic worsening in youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes in the Restoring Insulin Secretion (RISE) study. Diabetes Care 44:1938–47
    [Google Scholar]
  45. 45. 
    Dabelea D, Hanson RL, Bennett PH et al. 1998. Increasing prevalence of type II diabetes in American Indian children. Diabetologia 41:904–10
    [Google Scholar]
  46. 46. 
    Amed S, Dean HJ, Panagiotopoulos C et al. 2010. Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: a prospective national surveillance study. Diabetes Care 33:786–91
    [Google Scholar]
  47. 47. 
    Amutha A, Unnikrishnan R, Anjana RM, Mohan V. 2017. Prepubertal childhood onset type 2 diabetes mellitus: four case reports. J. Assoc. Physicians India 65:43–46
    [Google Scholar]
  48. 48. 
    Hutchins J, Barajas RA, Hale D et al. 2017. Type 2 diabetes in a 5-year-old and single center experience of type 2 diabetes in youth under 10. Pediatr. Diabetes 18:674–77
    [Google Scholar]
  49. 49. 
    Astudillo M, Tosur M, Castillo B et al. 2021. Type 2 diabetes in prepubertal children. Pediatr. Diabetes. https://doi.org/10.1111/pedi.13254
    [Crossref] [Google Scholar]
  50. 50. 
    Sellers EA, Triggs-Raine B, Rockman-Greenberg C, Dean HJ. 2002. The prevalence of the HNF-1α G319S mutation in Canadian aboriginal youth with type 2 diabetes. Diabetes Care 25:2202–6
    [Google Scholar]
  51. 51. 
    Dabelea D, Crume T. 2011. Maternal environment and the transgenerational cycle of obesity and diabetes. Diabetes 60:1849–55
    [Google Scholar]
  52. 52. 
    Mohn A, Polidori N, Castorani V et al. 2021. Hyperglycaemic hyperosmolar state in an obese prepubertal girl with type 2 diabetes: case report and critical approach to diagnosis and therapy. Ital. J. Pediatr. 47:38
    [Google Scholar]
  53. 53. 
    Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. 2010. Epidemiology of type 1 diabetes. Endocrinol. Metab. Clin. N. Am. 39:481–97
    [Google Scholar]
  54. 54. 
    Mauvais-Jarvis F, Bairey Merz N, Barnes PJ et al. 2020. Sex and gender: modifiers of health, disease, and medicine. Lancet 396:565–82
    [Google Scholar]
  55. 55. 
    Mayer-Davis EJ, Lawrence JM, Dabelea D et al. 2017. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N. Engl. J. Med. 376:1419–29
    [Google Scholar]
  56. 56. 
    Savic Hitt TA, Katz LEL 2020. Pediatric type 2 diabetes: not a mini version of adult type 2 diabetes. Endocrinol. Metab. Clin. N. Am. 49:679–93
    [Google Scholar]
  57. 57. 
    Huebschmann AG, Huxley RR, Kohrt WM et al. 2019. Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life course. Diabetologia 62:1761–72
    [Google Scholar]
  58. 58. 
    Castillo B, Astudillo M, Tosur M et al. 2020. Characteristics of type 2 diabetes in female and male youths Paper presented at European Association of Paediatric Societies Congress, online Oct. 16–19
  59. 59. 
    Kelsey MM, Braffett BH, Geffner ME et al. 2018. Menstrual dysfunction in girls from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. J. Clin. Endocrinol. Metab. 103:2309–18
    [Google Scholar]
  60. 60. 
    Nokoff N, Thurston J, Hilkin A et al. 2019. Sex differences in effects of obesity on reproductive hormones and glucose metabolism in early puberty. J. Clin. Endocrinol. Metab. 104:4390–97
    [Google Scholar]
  61. 61. 
    Kelsey MM, Bjornstad P, McFann K, Nadeau K 2016. Testosterone concentration and insulin sensitivity in young men with type 1 and type 2 diabetes. Pediatr. Diabetes 17:184–90
    [Google Scholar]
  62. 62. 
    Nadeau KJ, Zeitler PS, Bauer TA et al. 2009. Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity. J. Clin. Endocrinol. Metab. 94:3687–95
    [Google Scholar]
  63. 63. 
    Zeitler P, Hirst K, Copeland KC et al. 2015. HbA1c after a short period of monotherapy with metformin identifies durable glycemic control among adolescents with type 2 diabetes. Diabetes Care 38:2285–92
    [Google Scholar]
  64. 64. 
    Zeitler P, Hirst K, Pyle L et al. 2012. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N. Engl. J. Med. 366:2247–56
    [Google Scholar]
  65. 65. 
    Berkowitz RI, Marcus MD, Anderson BJ et al. 2018. Adherence to a lifestyle program for youth with type 2 diabetes and its association with treatment outcome in the TODAY clinical trial. Pediatr. Diabetes 19:191–98
    [Google Scholar]
  66. 66. 
    Seghieri G, Policardo L, Anichini R et al. 2017. The effect of sex and gender on diabetic complications. Curr. Diabetes Rev. 13:148–60
    [Google Scholar]
  67. 67. 
    Levitt Katz L, Gidding SS, Bacha F et al. 2015. Alterations in left ventricular, left atrial, and right ventricular structure and function to cardiovascular risk factors in adolescents with type 2 diabetes participating in the TODAY clinical trial. Pediatr. Diabetes 16:39–47
    [Google Scholar]
  68. 68. 
    Shah AS, El Ghormli L, Vajravelu ME et al. 2019. Heart rate variability and cardiac autonomic dysfunction: prevalence, risk factors, and relationship to arterial stiffness in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Diabetes Care 42:2143–50
    [Google Scholar]
  69. 69. 
    Shah AS, El Ghormli L, Gidding SS et al. 2018. Prevalence of arterial stiffness in adolescents with type 2 diabetes in the TODAY cohort: relationships to glycemic control and other risk factors. J. Diabetes Complicat. 32:740–45
    [Google Scholar]
  70. 70. 
    Zhao K, Ju H, Wang H 2019. Metabolic characteristics of obese children with fatty liver. Medicine 98:e14939
    [Google Scholar]
  71. 71. 
    Bjornstad P, Cherney DZ. 2018. Renal hyperfiltration in adolescents with type 2 diabetes: physiology, sex differences, and implications for diabetic kidney disease. Curr. Diabetes Rep. 18:22
    [Google Scholar]
  72. 72. 
    Klingensmith GJ, Pyle L, Arslanian S et al. 2010. The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY Study. Diabetes Care 33:1970–75
    [Google Scholar]
  73. 73. 
    Rivera-Vega MY, Flint A, Winger DG et al. 2015. Obesity and youth diabetes: distinguishing characteristics between islet cell antibody positive versus negative patients over time. Pediatr. Diabetes 16:375–81
    [Google Scholar]
  74. 74. 
    Praveen PA, Hockett CW, Ong TC et al. 2021. Diabetic ketoacidosis at diagnosis among youth with type 1 and type 2 diabetes: results from SEARCH (United States) and YDR (India) registries. Pediatr. Diabetes 22:40–46
    [Google Scholar]
  75. 75. 
    Mulukutla SN, Hsu JW, Gaba R et al. 2018. Arginine metabolism is altered in adults with A β+ ketosis-prone diabetes. J. Nutr. 148:185–93
    [Google Scholar]
  76. 76. 
    Patel SG, Hsu JW, Jahoor F et al. 2013. Pathogenesis of A β+ ketosis-prone diabetes. Diabetes 62:912–22
    [Google Scholar]
  77. 77. 
    Tommerdahl KL, Baumgartner K, Schäfer M et al. 2021. Impact of obesity on measures of cardiovascular and kidney health in youth with type 1 diabetes as compared with youth with type 2 diabetes. Diabetes Care 44:795–803
    [Google Scholar]
  78. 78. 
    Libman IM, Miller KM, DiMeglio LA et al. 2015. Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: a randomized clinical trial. JAMA 314:2241–50
    [Google Scholar]
  79. 79. 
    Cree-Green M, Bergman BC, Cengiz E et al. 2019. Metformin improves peripheral insulin sensitivity in youth with type 1 diabetes. J. Clin. Endocrinol. Metab. 104:3265–78
    [Google Scholar]
  80. 80. 
    Pihoker C, Gilliam LK, Ellard S et al. 2013. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. J. Clin. Endocrinol. Metab. 98:4055–62
    [Google Scholar]
  81. 81. 
    Shields BM, McDonald TJ, Ellard S et al. 2012. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia 55:1265–72
    [Google Scholar]
  82. 82. 
    Gloyn AL, Pearson ER, Antcliff JF et al. 2004. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N. Engl. J. Med. 350:1838–49
    [Google Scholar]
  83. 83. 
    Gloyn AL, Weedon MN, Owen KR et al. 2003. Large-scale association studies of variants in genes encoding the pancreatic β-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes 52:568–72
    [Google Scholar]
  84. 84. 
    Nielsen EM, Hansen L, Carstensen B et al. 2003. The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes 52:573–77
    [Google Scholar]
  85. 85. 
    Sachse G, Haythorne E, Hill T et al. 2021. The KCNJ11-E23K gene variant hastens diabetes progression by impairing glucose-induced insulin secretion. Diabetes 70:1145–56
    [Google Scholar]
  86. 86. 
    Jahromi MM, Eisenbarth GS. 2007. Cellular and molecular pathogenesis of type 1A diabetes. Cell Mol. Life Sci. 64:865–72
    [Google Scholar]
  87. 87. 
    Shah AS, Nadeau KJ. 2020. The changing face of paediatric diabetes. Diabetologia 63:683–91
    [Google Scholar]
  88. 88. 
    Kavey RE, Allada V, Daniels SR et al. 2007. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research. J. Cardiovasc. Nurs. 22:218–53
    [Google Scholar]
  89. 89. 
    Expert Panel Integr. Guid. Cardiovasc. Health Risk Reduct. Child. Adolesc 2011. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: summary report. Pediatrics 128:Suppl. 5S213–56
    [Google Scholar]
  90. 90. 
    Dabelea D, Stafford JM, Mayer-Davis EJ et al. 2017. Association of type 1 diabetes versus type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA 317:825–35
    [Google Scholar]
  91. 91. 
    Hamman RF, Bell RA, Dabelea D et al. 2014. The SEARCH for Diabetes in Youth study: rationale, findings, and future directions. Diabetes Care 37:3336–44
    [Google Scholar]
  92. 92. 
    Nadeau KJ, Klingensmith G, Zeitler P. 2005. Type 2 diabetes in children is frequently associated with elevated alanine aminotransferase. J. Pediatr. Gastroenterol. Nutr. 41:94–98
    [Google Scholar]
  93. 93. 
    Dart AB, Martens PJ, Rigatto C et al. 2014. Earlier onset of complications in youth with type 2 diabetes. Diabetes Care 37:436–43
    [Google Scholar]
  94. 94. 
    Wilmot E, Idris I. 2014. Early onset type 2 diabetes: risk factors, clinical impact and management. Ther. Adv. Chronic Dis. 5:234–44
    [Google Scholar]
  95. 95. 
    Sattar N. 2013. Gender aspects in type 2 diabetes mellitus and cardiometabolic risk. Best Pract. Res. Clin. Endocrinol. Metab. 27:501–7
    [Google Scholar]
  96. 96. 
    RISE Consort 2018. Metabolic contrasts between youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes: I. Observations using the hyperglycemic clamp. Diabetes Care 41:1696–706
    [Google Scholar]
  97. 97. 
    Arslanian SA, El Ghormli L, Kim JY et al. 2021. OGTT glucose response curves, insulin sensitivity, and β-cell function in RISE: comparison between youth and adults at randomization and in response to interventions to preserve β-cell function. Diabetes Care 44:817–25
    [Google Scholar]
  98. 98. 
    Utzschneider KM, Tripputi MT, Kozedub A et al. 2020. β-cells in youth with impaired glucose tolerance or early type 2 diabetes secrete more insulin and are more responsive than in adults. Pediatr. Diabetes 21:1421–29
    [Google Scholar]
  99. 99. 
    Dabelea D, Mayer-Davis EJ, Andrews JS et al. 2012. Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth Study. Diabetologia 55:3359–68
    [Google Scholar]
  100. 100. 
    Chan JC, Lau ES, Luk AO et al. 2014. Premature mortality and comorbidities in young-onset diabetes: a 7-year prospective analysis. Am. J. Med. 127:616–24
    [Google Scholar]
  101. 101. 
    Hannon TS, Arslanian SA. 2015. The changing face of diabetes in youth: lessons learned from studies of type 2 diabetes. Ann. N. Y. Acad. Sci. 1353:113–37
    [Google Scholar]
  102. 102. 
    Huo X, Gao L, Guo L et al. 2016. Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study. Lancet Diabetes Endocrinol 4:115–24
    [Google Scholar]
  103. 103. 
    Hillier TA, Pedula KL. 2003. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care 26:2999–3005
    [Google Scholar]
  104. 104. 
    Pavkov ME, Bennett PH, Knowler WC et al. 2006. Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. JAMA 296:421–26
    [Google Scholar]
  105. 105. 
    Chuang LM, Soegondo S, Soewondo P et al. 2006. Comparisons of the outcomes on control, type of management and complications status in early onset and late onset type 2 diabetes in Asia. Diabetes Res. Clin. Pract. 71:146–55
    [Google Scholar]
  106. 106. 
    TODAY Group 2021. Long-term complications in youth-onset type 2 diabetes. N. Engl. J. Med. 385:5416–26
    [Google Scholar]
  107. 107. 
    Nadeau KJ, Anderson BJ, Berg EG et al. 2016. Youth-onset type 2 diabetes consensus report: current status, challenges, and priorities. Diabetes Care 39:1635–42
    [Google Scholar]
  108. 108. 
    TR Consort 2019. Effects of treatment of impaired glucose tolerance or recently diagnosed type 2 diabetes with metformin alone or in combination with insulin glargine on β-cell function: comparison of responses in youth and adults. Diabetes 68:1670–80
    [Google Scholar]
  109. 109. 
    Punthakee Z, Alméras N, Després JP et al. 2014. Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines and glucose in persons with impaired fasting glucose or impaired glucose tolerance: a sub-study of the DREAM Trial. Diabetes Med 31:1086–92
    [Google Scholar]
  110. 110. 
    Dhaliwal R, Shepherd JA, El Ghormli L et al. 2019. Changes in visceral and subcutaneous fat in youth with type 2 diabetes in the TODAY study. Diabetes Care 42:1549–59
    [Google Scholar]
  111. 111. 
    Tamborlane WV, Barrientos-Pérez M, Fainberg U et al. 2019. Liraglutide in children and adolescents with type 2 diabetes. N. Engl. J. Med. 381:637–46
    [Google Scholar]
  112. 112. 
    Dabelea D, Pihoker C, Talton JW et al. 2011. Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth study. Diabetes Care 34:1628–33
    [Google Scholar]
  113. 113. 
    Redondo MJ, Balasubramanyam A. 2021. Towards an improved classification of type 2 diabetes: lessons from research into the heterogeneity of a complex disease. J. Clin. Endocrinol. Metab. https://doi.org/10.1210/clinem/dgab545
    [Crossref] [Google Scholar]
  114. 114. 
    Dixon JB, Zimmet P, Alberti KG et al. 2011. Bariatric surgery: an IDF statement for obese type 2 diabetes. Diabetes Med 28:628–42
    [Google Scholar]
  115. 115. 
    Chung WK, Erion K, Florez JC et al. 2020. Precision medicine in diabetes: a consensus report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 43:1617–35
    [Google Scholar]
  116. 116. 
    Chung WK, Erion K, Florez JC et al. 2020. Precision medicine in diabetes: a consensus report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 63:1671–93
    [Google Scholar]
  117. 117. 
    Redondo MJ, Hagopian WA, Oram R et al. 2020. The clinical consequences of heterogeneity within and between different diabetes types. Diabetologia 63:2040–48
    [Google Scholar]
/content/journals/10.1146/annurev-med-042120-012033
Loading
  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error