Youth-Onset Type 2 Diabetes Consensus Report: Current Status, Challenges, and Priorities

Kristen J Nadeau, Barbara J Anderson, Erika G Berg, Jane L Chiang, Hubert Chou, Kenneth C Copeland, Tamara S Hannon, Terry T-K Huang, Jane L Lynch, Jeff Powell, Elizabeth Sellers, William V Tamborlane, Philip Zeitler, Kristen J Nadeau, Barbara J Anderson, Erika G Berg, Jane L Chiang, Hubert Chou, Kenneth C Copeland, Tamara S Hannon, Terry T-K Huang, Jane L Lynch, Jeff Powell, Elizabeth Sellers, William V Tamborlane, Philip Zeitler

Abstract

Type 2 diabetes is a significant and increasing burden in adolescents and young adults. Clear strategies for research, prevention, and treatment of the disease in these vulnerable patients are needed. Evidence suggests that type 2 diabetes in children is different not only from type 1 but also from type 2 diabetes in adults. Understanding the unique pathophysiology of type 2 diabetes in youth, as well as the risk of complications and the psychosocial impact, will enable industry, academia, funding agencies, advocacy groups, and regulators to collectively evaluate both current and future research, treatment, and prevention approaches. This Consensus Report characterizes type 2 diabetes in children, evaluates the fundamental differences between childhood and adult disease, describes the current therapeutic options, and discusses challenges to and approaches for developing new treatments.

© 2016 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Prevalence of youth-onset type 2 diabetes by race/ethnicity. 2009 prevalence of type 2 diabetes among youth, as published by the SEARCH for Diabetes in Youth study (4). Prevalence is reported per 10,000 population at risk for type 2 diabetes (ages 10–19 years). AA, African American; AI, American Indian; API, Asian Pacific Islander; H, Hispanic; NHW, non-Hispanic white.
Figure 2
Figure 2
β-Cell failure rates in adults versus youth with type 2 diabetes. A comparison of medication treatment failure rates and percent change in surrogate measures of insulin sensitivity and β-cell function as reported in the TODAY study (youth) versus adult studies (A Diabetes Outcome Progression Trial [ADOPT], U.S. Department of Defense Database [US DOD], and UK Prospective Diabetes Study [UKPDS]). Note that the studies had different primary end points and therefore this is an approximate comparison, as there have been no head-to-head comparisons (,,–16,67,68). Met, metformin; Rosi, rosiglitazone.
Figure 3
Figure 3
Few patients with youth-onset type 2 diabetes are available to participate in clinical trials. The population of youth-onset type 2 diabetes is small, approximately 20,000–25,000 in the U.S., compared with the approximately 20 million adults. Barriers to clinical trial participation include the paucity of centers with dedicated resources for pediatric type 2 diabetes trials, SES challenges inherent to the population, and the many study entry requirements that exclude study eligibility before and after formal study screening procedures (69). T2D, type 2 diabetes. *Numbers are from Imperatore et al. (69).

References

    1. Zeitler P, Chou HS, Copeland KC, Geffner M. Clinical trials in youth-onset type 2 diabetes: needs, barriers, and options. Curr Diab Rep 2015;15:28.
    1. Berends LM, Ozanne SE. Early determinants of type-2 diabetes. Best Pract Res Clin Endocrinol Metab 2012;26:569–580
    1. Lawrence JM, Imperatore G, Pettitt DJ, et al. . Incidence of diabetes in United States youth by diabetes type, race/ethnicity, and age, 2008–2009 (Abstract). Diabetes 2014;63(Suppl. 1):A407
    1. Dabelea D, Mayer-Davis EJ, Saydah S, et al. .; SEARCH for Diabetes in Youth Study . Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA 2014;311:1778–1786
    1. Fazeli Farsani S, van der Aa MP, van der Vorst MMJ, Knibbe CA, de Boer A. Global trends in the incidence and prevalence of type 2 diabetes in children and adolescents: a systematic review and evaluation of methodological approaches. Diabetologia 2013;56:1471–1488
    1. Petitti DB, Klingensmith GJ, Bell RA, et al. .; SEARCH for Diabetes in Youth Study Group Glycemic control in youth with diabetes: the SEARCH for Diabetes in Youth Study. J Pediatr 2009;155:668–672.e1–e3
    1. Hamman RF, Bell RA, Dabelea D, et al. .; SEARCH for Diabetes in Youth Study Group . The SEARCH for Diabetes in Youth study: rationale, findings, and future directions. Diabetes Care 2014;37:3336–3344
    1. Fu J, Prasad HC. Changing epidemiology of metabolic syndrome and type 2 diabetes in Chinese youth. Curr Diab Rep 2014;14:447.
    1. Prasad AN. Type 2 diabetes mellitus in young need for early screening. Indian Pediatr 2011;48:683–688
    1. Kelsey MM, Geffner ME, Guandalini C, et al. ; Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) Study Group. Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study. Pediatr Diabetes 2016;17:212–221
    1. Zeitler P, Hirst K, Pyle L, et al. .; TODAY Study Group . A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 2012;366:2247–2256
    1. TODAY Study Group Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and β-cell function in TODAY. Diabetes Care 2013;36:1749–1757
    1. Zeitler P, Hirst K, Copeland KC, et al. .; TODAY Study Group . HbA1c after a short period of monotherapy with metformin identifies durable glycemic control among adolescents with type 2 diabetes. Diabetes Care 2015;38:2285–2292
    1. Rascati K, Richards K, Lopez D, Cheng L-I, Wilson J. Progression to insulin for patients with diabetes mellitus on dual oral antidiabetic therapy using the US Department of Defense Database. Diabetes Obes Metab 2013;15:901–905
    1. Kahn SE. Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab 2001;86:4047–4058
    1. Kahn SE, Lachin JM, Zinman B, et al. .; ADOPT Study Group . Effects of rosiglitazone, glyburide, and metformin on β-cell function and insulin sensitivity in ADOPT. Diabetes 2011;60:1552–1560
    1. Hannon TS, Janosky J, Arslanian SA. Longitudinal study of physiologic insulin resistance and metabolic changes of puberty. Pediatr Res 2006;60:759–763
    1. Copeland KC, Zeitler P, Geffner M, et al. .; TODAY Study Group . Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab 2011;96:159–167
    1. Klingensmith GJ, Connor CG, Ruedy KJ, et al. ; Pediatric Diabetes Consortium. Presentation of youth with type 2 diabetes in the Pediatric Diabetes Consortium. Pediatr Diabetes 2016;17:266–273
    1. 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;8:384–390
    1. Hannon TS, Arslanian SA. The changing face of diabetes in youth: lessons learned from studies of type 2 diabetes. Ann N Y Acad Sci 2015;1353:113–137
    1. 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;37:436–443
    1. Klingensmith GJ, Pyle L, Nadeau KJ, et al. ;TODAY Study Group. Pregnancy outcomes in youth with type 2 diabetes: the TODAY study experience. Diabetes Care 2016;39:122–129
    1. Dabelea D, Hanson RL, Lindsay RS, et al. . Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 2000;49:2208–2211
    1. Mendelson M, Cloutier J, Spence L, Sellers E, Taback S, Dean H. Obesity and type 2 diabetes mellitus in a birth cohort of First Nation children born to mothers with pediatric-onset type 2 diabetes. Pediatr Diabetes 2011;12:219–228
    1. World Health Organization Social Determinants of Health. The Solid Facts. 2nd edition. Wilkinson R, Marmot M, Eds. [Internet]. Available from . Accessed 21 December 2015.
    1. Egerter S, Braveman P, Sadegh-Nobari T, Grossman-Kahn R, Dekker M Robert Wood Johnson Foundation Commission to Build a Healthier America. Exploring the Social Determinants of Health. Education and Health, Issue Brief 5 [Internet], 2011. . Accessed 21 December 2015
    1. Gracey M, King M. Indigenous health part 1: determinants and disease patterns. Lancet 2009;374:65–75
    1. McEwen BS, Stellar E. Stress and the individual. Mechanisms leading to disease. Arch Intern Med 1993;153:2093–2101
    1. Braveman P, Gottlieb L. The social determinants of health: it’s time to consider the causes of the causes. Public Health Rep 2014;129 Suppl. 2:19–31
    1. Duncan AE, Auslander WF, Bucholz KK, Hudson DL, Stein RI, White NH. Relationship between abuse and neglect in childhood and diabetes in adulthood: differential effects by sex, national longitudinal study of adolescent health. Prev Chronic Dis 2015;12:E70.
    1. Garg A, Jack B, Zuckerman B. Addressing the social determinants of health within the patient-centered medical home: lessons from pediatrics. JAMA 2013;309:2001–2002
    1. Glazier RH, Bajcar J, Kennie NR, Willson K. A systematic review of interventions to improve diabetes care in socially disadvantaged populations. Diabetes Care 2006;29:1675–1688
    1. Brackney DE, Cutshall M. Prevention of type 2 diabetes among youth: a systematic review, implications for the school nurse. J Sch Nurs 2015;31:6–21
    1. Ho M, Garnett SP, Baur LA, et al. . Impact of dietary and exercise interventions on weight change and metabolic outcomes in obese children and adolescents: a systematic review and meta-analysis of randomized trials. JAMA Pediatr 2013;167:759–768
    1. McGavock J, Dart A, Wicklow B Lifestyle therapy for the treatment of youth with type 2 diabetes. Curr Diab Rep 2015;15:568
    1. Savoye M, Nowicka P, Shaw M, et al. . Long-term results of an obesity program in an ethnically diverse pediatric population. Pediatrics 2011;127:402–410
    1. Savoye M, Caprio S, Dziura J, et al. . Reversal of early abnormalities in glucose metabolism in obese youth: results of an intensive lifestyle randomized controlled trial. Diabetes Care 2014;37:317–324
    1. Protudjer JLP, Dumontet J, McGavock JM. My voice: a grounded theory analysis of the lived experience of type 2 diabetes in adolescence. Can J Diabetes 2014;38:229–236
    1. Hood KK, Beavers DP, Yi-Frazier J, et al. . Psychosocial burden and glycemic control during the first 6 years of diabetes: results from the SEARCH for Diabetes in Youth study. J Adolesc Health 2014;55:498–504
    1. 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;34:2205–2207
    1. Frerichs L, Brittin J, Robbins R, et al. SaludABLEOmaha: improving readiness to address obesity through healthy lifestyle in a Midwestern Latino community, 2011–2013. Prev Chronic Dis 2015;12:E20
    1. Huang TT, Drewnosksi A, Kumanyika S, Glass TA. A systems-oriented multilevel framework for addressing obesity in the 21st century. Prev Chronic Dis 2009;6:A82.
    1. Benavides S, Caballero J. Ashtanga yoga for children and adolescents for weight management and psychological well being: an uncontrolled open pilot study. Complement Ther Clin Pract 2009;15:110–114
    1. Shalitin S, Ashkenazi-Hoffnung L, Yackobovitch-Gavan M, et al. . Effects of a twelve-week randomized intervention of exercise and/or diet on weight loss and weight maintenance, and other metabolic parameters in obese preadolescent children. Horm Res 2009;72:287–301
    1. Weigensberg MJ, Lane CJ, Ávila Q, et al. . Imagine HEALTH: results from a randomized pilot lifestyle intervention for obese Latino adolescents using Interactive Guided ImagerySM. BMC Complement Altern Med 2014;14:28.
    1. Edwards RW, Jumper-Thurman P, Plested BA, Oetting ER, Swanson L. Community readiness: research to practice. J Community Psychol 2000;28:291–307
    1. Committee on Accelerating Progress in Obesity Prevention, Institute of Medicine Accelerating Progress in Obesity Prevention: Solving the Weight of the Nation. 1st ed. Washington, D.C., National Academies Press, 2012, 478 pp
    1. The Oxford Handbook of the Social Science of Obesity. 1st ed. Oxford, U.K., Oxford University Press, 2011
    1. Shaibi GQ, Konopken Y, Hoppin E, Keller CS, Ortega R, Castro FG. Effects of a culturally grounded community-based diabetes prevention program for obese Latino adolescents. Diabetes Educ 2012;38:504–512
    1. Collective Impact Forum [Internet]. Available from . Accessed 21 October 2015
    1. Bacha F, Pyle L, Nadeau K, et al. .; TODAY Study Group . Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study. Pediatr Diabetes 2012;13:376–383
    1. Mencin AA, Loomba R, Lavine JE. Caring for children with NAFLD and navigating their care into adulthood. Nat Rev Gastroenterol Hepatol 2015;12:617–628
    1. Bjornstad P, Maahs DM, Cherney DZ, et al. . Insulin sensitivity is an important determinant of renal health in adolescents with type 2 diabetes. Diabetes Care 2014;37:3033–3039
    1. 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;94:3687–3695
    1. Matthews KA, Pantesco EJ. Sleep characteristics and cardiovascular risk in children and adolescents: an enumerative review. Sleep Med 2016;18:36–49
    1. [Internet]. Available from . Accessed 6 January 2016
    1. U.S. Food and Drug Administration [Internet]. Available from . Accessed 6 January 2016
    1. Tamborlane WV, Klingensmith G. Crisis in care: limited treatment options for type 2 diabetes in adolescents and youth. Diabetes Care 2013;36:1777–1778
    1. Karres J, Pratt V, Guettier J-M, et al. . Joining forces: a call for greater collaboration to study new medicines in children and adolescents with type 2 diabetes. Diabetes Care 2014;37:2665–2667
    1. Karres J, Tomasi P. New medicines for type 2 diabetes in adolescents: many products, few patients. Expert Rev Clin Pharmacol 2013;6:227–229
    1. Crume TL, Hamman RF, Isom SP, et al. . Factors influencing time to case ascertainment in youth with type 1 (T1D) and type 2 diabetes (T2D) in the SEARCH for Diabetes in Youth study (Abstract). Diabetes 2013;62(Suppl. 1):A412
    1. Nambam B, Silverstein J, Cheng P, et al. .; Pediatric Diabetes Consortium. A cross-sectional view of the current state of treatment of youth with type 2 diabetes in the USA: enrollment data from the Pediatric Diabetes Consortium Type 2 Diabetes Registry. Pediatr Diabetes. 11 March 2016 [Epub ahead of print]. DOI: 10.1111/pedi.12377
    1. Tamborlane WV, Haymond MW, Dunger D, et al. .; NICHD Diabetes Working Group . Expanding treatment options for youth with type 2 diabetes: current problems and proposed solutions: a white paper from the NICHD Diabetes Working Group. Diabetes Care 2016;39:323–329
    1. Anderson BJ, McKay SV. Barriers to glycemic control in youth with type 1 diabetes and type 2 diabetes. Pediatr Diabetes 2011;12:197–205
    1. Song SH. Complication characteristics between young-onset type 2 versus type 1 diabetes in a UK population. BMJ Open Diabetes Res Care 2015;3:e000044
    1. Kahn SE, Haffner SM, Heise MA, et al. .; ADOPT Study Group . Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427–2443
    1. Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC; UK Prospective Diabetes Study (UKPDS) Group . UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. Diabet Med 1998;15:297–303
    1. Imperatore G, Boyle JP, Thompson TJ, et al. .; SEARCH for Diabetes in Youth Study Group . 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 2012;35:2515–2520

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