xxxxx

1.0.0.0 Type 1 Di­a­betes

1.1.0.0 In­tro­duc­tion

The Amer­i­can Di­a­betes As­so­ci­a­tion (ADA) “Stan­dards of Med­i­cal Care in Di­a­betes” in­cludes ADA’s cur­rent clin­i­cal prac­tice rec­om­men­da­tions and is in­tend­ed to pro­vide the com­po­nents of di­a­betes care, gen­er­al treat­ment goals and guide­lines, and tools to eval­u­ate qual­i­ty of care. Mem­bers of the ADA Pro­fes­sion­al Prac­tice Com­mit­tee, a mul­ti­dis­ci­plinary ex­pert com­mit­tee, are re­spon­si­ble for up­dat­ing the Stan­dards of Care an­nu­al­ly, or more fre­quent­ly as war­rant­ed. For a de­tailed de­scrip­tion of ADA stan­dards, state­ments, and re­ports, as well as the ev­i­dence-‍grad­ing sys­tem for ADA’s clin­i­cal prac­tice rec­om­men­da­tions, please refer to the Stan­dards of Care In­tro­duc­tion. Read­ers who wish to com­ment on the Stan­dards of Care are in­vit­ed to do so at pro­fes­sion­al.di­a­betes.org/‍SOC.

The man­age­ment of di­a­betes in chil­dren and ado­les­cents can­not sim­ply be de­rived from care rou­tine­ly pro­vided to adults with di­a­betes. The epi­demi­ol­o­gy, patho­phys­i­ol­o­gy, de­vel­op­men­tal con­sid­er­a­tions, an­dre­sponse tother­a­py inpe­di­atric-‍onset di­a­betes are dif­fer­ent from adult di­a­betes. There are also dif­fer­ences in rec­om­mend­ed care for chil­dren and ado­les­cents with type 1 as op­posed to type 2 di­a­betes. This sec­tion first ad­dress­es care for chil­dren and ado­les­cents with type 1 di­a­betes and next ad­dress­es care for chil­dren and ado­les­cents with type 2 di­a­betes. Fig­ure 13.1 pro­vides guid­ance on man­ag­ing new-‍onset di­a­betes in over­weight youth be­fore type 1 or type 2 di­a­betes is di­ag­nosed and so ap­plies to all over­weight youth. Last­ly, guid­ance is pro­vided in this sec­tion on tran­si­tion of care from pe­di­atric to adult pro­viders to en­sure that the con­tin­u­um of care is ap­pro­pri­ate as the child with di­a­betes de­vel­ops into adult­hood. Due to the na­ture of clin­i­cal re­search in chil­dren, the rec­om­men­da­tions for chil­dren and ado­les­cents with di­a­betes are less like­ly to be based on clin­i­cal trial ev­i­dence. How­ev­er, ex­pert opin­ion and a re­view of avail­able and rel­e­vant ex­per­i­men­tal data are sum­ma­rized in the Amer­i­can Di­a­betes As­so­ci­a­tion (ADA) po­si­tion state­ments “Type 1 Di­a­betes in Chil­dren and Ado­les­cents” (1) and “Eval­u­a­tion and Man­age­ment of Youth-‍Onset Type 2 Di­a­betes” (2). The ADA con­sen­sus re­port “Youth-‍Onset Type 2 Di­a­betes Con­sen­sus Re­port: Cur­rent Sta­tus, Chal­lenges, and Pri­or­i­ties” (3) char­ac­ter­izes type 2 di­a­betes in chil­dren and eval­u­ates treat­ment op­tions as well, but also dis­cuss­es knowl­edge gaps and re­cruit­ment chal­lenges in clin­i­cal and trans­la­tion­al re­search in youth-‍onset type 2 di­a­betes.

TYPE 1 DI­A­BETES

Type 1 di­a­betes is the most­com­mon form of di­a­betes in youth (4), al­though re­cent data sug­gest­that itmay ac­count­for a large pro­por­tionof­cas­es di­ag­nosed in adultlife (5). The pro­vider must con­sid­er the unique as­pects of care and man­age­ment of chil­dren and ado­les­cents with type 1 di­a­betes, such as changes in in­sulin sen­si­tiv­i­ty re­lat­ed to phys­i­cal growth and sex­u­al mat­u­ra­tion, abil­i­ty to pro­vide self-‍care, su­per­vi­sion in the child care and school en­vi­ron­ment, neu­ro­log­i­cal vulnerabil­i­ty to hy­po­glycemia and hy­per­glycemia in young chil­dren, as well as pos­si­ble ad­verse neu­rocog­ni­tive ef­fects of di­a­bet­ic ke­toaci­do­sis (DKA) (6,7). At­ten­tion to fam­i­ly dy­nam­ics, de­vel­op­men­tal stages, and phys­i­o­log­ic dif­fer­ences re­lat­ed to sex­u­al ma­tu­ri­ty is es­sen­tial in de­vel­op­ing and im­ple­ment­ing an op­ti­mal di­a­betes treat­ment plan (8).

A mul­ti­dis­ci­plinary team of spe­cial­ists trained in pe­di­atric di­a­betes man­age­ment and sen­si­tive to the chal­lenges of chil­dren and ado­les­cents with type 1 di­a­betes and their fam­i­lies should pro­vide care for this pop­u­la­tion. It is es­sen­tial that di­a­betes self-‍man­age­ment ed­u­ca­tion and sup­port, med­i­cal nu­tri­tion ther­a­py, and psy­choso­cial sup­port be pro­vided at di­ag­no­sis and reg­u­lar­ly there­after in a de­vel­op­men­tally ap­pro­pri­ate for­mat that builds on prior knowl­edge by in­di­vid­u­als ex­pe­ri­enced with the ed­u­ca­tional, nu­tri­tional, be­hav­ioral, and emo­tion­al needs of the grow­ing child and fam­i­ly. The ap­pro­pri­ate bal­ance be­tween adult su­per­vi­sion and in­de­pen­dent self­care should be defined at the first in­ter­ac­tion and reeval­u­ated at sub­se­quent vis­its, with the ex­pec­ta­tion that it will evolve as the ado­les­cent grad­u­al­ly be­comes an emerg­ing young adult.

Sug­gest­ed ci­ta­tion: Amer­i­can Di­a­betes As­so­ci­a­tion. 13. Chil­dren and ado­les­cents: Stan­dards of Med­i­cal Care in Di­a­betesd2019. Di­a­betes Care 2019;42(Suppl. 1):S148–S164 © 2018 by the Amer­i­can Di­a­betes As­so­ci­a­tion. Read­ers may use this ar­ti­cle as long as the work is prop­er­ly cited, the use is ed­u­ca­tional and not for prof­it, and the work is not al­tered. More infor­mation is avail­able at http://www.di­a­betesjournals .org/‍content/‍license.

xxxxx

1.2.0.0 Di­a­betes Self-‍man­age­ment Ed­u­ca­tion and Sup­port

No mat­ter how sound the med­i­cal reg­i­men, it can only be ef­fec­tive if the fam­i­ly and/‍or af­fect­ed in­di­vid­u­als are able to im­ple­ment it. Fam­i­ly in­volve­ment is a vital com­po­nent of op­ti­mal di­a­betes man­age­ment through­out child­hood and ado­les­cence. Health care pro­viders in the di­a­betes care team who care for chil­dren and ado­les­cents must be ca­pa­ble of eval­u­at­ing the ed­u­ca­tional, be­hav­ioral, emo­tion­al, and psy­choso­cial fac­tors that im­pact im­ple­mentation of a treat­ment plan and must work with the in­di­vid­u­al and fam­i­ly to over­come bar­ri­ers or redefine goals as ap­pro­pri­ate. Di­a­betes self-‍man­age­ment ed­u­ca­tion and sup­port re­quires pe­ri­od­ic re­as­sess­ment, es­pe­cial­ly as the youth grows, de­vel­ops, and ac­quires the need for greater in­de­pen­dent self-‍care skills. In ad­di­tion, it is nec­es­sary to as­sess the ed­u­ca­tional needs and skills of day care pro­viders, school nurs­es, or other school per­son­nel who par­tic­i­pate in the care of the young child with di­a­betes (9).

xxxxx

1.3.0.0 Nu­tri­tion Ther­a­py

Di­etary man­age­ment should be in­di­vid­u­al­ized: fam­i­ly habits, food pref­er­ences, re­li­gious or cul­tur­al needs, sched­ules, phys­i­cal ac­tiv­i­ty, and the pa­tient’s and fam­i­ly’s abil­i­ties in nu­mer­a­cy, lit­er­a­cy, and self-‍man­age­ment should be con­sid­ered. Di­eti­tian vis­its should in­clude as­sessment for changes in food pref­er­ences over time, ac­cess to food, growth and de­vel­op­ment, weight sta­tus, car­dio­vas­cu­lar risk, and po­ten­tial for eat­ing dis­or­ders. Di­etary ad­her­ence is as­so­ci­at­ed with bet­ter glycemic con­trol in youth with type 1 di­a­betes (10).

xxxxx

1.4.0.0 Phys­i­cal Ac­tiv­i­ty and Ex­er­cise

Ex­er­cise pos­i­tive­ly af­fects in­sulin sen­si­tiv­i­ty, phys­i­cal fitness, strength build­ing, weight man­age­ment, so­cial in­ter­ac­tion, mood, self-‍es­teem build­ing, and cre­ation of health­ful habits for adult­hood, but it also has the po­ten­tial to cause both hy­po­glycemia and hy­per­glycemia.

See below for strate­gies to mit­i­gate hy­po­glycemia risk and min­i­mize hy­per­glycemia with ex­er­cise. For an in-‍depth dis­cus­sion, see re­cently pub­lished re­views and guide­lines (11-13).

Over­all, it is rec­om­mend­ed that youth with type 1 di­a­betes par­tic­i­pate in 60 min of mod­er­ate-‍ (e.g., brisk walk­ing, danc­ing) to vig­or­ous-‍ (e.g., run­ning, jump­ing rope in­ten­si­ty aer­o­bic ac­tiv­i­ty daily, in­clud­ing re­sis­tance and flex­i­bil­i­ty train­ing (14). Al­though un­com­mon in the pe­di­atric pop­u­la­tion, pa­tients should be med­i­cally eval­u­ated for co­mor­bid con­di­tions or di­a­betes com­pli­ca­tions that­may re­strict­par­tic­i­pa­tion in an ex­er­cise pro­gram. As hy­per­glycemia can occur be­fore, dur­ing, and after phys­i­cal ac­tiv­i­ty, it is im­por­tant to en­sure that the el­e­vat­ed glu­cose level is not re­lat­ed to in­sulin deficien­cy that would lead to wors­en­ing hy­per­glycemia with ex­er­cise and ke­to­sis risk. In­tense ac­tiv­i­ty should be post­poned with marked hy­per­glycemia (glu­cose ≥350 mg/dL [19.4 mmol/‍L]), mod­er­ate to large urine ke­tones, and/‍or b-‍hydroxybutyrate (B-OHB) >1.5 mmol/‍L. Cau­tion may be need­ed when B-OHB lev­els are ≥0.6 mmol/‍L (10,11).

The pre­ven­tion and treat­ment of hy­po­glycemia as­so­ci­at­ed with phys­i­cal ac­tiv­i­ty in­clude de­creas­ing the pran­di­al in­sulin for the meal/‍snack be­fore ex­er­cise and/‍or in­creas­ing food in­take. Pa­tients on in­sulin pumps can lower basal rates by ˜10–50% or more or sus­pend for 1–2 h dur­ing ex­er­cise (15). De­creas­ing basal rates or long act­ing in­sulin doses by ˜20% after ex­er­cise may re­duce de­layed ex­er­cise-induced hy­po­glycemia (16). Ac­ces­si­ble rapid-‍act­ing car­bo­hy­drates and fre­quent blood glu­cose mon­i­tor­ing be­fore, dur­ing, and after ex­er­cise, with or with­out con­tin­u­ous glu­cose mon­i­tor­ing, max­i­mize safe­ty with ex­er­cise.

Blood glu­cose tar­gets prior to ex­er­cise should be 90–250 mg/dL (5.0–13.9 mmol/‍L). Con­sid­er ad­di­tional car­bo­hy­drate in­take dur­ing and/‍or after ex­er­cise, de­pend­ing on the du­ra­tion and in­ten­si­ty of phys­i­cal ac­tiv­i­ty, to pre­vent hy­po­glycemia. For low- to mod­er­ate-‍in­ten­si­ty aer­o­bic ac­tiv­i­ties (30260 min), and if the pa­tient is fast­ing, 10215 g of car­bo­hy­drate may pre­vent hy­po­glycemia (17). After in­sulin bo­lus­es (rel­a­tive hyperin­sulinemia), con­sid­er 0.5–1.0 g of car­bo­hy­drates/kg per hour of ex­er­cise (˜30–60 g), which is sim­i­lar to car­bo­hy­drate re­quire­ments to op­ti­mize per­for­mance in ath­letes with­out type 1 di­a­betes (18-20).

In ad­di­tion, obe­si­ty is as com­mon in chil­dren and ado­les­cents with type 1 di­a­betes as in those with­out di­a­betes. It is as­so­ci­at­ed with high­er fre­quen­cy of car­dio­vas­cu­lar risk fac­tors, and it dis­pro­por­tion­ate­ly af­fects racial/‍eth­nic mi­nori­ties in the U.S. (21-25). There­fore, di­a­betes care pro­viders should mon­i­tor weight sta­tus and en­cour­age a healthy diet, ex­er­cise, and healthy weight as key com­po­nents of pe­di­atric type 1 di­a­betes care.

xxxxx

1.5.0.0 School and Child Care

As a large por­tion of a child’s day is spent in school, close com­mu­ni­ca­tion with and the co­op­er­a­tion of school or day care per­son­nel are es­sen­tial for op­ti­mal di­a­betes man­age­ment, safe­ty, and max­i­mal aca­dem­ic op­por­tu­ni­ties. Refer to the ADA po­si­tion state­ments “Di­a­betes Care in the School Set­ting” (26) and “Care of Young Chil­dren With Di­a­betes in the Child Care Set­ting” (27) for ad­di­tional de­tails.

xxxxx

1.6.0.0 Psychoso­cial Is­sues

Rapid and dy­nam­ic cog­ni­tive, de­vel­op­men­tal, and emo­tion­al changes occur dur­ing child­hood, ado­les­cence, and emerg­ing adult­hood. Di­a­betes man­age­ment dur­ing child­hood and ado­les­cence places sub­stan­tial bur­dens on the youth and fam­i­ly, ne­ces­si­tat­ing on­go­ing as­sessment of psy­choso­cial sta­tus and di­a­betes dis­tress in the pa­tient and the care­giv­er dur­ing rou­tine di­a­betes vis­its (28-34). Early de­tection of de­pres­sion, anx­i­ety, eat­ing dis­or­ders, and learn­ing disabil­i­ties can fa­cil­i­tate ef­fec­tive treat­ment op­tions and help min­i­mize ad­verse ef­fects on di­a­betes man­age­ment and dis­ease out­comes (33,35). There are val­i­dat­ed tools, such as the Prob­lem Areas in Di­a­betes-‍ Teen (PAID-‍T) and Par­ent (P-PAID-‍Teen) (34), that can be used in as­sessing di­a­betes-‍specific dis­tress in youth start­ing at age 12 years and in their par­ent care­giv­ers. Fur­ther­more, the com­plex­i­ties of di­a­betes man­age­ment re­quire on­go­ing par­ental in­volve­ment in care through­out child­hood with de­vel­op­men­tally ap­pro­pri­ate fam­i­ly team­work be­tween the grow­ing child/‍teen and par­ent in order to main­tain ad­her­ence and to pre­vent de­te­ri­o­ra­tion in glycemic con­trol (36,37). As di­a­betes-‍specific fam­i­ly conflict is re­lat­ed to poor­er ad­her­ence and glycemic con­trol, it is ap­pro­pri­ate to in­quire about such conflict dur­ing vis­its and to ei­ther help to ne­go­ti­ate a plan for res­o­lu­tion or refer to an ap­pro­pri­ate men­tal health spe­cial­ist (38). Mon­i­tor­ing of so­cial ad­just­ment (peer re­la­tionships) and school per­for­mance can fa­cil­i­tate both well-‍being and aca­dem­ic achieve­ment (39). Subop­ti­mal glycemic con­trol is a risk fac­tor for underper­for­mance at school and in­creased ab­sen­teeism (40). Shared de­ci­sion mak­ing with youth re­gard­ing the adop­tion of reg­i­men com­po­nents and self-‍man­age­ment be­hav­iors can im­prove di­a­betes self-‍efficacy, ad­her­ence, and metabol­ic out­comes (22,41).

Al­though cog­ni­tive abil­i­ties vary, the eth­i­cal po­si­tion often adopt­ed is the “ma­ture minor rule,” where­by chil­dren after age 12 or 13 years who ap­pear to be “ma­ture” have the right to con­sent or with­hold con­sent to gen­er­al med­i­cal treat­ment, ex­cept in cases in which re­fusal would significant­ly en­dan­ger health (42).

Be­gin­ning at the onset of pu­ber­ty or at di­ag­no­sis of di­a­betes, all ado­les­cent girls and women with child­bear­ing po­ten­tial should re­ceive ed­u­ca­tion about the risks of malfor­mations as­so­ci­at­ed with poor metabol­ic con­trol and the use of ef­fec­tive con­tra­cep­tion to pre­vent un­planned preg­nan­cy. Pre­con­cep­tion coun­sel­ing using de­vel­op­men­tally ap­pro­pri­ate ed­u­ca­tional tools en­ables ado­les­cent girls to make well-‍in­formed de­ci­sions (43). Pre-‍con­cep­tion coun­sel­ing re­sources tai­lored for ado­les­cents are avail­able at no cost through the ADA (44). Refer to the ADA po­si­tion state­ment “Psychoso­cial Care for Peo­ple With Di­a­betes” for fur­ther de­tails (35).

Youth with type 1 di­a­betes have an in­creased risk of dis­or­dered eat­ing be­hav­ior as well as clin­i­cal eat­ing dis­or­ders with se­ri­ous short-‍term and long-‍term neg­a­tive ef­fects on di­a­betes out­comes and health in gen­er­al. There­fore, it is im­por­tant to screen for eat­ing dis­or­ders in youth with type 1 di­a­betes using tools such as the Di­a­betes Eat­ing Prob­lems Sur­vey-‍Re­vised (DEPS-‍R) to allow for early di­ag­no­sis and in­ter­ven­tion (45-48).

Screen­ing

Screen­ing for psy­choso­cial dis­tress and men­tal health prob­lems is an im­por­tant com­po­nent of on­go­ing care. It is im­por­tant to con­sid­er the im­pact of di­a­betes on qual­i­ty of life as well as the de­vel­op­ment of men­tal health prob­lems re­lat­ed to di­a­betes dis­tress, fear of hy­po­glycemia (and hy­per­glycemia), symp­toms of anx­i­ety, dis­or­dered eat­ing be­hav­iors as well as eat­ing dis­or­ders, and symp­toms of de­pres­sion (49). Con­sid­er as­sessing youth for di­a­betes dis­tress, gen­er­ally start­ing at 7 or 8 years of age (35). Con­sid­er screen­ing for de­pres­sion and dis­or­dered eat­ing be­hav­iors using avail­able screen­ing tools (28,45). With re­spect to dis­or­dered eat­ing, it is im­por­tant to rec­og­nize the unique and dan­ger­ous dis­or­dered eat­ing be­hav­ior of in­sulin omis­sion for weight con­trol in type 1 di­a­betes (50). The pres­ence of a men­tal health pro­fes­sion­al on pe­di­atric mul­ti­dis­ci­plinary teams high­lights the im­por­tance of at­tend­ing to the psy­choso­cial is­sues of di­a­betes. These psy­choso­cial fac­tors are significant­ly re­lat­ed to self-‍man­age­ment difficul­ties, subop­ti­mal glycemic con­trol, re­duced qual­i­ty of life, and high­er rates of acute and chron­ic di­a­betes com­pli­ca­tions.

xxxxx

1.7.0.0 Glycemic Con­trol

Table 13.1—Blood glu­cose and A1C tar­gets for chil­dren and ado­les­cents with type 1 di­a­betes

Please refer to Sec­tion 7 “Di­a­betes Tech­nol­o­gy” for more infor­mation on the use of blood glu­cose me­ters, con­tin­u­ous glu­cose mon­i­tors, and in­sulin pumps. More infor­mation on in­sulin in­jec­tion tech­nique can be found in Sec­tion 9 “Phar­ma­co­log­ic Ap­proach­es to Glycemic Treat­ment,” p. S90.

Cur­rent stan­dards for di­a­betes man­age­ment reflect the need to lower glu­cose as safe­ly as pos­si­ble. This should be done with step­wise goals. When es­tab­lish­ing in­di­vid­u­al­ized glycemic tar­gets, spe­cial con­sid­eration should be given to the risk of hy­po­glycemia in young chil­dren (aged <6 years) who are often un­able to rec­og­nize, ar­tic­u­late, and/‍or man­age hy­po­glycemia. How­ev­er, reg­istry data in­di­cate that lower A1C can be achieved in chil­dren, in­clud­ing those <6 years, with­out in­creased risk of se­vere hy­po­glycemia (51,52).

Type 1 di­a­betes can be as­so­ci­at­ed with ad­verse ef­fects on cog­ni­tion dur­ing child­hood and ado­les­cence. Fac­tors that con­tribute to ad­verse ef­fects on brain de­vel­op­ment and func­tion in­clude young age or DKA at onset of type 1 di­a­betes, se­vere hy­po­glycemia at <6 years of age, and chron­ic hy­per­glycemia (53,54). How­ev­er, metic­u­lous use of new ther­a­peu­tic modal­i­ties such as rap­i­dand long-‍act­ing in­sulin analogs, tech­no­log­i­cal ad­vances (e.g., con­tin­u­ous glu­cose mon­i­tors, low-‍glu­cose sus­pend in­sulin pumps, and au­to­mat­ed in­sulin de­liv­ery sys­tems), and in­ten­sive self-‍man­age­ment ed­u­ca­tion now make it more fea­si­ble to achieve ex­cel­lent glycemic con­trol while re­duc­ing the in­ci­dence of se­vere hy­po­glycemia (55-64). In­ter­mit­tent­ly scanned con­tin­u­ous glu­cose mon­i­tors (some­times re­ferred to as “flash” con­tin­u­ous glu­cose mon­i­tors) are not cur­rently ap­proved for use in chil­dren and ado­les­cents. A strong re­la­tionship ex­ists be­tween fre­quen­cy of blood glu­cose mon­i­tor­ing and glycemic con­trol (57-66).

The Di­a­betes Con­trol and Com­pli­ca­tions Trial (DCCT), which did not en­roll chil­dren <13 years of age, demon­strat­ed that near nor­mal­iza­tion of blood glu­cose lev­els was more difficult to achieve in ado­les­cents than in adults. Nev­er­the­less, the in­creased use of basal-‍bolus reg­i­mens, in­sulin pumps, fre­quent blood glu­cose mon­i­tor­ing, goal set­ting, and im­proved pa­tient ed­u­ca­tion in youth from in­fan­cy through ado­les­cence has been as­so­ci­at­ed with more chil­dren reach­ing the blood glu­cose tar­gets rec­om­mend­ed by ADA (67-70), par­tic­u­lar­ly in those fam­i­lies in which both the par­ents and the child with di­a­betes par­tic­i­pate joint­ly to per­form the re­quired di­a­betes-‍re­lat­ed tasks. Fur­ther­more, stud­ies doc­u­ment­ing neu­rocog­ni­tive imag­ing dif­fer­ences re­lat­ed to hy­per­glycemia in chil­dren pro­vide an­oth­er mo­ti­va­tion for low­er­ing glycemic tar­gets (6).

In se­lect­ing glycemic tar­gets, the long-‍term health benefits of achiev­ing a lower A1C should be bal­anced against the risks of hy­po­glycemia and the de­vel­op­men­tal bur­dens of in­ten­sive reg­i­mens in chil­dren and youth. Inad­di­tion, achiev­ing lower A1C lev­els is like­ly fa­cil­i­tated by set­ting lower A1C tar­gets (51,71). A1C and blood glu­cose tar­gets are pre­sent­ed in Table 13.1. Lower goals may be pos­si­ble dur­ing the “hon­ey­moon” phase of type 1 di­a­betes.

Key Con­cepts in Set­ting Glycemic Tar­gets

Tar­gets should be in­di­vid­u­al­ized, and lower tar­gets may be rea­son­able based on a benefit-‍risk as­sessment.

Blood glu­cose tar­gets should be modi- fied in chil­dren with fre­quent hy­po­glycemia or hy­po­glycemia un­awareness.

Postpran­di­al blood glu­cose val­ues should be mea­sured when there is a dis­crep­an­cy be­tween prepran­di­al blood glu­cose val­ues and A1C lev­els and to as­sess prepran­di­al in­sulin doses in those on basal-‍bolus or pump reg­i­mens.

xxxxx

1.8.0.0 Au­toim­mune Con­di­tions

1.8.1.0 Rec­om­men­da­tions

Be­cause of the in­creased fre­quen­cy of other au­toim­mune dis­eases in type 1 di­a­betes, screen­ing for thy­roid dysfunc­tion and celi­ac dis­ease should be con­sid­ered (72,73). Pe­ri­od­ic screen­ing in asymp­tomat­ic in­di­vid­u­als has been rec­om­mend­ed, but the op­ti­mal fre­quen­cy of screen­ing is un­clear.

Al­though much less com­mon than thy­roid dysfunc­tion and celi­ac dis­ease, other au­toim­mune con­di­tions, such as Ad­di­son dis­ease (pri­ma­ry adrenal insufficien­cy), au­toim­mune hep­ati­tis, au­toim­mune gas­tri­tis, der­mato­myosi­tis, and myas­the­nia gravis, occur more com­monly in the pop­u­la­tion with type 1 di­a­betes than in the gen­er­al pe­di­atric pop­u­la­tion and should be as­sessed and mon­i­tored as clin­i­cally in­di­cated. In ad­di­tion, rel­a­tives of pa­tients should be of­fered test­ing for islet au­toan­ti­bod­ies through re­search stud­ies (e.g., Tri­al­Net) for early di­ag­no­sis of preclin­i­cal type 1 di­a­betes (stages 1 and 2).

xxxxx

1.8.2.0 Thy­roid Dis­ease

xxxxx

1.8.3.0 Celi­ac Dis­ease

Celi­ac dis­ease is an im­mune-‍me­di­at­ed dis­or­der that oc­curs with in­creased fre­quen­cy in pa­tients with type 1 di­a­betes (1.6–16.4% of in­di­vid­u­als com­pared with 0.3–1% in the gen­er­al pop­u­la­tion) (72,73,80–83).

Screen­ing for celi­ac dis­ease in­cludes mea­sur­ing serum lev­els of IgA and tis­sue trans­g­lu­tam­i­nase an­ti­bod­ies, or, with IgA deficien­cy, screen­ing can in­clude mea­sur­ing IgG tis­sue trans­g­lu­tam­i­nase an­ti­bod­ies or IgG deami­dat­ed gliadin pep­tide an­ti­bod­ies. Be­cause most cases of celi­ac dis­ease are di­ag­nosed with­in the first 5 years after the di­ag­no­sis of type 1 di­a­betes, screen­ing should be con­sid­ered at the time of di­ag­no­sis and re­peat­ed at 2 and then 5 years (82) or if clin­i­cal symp­toms in­di­cate, such as poor growth or in­creased hy­po­glycemia (83,84).

Al­though celi­ac dis­ease can be di­ag­nosed more than 10 years after di­a­betes di­ag­no­sis, there are insufficient data after 5 years to de­ter­mine the op­ti­mal screen­ing fre­quen­cy. Mea­surement of tis­sue trans­g­lu­tam­i­nase an­ti­body should be con­sid­ered at other times in pa­tients with symp­toms sug­gestive of celi­ac dis­ease (82). Mon­i­tor­ing for symp­toms should in­clude as­sessment of lin­ear growth and weight gain (83,84). A small-‍bowel biop­sy in an­ti­body-pos­i­tive chil­dren is rec­om­mend­ed to confirm the di­ag­no­sis (85). Eu­ro­pean guide­lines on screen­ing for celi­ac dis­ease in chil­dren (not specific to chil­dren with type 1 di­a­betes) sug­gest that biop­sy may not be nec­es­sary in symp­tomat­ic chil­dren with high an­ti­body titers (i.e., greater than 10 times the upper limit of nor­mal) pro­vided that fur­ther test­ing is per­formed (verification of en­domysial an­ti­body pos­i­tiv­i­ty on a sep­a­rate blood sam­ple). Whether this ap­proach may be ap­pro­pri­ate for asymp­tomat­ic chil­dren in high-‍risk groups re­mains an open ques­tion, though ev­i­dence is emerg­ing (86). It is also ad­vis­able to check for celi­ac dis­ease–as­so­ci­at­ed HLA types in pa­tients who are di­ag­nosed with­out a small in­testi­nal biop­sy. In symp­tomat­ic chil­dren with type 1 di­a­betes and confirmed celi­ac dis­ease, gluten-‍free diets re­duce symp­toms and rates of hy­po­glycemia (87). The chal­leng­ing di­etary re­stric­tions as­so­ci­at­ed with hav­ing both type 1 di­a­betes and celi­ac dis­ease place a significant bur­den on in­di­vid­u­als. There­fore, a biop­sy to confirm the di­ag­no­sis of celi­ac dis­ease is rec­om­mend­ed, es­pe­cial­ly in asymp­tomat­ic chil­dren, be­fore es­tab­lish­ing a di­ag­no­sis of celi­ac dis­ease (88) and en­dors­ing significant di­etary changes. A gluten-‍free diet was beneficial in asymp­tomat­ic adults with pos­i­tive an­ti­bod­ies confirmed by biop­sy (89).

xxxxx

1.9.0.0 Car­dio­vas­cu­lar Risk Fac­tors Mgmt.

1.9.1.0 Hy­per­ten­sion

Blood pres­sure mea­sure­ments should be per­formed using the ap­pro­pri­ate size cuff with the child seat­ed and re­laxed. Hy­per­ten­sion should be confirmed on at least 3 sep­a­rate days. Eval­u­a­tion should pro­ceed as clin­i­cally in­di­cated (90). Treat­ment is gen­er­ally ini­ti­at­ed with an ACE in­hibitor, but an an­giotensin re­cep­tor block­er can be used if the ACE in­hibitor is not tol­er­at­ed (e.g., due to cough) (91).

Nor­mal blood pres­sure lev­els for age, sex, and height and ap­pro­pri­ate meth­ods for mea­sure­ment are avail­able on­line at nhlbi.nih.gov/files/docs/re­sources/heart/hbp_ped.pdf.

xxxxx

1.9.2.0 Dys­lipi­demia

Pop­u­la­tion-‍based stud­ies es­ti­mate that 14–45% of chil­dren with type 1 di­a­betes have two or more atheroscle­rot­ic car­dio­vas­cu­lar dis­ease (ASCVD) risk fac­tors (92-94), and the preva­lence of car­dio­vas­cu­lar dis­ease (CVD) risk fac­tors in­creas­es with age (94) and among racial/‍ eth­nic mi­nori­ties (21), with girls hav­ing a high­er risk bur­den than boys (93).

Patho­phys­i­ology.

The atheroscle­rot­ic pro­cess be­gins in child­hood, and al­though ASCVD events are not ex­pect­ed to occur dur­ing child­hood, ob­ser­va­tions using a va­ri­ety of method­olo­gies show that youth with type 1 di­a­betes may have subclin­i­cal CVD with­in the first decade of di­ag­no­sis (95-97). Stud­ies of carotid in­ti­ma-‍media thick­ness have yield­ed incon­sistent re­sults (90,91).

Treat­ment.

Pe­di­atric lipid guide­lines pro­vide some guid­ance rel­e­vant to chil­dren with type 1 di­a­betes (90,98–100); how­ev­er, there are few stud­ies on mod­i­fy­ing lipid lev­els in chil­dren with type 1 di­a­betes. A 6-‍month trial of di­etary coun­sel­ing pro­duced a significant im­provement in lipid lev­els (101); like­wise, a lifestyle in­ter­ven­tion trial with 6 months of ex­er­cise in ado­les­cents demon­strat­ed im­provement in lipid lev­els (102).

Al­though in­ter­ven­tion data are sparse, the Amer­i­can Heart As­so­ci­a­tion cat­e­go­rizes chil­dren with type 1 di­a­betes in the high­est tier for car­dio­vas­cu­lar risk and rec­om­mends both lifestyle and phar­ma­co­log­ic treat­ment for those with el­e­vat­ed LDL choles­terol lev­els (100,103). Ini­tial ther­a­py should be with a nu­tri­tion plan that re­stricts sat­u­rat­ed fat to 7% of total calo­ries and di­etary choles­terol to 200 mg/‍day. Data from ran­dom­ized clin­i­cal tri­als in chil­dren as young as 7 months of age in­di­cate that this diet is safe and does not in­ter­fere with nor­mal growth and de­vel­op­ment (104).

For chil­dren with a significant fam­i­ly his­to­ry of CVD, the Na­tion­al Heart, Lung, and Blood In­sti­tute rec­om­mends ob­tain­ing a fast­ing lipid panel be­gin­ning at 2 years of age (98). Abnor­mal re­sults from a ran­dom lipid panel should be confirmed with a fast­ing lipid panel. Data from the SEARCH for Di­a­betes in Youth (SEARCH) study show that im­proved glu­cose con­trol over a 2-year pe­ri­od is as­so­ci­at­ed with a more fa­vor­able lipid profile; how­ev­er, im­proved glycemic con­trol alone will not nor­malize lipids in youth with type 1 di­a­betes and dys­lipi­demia (105).

Nei­ther long-‍term safe­ty nor car­dio­vas­cu­lar out­come efficacy of statin ther­a­py has been es­tab­lished for chil­dren; how­ev­er, stud­ies have shown short-‍term safe­ty equiv­a­lent to that seen in adults and efficacy in low­er­ing LDL choles­terol lev­els in fa­mil­ial hypercholes­terolemiaorse­vere hy­per­lipi­demia, im­prov­ing en­dothe­lial func­tion and caus­ing re­gres­sion of carotid in­ti­mal thick­en­ing (106,107). Statins are not ap­proved for pa­tients aged <10 years, and statin treat­ment should gen­er­ally not be used in chil­dren with type 1 di­a­betes be­fore this age. Statins are contrain­di­cated in preg­nan­cy; there­fore, pre­ven­tion of un­planned preg­nan­cies is of paramount im­por­tance for post­pu­ber­tal girls (see Sec­tion 14 “Man­age­ment of Di­a­betes in Preg­nan­cy” for more infor­mation). The mul­ti­cen­ter, ran­dom­ized, placebo-con­trolled Ado­les­cent Type 1 Di­a­betes Cardio-‍Renal In­ter­ven­tion Trial (AdDIT) pro­vides safe­ty data on phar­ma­co­log­ic treat­ment with an ACE in­hibitor and statin in ado­les­cents with type 1 di­a­betes.

xxxxx

1.9.3.0 Smok­ing

The ad­verse health ef­fects of smok­ing are well rec­og­nized with re­spect to fu­ture can­cer and CVD risk. De­spite this, smok­ing rates are significant­ly high­er among youth with di­a­betes than among youth with­out di­a­betes (108,109). In youth with di­a­betes, it is im­por­tant to avoid ad­di­tional CVD risk fac­tors. Smok­ing in­creas­es the risk of onset of al­bu­min-‍uria; there­fore, smok­ing avoid­ance is im­por­tant to pre­vent both mi­crovas­cu­lar and macrovas­cu­lar com­pli­ca­tions (98, 110). Dis­cour­ag­ing cigarette smok­ing, in­clud­ing e-‍cigarettes (111,112), is an im­por­tant part of rou­tine di­a­betes care. In younger chil­dren, it is im­por­tant to as­sess ex­po­sure to cigarette smoke in the home be­cause of the ad­verse ef­fects of se­cond­hand smoke and to dis­cour­age youth from ever smok­ing if ex­posed to smok­ers in child­hood.

xxxxx

1.10.0.0 Mi­crovas­cu­lar Com­pli­ca­tions

1.10.1.0 Nephropa­thy

Data from 7,549 par­tic­i­pants <20 years of age in the T1D Ex­change clin­ic reg­istry em­pha­size the im­por­tance of good glycemic and blood pres­sure con­trol, par­tic­u­lar­ly as di­a­betes du­ra­tion in­creas­es, in order to re­duce the risk of di­a­bet­ic kid­ney dis­ease. The data also un­der­score the im­por­tance of rou­tine screen­ing to en­sure early di­ag­no­sis and time­ly treat­ment of al­bu­minuria (113). An es­ti­ma­tion of glomeru­lar filtra­tion rate (GFR), cal­cu­lat­ed using GFR es­ti­mat­ing equa­tions from the serum cre­a­ti­nine, height, age, and sex (114), should be con­sid­ered at base­line and re­peat­ed as in­di­cated based on clin­i­cal sta­tus, age, di­a­betes du­ra­tion, and ther­a­pies. Im­proved meth­ods are need­ed to screen for early GFR loss, since es­ti­mated GFR is in­ac­cu­rate at GFR >60 mL/‍min/‍1.73 m2 (114,115). The AdDIT study in ado­les­cents with type 1 di­a­betes demon­strat­ed safe­ty of ACE in­hibitor treat­ment, but the treat­ment did not change the al­bu­min-‍to-‍cre­a­ti­nine ratio over the course of the study (90).

xxxxx

1.10.2 Retinopa­thy

xxxxx

1.10.3.0 Neu­ropa­thy

xxxxx

2.0.0.0 TYPE 2 DI­A­BETES

2.1.0.0 In­tro­duc­tion

For infor­mation on test­ing for type 2 di­a­betes and predi­a­betes in chil­dren and ado­les­cents, please refer to Sec­tion 2 “Clas­sification and Di­ag­no­sis of Di­a­betes.” For ad­di­tional sup­port for these rec­om­men­da­tions, see the ADA po­si­tion state­ment “Eval­u­a­tion and Man­age­ment of Youth-‍Onset Type 2 Di­a­betes” (2).

Type 2 di­a­betes in youth has in­creased over the past 20 years, and re­cent es­ti­mates sug­gest an in­ci­dence of ;5,000 new cases per year in the U.S. (119). The Cen­ters for Dis­ease Con­trol and Pre­ven­tion pub­lished pro­jec­tions for type 2 di­a­betes preva­lence using the SEARCH database; as­sum­ing a 2.3% an­nu­al in­crease, the preva­lence in those under 20 years of age will quadru­ple in 40 years (120,121).

Ev­i­dence sug­gests that type 2 di­a­betes in youth is dif­fer­ent not only from type 1 di­a­betes but also from type 2 di­a­betes in adults and has unique fea­tures, such as a more rapid­ly pro­gres­sive de­cline in β-cell func­tion and ac­cel­er­at­ed de­vel­op­ment of di­a­betes com­pli­ca­tions (2,122). Type 2 di­a­betes dis­pro­por­tion­ate­ly im­pacts youth of eth­nic and racial mi­nori­ties and can occur in com­plex psy­choso­cial and cul­tur­al en­vi­ron­ments, which may make it difficult to sus­tain healthy lifestyle changes and self-‍man­age­ment be­hav­iors (22,123–126). Ad­di­tion­al risk fac­tors as­so­ci­at­ed with type 2 di­a­betes in youth in­clude adi­pos­i­ty, fam­i­ly his­to­ry of di­a­betes, fe­male sex, and low so­cioe­co­nom­ic sta­tus (122).

As with type 1 di­a­betes, youth with type 2 di­a­betes spend much of the day in school. There­fore, close com­mu­ni­ca­tion with and the co­op­er­a­tion of school per­son­nel are es­sen­tial for op­ti­mal di­a­betes man­age­ment, safe­ty, and max­i­mal aca­dem­ic op­por­tu­ni­ties.

xxxxx

2.2.0.0 Screen­ing and Di­ag­no­sis

In the last decade, the in­ci­dence and preva­lence of type 2 di­a­betes in ado­les­cents has in­creased dra­mat­i­cal­ly, es­pe­cial­ly in racial and eth­nic mi­nor­i­ty pop­u­la­tions (98,127). A few re­cent stud­ies sug­gest oral glu­cose tol­er­ance tests or fast­ing plas­ma glu­cose val­ues as more suit­able di­ag­nos­tic tests than A1C in the pe­di­atric pop­u­la­tion, es­pe­cial­ly among cer­tain eth­nicities (128), al­though fast­ing glu­cose alone may over­diag­nose di­a­betes in chil­dren (129,130). In ad­di­tion, many of these stud­ies do not rec­og­nize that di­a­betes di­ag­nos­tic cri­te­ria are based on long-‍term health out­comes, and val­i­da­tions are not cur­rently avail­able in the pe­di­atric pop­u­la­tion (131). ADA acknowl­edges the lim­it­ed data sup­porting A1C for di­ag­nos­ing type 2 di­a­betes in chil­dren and ado­les­cents. Al­though A1C is not rec­om­mend­ed for di­ag­no­sis of di­a­betes in chil­dren with cys­tic fibro­sis or symp­toms sug­gestive of acute onset of type 1 di­a­betes, and only A1C as­says with­out in­ter­ference are ap­pro­pri­ate for chil­dren with hemoglobinopathies, ADA con­tin­ues to rec­om­mend A1C for di­ag­no­sis of type 2 di­a­betes in this pop­u­la­tion (132,133).

xxxxx

2.3.0.0 Di­ag­nos­tic Chal­lenges

Given the cur­rent obe­si­ty epi­dem­ic, dis­tin­guish­ing be­tween type 1 and type 2 di­a­betes in chil­dren can be difficult. Over­weight and obe­si­ty are com­mon in chil­dren with type 1 di­a­betes (23), and di­a­betes-‍as­so­ci­at­ed au­toan­ti­bod­ies and ke­to­sis may be pre­sent in pe­di­atric pa­tients with fea­tures of type 2 di­a­betes (in­clud­ing obe­si­ty and acan­tho­sis ni­gri­cans) (129). The pres­ence of islet auto-‍an­ti­bod­ies has been as­so­ci­at­ed with faster pro­gres­sion to in­sulin deficien­cy (129). At onset, DKA oc­curs in ˜6% of youth aged 10–19 years with type 2 di­a­betes (134). Al­though un­com­mon, type 2 di­a­betes has been ob­served in pre­pu­ber­tal chil­dren under the age of 10, and thus it should be part of the dif­fer­ential in chil­dren with sug­gestive symp­toms (135). Fi­nal­ly, obe­si­ty (136) and type 2 di­a­betes–as­so­ci­at­ed ge­net­ic fac­tors may (137) con­tribute to the de­vel­op­ment of type 1 di­a­betes in some in­di­vid­u­als, which fur­ther blurs the lines be­tween di­a­betes types. How­ev­er, ac­cu­rate di­ag­no­sis is crit­i­cal, as treat­ment reg­i­mens, ed­u­ca­tional ap­proaches, di­etary ad­vice, and out­comes dif­fer marked­ly be­tween pa­tients with the two di­ag­noses.

xxxxx

2.4.0.0 Man­age­ment

2.4.1.0 Rec­om­men­da­tions

xxxxx

2.4.2 Overview

Treat­ment of youth-‍onset type 2 di­a­betes should in­clude lifestyle man­age­ment, di­a­betes self-‍man­age­ment ed­u­ca­tion, and phar­ma­co­log­ic treat­ment. Ini­tial treat­ment of youth with obe­si­ty and di­a­betes must take into ac­count that di­a­betes type is often uncer­tain in the first few weeks of treat­ment, due to over­lap in pre­sentation, and that a sub­stan­tial per­cent­age of youth with type 2 di­a­betes will pre­sent with clin­i­cally significant ke­toaci­do­sis (138). There­fore, ini­tial ther­a­py should ad­dress the hy­per­glycemia and as­so­ci­at­ed metabol­ic de­range­ments irre­spective of ul­ti­mate di­a­betes type, with ad­just­ment of ther­a­py once metabol­ic com­pen­sa­tion has been es­tab­lished and sub­se­quent infor­mation, such as islet autoan­ti­body re­sults, be­comes avail­able. Fig­ure 13.1 pro­vides an ap­proach to ini­tial treat­ment of new-‍onset di­a­betes in over­weight youth.

Glycemic tar­gets should be in­di­vid­u­al­ized, tak­ing into con­sid­eration long-‍term health benefits of more strin­gent tar­gets as well as risk for ad­verse ef­fects, such as hy­po­glycemia. A lower tar­get A1C in youth with type 2 di­a­betes when com­pared with those rec­om­mend­ed in type 1 di­a­betes is justified by lower risk of hy­po­glycemia and high­er risk of com­pli­ca­tions (139-142).

Pa­tients and their fam­i­lies must pri­or­i­tize lifestyle modifications such as eat­ing a bal­anced diet, achiev­ing and main­taining a healthy weight, and ex­er­cising reg­u­lar­ly. A fam­i­ly-cen­tered ap­proach to nu­tri­tion and lifestyle modi- fication is es­sen­tial in chil­dren with type 2 di­a­betes, and nu­ti­tion rec­om­men­da­tions should be cul­tur­al­ly ap­pro­pri­ate and sen­si­tive to fam­i­ly re­sources (see Sec­tion “Lifestyle Man­age­ment”). Given the com­plex so­cial and en­vi­ron­men­tal con­text sur­round­ing youth with type 2 di­a­betes, in­di­vid­u­al-‍level lifestyle in­ter­ven­tions may not be sufficient to tar­get the com­plex in­ter­play of fam­i­ly dy­nam­ics, men­tal health, com­mu­ni­ty readi­ness, and the broad­er en­vi­ron­men­tal sys­tem (2).

A mul­ti­dis­ci­plinary di­a­betes team, in­clud­ing a physi­cian, di­a­betes nurse ed­u­ca­tor, reg­is­tered di­eti­tian, and psy­chol­o­gist or so­cial work­er, is es­sen­tial. In ad­di­tion to blood glu­cose con­trol and self-‍man­age­ment ed­u­ca­tion (143-145), ini­tial treat­ment must in­clude man­age­ment of co­mor­bidities such as obe­si­ty, dys­lipi­demia, hy­per­ten­sion, and mi­crovas­cu­lar com­pli­ca­tions.

Cur­rent phar­ma­co­log­ic treat­ment op­tions for youth-‍onset type 2 di­a­betes are lim­it­ed to two ap­proved drugsdin­sulin and met­formin (2). Pre­sen­ta­tion with ke­toaci­do­sis or marked ke­to­sis re­quires a pe­ri­od of in­sulin ther­a­py until fast­ing and postpran­di­al glycemia have been re­stored to nor­mal or near-‍nor­mal lev­els. Met­formin ther­a­py may be used as an ad­junct after res­o­lu­tion of ke­to­sis/ ke­toaci­do­sis. Ini­tial treat­ment should also be with in­sulin when the dis­tinc­tion be­tween type 1 di­a­betes and type 2 di­a­betes is un­clear and in pa­tients who have ran­dom blood glu­cose con­cen­tra­tions ≥250 mg/dL (13.9 mmol/‍L) and/‍or A1C ≥8.5% (69 mmol/‍mol) (146). In­sulin is need­ed when the glycemic tar­get is not met on met­formin alone, or if there is met­formin intol­er­ance or renal or hep­at­ic insufficien­cy (147).

When in­sulin treat­ment is not re­quired, ini­ti­a­tion of met­formin is rec­om­mend­ed. The Treat­ment Op­tions for Type 2 Di­a­betes in Ado­les­cents and Youth (TODAY) study found that met­formin alone pro­vided durable glycemic con­trol (A1C ≤8% [64 mmol/‍mol] for 6 months) in ap­prox­i­mate­ly half of the sub­jects (148). To date, the TODAY study is the only trial com­bin­ing lifestyle and met­formin ther­a­py in youth with type 2 di­a­betes; the com­bi­na­tion did not per­form bet­ter than met­formin alone in achiev­ing durable glycemic con­trol (148).

xxxxx

2.4.3.0 Metabol­ic Surgery

The re­sults of weight-‍loss and lifestyle in­ter­ven­tions for obe­si­ty in chil­dren and ado­les­cents have been dis­ap­point­ing, and no ef­fec­tive and safe phar­ma­co­log­ic in­ter­ven­tion is avail­able or ap­proved by the U.S. Food and Drug Ad­min­is­tra­tion in youth. Over the last decade, weight-‍loss surgery has been in­creas­ingly per­formed in ado­les­cents with obe­si­ty. Small ret­ro­spec­tive anal­y­ses and a re­cent prospec­tive mul­ti­cen­ter nonran­dom­ized study sug­gest that bariatric or metabol­ic surgery may have benefits in obese ado­les­cents with type 2 di­a­betes sim­i­lar to those ob­served in adults. Teenagers ex­pe­ri­ence sim­i­lar de­grees of weight loss, di­a­betes re­mis­sion, and im­provement of cardiometabol­ic risk fac­tors for at least 3 years after surgery (149). No ran­dom­ized tri­als, how­ev­er, have yet com­pared the ef­fec­tiveness and safe­ty of surgery to those of con­ven­tion­al treat­ment op­tions in ado­les­cents (150). The guide­lines used as an in­di­ca­tion for metabol­ic surgery in ado­les­cents gen­er­ally in­clude BMI >35 kg/m2 with co­mor­bidities or BMI >40 kg/m2 with or with­out co­mor­bidities (151-162). A num­ber of groups, in­clud­ing the Pe­di­atric Bariatric Study Group and the Teen Lon­gi­tu­di­nal As­sessment of Bariatric Surgery (Teen-‍LABS) Study have demon­strat­ed the ef­fec­tiveness of metabol­ic surgery in ado­les­cents (155-161).

xxxxx

2.5.0.0 Pre­ven­tion and Man­age­ment of Di­a­betes Com­pli­ca­tions

Co­mor­bidi­ties may al­ready be pre­sent at the time of di­ag­no­sis of type 2 di­a­betes in youth (122,163). There­fore, blood pres­sure mea­sure­ment, a fast­ing lipid panel, as­sessment of ran­dom urine al­bu­min-‍to-‍cre­a­ti­nine ratio, and a di­lat­ed eye ex­am­i­na­tion should be per­formed at di­ag­no­sis. There­after, screen­ing guide­lines and treat­ment rec­om­men­da­tions for hy­per­ten­sion, dys­lipi­demia, urine al­bu­min ex­cre­tion, and retinopa­thy are sim­i­lar to those for youth with type 1 di­a­betes. Ad­di­tion­al prob­lems that may need to be ad­dressed in­clude polycys­tic ovary dis­ease and other co­mor­bidities as­so­ci­at­ed with pe­di­atric obe­si­ty, such as sleep apnea, hep­at­ic steato­sis, or­tho­pe­dic com­pli­ca­tions, and psy­choso­cial con­cerns. The ADA po­si­tion state­ment “Eval­u­a­tion and Man­age­ment of Youth-‍Onset Type 2 Di­a­betes” (2) pro­vides guid­ance on the pre­ven­tion, screen­ing, and treat­ment of type 2 di­a­betes and its co­mor­bidities in chil­dren and ado­les­cents.

Youth-‍onset type 2 di­a­betes is as­so­ci­at­ed with significant mi­crovas­cu­lar and macrovas­cu­lar risk bur­den and a sub­stan­tial in­crease in the risk of car­dio­vas­cu­lar mor­bid­i­ty and mor­tal­i­ty at an ear­li­er age than those di­ag­nosed later in life (164). The high­er com­pli­ca­tion risk in ear­li­er-‍onset type 2 di­a­betes is like­ly re­lat­ed to pro­longed life­time ex­po­sure to hy­per­glycemia and other athero­genic risk fac­tors, in­clud­ing in­sulin re­sis­tance, dys­lipi­demia, hy­per­ten­sion, and chron­ic inflam­ma­tion. There is low risk of hy­po­glycemia in youth with type 2 di­a­betes, even if they are being treat­ed with in­sulin (165), and there are high rates of com­pli­ca­tions (139-142). These di­a­betes co­mor­bidities also ap­pear to be high­er than in youth with type 1 di­a­betes de­spite short­er di­a­betes du­ra­tion and lower A1C (163). In ad­di­tion, the pro­gres­sion of vas­cu­lar abnor­malities ap­pears to be more pro­nounced in youth-‍onset type 2 di­a­betes com­pared with type 1 di­a­betes of sim­i­lar du­ra­tion, in­clud­ing is­chemic heart dis­ease and stroke (166).

xxxxx

2.6.0.0 Psychoso­cial Fac­tors

Most youth with type 2 di­a­betes come from racial/‍eth­nic mi­nor­i­ty groups, have low so­cioe­co­nom­ic sta­tus, and often ex­pe­ri­ence mul­ti­ple psy­choso­cial stres­sors (22,35,123–126). Con­sid­eration of the sociocul­tur­al con­text and ef­forts to per­son­al­ize di­a­betes man­age­ment are of crit­i­cal im­por­tance to min­i­mize bar­ri­ers to care, en­hance ad­her­ence, and max­i­mize re­sponse to treat­ment.

Ev­i­dence about psy­chi­atric dis­or­ders and symp­toms in youth with type 2 di­a­betes is lim­it­ed (167-171), but given the sociocul­tur­al con­text for many youth and the med­i­cal bur­den and obe­si­ty as­so­ci­at­ed with type 2 di­a­betes, on­go­ing surveil­lance of men­tal health/be­hav­ioral health is in­di­cated. Symp­toms of de­pres­sion and dis­or­dered eat­ing are com­mon and as­so­ci­at­ed with poor­er glycemic con­trol (168,172,173).

Many of the drugs pre­scribed for di­a­betes and psy­chi­atric dis­or­ders are as­so­ci­at­ed with weight gain and can in­crease pa­tients’ con­cerns about eat­ing, body shape, and weight (174,175). The TODAY study doc­u­ment­ed (176) that de­spite dis­ease-‍ and age-‍specific coun­sel­ing, 10.2% of the fe­males in the co­hort be­came preg­nant over an av­er­age of 3.8 years of study par­tic­i­pa­tion. Of note, 26.4% of preg­nan­cies ended in a mis­car­riage, still­birth, or in­trauter­ine death, and 20.5% of the live-‍born in­fants had a major con­gen­i­tal anomaly.

xxxxx

3.0.0.0 TRAN­SI­TION FROM PE­DI­ATRIC TO ADULT CARE

Care and close su­per­vi­sion of di­a­betes man­age­ment are in­creas­ingly shift­ed from par­ents and other adults to the youth with type 1 or type 2 di­a­betes through­out child­hood and ado­les­cence. The shift from pe­di­atric to adult health care pro­viders, how­ev­er, often oc­curs abrupt­ly as the older teen en­ters the next de­vel­op­men­tal stage, re­ferred to as emerg­ing adult­hood (177), which is a crit­i­cal pe­ri­od for young peo­ple who have di­a­betes. Dur­ing this pe­ri­od of major life tran­si­tions, youth begin to move out of their par­ents’ homes and must be­come fully re­spon­si­ble for their di­a­betes care. Their new re­spon­si­bil­i­ties in­clude self-‍man­age­ment of their di­a­betes, mak­ing med­i­cal ap­point­ments, and financ­ing health care, once they are no longer cov­ered by their par­ents’ health in­sur­ance plans (on­go­ing cov­er­age until age 26 years is cur­rently avail­able under pro­vi­sions of the U.S. Af­ford­able Care Act). In ad­di­tion to laps­es in health care, this is also a pe­ri­od as­so­ci­at­ed with de­te­ri­o­ra­tion in glycemic con­trol; in­creased oc­cur­rence of acute com­pli­ca­tions; psy­choso­cial, emo­tion­al, and be­hav­ioral chal­lenges; and the emer­gence of chron­ic com­pli­ca­tions (178-181). The tran­si­tion pe­ri­od from pe­di­atric to adult care is prone to frag­men­ta­tion in health care de­liv­ery, which may ad­versely im­pact health care qual­i­ty, cost, and out­comes (182).

Al­though sci­en­tific ev­i­dence is lim­it­ed, it is clear that com­pre­hen­sive and co­or­di­nat­ed plan­ning that be­gins in early ado­les­cence is nec­es­sary to fa­cil­i­tate a seam­less tran­si­tion from pe­di­atric to adult health care (178,179,183,184). A com­pre­hen­sive dis­cus­sion re­gard­ing the chal­lenges faced dur­ing this pe­ri­od, in­clud­ing specific rec­om­men­da­tions, is found in the ADA po­si­tion state­ment “Di­a­betes Care for Emerg­ing Adults: Rec­om­men­da­tions for Tran­si­tion From Pe­di­atric to Adult Di­a­betes Care Sys­tems” (179).

The En­docrine So­ci­ety in col­lab­o­ra­tion with the ADA and other or­ga­ni­za­tions has de­vel­oped tran­si­tion tools for clin­icians and youth and fam­i­lies (184).

xxxxx

4.0.0.0 Ref­er­ences

1. Chi­ang JL, Maahs DM, Gar­vey KC, et al. Type 1 di­a­betes in chil­dren and ado­les­cents: a po­si­tion state­mentby the Amer­i­can Di­a­betes As­so­ci­a­tion. Di­a­betes Care 2018;41:2026–2044
2. Ar­sla­ni­an S, Bacha F, Grey M, Mar­cus MD,

   White NH, Zeitler P. Eval­u­a­tion and man­age­ment of youth-‍onset type 2 di­a­betes: a po­si­tion

   state­mentby the Amer­i­can Di­a­betes As­so­ci­a­tion. Di­a­betes Care 2018;41:2648–2668

3. Nadeau KJ, An­der­son BJ, Berg EG, et al. Youth-‍onset type 2 di­a­betes con­sen­sus re­port: cur­rent sta­tus, chal­lenges, and pri­or­i­ties. Di­a­betes Care 2016;39:1635–1642
4. Mayer-‍Davis EJ, Lawrence JM, Dabe­lea D, et al.; SEARCH for Di­a­betes in Youth Study. In­ci­dence trends of type 1 and type 2 di­a­betes among youths, 2002–2012. N Engl J Med 2017; 376:1419–1429
5. Thomas NJ, Jones SE, Wee­don MN, Shields BM, Oram RA, Hat­ter­s­ley AT. Fre­quen­cy and phe­no­type of type 1 di­a­betes in the first six decades of life: a cross-sec­tional, ge­net­ically stratified sur­vival anal­y­sis from UK Biobank. Lancet Di­a­betes En­docrinol 2018;6:122–129
6. Barnea-‍Goraly N, Raman M, Mazai­ka P, et al.; Di­a­betes Re­search in Chil­dren Net­work (Direc-‍ Net). Al­ter­ations in white mat­ter struc­ture in young chil­dren with type 1 di­a­betes. Di­a­betes Care 2014;37:332–340
7. Cameron FJ, Scratch SE, Nade­baum C, et al.; DKA Brain In­jury Study Group. Neu­ro­log­i­cal con­se­quences of di­a­bet­ic ke­toaci­do­sis at ini­tial pre­sentation of type 1 di­a­betes in a prospec­tive co­hort study of chil­dren. Di­a­betes Care 2014;37: 1554–1562
8. Markowitz JT, Gar­vey KC, Laf­fel LMB. Developmen­tal changes in the roles of pa­tients and fam­i­lies in type 1 di­a­betes man­age­ment. Curr Di­a­betes Rev 2015;11:231–238
9. Driscoll KA, Volken­ing LK, Haro H, et al. Are chil­dren with type 1 di­a­betes safe at school? Ex­am­in­ing par­ent per­cep­tions. Pe­di­atr Di­a­betes 2015;16:613–620
10. Mehta SN, Volken­ing LK, An­der­son BJ, et al.; Fam­i­ly Man­age­ment of Child­hood Di­a­betes Study Steer­ing Com­mit­tee. Di­etary be­hav­iors pre­dict glycemic con­trol in youth with type 1 di­a­betes. Di­a­betes Care 2008;31:1318–1320
11. Rid­dell MC, Gallen IW, Smart CE, et al. Ex­er­cise man­age­ment in type 1 di­a­betes: a con­sen­sus state­ment. Lancet Di­a­betes En­docrinol 2017;5:377–390
12. Col­berg SR, Sigal RJ, Yard­ley JE, et al. Phys­i­cal ac­tiv­i­ty/ex­er­cise and di­a­betes: a po­si­tion state­ment of the Amer­i­can Di­a­betes As­so­ci­a­tion. Di­a­betes Care 2016;39:2065–2079
13. Robert­son K, Adolf­s­son P, Schein­er G, Hanas R, Rid­dell MC. Ex­er­cise in chil­dren and ado­les­cents with di­a­betes. Pe­di­atr Di­a­betes 2009;10 (Suppl. 12):154–168
14. U.S. De­part­ment of Health and Human Ser­vices. 2008 phys­i­cal ac­tiv­i­ty guide­lines for Amer­i­cans: index [In­ter­net]. Avail­able from https:// health.gov/paguide­lines/guide­lines/default. aspx. Ac­cessed 16 Oc­to­ber 2018
15. Tsa­likian E, Koll­man C, Tam­bor­lane WB, et al.; Di­a­betes Re­search in Chil­dren Net­work (Di­rec­Net) Study Group. Pre­ven­tion of hy­po­glycemia dur­ing ex­er­cise in chil­dren with type 1 di­a­betes by sus­pending basal in­sulin. Di­a­betes Care 2006;29:2200–2204
16. Ta­plin CE, Cobry E, Mess­er L, Mc­Fann K, Chase HP, Fiallo-‍Scharer R. Pre­vent­ing post-‍ex­er­cise noc­tur­nal hy­po­glycemia in chil­dren with type 1 di­a­betes. J Pe­di­atr 2010;157: 784–788.e1
17. Rid­dell MC, 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 2011; 13:819–825

18. Francesca­to MP, Stel G, Sten­ner E, Geat M. Pro­longed ex­er­cise in type 1 di­a­betes: per­for­mance of a cus­tomiz­able al­go­rithm to es­ti­mate the car­bo­hy­drate sup­ple­ments to min­i­mize glycemic imbal­ances. PLoS One 2015;10:e0125220
19. 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 2015;115:2599–2607
20. Baker LB, Rollo I, Stein KW, Jeuk­endrup AE. Acute ef­fects of car­bo­hy­drate sup­ple­men­ta­tion on in­ter­mit­tent sports per­for­mance. Nu­tri­ents 2015;7:5733–5763
21. Re­don­do MJ, Lib­man I, Cheng P, et al.; Pe­di­atric Di­a­betes Con­sor­tium. Racial/eth­nic mi­nor­i­ty youth with re­cent-‍onset type 1 di­a­betes have poor prog­nos­tic fac­tors. Di­a­betes Care 2018;41:1017–1024
22. Liu LL, Lawrence JM, Davis C, et al.; SEARCH for Di­a­betes in Youth Study Group. Preva­lence of over­weight and obe­si­ty in youth with di­a­betes in USA: the SEARCH for Di­a­betes in Youth study. Pe­di­atr Di­a­betes 2010;11:4–11
23. Du­Bose SN, Her­mann JM, Tam­bor­lane WV, et al.; Type 1 Di­a­betes Ex­change Clin­ic Net­work and Di­a­betes Prospec­tive Fol­low-‍up Reg­istry. Obe­si­ty in youth with type 1 di­a­betes in Ger­many, Aus­tria, and the Unit­ed States. J Pe­di­atr 2015;167:627–632.e4
24. Corbin KD, Driscoll KA, Prat­ley RE, Smith SR, Maahs DM, Mayer-‍Davis EJ; Ad­van­cing Care for Type 1 Di­a­betes and Obe­si­ty Net­work (ACT1ON). Obe­si­ty in type 1 di­a­betes: patho­phys­i­ol­o­gy, clin­i­cal im­pact, and mech­a­nisms. En­docr Rev 2018;39:629–663
25. Re­don­do MJ, Fos­ter NC, Lib­man IM, et al. Preva­lence of car­dio­vas­cu­lar risk fac­tors in youth with type 1 di­a­betes and el­e­vat­ed body mass index. Acta Di­a­betol 2016;53:271–277
26. Jack­son CC, Al­banese-‍O’Neill A, But­ler KL, et al. Di­a­betes care in the school set­ting: a po­si­tion state­ment of the Amer­i­can Di­a­betes As­so­ci­a­tion. Di­a­betes Care 2015;38:1958–1963
27. Simine­r­io LM, Al­banese-‍O’Neill A, Chi­ang JL, et al.; Amer­i­can Di­a­betes As­so­ci­a­tion. Care of young chil­dren with di­a­betes in the child care set­ting: a po­si­tion state­ment of the Amer­i­can Di­a­betes As­so­ci­a­tion. Di­a­betes Care 2014;37:2834–2842
28. Corathers SD, Kich­ler J, Jones N-HY, et al. Im­prov­ing de­pres­sion screen­ing for ado­les­cents with type 1 di­a­betes. Pe­di­atrics. 2013;132: e1395–e1402
29. 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
30. Ducat L, Philip­son LH, An­der­son BJ. The men­tal health co­mor­bidities of di­a­betes. JAMA 2014;312:691–692
31. Hag­ger V, Hen­drieckx C, Sturt J, Skin­ner TC, Speight J. Di­a­betes dis­tress among ado­les­cents with type 1 di­a­betes: a sys­tematic re­view. Curr Diab Rep 2016;16:9
32. An­der­son BJ, Laf­fel LM, Domenger C, et al. Fac­tors as­so­ci­at­ed with di­a­betes-‍specific health-‍re­lat­ed qual­i­ty of life in youth with type 1 di­a­betes: the glob­al TEENs study

    [pub­lished cor­rection ap­pears in Di­a­betes Care 2018;41:640]. Di­a­betes Care 2017;40:

    1002–1009

33. Hilliard ME, De Wit M, Wasser­man RM, et al. Screen­ing and sup­port for emo­tion­al bur­dens of youth with type 1 di­a­betes: strate­gies for di­a­betes care pro­viders. Pe­di­atr Di­a­betes 2018; 19:534–543
34. Shapiro JB, Vesco AT, Weil LEG, Evans MA, Hood KK, Weissberg-‍Benchell J. Psy­cho­me­t­ric prop­er­ties of the Prob­lem Areas in Di­a­betes: Teen and Par­ent of Teen ver­sions. J Pe­di­atr Psy­chol 2018;43:561–571
35. Young-‍Hyman D, de Groot M, Hill-‍Brig­gs F, Gon­za­lez JS, Hood K, Pey­rot M. Psychoso­cial care for peo­ple with di­a­betes: a po­si­tion state­ment of the Amer­i­can Di­a­betes As­so­ci­a­tion. Di­a­betes Care 2016;39:2126–2140
36. Katz ML, Volken­ing LK, But­ler DA, An­der­son BJ, Laf­fel LM. Fam­i­ly-‍based psychoed­u­ca­tion and Care Am­bas­sador in­ter­ven­tion to im­prove glycemic con­trol in youth with type 1 di­a­betes: a ran­dom­ized trial. Pe­di­atr Di­a­betes 2014;15:142–150
37. Laf­fel LMB, Vangsness L, Con­nell A, Goebel-‍ Fab­bri A, But­ler D, An­der­son BJ. Im­pact of am­bu­la­to­ry, fam­i­ly-focused team­work in­ter­ven­tion on glycemic con­trol in youth with type 1 di­a­betes. J Pe­di­atr 2003;142:409–416
38. An­der­son BJ, Vangsness L, Con­nell A, But­ler D, Goebel-‍Fab­bri A, Laf­fel LMB. Fam­i­ly conflict, ad­her­ence, and gly­caemic con­trol in youth with short du­ra­tion type 1 di­a­betes. Di­a­bet Med 2002; 19:635–642
39. Helge­son VS, Pal­ladi­no DK. Im­pli­ca­tions of psy­choso­cial fac­tors for di­a­betes out­comes among chil­dren with type 1 di­a­betes: a re­view. Soc Per­son­al Psy­chol Com­pass 2012;6:228–242
40. Mc­Carthy AM, Lind­gren S, Men­geling MA, Tsa­likian E, En­g­vall J. Fac­tors as­so­ci­at­ed with aca­dem­ic achieve­ment in chil­dren with type 1 di­a­betes. Di­a­betes Care 2003;26:112–117
41. Kuther TL. Med­i­cal de­ci­sion-‍mak­ing and mi­nors: is­sues of con­sent and as­sent. Ado­lescence 2003;38:343–358
42. Cole­man DL, Rosoff PM. The legal au­thor­i­ty of ma­ture mi­nors to con­sent to gen­er­al med­i­cal treat­ment. Pe­di­atrics 2013;131:786–793
43. Charron-‍Prochownik D, Serei­ka SM, Beck­er D, et al. Long-‍term ef­fects of the booster-en­hanced READY-‍Girls pre­con­cep­tion coun­sel­ing pro­gram on in­ten­tions and be­hav­iors for fam­i­ly plan­ning in teens with di­a­betes. Di­a­betes Care 2013;36:3870–3874
44. Charron-‍Prochownik D, Downs J. Di­a­betes and Re­pro­duc­tive Health for Girls. Alexan­dria, VA, Amer­i­can Di­a­betes As­so­ci­a­tion, 2016
45. Markowitz JT, But­ler DA, Volken­ing LK, An­ti­s­del JE, An­der­son BJ, Laf­fel LMB. Brief screen­ing tool for dis­or­dered eat­ing in di­a­betes: in­ter­nal con­sistency and ex­ter­nal va­lid­i­ty in a con­tem­po­rary sam­ple of pe­di­atric pa­tients with type 1 di­a­betes. Di­a­betes Care 2010;33:495–500
46. Goebel-‍Fab­bri AE. Dis­turbed eat­ing be­hav­iors and eat­ing dis­or­ders in type 1 di­a­betes: clin­i­cal significance and treat­ment rec­om­men­da­tions. Curr Diab Rep 2009;9:133–139
47. Atik Altınok Y, O¨ zgu¨r S, Meseri R, O¨ zen S,

    Dar­can S¸, Go¨ks¸en D. Reliabil­i­ty and va­lid­i­ty of the di­a­beteseat­ing prob­lemsurvey in Turk­ish chil­dren and ado­les­cents with type 1 di­a­betes mel­li­tus. J Clin Res Pe­di­atr En­docrinol 2017;9:323–328

48. Saßmann H, Al­brecht C, Busse-‍Widmann P, et al. Psy­cho­me­t­ric prop­er­ties of the Ger­man ver­sion of the Di­a­betes Eat­ing Prob­lem Sur­vey-‍ Re­vised: ad­di­tional benefit of dis­ease-‍specific screen­ing in ado­les­cents with type 1 di­a­betes. Di­a­bet Med 2015;32:1641–1647
49. Lawrence JM, Yi-‍Fra­zier JP, Black MH, et al.; SEARCH for Di­a­betes in Youth Study Group. De­mo­graph­ic and clin­i­cal cor­re­lates of di­a­betes-‍re­lat­ed qual­i­ty of life among youth with type 1 di­a­betes. J Pe­di­atr 2012;161:201–207.e2
50. Wist­ing L, Frøis­land DH, Skri­varhaug T, Dahl- Jørgensen K, Rø O. Dis­turbed eat­ing be­hav­ior and omis­sion of in­sulin in ado­les­cents re­ceiv­ing in­ten­sified in­sulin treat­ment: a na­tion­wide pop­u­la­tion-‍based study. Di­a­betes Care 2013;36: 3382–3387
51. Maahs DM, Her­mann JM, Du­Bose SN, et al.; DPV Ini­tia­tive; T1D Ex­change Clin­ic Net­work. Con­trast­ing the clin­i­cal care and out­comes of 2,622 chil­dren with type 1 di­a­betes less than 6 years of age in the Unit­ed States T1D Ex­change and Ger­man/Aus­trian DPV reg­istries. Di­a­betologia 2014;57:1578–1585
52. Haynes A, Her­mann JM, Miller KM, et al.; T1D Ex­change, WACDD and DPV reg­istries. Se­vere hy­po­glycemia rates are not as­so­ci­at­ed with HbA1c: a cross-sec­tional anal­y­sis of 3 con­tem­po­rary pe­di­atric di­a­betes reg­istry databas­es. Pe­di­atr Di­a­betes 2017;18:643–650
53. Ryan CM. Why is cog­ni­tive dysfunc­tion as­so­ci­at­ed with the de­vel­op­ment of di­a­betes early in life? The diathe­sis hy­poth­e­sis. Pe­di­atr Di­a­betes 2006;7:289–297
54. Cameron FJ. The im­pact of di­a­betes on brain func­tion in child­hood and ado­les­cence. Pe­di­atr Clin North Am 2015;62:911–927
55. Camp­bell MS, Schatz DA, Chen V, et al.; T1D Ex­change Clin­ic Net­work. A con­trast be­tween chil­dren and ado­les­cents with ex­cel­lent and poor con­trol: the T1D Ex­change clin­ic reg­istry ex­pe­ri­ence. Pe­di­atr Di­a­betes 2014;15:110–117
56. Coop­er MN, O’Con­nell SM, Davis EA, Jones TW. A pop­u­la­tion-‍based study of risk fac­tors for se­vere hy­po­gly­caemia in a con­tem­po­rary co­hort of child­hood-‍onset type 1 di­a­betes. Di­a­betologia 2013;56:2164–2170
57. Bergen­stal RM, Klonoff DC, Garg SK, et al.; AS­PIRE In-‍Home Study Group. Thresh­old-‍based in­sulin-‍pump in­ter­rup­tion for re­duc­tion of hy­po­glycemia. N Engl J Med 2013;369:224–232
58. Abra­ham MB, Davey R, O’Grady MJ, et al. Ef­fec­tive­ness of a pre­dic­tive al­go­rithm in the pre­ven­tion of ex­er­cise-induced hy­po­glycemia in type 1 di­a­betes. Di­a­betes Tech­nol Ther 2016;18: 543–550
59. Buck­ing­ham BA, Bai­ley TS, Chris­tiansen M, et al. Eval­u­a­tion of a pre­dic­tive low-‍glu­cose man­age­ment sys­tem in-‍clin­ic. Di­a­betes Tech­nol Ther 2017;19:288–292
60. Nimri R, Muller I, Atlas E, et al. MD-‍Logic overnight con­trol for 6 weeks of home use in pa­tients with type 1 di­a­betes: ran­dom­ized crossover trial. Di­a­betes Care 2014;37:3025–3032
61. Thabit H, Tauschmann M, Allen JM, et al. Home use of an artificial beta cell in type 1 di­a­betes. N Engl J Med 2015;373:2129–2140
62. Bergen­stal RM, Garg S, Weinz­imer SA, et al. Safe­ty of a hy­brid closed-‍loop in­sulin de­liv­ery sys­tem in pa­tients with type 1 di­a­betes. JAMA 2016;316:1407–1408

63. Ko­vatchev B, Cheng P, An­der­son SM, et al. Fea­si­bil­i­ty of long-‍term closed-‍loop con­trol: a mul­ti­cen­ter 6-‍month trial of 24/7 au­to­mat­ed in­sulin de­liv­ery. Di­a­betes Tech­nol Ther 2017;19:18–24
64. El-‍Khatib FH, Bal­liro C, Hillard MA, et al. Home useof a bi­hor­mon­al­bion­ic pan­creas ver­sus in­sulin pump ther­a­py in adults with type 1 di­a­betes: a mul­ti­cen­tre ran­domised crossover trial. Lancet 2017;389:369–380
65. Levine BS, An­der­son BJ, But­ler DA, An­ti­s­del JE, Brack­ett J, Laf­fel LM. Pre­dic­tors of glycemic con­trol and short-‍term ad­verse out­comes in youth with type 1 di­a­betes. J Pe­di­atr 2001; 139:197–203
66. Miller KM, Beck RW, Bergen­stal RM, et al.; T1D Ex­change Clin­ic Net­work. Ev­i­dence of a strong as­so­ci­a­tion be­tween fre­quen­cy of self-‍mon­i­tor­ing of blood glu­cose and hemoglobin A1c lev­els in T1D Ex­change clin­ic reg­istry par­tic­i­pants. Di­a­betes Care 2013;36:2009–2014
67. Rosen­bauer J, Dost A, Karges B, et al.; DPV Ini­tia­tive and the Ger­man BMBF Com­pe­tence Net­work Di­a­betes Mel­li­tus. Im­proved metabol­ic con­trol in chil­dren and ado­les­cents with type 1 di­a­betes: a trend anal­y­sis using prospec­tive mul­ti­cen­ter data from Ger­many and Aus­tria. Di­a­betes Care 2012;35:80–86
68. Cameron FJ, de Beau­fort C, Aanstoot HJ, et al.; Hvi­do­ere Interna­tion­al Study Group. Lessons from the Hvi­do­ere Interna­tion­al Study Group on child­hood di­a­betes: be dog­mat­ic about out­come and flex­i­ble in ap­proach. Pe­di­atr Di­a­betes 2013;14:473–480
69. Nimri R, Wein­trob N, Ben­za­quen H, Ofan R, Fay­man G, Phillip M. In­sulin pump ther­a­py in youth with type 1 di­a­betes: a ret­ro­spec­tive paired study. Pe­di­atrics 2006;117:2126–2131
70. Doyle EA, Weinz­imer SA, Stef­fen AT, Ahern JAH, Vin­cent M, Tam­bor­lane WVA. A ran­dom­ized, prospec­tive trial com­par­ing the efficacy of con­tin­u­ous sub­cu­ta­neous in­sulin in­fu­sion with mul­ti­ple daily in­jec­tions using in­sulin glargine. Di­a­betes Care 2004;27:1554–1558
71. Swift PGF, Skin­ner TC, de Beau­fort CE, et al.; Hvi­do­ere Study Group on Child­hood Di­a­betes. Tar­get set­ting in in­ten­sive in­sulin man­age­ment is as­so­ci­at­ed with metabol­ic con­trol: the Hvi­do­ere child­hood di­a­betes study group cen­tre dif­fer­ences study 2005. Pe­di­atr Di­a­betes 2010;11: 271–278
72. Hugh­es JW, Rid­dlesworth TD, DiMeglio LA, Miller KM, Rick­els MR, McGill JB. Au­toim­mune dis­eases in chil­dren and adults with type 1 di­a­betes from the T1D Ex­change Clin­ic Reg­istry. J Clin En­docrinol Metab 2016;101:4931–4937
73. Ka­haly GJ, Hansen MP. Type 1 di­a­betes as­so­ci­at­ed au­toim­mu­ni­ty. Au­toim­mun Rev 2016; 15:644–648
74. Rold´an MB, Alon­so M, Bar­rio R. Thy­roid au­toim­mu­ni­ty in chil­dren and ado­les­cents with type 1 di­a­betes mel­li­tus. Di­a­betes Nutr Metab 1999;12:27–31
75. Tri­o­lo TM, Arm­strong TK, Mc­Fann K, et al. Ad­di­tion­al au­toim­mune dis­ease found in 33% of pa­tients at type 1 di­a­betes onset. Di­a­betes Care 2011;34:1211–1213
76. Ko­r­donouri O, Deiss D, Danne T, Dorow A, Bassir C, Gr¨uters-‍Kieslich A. Pre­dic­tiv­i­ty of thy­roid au­toan­ti­bod­ies for the de­vel­op­ment of thy­roid dis­or­ders in chil­dren and ado­les­cents with type 1 di­a­betes. Di­a­bet Med 2002;19:518–521
77. Dost A, Rohrer TR, Fro¨hlich-‍Reiterer E, et al.; DPV Ini­tia­tive and the Ger­man Com­pe­tence Net­work Di­a­betes Mel­li­tus. Hyperthy­roidism in 276 chil­dren and ado­les­cents with type 1 di­a­betes from Ger­many and Aus­tria. Horm Res Pae­di­a­tr 2015;84:190–198
78. Jons­dot­tir B, Lars­son C, Carls­son A, et al.; Bet­ter Di­a­betes Di­ag­no­sis Study Group. Thy­roid and islet au­toan­ti­bod­ies pre­dict au­toim­mune thy­roid dis­ease at type 1 di­a­betes di­ag­no­sis. J Clin En­docrinol Metab 2017;102:1277–1285
79. Mohn A, Di Michele S, Di Luzio R, Tu­mi­ni S, Chiarel­li F. The ef­fect of subclin­i­cal hypothy­roidism on metabol­ic con­trol in chil­dren and ado­les­cents with type 1 di­a­betes mel­li­tus. Di­a­bet Med 2002;19:70–73
80. Holmes GKT. Screen­ing for coeli­ac dis­ease in type 1 di­a­betes. Arch Dis Child 2002;87:495– 498
81. Rew­ers M, Liu E, Sim­mons J, Re­don­do MJ, Hof­fen­berg EJ. Celi­ac dis­ease as­so­ci­at­ed with type 1 di­a­betes mel­li­tus. En­docrinol Metab Clin North Am 2004;33:197–214
82. Pham-‍Short A, Don­aghue KC, Am­bler G, Phe­lan H, Twigg S, Craig ME. Screen­ing for celi­ac dis­ease in type 1 di­a­betes: a sys­tematic re­view. Pe­di­atrics 2015;136:e170–e176
83. Craig ME, Prinz N, Boyle CT, et al.; Aus­tralasian Di­a­betes Data Net­work (ADDN); T1D Ex­change Clin­ic Net­work (T1DX); Na­tion­al Pae­di­a­tric Di­a­betes Audit (NPDA) and the Royal Col­lege of Pae­di­a­trics and Child Health; Prospec­tive Di­a­betes Fol­low-‍up Reg­istry (DPV) ini­tia­tive. Preva­lence of celi­ac dis­ease in 52,721 youth with type 1 di­a­betes: interna­tion­al com­par­i­son across three con­ti­nents. Di­a­betes Care 2017;40:1034–1040
84. Sim­mons JH, Fos­ter NC, Rid­dlesworth TD, et al.; T1D Ex­change Clin­ic Net­work. Sex- and age-‍de­pen­dent ef­fects of celi­ac dis­ease on growth and weight gain in chil­dren with type 1 di­a­betes: anal­y­sis of the Type 1 Di­a­betes Ex­change Clin­ic Reg­istry. Pe­di­atr Di­a­betes 2018;19:741–748
85. Rubio-‍Tapia A, Hill ID, Kelly CP, Calder­wood AH, Mur­ray JA; Amer­i­can Col­lege of Gas­troen­terol­o­gy. ACG clin­i­cal guide­lines: di­ag­no­sis and man­age­ment of celi­ac dis­ease. Am J Gas­troen­terol 2013;108:656–676
86. Paul SP, Sand­hu BK, Spray CH, Ba­sude D, Ra­mani P. Ev­i­dence sup­porting serol­o­gy-‍based path­way for di­ag­nos­ing celi­ac dis­ease in asymp­tomat­ic chil­dren from high-‍risk groups. J Pe­di­atr Gas­troen­terol Nutr 2018;66:641–644
87. Abid N, Mc­Glone O, Card­well C, Mc­Cal­lion W, Car­son D. Clin­ical and metabol­ic ef­fects of gluten free diet in chil­dren with type 1 di­a­betes and coeli­ac dis­ease. Pe­di­atr Di­a­betes 2011;12:322–325
88. Husby S, Ko­let­zko S, Korponay-‍Szab´o IR, et al.; ESPGHAN Work­ing Group on Coeli­ac Dis­ease Di­ag­no­sis; ESPGHAN Gas­troen­terol­o­gy Com­mit­tee; Eu­ro­pean So­ci­ety for Pe­di­atric Gas­troen­terol­o­gy, Hep­a­tol­o­gy, and Nu­tri­tion. Eu­ro­pean So­ci­ety for Pe­di­atric Gas­troen­terol­o­gy, Hep­a­tol­o­gy, and Nu­tri­tion guide­lines for the di­ag­no­sis of coeli­ac dis­ease. J Pe­di­atr Gas­troen­terol Nutr 2012;54:136–160
89. Kurp­pa K, Paavola A, Collin P, et al. Ben­e­fits of a gluten-‍free diet for asymp­tomat­ic pa­tients with sero­log­ic mark­ers of celi­ac dis­ease. Gas­troen­terol­o­gy 2014;147:610–617.e1
90. Mar­cov­ec­chio ML, Chiesa ST, Bond S, et al.; AdDIT Study Group. ACE in­hibitors and statins in ado­les­cents with type 1 di­a­betes. N Engl J Med 2017;377:1733–1745
91. de Fer­ran­ti SD, de Boer IH, Fon­se­ca V, et al. Type 1 di­a­betes mel­li­tus and car­dio­vas­cu­lar dis­ease: a sci­en­tific state­mentfrom the Amer­i­can Heart As­so­ci­a­tion and Amer­i­can Di­a­betes As­so­ci­a­tion. Cir­cu­la­tion 2014;130:1110–1130
92. 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;29:1891–1896
93. Margeirs­dot­tir HD, Larsen JR, Brun­borg C, Over­by NC, Dahl-‍Jørgensen K; Nor­we­gian Study Group for Child­hood Di­a­betes. High preva­lence of car­dio­vas­cu­lar risk fac­tors in chil­dren and ado­les­cents with type 1 di­a­betes: a pop­u­la­tion-‍based study. Di­a­betologia 2008; 51:554–561
94. Schwab KO, Do­er­fer J, Heck­er W, et al.; DPV Ini­tia­tive of the Ger­man Work­ing Group for Pe­di­atric Di­a­betology. Spec­trum and preva­lence of athero­genic risk fac­tors in 27,358 chil­dren, ado­les­cents, and young adults with type 1 di­a­betes: cross-sec­tional data from the Ger­man di­a­betes doc­u­men­ta­tion and qual­i­ty man­age­ment sys­tem (DPV). Di­a­betes Care 2006;29:218– 225
95. Singh TP, Groehn H, Kazmers A. Vas­cu­lar func­tion and carotid in­ti­mal-medial thick­ness in chil­dren with in­sulin-dependent di­a­betes mel­li­tus. J Am Coll Car­di­ol 2003;41:661–665
96. Haller MJ, Stein J, Shus­ter J, et al. Pe­riph­er­al artery tonom­e­try demon­strates al­tered en­dothe­lial func­tion in chil­dren with type 1 di­a­betes. Pe­di­atr Di­a­betes 2007;8:193–198
97. Urbina EM, Wadwa RP, Davis C, et al. Preva­lence of in­creased ar­te­ri­al stiff­ness in chil­dren with type 1 di­a­betes mel­li­tus dif­fers by mea­sure­ment site and sex: the SEARCH for Di­a­betes in Youth Study. J Pe­di­atr 2010;156:731–737.e1
98. Ex­pert Panel on In­te­grat­ed Guide­lines for Car­dio­vas­cu­lar Health and Risk Re­duc­tion in Chil­dren and Ado­les­cents; Na­tion­al Heart, Lung, 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
99. Daniels SR, Greer FR; Com­mit­tee on Nu­tri­tion. Lipid screen­ing and car­dio­vas­cu­lar health in child­hood. Pe­di­atrics 2008;122:198–208
100. Kavey R-EW, Al­la­da V, Daniels SR, et al.; Amer­i­can Heart As­so­ci­a­tion Ex­pert Panel on Pop­u­la­tion and Pre­ven­tion Sci­ence; Amer­i­can Heart As­so­ci­a­tion Coun­cil on Car­dio­vas­cu­lar Dis­ease in the Young; Amer­i­can Heart As­so­ci­a­tion Coun­cil on Epi­demi­ol­o­gy and Pre­ven­tion; Amer­i­can Heart As­so­ci­a­tion Coun­cil on Nu­tri­tion, Phys­i­cal Ac­tiv­i­ty and Metabolism; Amer­i­can Heart As­so­ci­a­tion Coun­cil on High Blood Pres­sure Re­search; Amer­i­can Heart As­so­ci­a­tion Coun­cil on Car­dio­vas­cu­lar Nurs­ing; Amer­i­can Heart As­so­ci­a­tion Coun­cil on the Kid­ney in Heart Dis­ease; In­ter­dis­ci­plinary Work­ing Group on Qual­i­ty of Care and Out­comes Re­search. 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 S162 Chil­dren and Ado­les­cents Di­a­betes Care Vol­ume 42, Sup­ple­ment 1, Jan­uary 2019 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: en­dorsed by the Amer­i­can Acade­my of Pe­di­atrics. Cir­cu­la­tion 2006;114:2710–2738
101. Cadario F, Pro­dam F, Pasqual­ic­chio S, et al. Lipid profile and nu­tri­tional in­take in chil­dren and ado­les­cents with type 1 di­a­betes im­prove after a struc­tured di­eti­cian train­ing to a Mediter­ranean-‍style diet. J En­docrinol In­vest 2012;35:160–168
102. Salem MA, AboE­lAs­rar MA, El­bar­bary NS, El­Hi­laly RA, Re­faat YM. Is ex­er­cise a ther­a­peu­tic tool for im­provement of car­dio­vas­cu­lar risk fac­tors in ado­les­cents with type 1 di­a­betes mel­li­tus? A ran­domised con­trolled trial. Di­a­betol Metab Syndr 2010;2:47
103. Mc­Crindle BW, Urbina EM, Den­ni­son BA, et al.; Amer­i­can Heart As­so­ci­a­tion Atheroscle­ro­sis, Hy­per­ten­sion, and Obe­si­ty in Youth Com­mit­tee; Amer­i­can Heart As­so­ci­a­tion Coun­cil of Car­dio­vas­cu­lar Dis­ease in the Young; Amer­i­can Heart As­so­ci­a­tion Coun­cil on Car­dio­vas­cu­lar Nurs­ing. Drug ther­a­py of high-‍risk lipid abnor­malities in chil­dren and ado­les­cents: a sci­en­tific state­ment from the Amer­i­can Heart As­so­ci­a­tion Atheroscle­ro­sis, Hy­per­ten­sion, and Obe­si­ty in Youth Com­mit­tee, Coun­cil of Car­dio­vas­cu­lar Dis­ease in the Young, with the Coun­cil on Car­dio­vas­cu­lar Nurs­ing. Cir­cu­la­tion 2007;115: 1948–1967
104. Salo P, Vi­ikari J, Ha¨ma¨la¨inen M, et al. Serum choles­terol ester fatty acids in 7- and 13-‍month-old chil­dren in a prospec­tive ran­dom­ized trial of a low-‍sat­u­rat­ed fat, low-‍choles­terol diet: the STRIP baby pro­ject: Spe­cial Turku coro­nary Risk fac­tor In­ter­ven­tion Pro­ject for chil­dren. Acta Pae­di­a­tr 1999;88:505–512
105. Maahs DM, Dabe­lea D, D’Agosti­no RB Jr, et al.; SEARCH for Di­a­betes in Youth Study. Glu­cose con­trol pre­dicts 2-year change in lipid profile in youth with type 1 di­a­betes. J Pe­di­atr 2013;162:101–107.e1
106. Mc­Crindle BW, Ose L, Marais AD. Efficacy and safe­ty of ator­vas­tatin in chil­dren and ado­les­cents with fa­mil­ial hypercholes­terolemia or se­vere hy­per­lipi­demia: a mul­ti­cen­ter, ran­dom­ized, placebo-con­trolled trial. J Pe­di­atr 2003;143:74–80
107. Wieg­man A, Hut­ten BA, de Groot E, et al. Efficacy and safe­ty of statin ther­a­py in chil­dren with fa­mil­ial hypercholes­terolemia: a ran­dom­ized con­trolled trial. JAMA 2004;292:331–337
108. Karter AJ, Stevens MR, Gregg EW, et al. Ed­u­ca­tional dis­par­i­ties in rates of smok­ing among di­a­bet­ic adults: the Trans­lat­ing Re­search Into Ac­tion for Di­a­betes study. Am J Pub­lic Health 2008;98:365–370
109. Reynolds K, Liese AD, An­der­son AM, et al. Preva­lence of to­bac­co use and as­so­ci­a­tion be­tween cardiometabol­ic risk fac­tors and cigarette smok­ing in youth with type 1 or type 2 di­a­betes mel­li­tus. J Pe­di­atr 2011;158:594–601.e1
110. Scott LJ, War­ram JH, Hanna LS, Laf­fel LM, Ryan L, Krolews­ki AS. A nonlin­ear ef­fect of hy­per­glycemia and cur­rent cigarette smok­ing are major de­ter­mi­nants of the onset of microal­bu­minuria in type 1 di­a­betes. Di­a­betes 2001; 50:2842–2849
111. Chaf­fee BW, Watkins SL, Glantz SA. Elec­tron­ic cigarette use and pro­gres­sion from ex­per­i­men­ta­tion to es­tab­lished smok­ing. Pe­di­atrics 2018;141:e20173594

112. Audrain-‍Mc­Gov­ern J, Stone MD, Bar­ring­ton-‍Trimis J, Unger JB, Lev­en­thal AM. Ado­les­cent e-‍cigarette, hookah, and con­ven­tion­al cigarette use and sub­se­quent mar­i­jua­na use. Pe­di­atrics 2018;142:e20173616
113. Daniels M, Du­Bose SN, Maahs DM, et al.; T1D Ex­change Clin­ic Net­work. Fac­tors as­so­ci­at­ed with microal­bu­minuria in 7,549 chil­dren and ado­les­cents with type 1 di­a­betes in the T1D Ex­change clin­ic reg­istry. Di­a­betes Care 2013;36: 2639–2645
114. Schwartz GJ, Work DF. Mea­surement and es­ti­ma­tion of GFR in chil­dren and ado­les­cents. Clin J Am Soc Nephrol 2009;4:1832–1843
115. Inker LA, Schmid CH, Tighiouart H, et al.; CKD-‍EPI In­vestigators. Es­ti­mat­ing glomeru­lar filtra­tion rate from serum cre­a­ti­nine and cys­tatin C. N Engl J Med 2012;367:20–29
116. Cho YH, Craig ME, Hing S, et al. Mi­crovas­cu­lar com­pli­ca­tions as­sessment in ado­les­cents with 2- to 5-yr du­ra­tion of type 1 di­a­betes from 1990 to 2006. Pe­di­atr Di­a­betes 2011;12:682– 689
117. Jaisw­al M, Divers J, Dabe­lea D, et al. Preva­lence of and risk fac­tors for di­a­bet­ic pe­riph­er­al neu­ropa­thy in youth with type 1 and type 2 di­a­betes: SEARCH for Di­a­betes in Youth Study. Di­a­betes Care 2017;40:1226–1232
118. Pop-‍Busui R, Boul­ton AJM, Feld­man EL, et al. Di­a­bet­ic neu­ropa­thy: a po­si­tion state­ment by the Amer­i­can Di­a­betes As­so­ci­a­tion. Di­a­betes Care 2017;40:136–154
119. 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
120. 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
121. Pet­titt DJ, Tal­ton J, Dabe­lea D, et al.; SEARCH for Di­a­betes in Youth Study Group. Preva­lence of di­a­betes in U.S. youth in 2009: the SEARCH­for Di­a­betesin Youth Study. Di­a­betes Care 2014;37:402–408
122. 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
123. Ar­sla­ni­an SA. Metabol­ic dif­fer­ences be­tween Cau­casian and African-‍Amer­i­can chil­dren and the re­la­tionship to type 2 di­a­betes mel­li­tus. J Pe­di­atr En­docrinol Metab 2002;15(Suppl. 1): 509–517
124. Naughton MJ, Rug­giero AM, Lawrence JM, et al.; SEARCH for Di­a­betes in Youth Study Group. Health-‍re­lat­ed qual­i­ty of life of chil­dren and ado­les­cents with type 1 or type 2 di­a­betes mel­li­tus: SEARCH for Di­a­betes in Youth Study. Arch Pe­di­atr Ado­lesc Med 2008;162:649–657
125. Wad­den TA, Webb VL, Moran CH, Bail­er BA. Lifestyle modification for obe­si­ty: new de­vel­op­ments in diet, phys­i­cal ac­tiv­i­ty, and be­hav­ior ther­a­py. Cir­cu­la­tion 2012;125:1157–1170
126. Whalen DJ, Belden AC, Till­man R, Barch DM, Luby JL. Early ad­ver­si­ty, psy­chopathol­o­gy, and la­tent class profiles of glob­al phys­i­cal health from preschool through early ado­les­cence. Psy­cho­som Med 2016;78:1008–1018
127. 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
128. Buse JB, Kauf­man FR, Lin­der B, Hirst K, El Ghorm­li L, Willi S; HEALTHY Study Group. Di­a­betes screen­ing with hemoglobin A1c ver­sus fast­ing plas­ma glu­cose in a multieth­nic middl-‍school co­hort. Di­a­betes Care 2013;36:429–435
129. Klin­gen­smith GJ, Pyle L, Ar­sla­ni­an S, et al.; TODAY Study Group. The pres­ence of GAD and IA-2 an­ti­bod­ies in youth with a type 2 di­a­betes phe­no­type: re­sults from the TODAY study. Di­a­betes Care 2010;33:1970–1975
130. Han­non TS, Ar­sla­ni­an SA. The chang­ing face ofdi­a­betesinyouth: lessonslearnedfromstud­ies of type 2 di­a­betes. Ann N Y Acad Sci 2015;1353: 113–137
131. 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;2012:31
132. Kester LM, Hey H, Han­non TS. Using hemoglobin A1c for predi­a­betes and di­a­betes di­ag­no­sis in ado­les­cents: can adult rec­om­men­da­tions be up­held for pe­di­atric use? J Ado­lesc Health 2012;50:321–323
133. Wu E-L, Kazzi NG, Lee JM. Cost-ef­fec­tiveness of screen­ing strate­gies for iden­ti­fy­ing pe­di­atric di­a­betes mel­li­tus and dys­g­lycemia. JAMA Pe­di­atr 2013;167:32–39
134. Dabe­lea D, Rew­ers A, Staf­ford JM, et al.; SEARCH for Di­a­betes in Youth Study Group. Trends in the preva­lence of ke­toaci­do­sis at di­a­betes di­ag­no­sis: the SEARCH for Di­a­betes in Youth Study. Pe­di­atrics 2014;133:e938–e945
135. Hutchins J, Bara­jas RA, Hale D, Es­caname E, Lynch J. Type 2 di­a­betes in a 5-‍year-‍old and sin­gle cen­ter ex­pe­ri­ence of type 2 di­a­betes in youth under 10. Pe­di­atr Di­a­betes 2017;18:674–677
136. Fer­rara CT, Geyer SM, Liu Y-F, et al.; Type 1 Di­a­betes Tri­al­Net Study Group. Ex­cess BMI in child­hood: a modifiable risk fac­tor for type 1 di­a­betes de­vel­op­ment? Di­a­betes Care 2017;40: 698–701
137. Re­don­do MJ, Geyer S, Steck AK, et al.; Type 1 Di­a­betes Tri­al­Net Study Group. TCF7L2 ge­net­ic vari­ants con­tribute to phe­no­typ­ic het­ero­gene­ity of type 1 di­a­betes. Di­a­betes Care 2018;41:311– 317
138. Pinhas-‍Hamiel O, Dolan LM, Zeitler PS. Di­a­bet­ic ke­toaci­do­sis among obese African-‍ Amer­i­can ado­les­cents with NIDDM. Di­a­betes Care 1997;20:484–486
139. TODAY Study Group. Safe­ty and tolerabil­i­ty of the treat­ment of youth-‍onset type 2 di­a­betes: the TODAY ex­pe­ri­ence. Di­a­betes Care 2013;36: 1765–1771
140. TODAY Study Group. Retinopa­thy in youth with type 2 di­a­betes par­tic­i­pat­ing in the TODAY clin­i­cal trial. Di­a­betes Care 2013;36:1772–1774
141. 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;36:1758–1764
142. TODAY Study Group. Rapid rise in hy­per­ten­sion and nephropa­thy in youth with type 2 di­a­betes: the TODAY clin­i­cal trial. Di­a­betes Care 2013;36:1735–1741
143. Grey M, Schrein­er B, Pyle L. De­vel­op­ment of a di­a­betes ed­u­ca­tion pro­gram for youth with type 2 di­a­betes. Di­a­betes Educ 2009;35:108–116
144. Amer­i­can Di­a­betes As­so­ci­a­tion. Be Healthy Today; Be Healthy For Life [In­ter­net]. Avail­able from http:/‍/‍main.di­a­betes.org/dorg/PDFs/Type-‍ 2-Di­a­betes-‍in-Youth/Type-2-Di­a­betes-‍in-Youth.pdf. Ac­cessed 16 Oc­to­ber 2018
145. Atkin­son A, Rad­jen­ovic D. Meet­ing qual­i­ty stan­dards for self-‍man­age­ment ed­u­ca­tion in pe­di­atric type 2 di­a­betes. Di­a­betes Spec­tr 2007;20:40–46
146. Copeland KC, Sil­ver­stein J, Moore KR, et al. Man­age­ment of newly di­ag­nosed type 2 di­a­betes mel­li­tus (T2DM) in chil­dren and ado­les­cents. Pe­di­atrics 2013;131:364–382
147. Levitt Katz LE, Bacha F, Gid­ding SS, et al.; TODAY Study Group. Lipid profiles, inflam­ma­to­ry mark­ers, and in­sulin ther­a­py in youth with type 2 Di­a­betes. J Pe­di­atr 2018;196:208–216.e2
148. 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
149. Inge TH, Cour­coulas AP, Jenk­ins TM, et al.; Teen-‍LABS Con­sor­tium. Weight loss and health sta­tus 3 years after bariatric surgery in ado­les­cents. N Engl J Med 2016;374:113–123
150. Ru­bi­no F, Nathan DM, Eckel RH, et al.; Del­e­gates of the 2nd Di­a­betes Surgery Sum­mit. Metabol­ic surgery in the treat­ment al­go­rithm for type 2 di­a­betes: a joint state­ment by interna­tion­al di­a­betes or­ga­ni­za­tions. Di­a­betes Care 2016;39:861–877
151. Pratt JSA, Lenders CM, Dionne EA, et al. Best prac­tice up­dates for pe­di­atric/ado­les­cent weight loss surgery. Obe­si­ty (Sil­ver Spring) 2009; 17:901–910
152. Dolan K, Creighton L, Hop­kins G, Field­ing G. La­paro­scop­ic gas­tric band­ing in mor­bid­ly obese ado­les­cents. Obes Surg 2003;13:101– 104
153. Sug­er­man HJ, Sug­er­man EL, De­Maria EJ, et al. Bariatric surgery for se­verely obese ado­les­cents. J Gas­troin­test Surg 2003;7:102–108
154. Inge TH, Gar­cia V, Daniels S, et al. A mul­ti­dis­ci­plinary ap­proach to the ado­les­cent bariatric sur­gi­cal pa­tient. J Pe­di­atr Surg 2004; 39:442–447; dis­cus­sion 446–447
155. Law­son ML, Kirk S, Mitchell T, et al.; Pe­di­atric Bariatric Study Group. One-yearout­comes of Roux-‍en-‍Y gas­tric by­pass for mor­bid­ly obese ado­les­cents: a mul­ti­cen­ter study from the Pe­di­atric Bariatric Study Group. J Pe­di­atr Surg 2006;41:137–143
156. Inge TH, Zeller M, Har­mon C, et al. Teen- Lon­gi­tu­di­nal As­sessment of Bariatric Surgery: method­olog­i­cal fea­tures of the first prospec­tive mul­ti­cen­ter study of ado­les­cent bariatric surgery. J Pe­di­atr Surg 2007;42:1969–1971
157. Ells LJ, Mead E, Atkin­son G, et al. Surgery for the treat­ment of obe­si­ty in chil­dren and ado­les­cents. Cochrane Database Syst Rev 2015;6: CD011740

158. Michal­sky MP, Inge TH, Sim­mons M, et al.; Teen-‍LABS Con­sor­tium. Car­dio­vas­cu­lar risk fac­tors in se­verely obese ado­les­cents: the Teen Lon­gi­tu­di­nal As­sessment of Bariatric Surgery (Teen-‍LABS) study. JAMA Pe­di­atr 2015;169: 438–444
159. Zein­od­di­ni A, Hei­dari R, Talebpour M. La­paro­scop­ic gas­tric pli­ca­tion in mor­bid­ly obese ado­les­cents: aprospec­tivestudy. Surg Obes Relat Dis 2014;10:1135–1139
160. Go¨thberg G, Gronowitz E, Flod­mark C-E, et al. La­paro­scop­ic Roux-‍en-‍Y gas­tric by­pass in ado­les­cents with mor­bid obe­si­tydsur­gi­cal as­pects and clin­i­cal out­come. Semin Pe­di­atr Surg 2014;23:11–16
161. Inge TH, Pri­geon RL, Elder DA, et al. In­sulin sen­si­tiv­i­ty and β-cell func­tion im­prove after gas­tric by­pass in se­verely obese ado­les­cents. J Pe­di­atr 2015;167:1042–1048.e1
162. Styne DM, Ar­sla­ni­an SA, Con­nor EL, et al. Pe­di­atric obe­si­tydas­sessment, treat­ment, and pre­ven­tion: an En­docrine So­ci­ety clin­i­cal prac­tice guide­line. J Clin En­docrinol Metab 2017;102: 709–757
163. 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;29:1300–1306
164. Song SH, Hardis­ty CA. Early onset type 2 di­a­betes mel­li­tus: a harbinger for com­pli­ca­tions in later yearsdclin­i­cal ob­ser­va­tion from a sec­ondary care co­hort. QJM 2009;102:799–806
165. Zeitler P, Fu J, Tan­don N, et al.; Interna­tion­al So­ci­ety for Pe­di­atric and Ado­les­cent Di­a­betes. ISPAD Clin­ical Prac­tice Con­sen­sus Guide­lines 2014. Type 2 di­a­betes in the child and ado­les­cent. Pe­di­atr Di­a­betes 2014;15(Suppl. 20):26–46
166. 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
167. Ce­falu WT. “TODAY” reflects on the chang­ing “faces” of type 2 di­a­betes. Di­a­betes Care 2013;36:1732–1734
168. Lawrence JM, Stan­di­ford DA, Loots B, et al.; SEARCH for Di­a­betes in Youth Study. Preva­lence and cor­re­lates of de­pressed mood among youth with di­a­betes: the SEARCH for Di­a­betes in Youth study. Pe­di­atrics 2006;117:1348–1358
169. Levitt Katz LE, Swami S, Abra­ham M, et al. Neuropsy­chi­atric dis­or­ders at the pre­sentation of type 2 di­a­betes mel­li­tus in chil­dren. Pe­di­atr Di­a­betes 2005;6:84–89
170. Lewis-‍Ferna´ndez R, Rotheram-‍Borus MJ,

     Betts VT, et al. Re­think­ing fund­ing pri­or­i­ties in men­tal health re­search. Br J Psy­chi­a­try 2016;208: 507–509

171. Reinehr T. Type 2 di­a­betes mel­li­tus in chil­dren and ado­les­cents. World J Di­a­betes 2013;4:270–281
172. Pinhas-‍Hamiel O, Hamiel U, Levy-‍Shraga Y. Eat­ing dis­or­ders in ado­les­cents with type 1 di­a­betes: chal­lenges in di­ag­no­sis and treat­ment. World J Di­a­betes 2015;6:517–526
173. TODAY Study Group. Binge eat­ing, mood, and qual­i­ty of life in youth with type 2 di­a­betes:

     base­line data from the TODAY study. Di­a­betes Care 2011;34:858–860

174. Shel­ton RC. De­pres­sion, an­tide­pres­sants, and weight gain in chil­dren. Obe­si­ty (Sil­ver Spring) 2016;24:2450
175. Baeza I, Vigo L, de la Serna E, et al. The ef­fects of an­tipsy­chotics on weight gain, weight-‍re­lat­ed hor­mones and ho­mo­cys­teine in chil­dren and ado­les­cents: a 1-year fol­low-‍up study. Eur Child Ado­lesc Psy­chi­a­try 2017;26:35–46
176. Klin­gen­smith GJ, Pyle L, Nadeau KJ, et al. Preg­nan­cy out­comes in youth with type 2 di­a­betes: the TODAY study ex­pe­ri­ence. Di­a­betes Care 2016;39:122–129
177. Ar­nett JJ. Emerg­ing adult­hood: a the­o­ry of de­vel­op­ment from the late teens through the twen­ties. Am Psy­chol 2000;55:469–480
178. Weissberg-‍Benchell J, Wolpert H, An­der­son BJ. Tran­si­tioning from pe­di­atric to adult care: a new ap­proach to the post-‍ado­les­cent young per­son with type 1 di­a­betes. Di­a­betes Care 2007; 30:2441–2446
179. Pe­ters A, Laf­fel L; Amer­i­can Di­a­betes As­so­ci­a­tion Tran­si­tions Work­ing Group. Di­a­betes care for emerg­ing adults: rec­om­men­da­tions for tran­si­tion from pe­di­atric to adult di­a­betes care sys­tems: a po­si­tion state­ment of the Amer­i­can Di­a­betes As­so­ci­a­tion, with repre­sentation by the Amer­i­can Col­lege of Os­teo­path­ic Fam­i­ly Physi­cians, the Amer­i­can Acade­my of Pe­di­atrics, the Amer­i­can As­so­ci­a­tion of Clin­ical En­docrinologists, the Amer­i­can Os­teo­path­ic As­so­ci­a­tion, the Cen­ters for Dis­ease Con­trol and Pre­ven­tion, Chil­dren with Di­a­betes, The En­docrine So­ci­ety, the Interna­tion­al So­ci­ety for Pe­di­atric and Ado­les­cent Di­a­betes, Ju­ve­nile Di­a­betes Re­search Foun­da­tion Interna­tion­al, the Na­tion­al Di­a­betes Ed­u­ca­tion Pro­gram, and the Pe­di­atric En­docrine So­ci­ety (for­mer­ly Law­son Wilkins Pe­di­atric En­docrine So­ci­ety). Di­a­betes Care 2011;34:2477–2485
180. Bry­den KS, Pevel­er RC, Stein A, Neil A, Mayou RA, Dunger DB. Clin­ical and psy­cho­log­i­cal course of di­a­betes from ado­les­cence to young adult­hood: a lon­gi­tu­di­nal co­hort study. Di­a­betes Care 2001;24:1536–1540
181. Laing SP, Jones ME, Swerd­low AJ, Bur­den AC, Gatling W. Psychoso­cial and so­cioe­co­nom­ic risk fac­tors for pre­ma­ture death in young peo­ple with type 1 di­a­betes. Di­a­betes Care 2005;28: 1618–1623
182. Mays JA, Jack­son KL, Derby TA, et al. An eval­u­a­tion of recur­rent di­a­bet­ic ke­toaci­do­sis, frag­men­ta­tion of care, and mor­tal­i­ty across Chica­go, Illi­nois. Di­a­betes Care 2016;39:1671– 1676
183. Gar­vey KC, Fos­ter NC, Agar­w­al S, etal. Health care tran­si­tion prepa­ra­tion and ex­pe­ri­ences in a U.S. na­tion­al sam­ple of young adults with type 1 di­a­betes. Di­a­betes Care 2017;40:317–324
184. The En­docrine So­ci­ety. Man­ag­ing the tran­si­tion of care for pa­tients with type 1 di­a­betes [In­ter­net]. Avail­able from https://www .en­docrine.org/guide­lines-and-clin­i­cal-prac­tice/ qual­i­ty-im­provement-re­sources/clin­i­cal-prac­ticere­sources/ tran­si­tion-‍of-‍care. Ac­cessed 16 Oc­to­ber 2018