ISPAD Clinical Practice Consensus Guidelines 2018: Type 2 diabetes mellitus in youth

Pediatric Diabetes

Volumn 19, Issue , 2018, Pages 28-46

  Zeitler, Phillip ^a   Arslanian, Silva ^b   Fu, Junfen ^c   Pinhas Hamiel, Orit ^d   Reinehr, Thomas ^e   Tandon, Nikhil ^f   Urakami, Tatsuhiko ^g   Wong, Jencia ^h   Maahs, David M ⁱ  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b CHILDREN S HOSPITAL OF PITTSBURGH   (United States)

^c CHILDREN S HOSPITAL OF ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

^d TEL AVIV UNIVERSITY   (Israel)

^e UNIVERSITY OF WITTEN HERDECKE   (Germany)

^f ALL INDIA INSTITUTE OF MEDICAL SCIENCES   (India)

^g NIHON UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^h ROYAL PRINCE ALFRED HOSPITAL   (Australia)

ⁱ STANFORD UNIVERSITY   (United States)

Author keywords

ISPAD; type 2 diabetes; youth

Indexed keywords

ADOLESCENT; CHILD; CLASSIFICATION; CLINICAL PRACTICE; CONSENSUS; DIFFERENTIAL DIAGNOSIS; ENDOCRINE SYSTEM EXAMINATION; ENDOCRINOLOGY; HUMAN; INTERNATIONAL COOPERATION; MASS SCREENING; MEDICAL SOCIETY; NON INSULIN DEPENDENT DIABETES MELLITUS; ONSET AGE; ORGANIZATION AND MANAGEMENT; PEDIATRICS; PRACTICE GUIDELINE; PROCEDURES; STANDARDS;

ADOLESCENT; AGE OF ONSET; CHILD; CONSENSUS; DIABETES MELLITUS, TYPE 2; DIAGNOSIS, DIFFERENTIAL; DIAGNOSTIC TECHNIQUES, ENDOCRINE; ENDOCRINOLOGY; HUMANS; INTERNATIONAL COOPERATION; MASS SCREENING; PEDIATRICS; PRACTICE PATTERNS, PHYSICIANS'; SOCIETIES, MEDICAL;

EID: 85054103706     PISSN: 1399543X     EISSN: 13995448     Source Type: Journal    
DOI: 10.1111/pedi.12719     Document Type: Article

References (179)

1. Mayer-Davis EJ, Lawrence JM, Dabelea D, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002-2012. N Engl J Med. 2017;376(15):1419-1429
2. Nadeau KJ, Anderson BJ, Berg EG, et al. Youth-onset type 2 diabetes consensus report: current status, challenges, and priorities. Diabetes Care. 2016;39(9):1635-1642
3. Duncan GE. Prevalence of diabetes and impaired fasting glucose levels among US adolescents: National Health and nutrition examination survey, 1999-2002. Arch Pediatr Adolesc Med. 2006;160(5):523-528
4. Pinhas-Hamiel O, Zeitler P. The global spread of type 2 diabetes mellitus in children and adolescents. J Pediatr. 2005;146(5):693-700
5. Kitagawa T, Owada M, Urakami T, Yamauchi K. Increased incidence of non-insulin dependent diabetes mellitus among Japanese schoolchildren correlates with an increased intake of animal protein and fat. Clin Pediatr (Phila). 1998;37(2):111-115
6. Ehtisham S, Hattersley AT, Dunger DB, Barrett TG, British Society for Paediatric Endocrinology and Diabetes Clinical Trials Group. First UK survey of paediatric type 2 diabetes and MODY. Arch Dis Child. 2004;89(6):526-529
7. Wei JN, Sung FC, Li CY, et al. Low birth weight and high birth weight infants are both at an increased risk to have type 2 diabetes among schoolchildren in Taiwan. Diabetes Care. 2003;26(2):343-348
8. Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V. Type 2 diabetes in Asian-Indian urban children. Diabetes Care. 2003;26(4):1022-1025
9. Eppens MC, Craig ME, Jones TW, et al. Type 2 diabetes in youth from the Western Pacific region: glycaemic control, diabetes care and complications. Curr Med Res Opin. 2006;22(5):1013-1020
10. Sugihara S, Sasaki N, Kohno H, et al. Survey of current medical treatments for childhood-onset type 2 diabetes mellitus in Japan. Clin Pediatr Endocrinol. 2005;14(2):65-75
11. Fu JF, Liang L, Gong CX, et al. Status and trends of diabetes in Chinese children: analysis of data from 14 medical centers. World J Pediatr. 2013;9(2):127-134
12. Ye Q, Fu JF. Paediatric type 2 diabetes in China-Pandemic, progression, and potential solutions. Pediatr Diabetes. 2018;19(1):27-35
13. Zeitler P, Fu J, Tandon N, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Type 2 diabetes in the child and adolescent. Pediatr Diabetes. 2014;15(suppl 20):26-46
14. Druet C, Tubiana-Rufi N, Chevenne D, Rigal O, Polak M, Levy-Marchal C. Characterization of insulin secretion and resistance in type 2 diabetes of adolescents. J Clin Endocrinol Metab. 2006;91(2):401-404
15. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-853
16. Gungor N, Bacha F, Saad R, Janosky J, Arslanian S. Youth type 2 diabetes: insulin resistance, beta-cell failure, or both? Diabetes Care. 2005;28(3):638-644
17. TODAY Study Group, Zeitler P, Hirst K, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012;366(24):2247-2256
18. TODAY Study Group. Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care. 2013;36(6):1735-1741
19. TODAY Study Group. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and beta-cell function in TODAY. Diabetes Care. 2013;36(6):1749-1757
20. Bacha F, Gungor N, Lee S, Arslanian SA. Progressive deterioration of beta-cell function in obese youth with type 2 diabetes. Pediatr Diabetes. 2013;14(2):106-111
21. Gandica R, Zeitler P. Update on youth-onset type 2 diabetes: lessons learned from the treatment options for type 2 diabetes in adolescents and youth clinical trial. Adv Pediatr. 2016;63(1):195-209
22. Dabelea D, Stafford JM, Mayer-Davis EJ, et al. Association of type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA. 2017;317(8):825-835
23. Dyck RF, Jiang Y, Osgood ND. 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. 2014;38(4):237-243
24. Constantino MI, Molyneaux L, Limacher-Gisler F, et al. Long-term complications and mortality in young-onset diabetes: type 2 diabetes is more hazardous and lethal than type 1 diabetes. Diabetes Care. 2013;36(12):3863-3869
25. American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(suppl 1):S13-S27
26. Copeland KC, Zeitler P, Geffner M, et al. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011;96(1):159-167
27. Libman IM, Barinas-Mitchell E, Bartucci A, Robertson R, Arslanian S. Reproducibility of the oral glucose tolerance test in overweight children. J Clin Endocrinol Metab. 2008;93(11):4231-4237
28. Kapadia C, Zeitler P, Drugs and Therapeutics Committee of the Pediatric Endocrine Society. Hemoglobin A1c measurement for the diagnosis of type 2 diabetes in children. Int J Pediatr Endocrinol. 2012;2012(1):31
29. Chan CL, Pyle L, Newnes L, Nadeau KJ, Zeitler PS, Kelsey MM. Continuous glucose monitoring and its relationship to hemoglobin A1c and oral glucose tolerance testing in obese and prediabetic youth. J Clin Endocrinol Metab. 2015;100(3):902-910
30. Love-Osborne KA, Sheeder J, Svircev A, Chan C, Zeitler P, Nadeau KJ. Use of glycosylated hemoglobin increases diabetes screening for at-risk adolescents in primary care settings. Pediatr Diabetes. 2013;14(7):512-518
31. Bergenstal RM, Gal RL, Connor CG, et al. Racial differences in the relationship of glucose concentrations and hemoglobin A1c levels. Ann Intern Med. 2017;167(2):95-102
32. Diabetes Research in Children Network Study Group, Wilson DM, Kollman. Relationship of A1C to glucose concentrations in children with type 1 diabetes: assessments by high-frequency glucose determinations by sensors. Diabetes Care. 2008;31(3):381-385
33. Bottazzo GF, Bosi E, Cull CA, et al. IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71). Diabetologia. 2005;48(4):703-708
34. Turner R, Stratton I, Horton V, et al. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet. 1997;350(9087):1288-1293
35. Umpaichitra V, Banerji MA, Castells S. Autoantibodies in children with type 2 diabetes mellitus. J Pediatr Endocrinol Metab. 2002;15(suppl 1):525-530
36. Reinehr T, Schober E, Wiegand S, Thon A, Holl R, DP-Wiss Study Group. Beta-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification? Arch Dis Child. 2006;91(6):473-477
37. Klingensmith GJ, Pyle L, Arslanian S, et al. The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study. Diabetes Care. 2010;33(9):1970-1975
38. Laffel L, Chang N, Grey M, et al. Metformin monotherapy in youth with recent onset type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study. Pediatr Diabetes. 2012;13(5):369-375
39. Kelsey MM, Geffner ME, Guandalini C, et al. Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study. Pediatr Diabetes. 2016;17(3):212-221
40. Writing Group for the SfDiYSG, Dabelea D, Bell RA, et al. Incidence of diabetes in youth in the United States. JAMA. 2007;297(24):2716-2724
41. Pinhas-Hamiel O, Standiford D, Hamiel D, Dolan LM, Cohen R, Zeitler PS. The type 2 family: a setting for development and treatment of adolescent type 2 diabetes mellitus. Arch Pediatr Adolesc Med. 1999;153(10):1063-1067
42. Chan JC, Cheung CK, Swaminathan R, Nicholls MG, Cockram CS. Obesity, albuminuria and hypertension among Hong Kong Chinese with non-insulin-dependent diabetes mellitus (NIDDM). Postgrad Med J. 1993;69(809):204-210
43. Haynes A, Kalic R, Cooper M, Hewitt JK, Davis EA. Increasing incidence of type 2 diabetes in Indigenous and non-indigenous children in Western Australia, 1990-2012. Med J Aust. 2016;204(8):303
44. Schober E, Holl RW, Grabert M, et al. Diabetes mellitus type 2 in childhood and adolescence in Germany and parts of Austria. Eur J Pediatr. 2005;164(11):705-707
45. Schober E, Rami B, Grabert M, et al. Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database. Diabet Med. 2009;26(5):466-473
46. Urakami T, Kuwabara R, Habu M, et al. Clinical characteristics of non-obese children with type 2 diabetes mellitus without involvement of beta-cell autoimmunity. Diabetes Res Clin Pract. 2013;99(2):105-111
47. Rosenbloom AL. Obesity, insulin resistance, beta-cell autoimmunity, and the changing clinical epidemiology of childhood diabetes. Diabetes Care. 2003;26(10):2954-2956
48. Dabelea D, Rewers A, Stafford JM, et al. Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for diabetes in youth study. Pediatrics. 2014;133(4):e938-e945
49. Zeitler P, Haqq A, Rosenbloom A, Glaser N, Drugs and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Hyperglycemic hyperosmolar syndrome in children: pathophysiological considerations and suggested guidelines for treatment. J Pediatr. 2011;158(1):9-14.e2
50. Tfayli H, Bacha F, Gungor N, Arslanian S. Phenotypic type 2 diabetes in obese youth: insulin sensitivity and secretion in islet cell antibody-negative versus -positive patients. Diabetes. 2009;58(3):738-744
51. Tfayli H, Bacha F, Gungor N, Arslanian S. Islet cell antibody-positive versus -negative phenotypic type 2 diabetes in youth: does the oral glucose tolerance test distinguish between the two? Diabetes Care. 2010;33(3):632-638
52. Rivera-Vega MY, Flint A, Winger DG, Libman I, Arslanian S. Obesity and youth diabetes: distinguishing characteristics between islet cell antibody positive vs. negative patients over time. Pediatr Diabetes. 2015;16(5):375-381
53. Writing Team for the Diabetes C, Complications Trial/Epidemiology of Diabetes I, Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the epidemiology of diabetes interventions and complications (EDIC) study. JAMA. 2003;290(16):2159-2167
54. Nadeau KJ, Regensteiner JG, Bauer TA, et al. Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function. J Clin Endocrinol Metab. 2010;95(2):513-521
55. Nadeau KJ, Zeitler PS, Bauer TA, et al. Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity. J Clin Endocrinol Metab. 2009;94(10):3687-3695
56. Rubio-Cabezas O, Hattersley AT, Njolstad PR, et al. ISPAD clinical practice consensus guidelines 2014. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 2014;15(suppl 20):47-64
57. Dabelea D, Pihoker C, Talton JW, et al. Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study. Diabetes Care. 2011;34(7):1628-1633
58. Cali’ AMG, Bonadonna RC, Trombetta M, Weiss R, Caprio S. Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents. J Clin Endocrinol Metab. 2008;93(5):1767-1773
59. Bacha F, Lee S, Gungor N, Arslanian SA. From pre-diabetes to type 2 diabetes in obese youth: pathophysiological characteristics along the spectrum of glucose dysregulation. Diabetes Care. 2010;33(10):2225-2231
60. Burns SF, Bacha F, Lee SJ, Tfayli H, Gungor N, Arslanian SA. Declining beta-cell function relative to insulin sensitivity with escalating OGTT 2-h glucose concentrations in the nondiabetic through the diabetic range in overweight youth. Diabetes Care. 2011;34(9):2033-2040
61. Tfayli H, Lee S, Arslanian S. Declining beta-cell function relative to insulin sensitivity with increasing fasting glucose levels in the nondiabetic range in children. Diabetes Care. 2010;33(9):2024-2030
62. Reinehr T, Wolters B, Knop C, Lass N, Holl RW. Strong effect of pubertal status on metabolic health in obese children: a longitudinal study. J Clin Endocrinol Metab. 2015;100(1):301-308
63. Weiss R, Taksali SE, Tamborlane WV, Burgert TS, Savoye M, Caprio S. Predictors of changes in glucose tolerance status in obese youth. Diabetes Care. 2005;28(4):902-909
64. Kleber M, deSousa G, Papcke S, Wabitsch M, Reinehr T. Impaired glucose tolerance in obese white children and adolescents: three to five year follow-up in untreated patients. Exp Clin Endocrinol Diabetes. 2011;119(3):172-176
65. Kleber M, Lass N, Papcke S, Wabitsch M, Reinehr T, et al. One-year follow-up of untreated obese white children and adolescents with impaired glucose tolerance: high conversion rate to normal glucose tolerance1. Diabet Med. 2010;27(5):516-521
66. Love-Osborne KA, Sheeder JL, Nadeau KJ, Zeitler P. Longitudinal follow up of dysglycemia in overweight and obese pediatric patients. Pediatr Diabetes. 2018;19(2):199-204
67. Khokhar A, Umpaichitra V, Chin VL, Perez-Colon S. Metformin use in children and adolescents with prediabetes. Pediatr Clin North Am. 2017;64(6):1341-1353
68. Lindsay RS, Hanson RL, Bennett PH, Knowler WC. Secular trends in birth weight, BMI, and diabetes in the offspring of diabetic mothers. Diabetes Care. 2000;23(9):1249-1254
69. Dabelea D, Mayer-Davis EJ, Lamichhane AP, et al. Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: the SEARCH Case-Control Study. Diabetes Care. 2008;31(7):1422-1426
70. Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA. Earlier onset of complications in youth with type 2 diabetes. Diabetes Care. 2014;37(2):436-443
71. TODAY Study Group. Retinopathy in youth with type 2 diabetes participating in the TODAY clinical trial. Diabetes Care. 2013;36(6):1772-1774
72. TODAY Study Group. Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care. 2013;36(6):1758-1764
73. Marcus MD, Wilfley DE, El Ghormli L, et al. Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience. Pediatr Obes. 2017;12(4):337-345
74. Berkowitz RI, Marcus MD, Anderson BJ, et al. Adherence to a lifestyle program for youth with type 2 diabetes and its association with treatment outcome in the TODAY clinical trial. Pediatr Diabetes. 2018;19(2):191-198
75. Reinehr T, Schober E, Roth CL, Wiegand S, Holl R. Type 2 diabetes in children and adolescents in a 2-year follow-up: insufficient adherence to diabetes centers. Horm Res. 2008;69(2):107-113
76. Smart CE, Annan F, Bruno LP, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Nutritional management in children and adolescents with diabetes. Pediatr Diabetes. 2014;15(suppl 20):135-153
77. Cameron FJ, Amin R, de Beaufort C, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Diabetes in adolescence. Pediatr Diabetes. 2014;15(suppl 20):245-256
78. Copeland KC, Silverstein J, Moore KR, et al. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(2):364-382
79. Barlow SE, Expert C. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120(suppl 4):S164-S192
80. Fitch C, Keim KS, Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet. 2012;112(5):739-758
81. American Diabetes Association. 4. Lifestyle management: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(suppl 1):S38-S50
82. Dhuper S, Buddhe S, Patel S. Managing cardiovascular risk in overweight children and adolescents. Paediatr Drugs. 2013;15(3):181-190
83. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129(25 suppl 2):S102-S138
84. Chahal H, Fung C, Kuhle S, Veugelers PJ. Availability and night-time use of electronic entertainment and communication devices are associated with short sleep duration and obesity among Canadian children. Pediatr Obes. 2013;8(1):42-51
85. Lane A, Harrison M, Murphy N. Screen time increases risk of overweight and obesity in active and inactive 9-year-old Irish children: a cross sectional analysis. J Phys Act Health. 2014;11(5):985-991
86. Ash T, Taveras EM. Associations of short sleep duration with childhood obesity and weight gain: summary of a presentation to the National Academy of Science's Roundtable on Obesity Solutions. Sleep Health. 2017;3(5):389-392
87. Robinson TN. Reducing children's television viewing to prevent obesity: a randomized controlled trial. JAMA. 1999;282(16):1561-1567
88. Mays D, Streisand R, Walker LR, Prokhorov AV, Tercyak KP. Cigarette smoking among adolescents with type 1 diabetes: strategies for behavioral prevention and intervention. J Diabetes Complications. 2012;26(2):148-153
89. American Diabetes Association. 12. Children and adolescents: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(suppl 1):S126-S136
90. Zeitler P, Hirst K, Copeland KC, et al. HbA1c after a short period of monotherapy with metformin identifies durable glycemic control among adolescents with type 2 diabetes. Diabetes Care. 2015;38(12):2285-2292
91. American Diabetes Association. 8. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(suppl 1):S73-S85
92. Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565-4592
93. TODAY Study Group. Safety and tolerability of the treatment of youth-onset type 2 diabetes: the TODAY experience. Diabetes Care. 2013;36(6):1765-1771
94. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298(10):1180-1188
95. Gottschalk M, Danne T, Vlajnic A, Cara JF. Glimepiride versus metformin as monotherapy in pediatric patients with type 2 diabetes: a randomized, single-blind comparative study. Diabetes Care. 2007;30(4):790-794
96. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427-2443
97. Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA. 2007;298(10):1189-1195
98. Tuccori M, Filion KB, Yin H, Yu OH, Platt RW, Azoulay L. Pioglitazone use and risk of bladder cancer: population based cohort study. BMJ. 2016;352:i1541
99. Yang W, Liu J, Shan Z, et al. Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol. 2014;2(1):46-55
100. Mann JFE, Orsted DD, Brown-Frandsen K, et al. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med. 2017;377(9):839-848
101. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-322
102. Klein DJ, Battelino T, Chatterjee DJ, et al. Liraglutide's safety, tolerability, pharmacokinetics, and pharmacodynamics in pediatric type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Technol Ther. 2014;16(10):679-687
103. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128
104. Cherney DZI, Zinman B, Inzucchi SE, et al. Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5(8):610-621
105. Mahaffey KW, Neal B, Perkovic V, et al. Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS program (Canagliflozin Cardiovascular Assessment Study). Circulation. 2018;137(4):323-334
106. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657
107. Nicolle LE, Capuano G, Fung A, Usiskin K. Urinary tract infection in randomized phase III studies of canagliflozin, a sodium glucose co-transporter 2 inhibitor. Postgrad Med. 2014;126(1):7-17
108. Tanaka A, Node K. Increased amputation risk with canagliflozin treatment: behind the large cardiovascular benefit? Cardiovasc Diabetol. 2017;16(1):129
109. Shoukat S, Usmani NA, Soetan O, Qureshi F. Euglycemic diabetic ketoacidosis accompanied by severe hypophosphatemia during recovery in a patient with type 2 diabetes being treated with Canagliflozin/metformin combination therapy. Clin Diabetes. 2017;35(4):249-251
110. Inge TH, Jenkins TM, Xanthakos SA, et al. Long-term outcomes of bariatric surgery in adolescents with severe obesity (FABS-5+): a prospective follow-up analysis. Lancet Diabetes Endocrinol. 2017;5(3):165-173
111. Stefater MA, Inge TH. Bariatric surgery for adolescents with type 2 diabetes: an emerging therapeutic strategy. Curr Diab Rep. 2017;17(8):62
112. Ibanez L, Potau N, Marcos MV, de Zegher F. Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab. 1999;84(12):4739-4741
113. Dabelea D, Crume T. Maternal environment and the transgenerational cycle of obesity and diabetes. Diabetes. 2011;60(7):1849-1855
114. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA. 2001;285(19):2486-2497
115. Ford ES, Li C. Defining the metabolic syndrome in children and adolescents: will the real definition please stand up? J Pediatr. 2008;152(2):160-4.e13
116. Reinehr T. Metabolic syndrome in children and adolescents: a critical approach considering the interaction between pubertal stage and insulin resistance. Curr Diab Rep. 2016;16(1):8
117. Reinehr T, Wunsch R, Putter C, Scherag A. Relationship between carotid intima-media thickness and metabolic syndrome in adolescents. J Pediatr. 2013;163(2):327-32.e4
118. Zimmet P, Alberti KG, Kaufman F, et al. The metabolic syndrome in children and adolescents – an IDF consensus report. Pediatr Diabetes. 2007;8(5):299-306
119. Laurson KR, Welk GJ, Eisenmann JC. Diagnostic performance of BMI percentiles to identify adolescents with metabolic syndrome. Pediatrics. 2014;133(2):e330-e338
120. Chinese Work Group of Pediatric Metabolic Syndrome. Prevalence of metabolic syndrome of children and adolescent students in Chinese six cities. Zhonghua Er Ke Za Zhi. 2013;51(6):409-413
121. Tandon N, Garg MK, Singh Y, Marwaha RK. Prevalence of metabolic syndrome among urban Indian adolescents and its relation with insulin resistance (HOMA-IR). J Pediatr Endocrinol Metab. 2013;26(11–12):1123-1130
122. Amutha A, Anjana RM, Venkatesan U, et al. Incidence of complications in young-onset diabetes: comparing type 2 with type 1 (the young diab study). Diabetes Res Clin Pract. 2017;123:1-8
123. Donaghue KC, Wadwa RP, Dimeglio LA, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes. 2014;15(suppl 20):257-269
124. Kordonouri O, Klingensmith G, Knip M, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Other complications and diabetes-associated conditions in children and adolescents. Pediatr Diabetes. 2014;15(suppl 20):270-278
125. Freedman DS, Khan LK, Dietz WH, Srinivasan SR, Berenson GS. Relationship of childhood obesity to coronary heart disease risk factors in adulthood: the Bogalusa Heart Study. Pediatrics. 2001;108(3):712-718
126. Berenson GS, Srnivasan SR, Bogalusa Heart Study Group. Cardiovascular risk factors in youth with implications for aging: the Bogalusa Heart Study. Neurobiol Aging. 2005;26(3):303-307
127. Juonala M, Jarvisalo MJ, Maki-Torkko N, Kahonen M, Viikari JS, Raitakari OT. Risk factors identified in childhood and decreased carotid artery elasticity in adulthood: the Cardiovascular Risk in Young Finns Study. Circulation. 2005;112(10):1486-1493
128. Marcus MD, Foster GD, El Ghormli L, et al. Shifts in BMI category and associated cardiometabolic risk: prospective results from HEALTHY study. Pediatrics. 2012;129(4):e983-e991
129. Styne DM, Arslanian SA, Connor EL, et al. Pediatric obesity-assessment, treatment, and prevention: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102(3):709-757
130. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, National Heart, Lungs, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128(suppl 5):S213-S256
131. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703-713
132. Eppens MC, Craig ME, Cusumano J, et al. Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes. Diabetes Care. 2006;29(6):1300-1306
133. West NA, Hamman RF, Mayer-Davis EJ, et al. Cardiovascular risk factors among youth with and without type 2 diabetes: differences and possible mechanisms. Diabetes Care. 2009;32(1):175-180
134. Batisky DL. What is the optimal first-line agent in children requiring antihypertensive medication? Curr Hypertens Rep. 2012;14(6):603-607
135. Blowey DL. Update on the pharmacologic treatment of hypertension in pediatrics. J Clin Hypertens (Greenwich). 2012;14(6):383-387
136. American Diabetes Association. 9. Cardiovascular disease and risk management: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(suppl 1):S86-S104
137. Ettinger LM, Freeman K, DiMartino-Nardi JR, Flynn JT. Microalbuminuria and abnormal ambulatory blood pressure in adolescents with type 2 diabetes mellitus. J Pediatr. 2005;147(1):67-73
138. McGrath NM, Parker GN, Dawson P. Early presentation of type 2 diabetes mellitus in young New Zealand Maori. Diabetes Res Clin Pract. 1999;43(3):205-209
139. Sellers EAC, Yung G, Dean HJ. Dyslipidemia and other cardiovascular risk factors in a Canadian First Nation pediatric population with type 2 diabetes mellitus. Pediatr Diabetes. 2007;8(6):384-390
140. Dart AB, Sellers EA, Martens PJ, Rigatto C, Brownell MD, Dean HJ. High burden of kidney disease in youth-onset type 2 diabetes. Diabetes Care. 2012;35(6):1265-1271
141. Yokoyama H, Okudaira M, Otani T, et al. Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan. Kidney Int. 2000;58(1):302-311
142. Rodriguez BL, Fujimoto WY, Mayer-Davis EJ, et al. Prevalence of cardiovascular disease risk factors in U.S. children and adolescents with diabetes: the SEARCH for diabetes in youth study. Diabetes Care. 2006;29(8):1891-1896
143. Huang K, Zou CC, Yang XZ, Chen XQ, Liang L. Carotid intima-media thickness and serum endothelial marker levels in obese children with metabolic syndrome. Arch Pediatr Adolesc Med. 2010;164(9):846-851
144. Nadeau KJ, Maahs DM, Daniels SR, Eckel RH. Childhood obesity and cardiovascular disease: links and prevention strategies. Nat Rev Cardiol. 2011;8(9):513-525
145. Levitt Katz L, Gidding SS, Bacha F, et al. 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. 2015;16(1):39-47
146. Flint A, Arslanian S. Treatment of type 2 diabetes in youth. Diabetes Care. 2011;34(suppl 2):S177-S183
147. Wadwa RP, Urbina EM, Anderson AM, et al. Measures of arterial stiffness in youth with type 1 and type 2 diabetes: the SEARCH for diabetes in youth study. Diabetes Care. 2010;33(4):881-886
148. Lewy VD, Danadian K, Witchel SF, Arslanian S. Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome. J Pediatr. 2001;138(1):38-44
149. Amini M, Horri N, Farmani M, et al. Prevalence of polycystic ovary syndrome in reproductive-aged women with type 2 diabetes. Gynecol Endocrinol. 2008;24(8):423-427
150. Shafiee MN, Khan G, Ariffin R, et al. Preventing endometrial cancer risk in polycystic ovarian syndrome (PCOS) women: could metformin help? Gynecol Oncol. 2014;132(1):248-253
151. Nadeau KJ, Klingensmith G, Zeitler P. Type 2 diabetes in children is frequently associated with elevated alanine aminotransferase. J Pediatr Gastroenterol Nutr. 2005;41(1):94-98
152. Newton KP, Hou J, Crimmins NA, et al. Prevalence of prediabetes and type 2 diabetes in children with nonalcoholic fatty liver disease. JAMA Pediatr. 2016;170(10):e161971
153. Roberts EA. Non-alcoholic fatty liver disease (NAFLD) in children. Front Biosci. 2005;10:2306-2318
154. Hudson OD, Nunez M, Shaibi GQ. Ethnicity and elevated liver transaminases among newly diagnosed children with type 2 diabetes. BMC Pediatr. 2012;12:174
155. Sundaram SS, Zeitler P, Nadeau K. The metabolic syndrome and nonalcoholic fatty liver disease in children. Curr Opin Pediatr. 2009;21(4):529-535
156. Zhang HX, Fu JF, Huang K, Lai C, Liang L, Jiang KW. Quantitative assessment of intrahepatic fat content in children and adolescents with non-alcoholic fatty liver disease. Zhongguo Dang Dai Er Ke Za Zhi. 2012;14(8):598-603
157. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30(6):1356-1362
158. Reinehr T, Schmidt C, Toschke AM, Andler W. Lifestyle intervention in obese children with non-alcoholic fatty liver disease: 2-year follow-up study. Arch Dis Child. 2009;94(6):437-442
159. Rice TB, Foster GD, Sanders MH, et al. The relationship between obstructive sleep apnea and self-reported stroke or coronary heart disease in overweight and obese adults with type 2 diabetes mellitus. Sleep. 2012;35(9):1293-1298
160. Foster GD, Sanders MH, Millman R, et al. Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care. 2009;32(6):1017-1019
161. Shaw JE, Punjabi NM, Wilding JP, Alberti KG, Zimmet PZ, International Diabetes Federation Taskforce on Epidemiology and Prevention. Sleep-disordered breathing and type 2 diabetes: a report from the International Diabetes Federation Taskforce on Epidemiology and Prevention. Diabetes Res Clin Pract. 2008;81(1):2-12
162. Walders-Abramson N. Depression and quality of life in youth-onset type 2 diabetes mellitus. Curr Diab Rep. 2014;14(1):449
163. Pervanidou P, Chrousos GP. Metabolic consequences of stress during childhood and adolescence. Metabolism. 2012;61(5):611-619
164. Anderson BJ, Edelstein S, Abramson NW, et al. Depressive symptoms and quality of life in adolescents with type 2 diabetes: baseline data from the TODAY study. Diabetes Care. 2011;34(10):2205-2207
165. Lawrence JM, Standiford DA, Loots B, et al. Prevalence and correlates of depressed mood among youth with diabetes: the SEARCH for diabetes in youth study. Pediatrics. 2006;117(4):1348-1358
166. Walders-Abramson N, Venditti EM, Ievers-Landis CE, et al. Relationships among stressful life events and physiological markers, treatment adherence, and psychosocial functioning among youth with type 2 diabetes. J Pediatr. 2014;165(3):504-8 e1
167. Browne JL, Nefs G, Pouwer F, Speight J. Depression, anxiety and self-care behaviours of young adults with type 2 diabetes: results from the International Diabetes Management and Impact for Long-term Empowerment and Success (MILES) Study. Diabet Med. 2015;32(1):133-140
168. Pinhas-Hamiel O, Levy-Shraga Y. Eating disorders in adolescents with type 2 and type 1 diabetes. Curr Diab Rep. 2013;13(2):289-297
169. TODAY Study Group, Wilfley D, Berkowitz R, et al. Binge eating, mood, and quality of life in youth with type 2 diabetes: baseline data from the today study. Diabetes Care. 2011;34(4):858-860
170. Weinstock RS, Trief PM, El Ghormli L, et al. Parental characteristics associated with outcomes in youth with type 2 diabetes: results from the TODAY clinical trial. Diabetes Care. 2015;38(5):784-792
171. Rhodes ET, Prosser LA, Hoerger TJ, Lieu T, Ludwig DS, Laffel LM. Estimated morbidity and mortality in adolescents and young adults diagnosed with type 2 diabetes mellitus. Diabet Med. 2012;29(4):453-463
172. Hillier TA, Pedula KL. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care. 2003;26(11):2999-3005
173. Wong J, Molyneaux L, Constantino M, Twigg SM, Yue DK. Timing is everything: age of onset influences long-term retinopathy risk in type 2 diabetes, independent of traditional risk factors. Diabetes Care. 2008;31(10):1985-1990
174. Al-Saeed AH, Constantino MI, Molyneaux L, et al. An inverse relationship between age of type 2 diabetes onset and complication risk and mortality: the impact of youth-onset type 2 diabetes. Diabetes Care. 2016;39(5):823-829
175. Sackett DL, Holland WW. Controversy in the detection of disease. Lancet. 1975;2(7930):357-359
176. Baranowski T, Cooper DM, Harrell J, et al. Presence of diabetes risk factors in a large U.S. eighth-grade cohort. Diabetes Care. 2006;29(2):212-217
177. Type 2 diabetes in children and adolescents. American Diabetes Association. Diabetes Care. 2000;23(3):381-389
178. Urakami T, Kubota S, Nitadori Y, Harada K, Owada M, Kitagawa T. Annual incidence and clinical characteristics of type 2 diabetes in children as detected by urine glucose screening in the Tokyo metropolitan area. Diabetes Care. 2005;28(8):1876-1881
179. Wei JN, Chuang LM, Lin CC, Chiang CC, Lin RS, Sung FC. Childhood diabetes identified in mass urine screening program in Taiwan, 1993-1999. Diabetes Res Clin Pract. 2003;59(3):201-206