Evaluation and Management of Youth-Onset Type 2 Diabetes: A Position Statement by The American Diabetes Association

2648 Diabetes Care Volume 41, December 2018
Silva Arslanian,1,2 Fida Bacha,3

Evaluation and Management of Margaret Grey,4,5 Marsha D. Marcus,6
Neil H. White,7 and Philip Zeitler8
Youth-Onset Type 2 Diabetes:
A Position Statement by the
American Diabetes Association
Diabetes Care 2018;41:2648–2668 | https://doi.org/10.2337/dci18-0052
Although all types of diabetes result in hyperglycemia, the pathophysiology of each

type of diabetes is different. These guidelines summarize available data specific to
the comprehensive care of youth with type 2 diabetes. The objective is to enrich
the recognition of type 2 diabetes in youth, its risk factors, its pathophysiology,
its management, and the prevention of associated complications.
POSITION STATEMENT
PATHOPHYSIOLOGY
Glucose homeostasis is maintained by a balance between insulin secretion from the
pancreatic b-cells and sensitivity to insulin in skeletal muscle, adipose tissue, and liver
(1). When insulin sensitivity declines, insulin secretion must increase to maintain
glucose tolerance, and, in most youth, decreased insulin sensitivity due to puberty 1
Division of Pediatric Endocrinology, Metabo-
and/or obesity is compensated by increased insulin secretion. However, when b-cells lism, and Diabetes Mellitus, University of Pitts-
cannot secrete sufficient insulin to compensate for insulin resistance, abnormalities burgh, Pittsburgh, PA
2
in glucose homeostasis ensue, potentially progressing to prediabetes and type 2 Center for Pediatric Research in Obesity and
diabetes as b-cell function deteriorates further (2–9). The relationship between Metabolism, UPMC Children’s Hospital of Pitts-
burgh, Pittsburgh, PA
b-cell function and insulin sensitivity in adults and youth has been demonstrated 3
Children’s Nutrition Research Center, Texas
to be a hyperbolic function and can be described mathematically as the product of Children’s Hospital and Baylor College of Med-
insulin sensitivity and b-cell function, called the disposition index (DI) (1). The DI icine, Houston, TX
4
essentially expresses the amount of insulin being secreted relative to the degree Yale School of Nursing, New Haven, CT
5
of insulin resistance and is a constant for a given degree of glucose tolerance in any Yale School of Medicine, New Haven, CT
6
University of Pittsburgh School of Medicine,
one individual. Pittsburgh, PA
Overweight and obesity are major acquired contributors to the development of 7
Washington University School of Medicine in
insulin resistance, particularly in the face of the physiologic insulin resistance St. Louis, St. Louis, MO
characteristic of puberty. Robust pancreatic b-cell compensatory insulin secretion
8
Children’s Hospital Colorado and University of
maintains normal glucose homeostasis. However, in adolescents with obesity who Colorado School of Medicine, Aurora, CO
develop type 2 diabetes, there is severe peripheral and hepatic insulin resistance, with Corresponding author: Silva Arslanian, silva.
arslanian@chp.edu.
;50% lower peripheral insulin sensitivity than peers with obesity without diabetes,
along with increased fasting hepatic glucose production and inadequate first- and This position statement was reviewed and ap-
proved by the American Diabetes Assoication
second-phase insulin secretion, resulting in ;85% lower DI (2). Additional abnor- Professional Practice Committee and ratified
malities in youth with type 2 diabetes include impaired glucose sensitivity of insulin by the American Diabetes Association Board of
secretion, lower serum adiponectin concentrations, and reduced incretin effect Directors in September 2018.
(3,9–13). While upregulation of a-cell function with hyperglucagonemia has been For further information on the ADA evidence-
implicated in the pathophysiology of type 2 diabetes in adults (14,15), there are grading system and the levels of evidence, please
limited data in youth with type 2 diabetes, with studies showing either hyper- see Table 1 in the American Diabetes Associa-
tion’s Introduction section of the Standards of
glucagonemia or no difference from control subjects without diabetes (3,11,16,17). Medical Care in Diabetesd2018. Diabetes Care
Cross-sectional and longitudinal studies in youth with obesity along the spectrum of 2018;41(Suppl. 1):S2, https://doi.org/10.2337/
glycemia from normoglycemia to prediabetes to type 2 diabetes show, as in adults, dc18-SINT01.
that b-cell failure with declining insulin secretion relative to insulin sensitivity results The authors are solely responsible for the con-
in prediabetes and type 2 diabetes in high-risk youth (5–9,18–21). Importantly, tents of this article, which do not necessarily
however, prior to reaching the American Diabetes Association (ADA)-defined fast- represent the official views of the NIDDK.
ing and oral glucose tolerance test (OGTT)-stimulated glycemic cut points for the © 2018 by the American Diabetes Association.
diagnosis of prediabetes, youth, like adults, already demonstrate declining b-cell Readers may use this article as long as the work
is properly cited, the use is educational and not
function relative to insulin sensitivity (6–8). Also, youth with A1C in the at-risk/ for profit, and the work is not altered. More infor-
prediabetes category ($5.7 to ,6.5%) demonstrate impaired b-cell function mation is available at http://www.diabetesjournals
compared with those with A1C ,5.7% (22). A combination of obesity, genetics, .org/content/license.
care.diabetesjournals.org Arslanian and Associates 2649
the hormonal milieu, incretins and/or in Adolescents and Youth (TODAY) stress and/or depressed mood (48,49)
their effect, and metabolic alterations, cohort, one-third were born after a preg- and sleep-related disorders (50–52).
such as glucotoxicity and/or lipotoxicity, nancy complicated by preexisting diabe-
Risk Assessment and Diagnostic
are likely to contribute to deteriorating tes or GDM (35). In the SEARCH for
Criteria
b-cell function against the backdrop of Diabetes in Youth (SEARCH) study, a
insulin resistance, eventually culminating population-based study of the epide- Recommendations
in prediabetes and type 2 diabetes in at- miology of type 1 and type 2 diabetes c Risk-based screening for prediabe-
risk youth. Based on the baseline data in youth in the U.S., exposure to mater- tes and/or type 2 diabetes should
from the Restoring Insulin Secretion nal GDM or pregestational diabetes and be considered after the onset of
(RISE) study (23,24), there appear to maternal obesity were independently puberty or after 10 years of age,
be important differences in insulin sensi- associated with type 2 diabetes in ado- whichever occurs earlier, in chil-
tivity and b-cell function between youth lescents, with intrauterine exposure to dren and adolescents who are over-
and adults with similar degrees of dys- these two risk factors present in 47.2% weight (BMI $85th percentile) or
glycemia, including greater insulin resis- of type 2 diabetes in the cohort (36). obese (BMI $95th percentile) and
tance for any degree of adiposity and Age of onset of type 2 diabetes was also who have one or more additional
greater insulin secretion for any degree younger in those exposed to diabetes risk factors for diabetes (see Table 1
of insulin resistance in youth compared during gestation. for evidence grading).
with adults. Incidence and prevalence of type 2 c If tests are normal, repeat testing
diabetes are highest among youth from at a minimum of 3-year intervals E,
RISK, SCREENING, AND DIAGNOSIS a minority race/ethnicity (37), likely as or more frequently if BMI is in-
Risk Factors a consequence of many factors, includ- creasing. C
Nonmodifiable risk factors for youth- ing genetics, metabolic characteristics, c Fasting plasma glucose, 2-h plasma
onset type 2 diabetes include genetics/ cultural/environmental influences, and glucose after 75-g OGTT, or A1C can
epigenetics, manifested as a strong fam- quality of and access to health care. be used to test for prediabetes or
ily history of type 2 diabetes in first- or Several studies have demonstrated sig- diabetes. B
second-degree relatives; being the off- nificant differences by race/ethnicity in
spring of a pregnancy complicated by insulin sensitivity and secretion that Risk-based screening for prediabetes
gestational diabetes mellitus (GDM); mi- might heighten the risk of type 2 diabetes and/or type 2 diabetes is timed after
nority race/ethnicity; and physiologic (38–42). the onset of puberty or after 10 years of
insulin resistance of puberty. Metabolic Type 2 diabetes typically occurs in age, whichever occurs earlier, because
evidence of genetic susceptibility can adolescents at midpuberty (for example, the majority of youth-onset type 2 di-
be detected in the first decade of life, the mean age of diagnosis was 14 years abetes occurs during puberty, as stated
manifested as impaired insulin sensitivity in the TODAY study) (43), most likely above, and rarely in prepubertal children.
and reduced insulin secretion in other- precipitated by the physiologic, but However, some youth with obesity may
wise healthy youth with a family history transient, pubertal insulin resistance have earlier onset of puberty than usual,
of type 2 diabetes (25). This genetic sus- aggravating the preexisting metabolic necessitating screening before 10 years
ceptibility, when combined with environ- challenges of obesity. Cross-sectional and of age. In addition, in North America
mental factors conducive to obesity and longitudinal studies show that insulin almost all youth with type 2 diabetes
a sedentary lifestyle, may ultimately sensitivity declines by 25–30% as youth are overweight/obese, hence the re-
translate to type 2 diabetes. Indeed, in transition from prepuberty to puberty commendation to screen youth with
a study of youth with obesity, a genetic (44–46). In the presence of normally func- overweight/obesity. In other parts of the
risk score for b-cell dysfunction from tioning b-cells, puberty-related insulin world where youth with type 2 diabetes
five single nucleotide polymorphisms resistance is compensated by increased are not necessarily overweight and/or
was associated with a higher chance of insulin secretion/hyperinsulinemia, such obese, clinical judgment should guide
prediabetes and type 2 diabetes (26). that DI remains normal. In youth who are whom to screen. Although there is no
Dozens of specific genetic variants linked predisposed to develop prediabetes robust evidence-based rationale for the
to type 2 diabetes have been identified and/or type 2 diabetes, b-cell compensa- proposed frequency of testing, increas-
in adults (27,28), but these only account tion is inadequate with progressive de- ing BMI has been shown to be a predic-
for about 10% of its heritability (29,30). cline in the DI, ultimately resulting in tor of deteriorating glycemia and
Particular genetic variants that predis- dysglycemia (46,47). progression to type 2 diabetes (21).
pose to diabetes in youth have been In youth-onset type 2 diabetes, the Therefore, clinicians caring for youth
identified in Oji-Cree Native Canadians major modifiable risk factors are obesity with overweight/obesity with continued
(31) and African American youth (32), and lifestyle habits of excess nutritional increase in their BMI should be aware of
but information in other populations is intake, low physical activity, and in- the need for more frequent screening.
only now emerging. creased sedentary behaviors with de- The laboratory glycemia-based diag-
Evidence from both animal and hu- creased energy expenditure, resulting nostic criteria for diabetes and predia-
man studies suggests that maternal obe- in the surplus of energy being stored betes are the same for youth and adults,
sity and GDM contribute to obesity and as body fat. Other potentially modifiable regardless of type of diabetes (Table
type 2 diabetes in youth (33,34). In the risk factors for type 2 diabetes in ado- 2) (53). However, these criteria are
Treatment Options for Type 2 Diabetes lescents and young adults include chronic extrapolated from adults, and the
2650 Position Statement Diabetes Care Volume 41, December 2018
Table 1—Risk-based screening for type 2 diabetes or prediabetes in asymptomatic acceptable approach but should be
children and adolescents* in a clinical setting based on sound clinical judgment, rec-
Criteria ognition of the strengths and weak-
nesses of each test, and the facilities and
Testing should be considered in youth* who are overweight ($85%) or obese ($95%) A and who
have one or more additional risk factors based on the strength of their association with
resources available.
diabetes:
c Maternal history of diabetes or GDM during the child’s gestation A
Confirming Diabetes Type
c Family history of type 2 diabetes in first- or second-degree relative A
c Race/ethnicity (Native American, African American, Latino, Asian American, Pacific Recommendations
Islander) A c Children and adolescents with
c Signs of insulin resistance or conditions associated with insulin resistance (acanthosis
nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or small-for-gestational-
overweight/obesity in whom the
age birth weight) B diagnosis of type 2 diabetes is being
considered should have a panel of
*After the onset of puberty or after 10 years of age, whichever occurs earlier.
pancreatic autoantibodies tested
to exclude the possibility of auto-
immune type 1 diabetes. B
epidemiological studies that formed the effective at identifying glycemic abnor- c Genetic evaluation to exclude
basis for both glucose and A1C definitions malities on CGM, but the glycemic pat- monogenic diabetes should also
of diabetes did not include pediatric terns differ (57); abnormal A1C was be based on clinical characteristics
populations. Therefore, the exact rele- associated with higher overall and night- and presentation. B
vance of these definitions for pediatric time average glucose on CGM, while
populations remains unclear until more abnormal OGTT was associated with As stated above, youth with type 2 di-
data become available. more time spent above the normal glu- abetes in the U.S. are characteristically
The A1C test is universally available cose range during the day. Institution of overweight and/or obese, in mid- to late
and can be performed any time of the day A1C screening in a large primary care puberty, with overrepresentation of mi-
without need for fasting. However, sev- network increased provider adherence nority ethnic/racial groups and females
eral studies have questioned its validity in to screening recommendations com- (4,43,59). The clinical presentation varies
the pediatric population because of poor pared with OGTT screening while iden- widely from asymptomatic or minimally
sensitivity for identifying children with tifying the same prevalence of type 2 symptomatic, diagnosed incidentally
dysglycemia and underestimation of the diabetes (58). Furthermore, in this during routine laboratory testing, to a
prevalence of prediabetes and diabetes cohort, the progression to clinically severe presentation with symptomatic
(54–56). Fasting and OGTT criteria have confirmed diabetes was substantially hyperglycemia, weight loss, metabolic
not been validated in youth, either. more likely for those with A1C .6% decompensation, diabetic ketoacidosis
Studies using continuous glucose mon- (18.4%) than for those with levels 5.7– (DKA), or hyperglycemic hyperosmolar
itoring (CGM) in youth with obesity dem- 6.0% (1.3%). Therefore, screening with nonketotic (HHNK) syndrome (4).
onstrated that A1C and OGTT are equally fasting glucose, OGTT, or A1C is an Obesity is a consistent feature of
youth-onset type 2 diabetes in the
Table 2—Criteria for the diagnosis of prediabetes and diabetes U.S. However, because of the escalating
Prediabetes rates of obesity in the general popula-
tion, children with both type 1 diabetes
A1C 5.7% to ,6.5% (39 to ,48 mmol/mol). The test should be performed in a laboratory using and monogenic diabetes are also more
a method that is NGSP certified and standardized to the DCCT assay. likely to be overweight/obese than in the
IFG: fasting glucose $100 but ,126 mg/dL ($5.6 but ,7.0 mmol/L).
IGT: 2-h plasma glucose $140 but ,200 mg/dL ($7.8 but ,11.1 mmol/L) during an OGTT. The
past (60), making the clinical distinction
test should be performed as described by the World Health Organization, using a glucose load between type 2 diabetes and obese
containing the equivalent of 1.75 mg/kg (max 75 g) anhydrous glucose dissolved in water.* type 1 or monogenic diabetes difficult.
This was illustrated in the TODAY study
Diabetes
in which, of the 1,206 youth clinically
A1C $6.5% ($48 mmol/mol). The test should be performed in a laboratory using a method diagnosed with type 2 diabetes and
that is NGSP certified and standardized to the DCCT assay.*
screened for circulating GAD65 and
OR
FPG $126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.*
IA2 antibodies, 118 (9.8%) were antibody
OR positive (Ab1) (61). Even though these
2-h plasma glucose $200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed Ab1 individuals had clinical character-
as described by the World Health Organization, using a glucose load containing the istics that overlapped with the antibody-
equivalent of 1.75 mg/kg (max 75 g) anhydrous glucose dissolved in water* negative (Ab2) youth, they were less
OR likely to be obese, have features of
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma metabolic syndrome, have a family his-
glucose .200 mg/dL (11.1 mmol/L). tory of diabetes, be female, or be from a
FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; max, minority race/ethnicity, indicating a phe-
maximum. *In the absence of unequivocal hyperglycemia, result should be confirmed by notype more similar to their peers with
repeat testing.
type 1 diabetes. Pathophysiologically,
Ab2 youth with obesity are more insulin diabetes, genetic testing for monogenic complications (77–79), many of which
resistant than Ab1 youth with obesity, forms of diabetes should be considered are associated with poor glycemic con-
while Ab1 youth have more severe in- as well (67–69). trol, and rapid deterioration with in-
sulin deficiency (61–64). Fasting and creasing A1C. Finally, youth with type 2
stimulated C-peptide are significantly diabetes can be expected to have
GLYCEMIC TARGETS
lower in Ab1 youth with obesity and long disease duration and, therefore,
diabetes, though with appreciable over- Recommendations continued risk for accumulation of
lap (63). Moreover, Ab2 youth are more c A1C should be measured every glycemia-related complications. Taken
likely to exhibit features of the metabolic 3 months. E together, this evidence suggests that
syndrome (elevated systolic blood pres- c A reasonable A1C goal for most a more stringent A1C target can and
sure and ALT), while Ab1 youth have children and adolescents with should be attained in youth with type 2
significantly more frequent ketonuria at type 2 diabetes treated with oral diabetes.
initial presentation (61,64). The reported agents alone is ,7%. More strin- The evidence is insufficient regarding
rates of positive pancreatic autoanti- gent A1C goals (such as ,6.5%) the value of SMBG and how often test-
bodies in youth clinically diagnosed with may be appropriate for selected ing should be performed by youth with
type 2 diabetes vary from 10% to 75% individual patients if they can be type 2 diabetes not on insulin therapy.
(4,62), likely depending on the ratio of achieved without significant hypo- Until such data become available, the
type 1 and type 2 diabetes in the pop- glycemia or other adverse effects frequency of SMBG should be individu-
ulation. The clinical distinction between of treatment. Appropriate patients alized, taking into account patient and
youth with type 2 diabetes and youth might include those with short family burden, the value of the informa-
with obesity and type 1 or monogenic duration of diabetes and lesser tion obtained and how it will be used to
diabetes is further blurred because youth degrees of b-cell dysfunction and adjust therapy, and the associated hy-
with type 2 diabetes often present with patients treated with lifestyle or poglycemia risk.
some degree of ketosis, including DKA metformin only who achieve sig-
(65). nificant weight improvement. E LIFESTYLE MANAGEMENT
The distinction between these forms c A1C targets for youth on insulin
Diabetes Education and
of diabetes in youth with obesity has should be individualized, taking
Self-Management Skills
important implications for treatment into account the relatively low
(66), since Ab1 youth present more rate of hypoglycemia in youth- Recommendation
like individuals with type 1 diabetes, onset type 2 diabetes. E c All youth with type 2 diabetes and
progressing to insulin requirement c Home self-monitoring of blood glu- their families should receive compre-
more rapidly (61), and are at risk for cose (SMBG) regimens should be hensive diabetes self-management
other autoimmune disorders. Therefore, individualized, taking into consid- education/support that is specific
measurement of pancreatic autoanti- eration the pharmacologic treat- to youth with type 2 diabetes and is
bodies is recommended in all youth ment of the patient. E culturally competent. B
with clinical characteristics of type 2 di-
abetes. This testing should include Previous target A1C guidelines by the It has been well established that di-
GAD65 and IA2 antibodies, along with ADA and the International Society for abetes education is necessary, but not
insulin autoantibody in individuals who Pediatric and Adolescent Diabetes for sufficient, to enhance self-management
have not yet been exposed to exogenous youth with type 2 diabetes ranged in people with diabetes (80,81). The
insulin. The benefit of measurement of from ,6.5% to ,7.0% (70,71) and majority of these studies, however, fo-
ZnT8 antibody in individuals with phe- ,7.5% (72), mostly based on expert cused on adults with type 2 diabetes
notypic type 2 diabetes is not yet clear. opinion and extrapolated from youth and/or youth with type 1 diabetes. Since
We further recommend that antibod- with type 1 diabetes and adults with the population of youth with type 2
ies be measured in a laboratory aligned type 2 diabetes. However, accumulating diabetes is more likely to be of minority
with the National Institute of Diabetes evidence provides support for more ethnic/racial background than those with
and Digestive and Kidney Diseases appropriate goals. The TODAY study type 1 diabetes, and materials devel-
(NIDDK) Pancreatic Autoantibody Stan- showed that hypoglycemia is rare in oped for adults may not address issues
dardization Program because currently adolescents with type 2 diabetes, even of development in youth, culturally
available commercial assays may not be with insulin therapy (73), suggesting that appropriate programs specific to youth
sufficiently sensitive or specific. How- more stringent A1C targets are accept- with type 2 diabetes and their families
ever, in all cases, clinical judgment and able. Also in TODAY, individuals with an are necessary. Unfortunately, there are
the presence of other risk factors for A1C of .6.3% after 3 months of met- no randomized clinical trials of educa-
type 1 diabetes or type 2 diabetes should formin or an increasing A1C, even in the tion and support programs for youth
be considered in making the diagnosis, nondiabetes range (74), had a substan- with type 2 diabetes. Nonetheless, de-
and the health care team should remain tially increased risk for loss of glycemic scriptive reports suggest that programs
open to reconsidering the initial diagno- control, likely reflecting a greater de- that focus on building knowledge and
sis. Since 4.5–8.0% of youth with clinical gree of b-cell dysfunction (75,76). Fur- skills appropriate to this population are
features suggestive of type 2 diabetes thermore, individuals with youth-onset important in ensuring adequate self-
have been found to have monogenic type 2 diabetes have high rates of management.
In the TODAY trial (81), the diabetes cohort of youth with type 2 diabetes
c Patients should be screened for
education program included content reported symptoms of disordered eating
smoking and alcohol use at diag-
about type 2 diabetes physiology and behaviors, such as skipping insulin, vom-
nosis and regularly thereafter. C
treatment, building skills of healthy eat- iting, and using diet pills or laxatives,
ing habits, carbohydrate counting, por- and these behaviors were associated
The ADA position statement on the pro-
tion sizes, reading food labels, glucose with poorer glycemic control in females
vision of psychosocial care for people
monitoring, and ketone testing, as well as (89). Binge eating rates in the TODAY
living with diabetes recognizes the pro-
problem solving, risk reduction, and liv- cohort were high (26%) and were asso-
found influence of psychosocial factors
ing with diabetes. Full mastery of the ciated with more severe obesity, psycho-
on health outcomes and well-being (84).
program was achieved in an average of logical symptoms of disordered eating,
The recommendations herein are con-
5.5 90-min sessions. Factors associated and symptoms of depression (94).
sistent with those outlined in that posi-
with shorter time to mastery included More research is needed to evaluate
tion statement, an important resource
more recent diagnosis and not having to rates of diagnosable psychiatric disor-
for more detailed information about life-
use a translator, while sex, primary lan- ders, trauma, victimization, and psycho-
course issues and assessment of psycho-
guage of the youth and family, individual tropic drug use in youth with type 2
social comorbidities.
versus group sessions, or site of delivery diabetes. It also is important to elucidate
Most youth with type 2 diabetes come
were not. These program materials are the relationships among obesity, psychi-
from racial and ethnic minority groups,
available from the ADA as “Be Healthy atric disorders, and medication regimens
have low socioeconomic status, and
Today” (82). Given the lack of clinical because many of the drugs prescribed
have a family history of diabetes
trials of various educational approaches, for diabetes and psychiatric disorders
(37,85,86). Families often experience
it is unclear that this program is superior are associated with weight gain and in-
to other approaches. Nonetheless, the multiple stressors including food insecu- creased concerns about eating, shape,
program provides effective, engaging rity, employment and housing instability, and weight (95,96).
materials for youth with type 2 diabetes and difficulties with access to treatment; Finally, in accord with the ADA’s Stan-
that were designed specifically for this youth also may have been exposed to dards of Medical Care in Diabetesd2018
population. Until comparative trials of early adversity, which has been shown to (97), preconception counseling should
various approaches are completed, di- affect health over time (87). Providers be provided starting at puberty for all
abetes education using these materials should personalize approaches to diabe- girls of childbearing potential in order to
is appropriate (83). tes management to minimize barriers to increase understanding of risk related
care, enhance adherence, and maximize to diabetes and improve health prior to
response to treatment by taking into conception. In the TODAY study (98),
Psychosocial Factors consideration the sociocultural context despite counseling on pregnancy reduc-
of the patient and their family. tion designed specifically for youth with
Recommendations Youth with type 1 diabetes have high type 2 diabetes, 10.2% of the females in
c Providers should assess social con- rates of diabetes distress and psychiatric the cohort became pregnant over an
text, including potential food in- symptoms and diagnoses (in particular, average of 3.8 years of study participa-
security, housing stability, and depression and disordered eating behav- tion. Of note, 26.4% of pregnancies
financial barriers, and apply that iors) necessitating ongoing surveillance ended in a miscarriage, stillbirth, or in-
information to treatment deci- of mental and behavioral health. Evi- trauterine death, and 20.5% of the live-
sions. E dence about psychiatric disorders and born infants had a major congenital
c Use patient-appropriate standard- symptoms in youth with type 2 diabetes anomaly. These data confirm the impor-
ized and validated tools to assess is limited (88–92), but given the socio- tance of educating young women with
diabetes distress and mental/ cultural context and the medical burden, type 2 diabetes to time their pregnancies
behavioral health in youth with as well as preexisting obesity-associated to reduce risks to themselves and their
type 2 diabetes, with attention comorbidities together with type 2 di- offspring. More research regarding preg-
to symptoms of depression and abetes, ongoing surveillance of mental nancy outcomes in youth with type 2
disordered eating behaviors, and health/behavioral health is also indicated diabetes is needed.
refer to specialty care when indi- in youth with type 2 diabetes.
cated. B Symptoms of depression and disor- Lifestyle Modification, Weight
c When choosing glucose-lowering dered eating are common in youth with Management, Exercise, and Nutrition
or other medications for youth type 2 diabetes and associated with
with overweight/obesity and type Recommendations
poorer glycemic control (89). The prev-
2 diabetes, consider medication c Youth with overweight/obesity and
alence of clinically significant symptoms
adherence and treatment effects type 2 diabetes and their families
of depression among youth with type 2
on weight. E should be provided with develop-
diabetes was reported to be 8.6% in the
c Starting at puberty, preconception mentally and culturally appropriate
SEARCH cohort of youth with type 1 and
counseling should be incorporated comprehensive lifestyle programs
type 2 diabetes (89) and 14.8% in the
into routine diabetes clinic visits that are integrated with diabetes
TODAY cohort of youth with type 2 di-
for all females of childbearing po- management aiming to achieve 7–
abetes (93). In addition, more than 25%
tential. A 10% decrease in excess weight. C
of females and males in the SEARCH
were modest (103), those who re- An important first step is to integrate
c Given the necessity of long-term
ceived usual care showed increases in diabetes care and education, such as the
weight control and lifestyle man-
BMI over the period of observation, approach used in the TODAY trial, with
agement for children and adoles-
while the intervention group had con- ongoing lifestyle intervention for obesity
cents with type 2 diabetes, lifestyle
tinued improvements in body com- management (106) to maximize the im-
intervention should be based on a
position and insulin resistance relative pact of medical and lifestyle interven-
chronic care model and offered in
to those who did not receive weight tions over time. Comprehensive chronic
the context of diabetes care. E
management. care models have been recommended
c Youth with diabetes, like all chil-
The most pertinent evidence regard- for youth with obesity and chronic illness
dren, should be encouraged to
ing the impact of lifestyle interventions (112,113).
participate in at least 30–60 min
for youth with type 2 diabetes comes With the exception of orlistat, weight
of moderate to vigorous physical
from the TODAY study (104), where the loss medications are not approved for
activity at least 5 days per week
goal was to achieve 7–10% decrease in use in youth. The Endocrine Society
(and strength training on at least
percent overweight. The addition of life- guidelines for pediatric obesity (106)
3 days per week) B and should be
style intervention to metformin mono- review the limited evidence for effec-
encouraged to decrease sedentary
therapy was not associated with durable tiveness of current weight-loss medica-
behavior. C
metabolic control beyond that of met- tions and recommends that their use be
c Nutrition for youth with type 2
formin alone. Youth receiving metformin restricted to the research setting. More
diabetes, like all children, should
plus lifestyle intervention showed short- research into possible pharmacologic ap-
focus on healthy eating patterns
term, but not sustained, weight loss and proaches to augment lifestyle interven-
that emphasize consumption of
improvements in body composition rel- tions and their role in type 2 diabetes in
nutrient-dense, high-quality foods
ative to those in the two other interven- youth is urgently needed.
and decrease consumption of
tion groups (105). While 31% of youth
calorie-dense, nutrient-poor foods,
who received lifestyle intervention
particularly sugar-added bever-
achieved the preplanned goal of a de- PHARMACOLOGIC APPROACHES
ages. B
crease of $7% in percent overweight TO GLYCEMIC MANAGEMENT
c The utility of pharmacotherapy for
through 24 months of intervention, this
weight reduction in youth with Recommendations
result did not differ significantly from
type 2 diabetes remains limited c Initiate pharmacologic therapy, in
that obtained with metformin mono-
in the absence of approved, effec- addition to lifestyle therapy, at di-
therapy and no predictors of successful
tive, and safe medications and the agnosis of type 2 diabetes. A
weight loss were identified. However,
lack of clinical trials in youth with c In incidentally diagnosed or meta-
irrespective of treatment assignment,
type 2 diabetes. B bolically stable patients (A1C
sustained weight losses $7% of excess
,8.5% and asymptomatic), met-
body weight were associated with im-
Lifestyle modification programs that formin is the initial pharmacologic
provements in A1C, HDL, and C-peptide
incorporate evidence-informed behav- treatment of choice if renal func-
(105), indicating that obesity manage-
ioral strategies to promote changes in tion is normal. A
ment remains a crucial goal.
diet and physical activity (99) are a cor- c Youth with marked hyperglycemia
Components of a comprehensive pe-
nerstone of treatment for adults with (blood glucose $250 mg/dL, A1C
diatric lifestyle intervention are well es-
type 2 diabetes because the resulting $8.5%) without acidosis at diag-
tablished (106,107), including those for
reductions of 5–7% of initial body weight nosis who are symptomatic with
youth with severe obesity (108). These
are associated with improvements in polyuria, polydipsia, nocturia, and/
include the involvement of family at a
blood glucose levels and other risk pa- or weight loss should be treated
developmentally appropriate level and
rameters. Much less is known about the initially with basal insulin while
evidence-based behavioral strategies to
impact of lifestyle interventions in youth metformin is initiated and titrated.
facilitate enduring changes in nutrition
with type 2 diabetes, although 90% are B
and physical activity. Guidelines for phys-
overweight or obese. Family-based be- c In patients with ketosis/
ical activity and nutrition are based on
havioral weight management programs ketoacidosis, treatment with sub-
those recommended by the American
in school-aged children without diabetes cutaneous or intravenous insulin
Academy of Pediatrics (2007) (107) and
have a modest, but positive, impact on should be initiated to rapidly cor-
the Endocrine Society (2017) (106).
weight and cardiometabolic risk factors rect the hyperglycemia and the
Youth with type 2 diabetes frequently
but are less effective in adolescents and metabolic derangement. Once
have severe obesity, and it is particularly
children with more severe obesity (100– acidosis is resolved, metformin
important that behavior change goals
102). Intensive weight management, should be initiated while subcuta-
for diet and activity incorporate step-
neous insulin therapy is continued.
when compared with usual treatment, wise, achievable targets developed in
A
can have sustained benefits over a 2- conjunction with the youth and family
c In individuals presenting with se-
year period for ethnically and racially di- members, as appropriate.
vere hyperglycemia (blood glucose
verse inner-city children and adolescents Youth with type 2 diabetes will face
$600 mg/dL), assess for HHNK
with an average BMI .35 (102,103). increasing severity of obesity and diabe-
syndrome. A
Although BMI changes in treated youth tes complications as they age (109–111).
In the clinical setting, only a minority of Initial treatment of the youth with obe-
c In patients initially treated with
youth with type 2 diabetes are on lifestyle sity and diabetes must take into account
insulin and metformin who are
management alone (114,115) because it that diabetes type is often uncertain in
meeting glucose targets based
on home blood glucose monitoring,
is often inadequate for achieving and the first few weeks of treatment owing to
maintaining the desired level of glycemic overlap in presentation and that a sub-
insulin can be tapered over 2–
control and BMI improvement, with the stantial percentage of youth with type 2
6 weeks by decreasing the insulin
percentage of patients remaining on diabetes will present with clinically sig-
dose 10–30% every few days. B
lifestyle intervention alone declining fur- nificant ketoacidosis (65). Therefore, im-
c If the glycemic target is no longer
ther by 1 year (115). Therefore, in most mediate therapy should address the
met using metformin alone, or if
cases, the addition of pharmacologic in- hyperglycemia and associated metabolic
contraindications or intolerable
tervention early in the disease is war-
side effects of metformin develop, derangements irrespective of ultimate
ranted. As in adults, the pharmacologic
basal insulin therapy should be diabetes type, with adjustment of ther-
intervention should be a stepped pro-
initiated. B apy once metabolic compensation has
cess. However, since only metformin and
c If the combination of metformin been established and subsequent infor-
insulin are currently approved for the
plus basal insulin is ineffective at mation, such as antibody results, be-
treatment of diabetes in patients under
achieving or maintaining glycemic comes available.
18 years old, the approach in youth is
targets, more intensive approaches Figure 1 provides an approach to initial
more limited.
to insulin therapy may be initiated. treatment.
E
Initial Treatment Metformin
c The use of nonapproved medica-
Initial treatment of youth-onset type 2 Metformin is the preferred drug for initial
tions in youth with type 2 diabetes
diabetes should include metformin and/ treatment of type 2 diabetes in adults
is not recommended outside of
or insulin alone or in combination, based and youth. In the TODAY study, 48.3% of
research trials. B
on the metabolic status of the patient. youth with type 2 diabetes who were
Figure 1—Management of new-onset diabetes in overweight youth suspected to have type 2 diabetes based on risk factors listed in Table 1. MDI,
multiple daily injections.
enrolled, with less than 2 years (median data suggest that adolescents with long-acting insulin or initiation of multi-
8 months) of diabetes duration, main- type 2 diabetes who present initially ple daily injections of basal and premeal
tained adequate glycemic control (A1C with DKA, ketosis, or symptomatic hy- rapid-acting insulin should be consid-
,8.0%) on metformin alone for up to perglycemia can be managed success- ered, though adherence to the latter
6 years (104). However, youth were more fully with metformin alone, at least may be a barrier.
likely than adults to require additional initially after a short course of insulin Because severe insulin resistance is
pharmacologic treatment to meet glyce- therapy to establish glycemic stability characteristic of youth with type 2 di-
mic targets, with the other 51.7% of (117). For example, in the TODAY study, abetes, basal insulin doses above 1.5
youth on metformin requiring insulin more than 90% of the subjects screened units/kg/day may be required to achieve
by 4 years, with a median time to treat- for study participation were initially con- adequate glycemic control, particularly
ment failure of 11.8 months. trolled adequately on metformin alone for those youth with elevated A1C and
Asymptomatic youth with presumptive regardless of prior insulin therapy (117). glucotoxicity and youth who are in mid-
type 2 diabetes who present in a stable However, these TODAY participants were to late puberty. In these circumstances,
metabolic state and have A1C ,8.5% frequently contacted and closely moni- it may be appropriate to use more con-
should be started on metformin as initial tored by the research staff, a situation centrated insulin preparations (U-300
therapy if renal function is normal. Asymp- that may not be feasible in a clinical glargine [Toujeo], U-200 Tresiba, U-200
tomatic patients with A1C $8.5% may setting. Whether or not early treatment Humalog, U-500 regular) to avoid large-
also be given an initial trial of metformin with insulin provides unique benefits in volume injections that may further di-
monotherapy at the discretion of the youth with type 2 diabetes remains ques- minish medication adherence.
health care provider, especially if the tionable. The recently completed RISE The most significant adverse effect
patient and family situation suggest the Pediatric Medication Study in youth of insulin therapy in type 2 diabetes, as
promise of excellent adherence to life- with obesity with impaired glucose toler- in type 1 diabetes, is hypoglycemia. Al-
style change recommendations. ance or recent-onset type 2 diabetes did though the incidence of hypoglycemia
The recommended approach to met- not demonstrate benefits of 3 months of in youth with type 2 diabetes is low,
formin initiation is to start with a dose basal insulin glargine followed by 9 even with insulin therapy (73), patients
of 500–1,000 mg/day and gradually es- months of metformin compared with treated with insulin should be educated
calate it every 1–2 weeks, depending on metformin alone for 12 months in pre- about avoidance, recognition, and treat-
patient tolerability, to the recommended serving or restoring b-cell function (118). ment of hypoglycemia and should be
therapeutic dose of 1,000 mg b.i.d. It remains to be determined if longer instructed on the use of glucagon for
Slower dosage escalation may be needed periods of insulin treatment may prove treatment of severe hypoglycemia. Also,
if gastrointestinal side effects occur and, beneficial in preserving b-cell function. since insulin may result in weight gain,
in some cases, the maximum dose may not involvement of a nutritionist in patient
Ongoing Therapy care and education is essential when
be achievable. Extended-release metfor-
When the individualized glycemic target insulin is initiated.
min may have fewer gastrointestinal side
can no longer be met with metformin
effects and be more convenient for the
alone, or if metformin intolerance or Other Therapies
patient, but there are no studies in youth
renal insufficiency develops, insulin ther- Other than insulin and metformin, there
comparing extended-release metformin
apy should be initiated. This can be done are currently more than 25 medications in
to the standard metformin preparation.
alone or in combination with metformin, 10 general classes that are commercially
Metformin Plus Insulin unless metformin is contraindicated. Be- available and FDA-approved for treatment
Youth with marked hyperglycemia (blood cause studies indicate that adherence of type 2 diabetes in adults in the U.S.
glucose $250 mg/dL and/or A1C $8.5%) with insulin therapy is a challenge in (Table 3). It should be noted, however, that
without acidosis at diagnosis but who youth with type 2 diabetes (73,119), none of these are currently approved for
are symptomatic with polyuria, polydip- starting with a single daily dose of a use in youth (,18 years old), and while
sia, nocturia, and/or weight loss should long-acting insulin analog (glargine some of these agents have undergone
be treated initially with basal insulin [Lantus, Basalglar, Toujeo], detemir or are currently undergoing pharmaco-
while concurrently initiating and titrat- [Levemir], or degludec [Tresiba]) may kinetic, pharmacodynamics, and safety/
ing metformin. In patients with ketosis/ be preferred. Premixed insulins may be tolerability testing in small pediatric
ketoacidosis at diagnosis, treatment with appropriate in some circumstances. studies, no efficacy or long-term safety
subcutaneous or intravenous insulin should If the combination of metformin at the results have yet been reported in youth.
be initiated to rapidly correct the hyper- maximum tolerated dose (up to 1,000 mg Although the TODAY study demon-
glycemia and the metabolic derangement. b.i.d.) plus basal insulin at a maximum strated that the addition of rosiglitazone
Once acidosis is resolved, metformin dose of 1.5 units/kg/day is ineffective at to metformin improved the durability of
should be initiated while subcutane- achieving the glycemic target, medica- glycemic control (treatment failure rate
ous insulin therapy is continued (116). tion adherence should be actively ad- 38.6% for metformin plus rosiglitazone
In individuals presenting with severe dressed. When combined metformin vs. 51.7% for metformin alone) with no
hyperglycemia (blood glucose $600 and basal insulin therapy does not increased rate of adverse events over a
mg/dL), assess for HHNK syndrome. achieve targets, and in the absence of 3–6 year period in youth with recent-
Once glycemic stability is achieved, other approved drugs to treat diabetes in onset type 2 diabetes, it is premature
insulin may not be needed. Limited youth (,18 years old), higher doses of to recommend its widespread use in
Table 3—Drugs for treating type 2 diabetes in adults (not including insulin or insulin analogs) but not yet approved in
youth except for metformin
Available drugs in Approved in
Drug class this class Mechanism of action Significant adverse effects patients ,18 years old
Biguanides Metformin Decreases insulin resistance; reduces Gastrointestinal Yes
hepatic glucose production; increases Lactic acidosis
peripheral glucose uptake; decreases
gastrointestinal absorption of glucose
Sulfonylureas Glipizide Stimulates secretion of insulin from the Hypoglycemia No
Glimepiride b-cell Weight gain
Glyburide
Meglitinides Repaglinide Stimulates glucose-dependent secretion Hypoglycemia No
Nateglinide of insulin from the b-cell URI
Diarrhea
Headache
a-Glucosidase Acarbose Delays absorption of glucose by Flatulence No
inhibitors Miglitol intestines by inhibiting breakdown of Diarrhea
complex sugars Abdominal cramps
GLP-1 agonists Exenatide Incretin effect; slows gastric emptying; Acute pancreatitis No
Liraglutide enhances postprandial insulin C-cell hyperplasia/ medullary
Dulaglutide biosynthesis; improves b-cell function; thyroid carcinoma
Lixisenatide decreases appetite Nausea/vomiting
Albiglutide Hypoglycemia
Semaglutide Diarrhea
Headache
DPP-4 inhibitors Saxagliptin Inhibits DPP-4 enzyme, reducing Acute pancreatitis No
Sitagliptin endogenous GLP-1 breakdown URI
Alogliptin UTI
Linagliptin Nasopharyngitis
Headache
Amylin analog Pramlintide Inhibits postprandial glucagon secretion; Hypoglycemia No
delays gastric emptying; improves Nausea
satiety Anorexia
Abdominal pain
Thiazolidinediones Rosiglitazone PPAR-g inhibitor; increases insulin Edema No
Pioglitazone sensitivity in liver, muscle, and adipose Weight gain
tissue; decreases hepatic glucose Anemia
output Elevated liver enzymes
SGLT-2 inhibitors Canagliflozin Allows more glucose to be excreted in the Euglycemic ketoacidosis No
Dapagliflozin urine and hence lowers blood glucose UTI
Empagliflozin Candidal vulvovaginitis
Ertugliflozin
Bile acid Colesevelam Mechanism for glucose lowering is Gastrointestinal (gas, nausea, No
sequestrant unknown diarrhea, abdominal pain)
Weakness
Muscle pain
Dopamine-2 Bromocriptine Modulates hypothalamic regulation of Nausea/vomiting No
agonist (quick release) metabolism; increases insulin Fatigue
sensitivity Dizziness
Headache
DPP-4, dipeptidyl peptidase 4; GLP-1, glucagon-like peptide 1; PPAR, peroxisome proliferator–activated receptor; SGLT2, sodium–glucose
cotransporter 2; URI, upper respiratory infection; UTI, urinary tract infection.
youth with type 2 diabetes, especially implementation and completion of treatment options for this population of
since its use is not approved in the pe- such studies have been slow and patients.
diatric population. Even though many many barriers have been identified
of the newer agents approved in the (111). Therefore, we recommend that METABOLIC SURGERY
adult population are promising and the use of these medications in youth
Recommendations
may have particular benefits in youn- with type 2 diabetes be avoided outside
c Metabolic surgery may be consid-
ger individuals with diabetes, we can- of research trials. However, collabo-
ered for the treatment of adoles-
not recommend widespread use of ration among investigators, pharma-
cents with type 2 diabetes who are
these medications until additional ceutical sponsors, and governmental
markedly obese (BMI .35 kg/m2)
studies are completed. Unfortunately, regulators is urgently needed to expand
youth with type 2 diabetes from the macrovascular risk burden and a sub-
and who have uncontrolled
Teen-Longitudinal Assessment of Bariat- stantial increase in the risk of cardiovas-
glycemia and/or serious co-
ric Surgery (Teen-LABS) cohort who had cular morbidity and mortality at an
morbidities despite lifestyle and
undergone a bariatric surgical procedure earlier age than those individuals diag-
pharmacologic intervention. A
with youth with medically treated type 2 nosed later in life (148). The higher
c Metabolic surgery should be per-
diabetes from the TODAY cohort. Dur- complication risk in earlier-onset type
formed only by an experienced
ing 2 years, A1C decreased from 6.8% to 2 diabetes is likely to be related to
surgeon working as part of a well-
5.5% in Teen-LABS and increased from prolonged lifetime exposure to hy-
organized and engaged multidis-
6.4% to 7.8% in TODAY, BMI decreased perglycemia and other atherogenic risk
ciplinary team including surgeon,
by 29% in Teen-LABS and increased by factors, including insulin resistance, dys-
endocrinologist, nutritionist, behav-
3.7% in TODAY, elevated blood pres- lipidemia, hypertension, and chronic
ioral health specialist, and nurse. A
sure decreased from 45% to 20% of par- inflammation. These diabetes comorbid-
ticipants in Teen-LABS and increased ities also appear to be higher than in
Bariatric or metabolic surgery, includ-
from 22% to 41% in TODAY, and dys- youth with type 1 diabetes despite
ing Roux-en-Y gastric bypass, vertical
lipidemia decreased from 72% to 24% in shorter diabetes duration and lower
sleeve gastrectomy, laparoscopic adjust-
Teen-LAB versus no appreciable change A1C (149). In addition, the progression
able gastric banding, laparoscopic
in TODAY (142). of vascular abnormalities appears to
gastric plication, and biliopancreatic di-
Overall, studies in both adults and be more pronounced in type 2 diabe-
version, has been shown to significantly
adolescents suggest that those who tes diagnosed earlier in life compared
reduce weight, BMI (120), and cardio-
undergo bariatric surgery earlier in with type 1 diabetes of similar duration,
vascular comorbidities (121) in adults
the course of diabetes (that is, at a including ischemic heart disease and
with obesity and is now considered a
younger age or with higher baseline stroke (150,151).
standard component of care for adults
b-cell function) have a higher remission
with morbid obesity. Metabolic surgery
rate despite similar weight loss (143). Ini- Nephropathy
is also an effective strategy for preven-
tial diabetes remission rates in adults
tion (122,123) and treatment of type 2 Recommendations
range between 40% and 70%, whereas
diabetes in obese and severely obese c Blood pressure should be mea-
in adolescents the reported initial rates
(BMI $30 kg/m2) adults (124–129) and is sured at every visit. A
are as high as 68–100% (144). The long-
now endorsed as part of the algorithm c Blood pressure should be opti-
term durability of these remissions is un-
for treating type 2 diabetes in adults mized to reduce risk and/or slow
known and will require longer follow-up.
(127). the progression of diabetic kidney
Short-term and long-term complica-
Over the last decade, weight-loss sur- disease. A
tions of metabolic surgery need to be
gery has been increasingly performed in c If blood pressure is .95th percen-
taken into consideration. In Teen-LABS,
adolescents with obesity, but the long- tile for age, sex, and height, in-
13% of adolescents required a second
term experience remains limited. The creased emphasis should be
operative procedure and another 13%
current guidelines for metabolic sur- placed on lifestyle management
required an endoscopic procedure be-
gery in adolescents generally include to promote weight loss. If blood
cause of a complication (145). In the
BMI .35 kg/m2 with significant comor- pressure remains above the 95th
recent Teen-LABS/TODAY comparison,
bidities or BMI .40 kg/m2 with or with- percentile after 6 months, antihy-
30% of the youth with diabetes under-
out comorbidities (106,130–140). The pertensive therapy should be ini-
going surgical intervention required re-
Endocrine Society Clinical Practice Guide- tiated. C
admission and/or reoperation (142).
c Initial therapeutic options include
line on Pediatric Obesity discusses bar- Postoperative nutritional complications
iatric surgery for the management of ACE inhibitors or angiotensin recep-
(vitamin B12, thiamine, and vitamin D
pediatric obesity in detail, and interested tor blockers. Other blood pressure–
deficiency) are also prevalent. Long-term
readers can refer to it (106). Briefly, lowering agents may be added as
follow-up and further research is re-
positive outcomes of metabolic surgery needed. C
quired to better understand the mech-
c Protein intake should be at the
have included remission of type 2 dia- anisms by which metabolic surgery
betes, improvements in glucose homeo- recommended daily allowance of
improves type 2 diabetes and the short-
stasis in youth without diabetes, 0.8 g/kg/day. E
term and long-term benefits and risks
c Urine albumin/creatinine ratio
improvement in surrogate markers of of this procedure in youth. Quality of
(UACR) should be obtained at
insulin sensitivity and secretion, resolu- life and economic (cost-benefit) analy-
the time of diagnosis and annually
tion of sleep apnea, improvements in ses will also be important components
thereafter. An elevated UACR
nonalcoholic fatty liver disease (NAFLD), of ongoing follow-up and research
(.30 mg/g creatinine) should be
and improvements in cardiovascular dis- (146,147).
confirmed on two of three sam-
ease (CVD) risk factors, among others
ples. B
(106,134–141). Direct comparison be-
PREVENTION AND MANAGEMENT c Estimated glomerular filtration
tween the medical management of youth
OF DIABETES COMPLICATIONS rate (eGFR) should be determined
with type 2 diabetes and bariatric surgery
at the time of diagnosis and annu-
outcome, both short- and long-term, is Youth-onset type 2 diabetes is associ-
ally thereafter. E
very limited. A recent study compared ated with significant microvascular and
risk of nephropathy is much higher in myelinated fibers with numbness, tin-

c In nonpregnant youth with diabe-
youth with type 2 diabetes (158–161). gling, and poor balance along with re-
tes and hypertension, either an ACE
Spot UACR is generally recommended duced or absent reflexes, vibration
inhibitor or an angiotensin recep-
for screening of urinary albumin excre- perception, and monofilament sensa-
tor blocker is recommended for
tion, with an abnormal value confirmed tion. The “gold standard” for the diag-
those with modestly elevated
on two of three consecutive tests ob- nosis of DPN includes careful neurologic
UACR (30–299 mg/g creatinine)
tained on different days within a 3- to examination to rule out other potential
D and strongly recommended for
6-month period. Results can be affected causes of neuropathy and nerve conduc-
those with UACR .300 mg/g cre-
by orthostatic proteinuria, marked hy- tion velocity studies. The Diabetes Con-
atinine and/or eGFR ,60 mL/min/
perglycemia, exercise, menstruation, trol and Complications Trial (DCCT),
1.73 m2. E
recent intercourse, and sample contam- which used a combination of examina-
c For those with nephropathy, con-
ination. eGFR can be calculated from tion by a neurologist, nerve conduction
tinued monitoring (yearly UACR,
serum creatinine and the patient’s height velocity testing, and autonomic neurop-
eGFR, serum K) may aid in assessing
using the Schwartz equation. However, athy testing, clearly showed that im-
adherence and detecting progres-
recent studies suggest that this under- proved glycemic control reduced the
sion of disease. E
estimates hyperfiltration, which is highly incidence of diabetic neuropathy, both
c Referral to nephrology is recom-
prevalent in youth with type 2 diabetes, DPN and autonomic, by 44–60%.
mended in case of uncertainty of
and a combined estimation using serum However, most large prospective
etiology, worsening UACR, or de-
creatinine and serum cystatin C is pref- studies have not been able to include
crease in eGFR. E
erable when available (162). the gold standard of nerve conduction
In addition to optimizing glycemia, studies and have utilized less invasive
Diabetic kidney disease is diagnosed in
control of hypertension is important and less expensive approaches to the
the presence of elevated albumin excre-
to prevent and slow the progression diagnosis of diabetic neuropathy. The
tion and decreased eGFR and is the
of nephropathy. Therapeutic options in- most commonly used is the Michigan
leading cause of end-stage renal disease
clude the use of ACE inhibitors or angio- Neuropathy Screening Instrument
(152). Elevated UACR or albuminuria,
tensin receptor blockers (152,163–165). (MNSI). The MNSI is a self-administered
defined as .30 mg/g creatinine, and
If not tolerated, a calcium channel questionnaire (MNSIQ) and an examina-
hyperfiltration, defined as an eGFR be-
blocker or diuretic or combination ther- tion (MNSIE) for foot abnormalities,
tween 120 mL/min/1.73 m2 and 150
apy may be required if hypertension does distal vibration perception, and ankle
mL/min/1.73 m2 (153,154), are early ab-
not normalize on single-agent therapy. reflexes; the MNSI has been validated
normalities that indicate increased risk
in adults with type 1 diabetes as a screen-
of progression to diabetic kidney disease
ing tool for neuropathy (166–169). It
(154,155). Overt nephropathy is defined Neuropathy
should be noted, however, that the
as persistent proteinuria $500 mg/day Recommendations MNSIE does not include an assessment
or UACR $300 mg/g creatinine and an c Youth with type 2 diabetes should of small-fiber dysfunction.
eGFR ,60 mL/min/1.73 m2. be screened for the presence of Evidence of diabetic neuropathy using
Albuminuria and hyperfiltration de- neuropathy by foot examination at the MNSI was found in 26% of youth with
tected early in youth with type 2 diabe- diagnosis and annually. The exam- type 2 diabetes in the SEARCH study (168)
tes may occur because of obesity before ination should include inspection, and in 21% of an Australian cohort using
the onset of diabetes (156) and can be assessment of foot pulses, pinprick thermal (small fiber) and vibration (large
related to early vascular dysfunction and 10-g monofilament sensation fiber) threshold testing (149). In addition,
(157). In TODAY, the prevalence of micro- tests, testing of vibration sensa- more than half of the cohort had evi-
albuminuria was 6.3% at randomization tion using a 128-Hz tuning fork, dence of autonomic neuropathy (pupil-
(mean 7.8 months since diagnosis of and ankle reflexes. C lary reactivity) after a median duration
diabetes) and increased to 16.6% over c Prevention should focus on achiev- of diabetes of 1.3 years (149). In an Indian
3 years (79). This coincided with pro- ing glycemic goals. C cohort of mean age 16 years at diagnosis,
gression of dyslipidemia (from 4.5% at the prevalence of neuropathy increased
baseline to 11%) and hypertension (from Diabetic neuropathy can manifest as from 3% in those with diabetes dura-
11.6% at baseline up to 33%) (78,79) distal polyneuropathy (DPN), mononeu- tion ,5 years to 49% in those with
despite standardized therapy for these ropathy, and/or autonomic neuropathy. duration .15 years (170). In the SEARCH
comorbidities. The main determining Mononeuropathies are uncommon. DPN study, the prevalence of abnormal MNSI
factor in albuminuria progression was is usually the earliest clinically apparent was significantly higher in youth with
A1C, with 17% higher risk of developing manifestation of neuropathy in persons type 2 diabetes compared with those
albuminuria per 1% increase in A1C (79), with diabetes and most commonly with type 1 diabetes after adjustment for
consistent with findings in other studies presents with paresthesia, numbness, age and sex. This association was no
(149). Modifiable risk factors include or pain in the feet. DPN generally affects longer significant after adjustment for
obesity, dyslipidemia, hypertension, the small myelinated fibers first with the covariates of diabetes duration, waist
and glycemia (152). In some ethnic burning or stabbing pain and reduced circumference, blood pressure, HDL cho-
groups, particularly Pima Indians and or absent thermal and pinprick sen- lesterol, and microalbuminuria (168). In
First Nations people in Canada, the sation. It then progresses to larger the Australian cohort, the prevalence of
peripheral and autonomic neuropathy in of 4.9 years was 13.7%, with no evidence in clinical laboratories have been advo-
adolescents with type 2 diabetes was of macular edema or proliferative reti- cated to indicate abnormality (180).
similar to that of the type 1 diabetes nopathy (77). Retinopathy was associ- Among the noninvasive diagnostic tests,
cohort despite shorter diabetes duration ated with older age (19.1 vs. 17.9 years), MRI/MRS are currently the preferred
(1.3 vs. 6.8 years) and lower A1C (7.3% vs. longer duration of diabetes (5.6 vs. 4.7 imaging modalities, though of limited
8.5%) (149). In adolescents with type 1 years), and higher A1C (8.3% vs. 6.9%). clinical application (181). Liver ultra-
diabetes, data from the DCCT support the Moreover, the odds ratio for retinopathy sound, though a widely available clini-
importance of intensive glycemic ther- increased with increasing A1C, age, and cal tool, is operator dependent and
apy and reduction of A1C for the preven- duration of diabetes (77). In the SEARCH detects liver fat .30% with sensitivity
tion of diabetic neuropathy (171,172). study, the prevalence of retinopathy of 80%, but sensitivity is lower with
So far, such data do not exist in youth using retinal photography was 42% lower degrees of fatty infiltration and
with type 2 diabetes. at a mean age of 21 years and mean the presence of morbid obesity. Hence,
The ADA recommends that assess- duration of type 2 diabetes of 7.2 years its value in the early diagnosis of NAFLD
ment for symmetric DPN should in- (175). A1C and LDL cholesterol were is limited (181). Among the noninva-
clude a careful history and assessment significantly higher among those with sive modalities, elastography is useful
of either temperature or pinprick sensa- retinopathy compared with those within evaluating advanced fibrosis and cir-
tion (small-fiber function) and vibration out. In Pima Indians, retinopathy was rhosis (181) and is gaining wider accep-
sensation using a 128-Hz tuning fork (for detected only after age 20 years and only tance. Liver biopsy remains the gold
large-fiber function). All patients should after 5 years of diabetes duration (158). standard for diagnosis and staging of
have annual 10-g monofilament testing However, by 30 years of age, retinopathy liver disease and the only way to differ-
to identify feet at risk for ulceration and had developed in 45% of this population entiate between nonalcoholic steato-
amputation (173). Since it appears that (158). hepatitis and hepatic steatosis. Treatment
youth with type 2 diabetes develop DPN options for NAFLD remain limited, with
at least as frequently as adults, youth weight loss being most effective. Ther-
NAFLD
with type 2 diabetes should be screened apeutic agents tested in randomized
at the same frequency: at diagnosis and Recommendations clinical trials in youth include metformin,
annually. c Evaluation for NAFLD (by measur- vitamin E, and cysteamine, with no clear
ing ALT and AST) should be done at established benefit on histologic out-
diagnosis of type 2 diabetes and comes or sustained reduction in ALT
Retinopathy
annually thereafter. B (182–184).
Recommendations c Referral to gastroenterology
c Screening for retinopathy should should be considered for persis-
Obstructive Sleep Apnea
be performed by dilated fundo- tently elevated or worsening trans-
scopy or retinal photography at aminases. B Recommendation
or soon after diagnosis and annu- c Screening for symptoms of ob-
ally thereafter. C The prevalence of dysglycemia in youth structive sleep apnea (OSA) should
c Optimizing glycemia is recom- with NAFLD is higher than in those be done at each visit, and referral
mended to decrease the risk or slow without NAFLD (176). In a multicenter to a pediatric sleep specialist for
the progression of retinopathy. B cohort of youth with NAFLD, primarily of evaluation and a polysomnogram,
c Less frequent examination (every Hispanic descent, a third of the children if indicated, is recommended. OSA
2 years) may be considered if there with NAFLD had abnormalities in glucose should be treated when docu-
is adequate glycemic control and a metabolism; 23.4% had prediabetes and mented. B
normal eye exam. C 6.5% had type 2 diabetes (176). More-
over, type 2 diabetes in youth is associ- Sleep disturbance (insufficient or dis-
Diabetic retinopathy refers to changes ated with greater NAFLD histologic rupted sleep, circadian rhythm dysreg-
in the small vessels of the retina with the severity than in adults, which may ulation) and OSA are increasingly
occurrence of hemorrhages, microaneu- imply a heightened risk of progression recognized as being associated with
rysms, exudates, or abnormal vessels. The to fibrosis, cirrhosis, and hepatic failure obesity (185–189), insulin resistance
prevalence of retinopathy in youth with (176,177). Therefore, it is particularly in adults and children (52,190–195),
type 2 diabetes is reported to be between important to evaluate for NAFLD in youth and type 2 diabetes in adults (196–
2% and 40%, depending on the method- with obesity and type 2 diabetes. For 199), as well as risk for future CVD
ology used, the age of the participants, screening, transaminase levels are a clin- (200). Experimental sleep restriction
and the duration of diabetes. The prev- ical tool that is widely available and has a results in decreased glucose clearance
alence is higher with greater duration good sensitivity for the detection of more and postprandial glucose elevation
of the disease, although retinopa- advanced stages of hepatitis or fibrotic (193,201), decrease in glucose effective-
thy has been reported at diagnosis changes, but these tests are not disease ness, and variable decrease in insulin
(149,170,174). In the TODAY study, the specific; therefore, other causes of sensitivity (190,192,202). OSA may in-
prevalence of early retinopathy by digital chronic liver disease should be ruled fluence glycemic regulation in individ-
fundus photography at a mean age of out (178,179). Recently, population- uals with diabetes; in adults with type
18.1 years and mean duration of diabetes based cutoffs lower than those used 2 diabetes, treatment of OSA with
continuous positive airway pressure has versus regular menses had higher total
c Optimal cholesterol goals are LDL
been associated with improvement in testosterone, free androgen index, BMI,
,100 mg/dL (2.6 mmol/L), HDL
the glycemic profile (203), decreased and AST and lower sex hormone–binding
.35 mg/dL (0.905 mmol/L),
A1C, and improvement in insulin sensi- globulin and estradiol (215). Treatment
triglycerides ,150 mg/dL (1.7
tivity indices (204) as well as inflamma- of PCOS in adolescents includes lifestyle
mmol/L). E
tion (205) in some, but not all, studies. changes (216–218), the use of oral con-
c If LDL cholesterol is .130 mg/dL,
Further study is needed. traceptive pills (OCPs), and insulin sen-
blood glucose control should be
sitizers, such as metformin (213).
maximized and dietary counsel-
However, the use of some OCPs has
Polycystic Ovary Syndrome ing should be provided using the
been associated with unfavorable ef-
American Heart Association Step
Recommendations fects on indices of insulin sensitivity
2 diet. E
c Evaluate for polycystic ovary (219) and lipid profile (220). The use
c If LDL cholesterol remains above
syndrome (PCOS) in female ado- of metformin therapy for 3–12 months
goal after 6 months of dietary in-
lescents with type 2 diabetes, in- was associated with decrease in serum
tervention, initiate therapy with
cluding laboratory studies when androgens, improvement in lipid profile,
statin, with goal of LDL ,100
indicated. B induction of ovulation, and improvement
mg/dL. B
c Oral contraceptives for treatment in glucose tolerance and insulin sensitiv-
c If triglycerides are .400 mg/dL
of PCOS are not contraindicated for ity (216,221,222). Therefore, in girls with
(4.7 mmol/L) fasting or .1,000
girls with type 2 diabetes. C type 2 diabetes and PCOS, treatment
mg/dL (11.6 mmol/L) nonfasting,
c Metformin in addition to lifestyle with metformin in addition to lifestyle
optimize glycemia and begin fi-
modification is likely to improve the modification is likely to improve the
brate, with a goal of ,400 mg/dL
menstrual cyclicity and hyperan- metabolic dysfunction associated with
(4.7 mmol/L) fasting (to reduce risk
drogenism in girls with type 2 di- PCOS and may improve menstrual cy-
for pancreatitis). C
abetes. E clicity and hyperandrogenism (213,218).
However, for the girls in the TODAY
Although there have been no long-
PCOS affects 5–10% of females in the study, all of whom received metformin,
term studies of the outcome of
reproductive age-group and is charac- there was no treatment group (met-
cholesterol-lowering therapy in youth
terized by hyperandrogenism and amen- formin alone, metformin plus lifestyle,
with type 2 diabetes, studies in youth
orrhea or oligomenorrhea secondary to and metformin plus rosiglitazone) ef-
with familial hypercholesterolemia have
chronic anovulation (206,207). The prev- fect on menses or sex steroids at 12
shown reduction in carotid intima-media
alence of PCOS is significantly higher in and 24 months and no association of sex
thickness (IMT) with the use of statins
adolescent girls with obesity compared steroids with surrogate estimates of in-
(223,224), with similar efficacy and side
with adolescent girls without overweight/ sulin sensitivity or secretion (215). De-
effects as in adults. However, in a recent
obesity (208), but the prevalence in spite the potential negative effects of
multicenter, multinational study of youth
adolescent girls with type 2 diabetes is OCPs, which may not be shared by all
OCPs, on metabolic status and cardio- with type 1 diabetes, statin use did not
not well studied. Insulin resistance with
compensatory hyperinsulinemia are vascular risk, hormonal contraceptive have a significant effect on carotid IMT
metabolic features in both adult women therapy is more effective at addressing despite reductions in total LDL choles-
with PCOS with and without overweight/ the symptoms of hyperandrogenism terol and triglyceride concentrations
obesity (209) and in adolescent girls with and anovulation and is not contrain- (225). Although longitudinal, interven-
PCOS compared with control subjects of dicated in female youth with type 2 tional data with statins in youth-onset
similar age, body composition, and ab- diabetes (213). type 2 diabetes are not yet available,
dominal adiposity (210). In adolescent statin therapy in youth with type 2 di-
girls with PCOS and obesity, this in- abetes who do not meet LDL targets
CVD
creased insulin resistance when com- following lifestyle change intervention
bined with impaired b-cell function Recommendation is considered a reasonable approach
predisposes to prediabetes and type 2 c Intensive lifestyle interventions and aligned with overall recommenda-
diabetes (211), with higher prevalence focusing on weight loss, dyslipide- tions for dyslipidemia (226), given that
of impaired glucose tolerance (30%) and mia, hypertension, and dysglyce- dyslipidemia in youth tracks into adult-
type 2 diabetes (3.7%) (212). Therefore, mia are important to prevent overt hood and is anticipated to confer in-
it is important to obtain a menstrual macrovascular disease in early creased cardiovascular risk. Similarly,
history and evaluate female adolescents adulthood. E though there have been no studies of
with type 2 diabetes for signs and symp- the use of fibrates in youth with type 2
toms of hyperandrogenism (irregular Dyslipidemia diabetes and hypertriglyceridemia to
menses, hirsutism, acne) and to initiate prevent pancreatitis, extrapolation
Recommendations
appropriate diagnostic evaluation for from studies in adults supports the
c Lipid testing should be performed
PCOS if indicated (213,214). In the TODAY use of these agents for severe hyper-
when initial glycemic control has
cohort, 21% of adolescent girls who triglyceridemia in adolescents. Adoles-
been achieved and annually there-
were $1-year postmenarche had irreg- cent girls treated with statins or fibrates
after. B
ular menses. Those with irregular menses should receive counseling on potential
risk to the fetus and be encouraged to with adverse cardiac measures (240), chronological age, for those diagnosed
use effective birth control. though there was a protective effect between 15 and 30 years of age (246).
of cardiorespiratory fitness on functional Taken together, these data raise signif-
measures of cardiac structure and func- icant concern regarding the long-term
Cardiac Function Testing
tion in this group of largely sedentary outcome of youth-onset type 2 diabetes
Recommendation youth (241). Overall, studies to date and support the importance of aggres-
c Routine screening for heart disease indicate significant vascular dysfunction sive management of glycemia and CVD
with electrocardiogram, echocar- and greater risk of progression to overt risk factors in these youth.
diogram, or stress testing is not CVD in youth with obesity and type 2
recommended in asymptomatic diabetes. The vascular dysfunction may
TRANSITIONING FROM PEDIATRIC
youth with type 2 diabetes. B begin prior to the diagnosis of type 2
TO ADULT CARE
diabetes as a result of obesity and insulin
Macrovascular disease involves coro- resistance. Recommendation
nary, cerebral, and peripheral arterial In adults, type 2 diabetes is associated c Youth with type 2 diabetes should
disease. In adults, type 2 diabetes is with an increased risk of mortality, with be transferred to an adult-oriented
associated with doubling of risk for cardiac disease as a major cause of death diabetes specialist when deemed
CVD, including coronary heart disease (242); the excess mortality is related to appropriate by the patient and
and stroke as well as increased risk of worse glycemic control, impaired renal provider. E
heart failure, after adjusting for age, sex, function, and younger age at diabetes
smoking status, BMI, and systolic blood diagnosis (243). Youth-onset type 2 di- The process of transferring the pedi-
pressure (227). Diabetes duration is im- abetes appears to be associated with an atric patient to an adult health care
plicated as a major risk factor for CVD earlier onset of complications and an provider is a challenge that has only
(228,229), though there may also be a increased mortality risk compared with recently received attention in the liter-
worsened risk of CVD with early onset of type 1 diabetes (109,244,245). In a Swed- ature but is now recognized to be “im-
type 2 diabetes (228,230). While overt ish study, type 2 diabetes diagnosed portant and should begin well before
cardiovascular events are not expected in between 15 and 34 years of age was patients are transferred” (247). Both the
youth with type 2 diabetes, epidemio- associated with a higher standardized Society for Adolescent Medicine (248)
logical and clinical studies show that the mortality ratio than type 1 diabetes and the American Academy of Pediatrics,
atherosclerotic process starts during (2.9 and 1.8, respectively), with an in- along with other associations (249), have
childhood (231), with strong relation- creased hazard ratio for males versus position statements related to transition
ships between childhood obesity, females (P 5 0.0002) (244). Similarly, an of care for those with chronic diseases
elevated blood pressure, low HDL cho- epidemiological study from Australia and special medical needs that empha-
lesterol, and coronary artery disease in reported a significant mortality excess size the importance of a gradual and
adulthood (232–235). Furthermore, over 15–30 years of follow-up in individ- collaborative process starting a year or
studies of vascular function have dem- uals diagnosed with type 2 diabetes longer before the actual transition is to
onstrated subclinical vascular disease in between 15 and 30 years of age com- occur. Published literature on this sub-
adolescents with obesity and type 2 di- pared with type 1 diabetes, with a hazard ject recommends progressive implemen-
abetes, including elevated aortic pulse ratio of 2.0 (95% CI 1.2–3.2), despite tation as eight developmentally linked
wave velocity, a marker of vascular stiff- shorter average disease duration (26.9 steps (250,251).
ness (236), and increased carotid IMT, a vs. 36.5 years, P 5 0.01) and similar The ADA, in partnership with the other
structural measure of atherosclerosis, glycemic control (109). The mortality organizations of the ADA Transitions
compared with normoglycemic youth excess was related to an excess of car- Working Group (252), developed posi-
with and without overweight/obesity diovascular deaths in those with type 2 tion statements in 2011 (252), in
(237). In the SEARCH study, youth diabetes (50% vs. 30%, P , 0.05). In First 2014 (253), and in 2018 (254). Even
with type 2 diabetes had worse arterial Nations individuals, increased mortality for youth with type 1 diabetes, deficien-
stiffness than those with type 1 diabetes, with type 2 diabetes is reported in re- cies and gaps in the transition process
attributed to greater central adiposity lation to end-stage renal disease (159) have been demonstrated in observa-
and hypertension but not related to and is significantly higher than in indi- tional cross-sectional research. These
duration of diabetes or glycemic control viduals with youth-onset type 1 diabetes gaps are summarized in recent reviews
(238). In studies of obese youth with and (245). In a large cohort of 354 patients (250,252,255) and include minimal em-
without type 2 diabetes, carotid IMT was with type 2 diabetes diagnosed between pirical evidence about the best ap-
significantly related to glycemia, while 15 and 30 years of age compared with proaches, differences in the style and
aortic pulse wave velocity was related to a duration-matched cohort of 1,062 approach to health care delivery be-
insulin resistance and inflammation patients diagnosed between 40 and tween pediatric and adult health care
(239). In addition, total body and abdom- 50 years old, the negative effect of di- providers, lack of well-defined criteria
inal adiposity were significant determi- abetes on morbidity (albuminuria and of readiness for transition or tools to as-
nants of coronary artery calcifications in neuropathy scores) and mortality was sess readiness, gaps in health insurance
these youth (239). In TODAY, echocar- greatest for those diagnosed at a young coverage, changing social structure as
diographic evaluation revealed a rela- age. Standardized mortality adjusting adolescents enter young adulthood,
tionship of BMI and blood pressure for duration was highest, at any differences in learning styles of the patient
and teaching styles of the provider, and diabetes appear early, resulting in higher glucose concentrations in the nondiabetic
lack of health care provider training re- rates of morbidity and mortality com- through the diabetic range in overweight youth.
Diabetes Care 2011;34:2033–2040
lated to transition of care. pared with type 1 diabetes. Preexisting 8. Giannini C, Weiss R, Cali A, et al. Evidence for
Despite the prevailing evidence of the obesity and its comorbidities might play early defects in insulin sensitivity and secretion
need for better transition of care, there a key role in amplifying the complica- before the onset of glucose dysregulation in
are no controlled studies of the effec- tions of youth-onset type 2 diabetes. obese youths: a longitudinal study. Diabetes
tiveness of such programs in patients Intervention/prevention strategies for 2012;61:606–614
9. Weiss R, Caprio S, Trombetta M, Taksali SE,
with youth-onset type 2 diabetes. Pa- type 2 diabetes should not be limited to Tamborlane WV, Bonadonna R. Beta-cell func-
tients with type 1 diabetes have reduced youth with dysglycemia only, but youth tion across the spectrum of glucose tolerance in
dropout from medical care, increased with obesity at large. obese youth. Diabetes 2005;54:1735–1743
number of visits, and reduced pregnancy In closing, the present guidelines 10. Kobayashi K, Amemiya S, Higashida K, et al.
loss, DKA, and severe hypoglycemia dur- are based on current data, experi- Pathogenic factors of glucose intolerance in
obese Japanese adolescents with type 2 diabe-
ing the transition period using a “navi- ence, opinion, and gained “wisdom.” tes. Metabolism 2000;49:186–191
gator” to assist young adults (18–30 However, we anticipate that future 11. Elder DA, Prigeon RL, Wadwa RP, Dolan LM,
years old) (256–258). guidelines will change as more scientific D’Alessio DA. Beta-cell function, insulin sensitiv-
Since emerging adults with type 2 di- data emerge to support evidence-based ity, and glucose tolerance in obese diabetic and
abetes express similar concerns related recommendations. nondiabetic adolescents and young adults. J Clin
Endocrinol Metab 2006;91:185–191
to transition from pediatric to adult 12. Druet C, Tubiana-Rufi N, Chevenne D, Rigal
health care providers (259), the same O, Polak M, Levy-Marchal C. Characterization of
principles discussed above and steps to Duality of Interest. S.A. has served on a data insulin secretion and resistance in type 2 diabetes
facilitate transition that apply to those monitoring committee for AstraZeneca, data of adolescents. J Clin Endocrinol Metab 2006;91:
safety monitoring board for Boehringer Ingelheim, 401–404
with type 1 diabetes should be consid-
and advisory boards for Eli Lilly, Novo Nordisk, 13. Elder DA, Woo JG, D’Alessio DA. Impaired
ered in type 2 diabetes. and Sanofi-Aventis and has received research b-cell sensitivity to glucose and maximal insulin
grants from Eli Lilly and Novo Nordisk through secretory capacity in adolescents with type 2
her institution. F.B. has received grant sup- diabetes. Pediatr Diabetes 2010;11:314–321
CONCLUSIONS port through her institution from Johnson & 14. Defronzo RA. Banting Lecture. From the
Johnson and AstraZeneca. M.D.M. has served triumvirate to the ominous octet: a new para-
Even though our knowledge of youth- on the scientific advisory committee of WW digm for the treatment of type 2 diabetes
onset type 2 diabetes has increased International, Inc. P.Z. has served as a study mellitus. Diabetes 2009;58:773–795
tremendously over the last two decades, design consultant for Daichii Sankyo, Merck, 15. Tahrani AA, Bailey CJ, Del Prato S, Barnett
robust and evidence-based data are still Boeringer Ingelheim, Janssen, and Eli Lilly (all AH. Management of type 2 diabetes: new and
limited regarding diagnostic and thera- contracts with the University of Colorado) and future developments in treatment. Lancet 2011;
as a member of a data safety monitory board for 378:182–197
peutic approaches and prevention of Novo Nordisk. No other potential conflicts of 16. Umpaichitra V, Bastian W, Taha D, Banerji
complications. The current-day informa- interest relevant to this article were reported. MA, AvRuskin TW, Castells S. C-peptide and
tion indicates that there are fundamen- glucagon profiles in minority children with
tal differences in insulin sensitivity and References type 2 diabetes mellitus. J Clin Endocrinol Metab
b-cell function between youth and adults 1. Kahn SE, Prigeon RL, McCulloch DK, et al. 2001;86:1605–1609
with prediabetes and type 2 diabetes, Quantification of the relationship between in- 17. Weiss R, D’Adamo E, Santoro N, Hershkop K,
sulin sensitivity and beta-cell function in human Caprio S. Basal a-cell up-regulation in obese
which could possibly explain why some insulin-resistant adolescents. J Clin Endocrinol
subjects. Evidence for a hyperbolic function.
youth develop type 2 diabetes decades Diabetes 1993;42:1663–1672 Metab 2011;96:91–97
earlier than adults (23,24,260,261). 2. Gungor N, Bacha F, Saad R, Janosky J, 18. Bacha F, Gungor N, Lee S, Arslanian SA. In
Youth are more insulin resistant and Arslanian S. Youth type 2 diabetes: insulin re- vivo insulin sensitivity and secretion in obese
have b-cells that are hyperresponsive sistance, beta-cell failure, or both? Diabetes Care youth: what are the differences between normal
2005;28:638–644 glucose tolerance, impaired glucose tolerance,
to stimulation compared with adults
3. Michaliszyn SF, Mari A, Lee S, et al. b-Cell and type 2 diabetes? Diabetes Care 2009;32:
(23,24,260,261). Puberty-related physio- function, incretin effect, and incretin hormones 100–105
logic insulin resistance, particularly in in obese youth along the span of glucose toler- 19. Goran MI, Bergman RN, Avila Q, et al. Im-
obese youth, may play a role in this ance from normal to prediabetes to type 2 di- paired glucose tolerance and reduced b-cell
heightened insulin resistance. It remains abetes. Diabetes 2014;63:3846–3855 function in overweight Latino children with a
4. Umpierrez GE (Ed.). Therapy for Diabetes positive family history for type 2 diabetes. J Clin
an enigma, though, why some individuals Mellitus and Related Disorders. 6th ed. Alexan- Endocrinol Metab 2004;89:207–212
with youth-onset type 2 diabetes dem- dria, VA, American Diabetes Association, 2014 20. Weigensberg MJ, Ball GDC, Shaibi GQ, Cruz
onstrate durable control and others do 5. Bacha F, Lee S, Gungor N, Arslanian SA. From ML, Goran MI. Decreased b-cell function in
not (74). Furthermore, type 2 diabetes pre-diabetes to type 2 diabetes in obese youth: overweight Latino children with impaired fasting
appears to be more aggressive in youth pathophysiological characteristics along the glucose. Diabetes Care 2005;28:2519–2524
spectrum of glucose dysregulation. Diabetes 21. Weiss R, Taksali SE, Tamborlane WV, Burgert
than adults, with a faster rate of de- Care 2010;33:2225–2231 TS, Savoye M, Caprio S. Predictors of changes in
terioration of b-cell function (76) and 6. Tfayli H, Lee S, Arslanian S. Declining b-cell glucose tolerance status in obese youth. Diabe-
poorer response to glucose-lowering function relative to insulin sensitivity with in- tes Care 2005;28:902–909
medications (104). Future research creasing fasting glucose levels in the nondiabetic 22. Sjaarda LA, Michaliszyn SF, Lee S, et al. HbA1c
should probe the mechanisms responsi- range in children. Diabetes Care 2010;33:2024– diagnostic categories and b-cell function relative
2030 to insulin sensitivity in overweight/obese ado-
ble for this youth–adult contrast in the 7. Burns SF, Bacha F, Lee SJ, Tfayli H, Gungor N, lescents. Diabetes Care 2012;35:2559–2563
various aspects of type 2 diabetes. Lastly, Arslanian SA. Declining b-cell function relative to 23. RISE Consortium. Metabolic contrasts be-
complications in youth with type 2 insulin sensitivity with escalating OGTT 2-h tween youth and adults with impaired glucose
tolerance or recently diagnosed type 2 diabetes: 40. Hasson RE, Adam TC, Davis JN, et al. Ethnic 56. Lee JM, Wu E-L, Tarini B, Herman WH, Yoon E.
I. observations using the hyperglycemic clamp. differences in insulin action in obese African- Diagnosis of diabetes using hemoglobin A1c:
Diabetes Care 2018;41:1696–1706 American and Latino adolescents. J Clin Endo- should recommendations in adults be extrapo-
24. RISE Consortium. Metabolic contrasts be- crinol Metab 2010;95:4048–4051 lated to adolescents? J Pediatr 2011;158:947–
tween youth and adults with impaired glucose 41. Bacha F, Gungor N, Lee S, Arslanian SA. Type 952.e3
tolerance or recently diagnosed type 2 diabetes: 2 diabetes in youth: are there racial differences in 57. Chan CL, Pyle L, Newnes L, Nadeau KJ, Zeitler
II. observations using the oral glucose tolerance b-cell responsiveness relative to insulin sensi- PS, Kelsey MM. Continuous glucose monitoring
test. Diabetes Care 2018;41:1707–1716 tivity? Pediatr Diabetes 2012;13:259–265 and its relationship to hemoglobin A1c and oral
25. Arslanian SA, Bacha F, Saad R, Gungor N. 42. Weiss R, Dziura JD, Burgert TS, Taksali SE, glucose tolerance testing in obese and predia-
Family history of type 2 diabetes is associated Tamborlane WV, Caprio S. Ethnic differences in betic youth. J Clin Endocrinol Metab 2015;100:
with decreased insulin sensitivity and an im- beta cell adaptation to insulin resistance in obese 902–910
paired balance between insulin sensitivity and children and adolescents. Diabetologia 2006;49: 58. Love-Osborne KA, Sheeder JL, Nadeau KJ,
insulin secretion in white youth. Diabetes Care 571–579 Zeitler P. Longitudinal follow up of dysglycemia
2005;28:115–119 43. Copeland KC, Zeitler P, Geffner M, et al.; in overweight and obese pediatric patients.
26. Giannini C, Dalla Man C, Groop L, et al. Co- TODAY Study Group. Characteristics of adoles- Pediatr Diabetes 2018;19:199–204
occurrence of risk alleles in or near genes mod- cents and youth with recent-onset type 2 di- 59. Gungor N, Hannon T, Libman I, Bacha F,
ulating insulin secretion predisposes obese youth abetes: the TODAY cohort at baseline. J Clin Arslanian S. Type 2 diabetes mellitus in youth:
to prediabetes. Diabetes Care 2014;37:475–482 Endocrinol Metab 2011;96:159–167 the complete picture to date. Pediatr Clin North
27. Sartorius T, Staiger H, Ketterer C, et al. 44. Goran MI, Gower BA. Longitudinal study on Am 2005;52:1579–1609
Association of common genetic variants in the pubertal insulin resistance. Diabetes 2001;50: 60. DuBose SN, Hermann JM, Tamborlane WV,
MAP4K4 locus with prediabetic traits in hu- 2444–2450 et al.; Type 1 Diabetes Exchange Clinic Network
mans. PLoS One 2012;7:e47647 45. Hannon TS, Janosky J, Arslanian SA. Longi- and Diabetes Prospective Follow-up Registry.
28. Kwak SH, Park KS. Genetics of type 2 diabetes tudinal study of physiologic insulin resistance Obesity in youth with type 1 diabetes in Ger-
and potential clinical implications. Arch Pharm and metabolic changes of puberty. Pediatr Res many, Austria, and the United States. J Pediatr
Res 2013;36:167–177 2006;60:759–763 2015;167:627–632.e4
29. So H-C, Gui AHS, Cherny SS, Sham PC. 46. Ball GDC, Huang TT-K, Gower BA, et al. 61. Klingensmith GJ, Pyle L, Arslanian S, et al.;
Evaluating the heritability explained by known Longitudinal changes in insulin sensitivity, insulin TODAY Study Group. The presence of GAD and
susceptibility variants: a survey of ten complex secretion, and b-cell function during puberty. IA-2 antibodies in youth with a type 2 diabetes
diseases. Genet Epidemiol 2011;35:310–317 J Pediatr 2006;148:16–22 phenotype: results from the TODAY study. Di-
30. Billings LK, Florez JC. The genetics of type 2 47. Kelly LA, Lane CJ, Weigensberg MJ, Toledo- abetes Care 2010;33:1970–1975
diabetes: what have we learned from GWAS? Corral CM, Goran MI. Pubertal changes of insulin 62. Hannon TS, Arslanian SA. The changing face
Ann N Y Acad Sci 2010;1212:59–77 sensitivity, acute insulin response, and b-cell of diabetes in youth: lessons learned from stud-
31. Gill-Carey O, Hattersley AT. Genetics and function in overweight Latino youth. J Pediatr ies of type 2 diabetes. Ann N Y Acad Sci 2015;
type 2 diabetes in youth. Pediatr Diabetes 2007; 2011;158:442–446 1353:113–137
8(Suppl. 9):42–47 48. Carnethon MR, Kinder LS, Fair JM, Stafford 63. Bacha F, Gungor N, Lee S, de las Heras J,
32. Dabelea D, Dolan LM, D’Agostino R Jr, et al. RS, Fortmann SP. Symptoms of depression as a Arslanian S. Indices of insulin secretion during a
Association testing of TCF7L2 polymorphisms risk factor for incident diabetes: findings from liquid mixed-meal test in obese youth with di-
with type 2 diabetes in multi-ethnic youth. the National Health and Nutrition Examination abetes. J Pediatr 2013;162:924–929
Diabetologia 2011;54:535–539 Epidemiologic Follow-up Study, 1971-1992. 64. Tfayli H, Bacha F, Gungor N, Arslanian S.
33. Dabelea D. The predisposition to obesity Am J Epidemiol 2003;158:416–423 Phenotypic type 2 diabetes in obese youth:
and diabetes in offspring of diabetic mothers. 49. Hannon TS, Rofey DL, Lee S, Arslanian SA. insulin sensitivity and secretion in islet cell
Diabetes Care 2007;30(Suppl. 2):S169–S174 Depressive symptoms and metabolic markers of antibody-negative versus -positive patients. Di-
34. McMillen IC, Rattanatray L, Duffield JA, et al. risk for type 2 diabetes in obese adolescents. abetes 2009;58:738–744
The early origins of later obesity: pathways and Pediatr Diabetes 2013;14:497–503 65. Pinhas-Hamiel O, Dolan LM, Zeitler PS. Di-
mechanisms. Adv Exp Med Biol 2009;646:71–81 50. Cappuccio FP, D’Elia L, Strazzullo P, Miller abetic ketoacidosis among obese African-
35. Chernausek SD, Arslanian S, Caprio S, et al. MA. Quantity and quality of sleep and incidence American adolescents with NIDDM. Diabetes
Relationship between parental diabetes and of type 2 diabetes: a systematic review and Care 1997;20:484–486
presentation of metabolic and glycemic function meta-analysis. Diabetes Care 2010;33:414– 66. Smith RJ, Nathan DM, Arslanian SA, Groop L,
in youth with type 2 diabetes: baseline findings 420 Rizza RA, Rotter JI. Individualizing therapies in
from the TODAY trial. Diabetes Care 2016;39: 51. Hannon TS, Lee S, Chakravorty S, Lin Y, type 2 diabetes mellitus based on patient char-
110–117 Arslanian SA. Sleep-disordered breathing in acteristics: what we know and what we need to
36. Dabelea D, Mayer-Davis EJ, Lamichhane AP, obese adolescents is associated with visceral know. J Clin Endocrinol Metab 2010;95:1566–
et al. Association of intrauterine exposure to adiposity and markers of insulin resistance. 1574
maternal diabetes and obesity with type 2 Int J Pediatr Obes 2011;6:157–160 67. Kleinberger JW, Copeland KC, Gandica RG,
diabetes in youth: the SEARCH Case-Control 52. Koren D, Levitt Katz LE, Brar PC, Gallagher PR, et al. Monogenic diabetes in overweight and
Study. Diabetes Care 2008;31:1422–1426 Berkowitz RI, Brooks LJ. Sleep architecture and obese youth diagnosed with type 2 diabetes: the
37. Dabelea D, Mayer-Davis EJ, Saydah S, et al.; glucose and insulin homeostasis in obese ado- TODAY clinical trial. Genet Med 2018;20:583–
SEARCH for Diabetes in Youth Study. Prevalence lescents. Diabetes Care 2011;34:2442–2447 590
of type 1 and type 2 diabetes among children 53. American Diabetes Association. Classifica- 68. Pihoker C, Gilliam LK, Ellard S, et al.;
and adolescents from 2001 to 2009. JAMA 2014; tion and diagnosis of diabetes. Sec. 2. In Standard SEARCH for Diabetes in Youth Study Group.
311:1778–1786 of Medical Care in Diabetesd2017. Diabetes Prevalence, characteristics and clinical diagno-
38. Arslanian SA. Metabolic differences be- Care 2017;40(Suppl. 1):S11–S24 sis of maturity onset diabetes of the young due
tween Caucasian and African-American children 54. Buse JB, Kaufman FR, Linder B, Hirst K, El to mutations in HNF1A, HNF4A, and gluco-
and the relationship to type 2 diabetes mellitus. Ghormli L, Willi S; HEALTHY Study Group. Di- kinase: results from the SEARCH for Diabetes
J Pediatr Endocrinol Metab 2002;15(Suppl. 1): abetes screening with hemoglobin A1c versus in Youth. J Clin Endocrinol Metab 2013;98:
509–517 fasting plasma glucose in a multiethnic middle- 4055–4062
39. Bacha F, Saad R, Gungor N, Janosky J, school cohort. Diabetes Care 2013;36:429– 69. Hattersley AT, Greeley SAW, Polak M, et al.
Arslanian SA. Obesity, regional fat distribution, 435 ISPAD 2018 Consensus Guidelines: the diagno-
and syndrome X in obese black versus white 55. Nowicka P, Santoro N, Liu H, et al. Utility of sis and management of monogenic diabetes
adolescents: race differential in diabetogenic hemoglobin A1c for diagnosing prediabetes and in children and adolescents. Pediatr Diabetes.
and atherogenic risk factors. J Clin Endocrinol diabetes in obese children and adolescents. Di- 17 September 2018 [Epub before print]. DOI:
Metab 2003;88:2534–2540 abetes Care 2011;34:1306–1311 10.1111/pedi.12772
70. Zeitler P, Fu J, Tandon N, et al.; International 86. Naughton MJ, Ruggiero AM, Lawrence JM, ethnically diverse pediatric population. Pediat-
Society for Pediatric and Adolescent Diabetes. et al.; SEARCH for Diabetes in Youth Study Group. rics 2011;127:402–410
ISPAD Clinical Practice Consensus Guidelines Health-related quality of life of children and 104. TODAY Study Group. A clinical trial to main-
2014. Type 2 diabetes in the child and ado- adolescents with type 1 or type 2 diabetes tain glycemic control in youth with type 2 dia-
lescent. Pediatr Diabetes 2014;15(Suppl. 20): mellitus: SEARCH for Diabetes in Youth Study. betes. N Engl J Med 2012;366:2247–2256
26–46 Arch Pediatr Adolesc Med 2008;162:649–657 105. Marcus MD, Wilfley DE, El Ghormli L, et al.;
71. Zeitler P, Arslanian S, Fu J, et al. Type 2 di- 87. Whalen DJ, Belden AC, Tillman R, Barch DM, TODAY Study Group. Weight change in the
abetes mellitus (T2DM) in youth. Pediatr Di- Luby JL. Early adversity, psychopathology, and management of youth-onset type 2 diabetes:
abetes. 12 July 2018 [Epub before print]. DOI: latent class profiles of global physical health from the TODAY clinical trial experience. Pediatr Obes
10.1111/pedi.12719 preschool through early adolescence. Psycho- 2017;12:337–345
72. American Diabetes Association. 12. Children som Med 2016;78:1008–1018 106. Styne DM, Arslanian SA, Connor EL, et al.
and adolescents: Standards of Medical Care in 88. Cefalu WT. “TODAY” reflects on the changing Pediatric obesitydassessment, treatment, and
Diabetesd2018. Diabetes Care 2018;41(Suppl. “faces” of type 2 diabetes. Diabetes Care 2013; prevention: an Endocrine Society clinical practice
1):S126–S136 36:1732–1734 guideline. J Clin Endocrinol Metab 2017;102:
73. TODAY Study Group. Safety and tolerability 89. Lawrence JM, Standiford DA, Loots B, et al.; 709–757
of the treatment of youth-onset type 2 diabetes: SEARCH for Diabetes in Youth Study. Prevalence 107. Barlow SE; Expert Committee. Expert com-
the TODAY experience. Diabetes Care 2013;36: and correlates of depressed mood among youth mittee recommendations regarding the pre-
1765–1771 with diabetes: the SEARCH for Diabetes in Youth vention, assessment, and treatment of child
74. Zeitler P, Hirst K, Copeland KC, et al.; TODAY study. Pediatrics 2006;117:1348–1358 and adolescent overweight and obesity: sum-
Study Group. HbA1c after a short period of 90. Levitt Katz LE, Swami S, Abraham M, et al. mary report. Pediatrics 2007;120(Suppl. 4):
monotherapy with metformin identifies durable Neuropsychiatric disorders at the presentation S164–S192
glycemic control among adolescents with type 2 of type 2 diabetes mellitus in children. Pediatr 108. Kelly AS, Barlow SE, Rao G, et al.; American
diabetes. Diabetes Care 2015;38:2285–2292 Diabetes 2005;6:84–89 Heart Association Atherosclerosis, Hypertension,
75. Arslanian S, El Ghormli L, Bacha F, et al.; 91. Lewis-Fernández R, Rotheram-Borus MJ, and Obesity in the Young Committee of the
TODAY Study Group. Adiponectin, insulin sensi- Betts VT, et al. Rethinking funding priorities in Council on Cardiovascular Disease in the Young,
tivity, b-cell function, and racial/ethnic disparity mental health research. Br J Psychiatry 2016;208: Council on Nutrition, Physical Activity and Me-
in treatment failure rates in TODAY. Diabetes 507–509 tabolism, and Council on Clinical Cardiology.
Care 2017;40:85–93 92. Reinehr T. Type 2 diabetes mellitus in chil- Severe obesity in children and adolescents:
76. TODAY Study Group. Effects of metformin, dren and adolescents. World J Diabetes 2013;4: identification, associated health risks, and treat-
metformin plus rosiglitazone, and metformin 270–281 ment approaches: a scientific statement from
plus lifestyle on insulin sensitivity and b-cell 93. Anderson BJ, Edelstein S, Abramson NW, the American Heart Association. Circulation 2013;
function in TODAY. Diabetes Care 2013;36: et al. Depressive symptoms and quality of life in 128:1689–1712
1749–1757 adolescents with type 2 diabetes: baseline data 109. Constantino MI, Molyneaux L, Limacher-
77. TODAY Study Group. Retinopathy in from the TODAY study. Diabetes Care 2011;34: Gisler F, et al. Long-term complications and
youth with type 2 diabetes participating in 2205–2207 mortality in young-onset diabetes: type 2 di-
the TODAY clinical trial. Diabetes Care 2013; 94. Wilfley D, Berkowitz R, Goebel-Fabbri A, abetes is more hazardous and lethal than type 1
36:1772–1774 et al.; TODAY Study Group. Binge eating, diabetes. Diabetes Care 2013;36:3863–3869
78. TODAY Study Group. Lipid and inflammatory mood, and quality of life in youth with type 2 110. Imperatore G, Boyle JP, Thompson TJ, et al.;
cardiovascular risk worsens over 3 years in youth diabetes: baseline data from the today study. SEARCH for Diabetes in Youth Study Group.
with type 2 diabetes: the TODAY clinical trial. Diabetes Care 2011;34:858–860 Projections of type 1 and type 2 diabetes burden
Diabetes Care 2013;36:1758–1764 95. Shelton RC. Depression, antidepressants, in the U.S. population aged ,20 years through
79. TODAY Study Group. Rapid rise in hyper- and weight gain in children. Obesity (Silver 2050: dynamic modeling of incidence, mortality,
tension and nephropathy in youth with type 2 Spring) 2016;24:2450 and population growth. Diabetes Care 2012;35:
diabetes: the TODAY clinical trial. Diabetes Care 96. Baeza I, Vigo L, de la Serna E, et al. The effects 2515–2520
2013;36:1735–1741 of antipsychotics on weight gain, weight-related 111. Nadeau KJ, Anderson BJ, Berg EG, et al.
80. Padgett D, Mumford E, Hynes M, Carter R. hormones and homocysteine in children and Youth-onset type 2 diabetes consensus report:
Meta-analysis of the effects of educational and adolescents: a 1-year follow-up study. Eur Child current status, challenges, and priorities. Diabe-
psychosocial interventions on management of Adolesc Psychiatry 2017;26:35–46 tes Care 2016;39:1635–1642
diabetes mellitus. J Clin Epidemiol 1988;41: 97. American Diabetes Association. 13. Manage- 112. Dietz WH, Solomon LS, Pronk N, et al. An
1007–1030 ment of diabetes in pregnancy: Standards of integrated framework for the prevention and
81. Grey M, Schreiner B, Pyle L. Development Medical Care in Diabetesd2018. Diabetes Care treatment of obesity and its related chronic
of a diabetes education program for youth with 2018;41(Suppl. 1):S137–S143 diseases. Health Aff (Millwood) 2015;34:1456–
type 2 diabetes. Diabetes Educ 2009;35:108–116 98. Klingensmith GJ, Pyle L, Nadeau KJ, et al.; 1463
82. American Diabetes Association. Be Healthy TODAY Study Group. Pregnancy outcomes in 113. Wilfley DE, Staiano AE, Altman M, et al.;
Today; Be Healthy For Life [Internet]. Available youth with type 2 diabetes: the TODAY study Improving Access and Systems of Care for
from http://main.diabetes.org/dorg/PDFs/Type-2- experience. Diabetes Care 2016:39:122–129 Evidence-Based Childhood Obesity Treatment
Diabetes-in-Youth/Type-2-Diabetes-in-Youth.pdf. 99. Zylke JW, Bauchner H. The unrelenting chal- Conference Workgroup. Improving access and
Accessed 12 September 2017 lenge of obesity. JAMA 2016;315:2277–2278 systems of care for evidence-based childhood
83. Atkinson A, Radjenovic D. Meeting quality 100. Coles N, Birken C, Hamilton J. Emerging obesity treatment: conference key findings
standards for self-management education in pe- treatments for severe obesity in children and and next steps. Obesity (Silver Spring) 2017;
diatric type 2 diabetes. Diabetes Spectr 2007;20: adolescents. BMJ 2016;354:i4116 25:16–29
40–46 101. Danielsson P, Kowalski J, Ekblom Ö, Marcus 114. Rothman RL, Mulvaney S, Elasy TA, et al.
84. Young-Hyman D, de Groot M, Hill-Briggs F, C. Response of severely obese children and Self-management behaviors, racial disparities,
Gonzalez JS, Hood K, Peyrot M. Psychosocial care adolescents to behavioral treatment. Arch Pe- and glycemic control among adolescents with
for people with diabetes: a position statement diatr Adolesc Med 2012;166:1103–1108 type 2 diabetes. Pediatrics 2008;121:e912–e919
of the American Diabetes Association. Diabetes 102. Savoye M, Shaw M, Dziura J, et al. Effects 115. Shield JPH, Lynn R, Wan KC, Haines L,
Care 2016;39:2126–2140 of a weight management program on body Barrett TG. Management and 1 year outcome
85. Liu LL, Lawrence JM, Davis C, et al.; SEARCH composition and metabolic parameters in over- for UK children with type 2 diabetes. Arch Dis
for Diabetes in Youth Study Group. Prevalence of weight children: a randomized controlled trial. Child 2009;94:206–209
overweight and obesity in youth with diabetes in JAMA 2007;297:2697–2704 116. Zeitler P, Haqq A, Rosenbloom A, Glaser
USA: the SEARCH for Diabetes in Youth study. 103. Savoye M, Nowicka P, Shaw M, et al. Long- N; Drugs and Therapeutics Committee of the
Pediatr Diabetes 2010;11:4–11 term results of an obesity program in an Lawson Wilkins Pediatric Endocrine Society.
Hyperglycemic hyperosmolar syndrome in chil- 132. Sugerman HJ, Sugerman EL, DeMaria EJ, Policy Lab results. Diabetes Care 2016;39:954–
dren: pathophysiological considerations and et al. Bariatric surgery for severely obese 963
suggested guidelines for treatment. J Pediatr adolescents. J Gastrointest Surg 2003;7:102– 147. Morton JM. Ethnic considerations for met-
2011;158:9–14.e2. 108 abolic surgery. Diabetes Care 2016;39:949–
117. Kelsey MM, Geffner ME, Guandalini C, 133. Inge TH, Garcia V, Daniels S, et al. A 953
et al.; Treatment Options for Type 2 Diabetes multidisciplinary approach to the adolescent 148. Song SH, Hardisty CA. Early onset type 2
in Adolescents and Youth Study Group. Presen- bariatric surgical patient. J Pediatr Surg 2004; diabetes mellitus: a harbinger for complications
tation and effectiveness of early treatment of 39:442–447; discussion 446–447 in later yearsdclinical observation from a sec-
type 2 diabetes in youth: lessons from the TODAY 134. Lawson ML, Kirk S, Mitchell T, et al.; Pe- ondary care cohort. QJM 2009;102:799–806
study. Pediatr Diabetes 2016:17:212–221 diatric Bariatric Study Group. One-year outcomes 149. Eppens MC, Craig ME, Cusumano J, et al.
118. RISE Consortium. Impact of insulin and of Roux-en-Y gastric bypass for morbidly obese Prevalence of diabetes complications in adoles-
metformin versus metformin alone on b-cell adolescents: a multicenter study from the Pe- cents with type 2 compared with type 1 diabetes.
function in youth with impaired glucose toler- diatric Bariatric Study Group. J Pediatr Surg Diabetes Care 2006;29:1300–1306
ance or recently diagnosed type 2 diabetes. 2006;41:137–143 150. Song SH. Complication characteristics be-
Diabetes Care 2018;41:1717–1725 135. Inge TH, Zeller M, Harmon C, et al. Teen- tween young-onset type 2 versus type 1 diabetes
119. Levitt Katz LE, Bacha F, Gidding SS, et al.; Longitudinal Assessment of Bariatric Surgery: in a UK population. BMJ Open Diabetes Res Care
TODAY Study Group. Lipid profiles, inflammatory methodological features of the first prospective 2015;3:e000044
markers, and insulin therapy in youth with type 2 multicenter study of adolescent bariatric sur- 151. Dabelea D, Stafford JM, Mayer-Davis EJ,
diabetes. J Pediatr 2018;196:208–216.e2 gery. J Pediatr Surg 2007;42:1969–1971 et al.; SEARCH for Diabetes in Youth Research
120. Blackburn GL, Hutter MM, Harvey AM, et al. 136. Ells LJ, Mead E, Atkinson G, et al. Surgery for Group. Association of type 1 diabetes vs type 2
Expert panel on weight loss surgery: executive the treatment of obesity in children and ado- diabetes diagnosed during childhood and ado-
report update. Obesity (Silver Spring) 2009;17: lescents. Cochrane Database Syst Rev 2015;6: lescence with complications during teenage
842–862 CD011740 years and young adulthood. JAMA 2017;317:
121. Adams TD, Arterburn DE, Nathan DM, Eckel 137. Michalsky MP, Inge TH, Simmons M, et al.; 825–835
RH. Clinical outcomes of metabolic surgery: Teen-LABS Consortium. Cardiovascular risk fac- 152. Tuttle KR, Bakris GL, Bilous RW, et al. Di-
microvascular and macrovascular complications. tors in severely obese adolescents: the Teen abetic kidney disease: a report from an ADA
Diabetes Care 2016;39:912–923 Longitudinal Assessment of Bariatric Surgery Consensus Conference. Diabetes Care 2014;37:
122. Carlsson LMS, Peltonen M, Ahlin S, et al. (Teen-LABS) Study. JAMA Pediatr 2015;169: 2864–2883
Bariatric surgery and prevention of type 2 di- 438–444 153. Magee GM, Bilous RW, Cardwell CR, Hunter
abetes in Swedish obese subjects. N Engl J Med 138. Zeinoddini A, Heidari R, Talebpour M. SJ, Kee F, Fogarty DG. Is hyperfiltration associated
2012;367:695–704 Laparoscopic gastric plication in morbidly obese with the future risk of developing diabetic ne-
123. Plum L, Ahmed L, Febres G, et al. Compar- adolescents: a prospective study. Surg Obes Relat phropathy? A meta-analysis. Diabetologia 2009;
ison of glucostatic parameters after hypocaloric Dis 2014;10:1135–1139 52:691–697
diet or bariatric surgery and equivalent weight 139. Göthberg G, Gronowitz E, Flodmark C-E, 154. Ruggenenti P, Porrini EL, Gaspari F, et al.;
loss. Obesity (Silver Spring) 2011;19:2149– et al. Laparoscopic Roux-en-Y gastric bypass in GFR Study Investigators. Glomerular hyperfiltra-
2157 adolescents with morbid obesitydsurgical as- tion and renal disease progression in type 2
124. Schauer PR, Kashyap SR, Wolski K, et al. pects and clinical outcome. Semin Pediatr Surg diabetes. Diabetes Care 2012;35:2061–2068
Bariatric surgery versus intensive medical ther- 2014;23:11–16 155. Chida S, Fujita Y, Ogawa A, et al. Levels of
apy in obese patients with diabetes. N Engl J Med 140. Inge TH, Prigeon RL, Elder DA, et al. Insulin albuminuria and risk of developing macroalbu-
2012;366:1567–1576 sensitivity and b-cell function improve after minuria in type 2 diabetes: historical cohort
125. Schauer PR, Bhatt DL, Kirwan JP, et al.; gastric bypass in severely obese adolescents. J study. Sci Rep 2016;6:26380
STAMPEDE Investigators. Bariatric surgery ver- Pediatr 2015;167:1042–1048.e1 156. Burgert TS, Dziura J, Yeckel C, et al. Micro-
sus intensive medical therapy for diabetesd5- 141. Inge TH, Miyano G, Bean J, et al. Reversal of albuminuria in pediatric obesity: prevalence
year outcomes. N Engl J Med 2017;376:641–651 type 2 diabetes mellitus and improvements and relation to other cardiovascular risk factors.
126. Mingrone G, Panunzi S, De Gaetano A, et al. in cardiovascular risk factors after surgical Int J Obes (Lond) 2006;30:273–280
Bariatric-metabolic surgery versus conventional weight loss in adolescents. Pediatrics 2009; 157. Bartz SK, Caldas MC, Tomsa A,
medical treatment in obese patients with type 2 123:214–222 Krishnamurthy R, Bacha F. Urine albumin-to-
diabetes: 5 year follow-up of an open-label, 142. Inge TH, Laffel LM, Jenkins TM, et al.; Teen– creatinine ratio: a marker of early endothelial
single-centre, randomised controlled trial. Lan- Longitudinal Assessment of Bariatric Surgery dysfunction in youth. J Clin Endocrinol Metab
cet 2015;386:964–973 (Teen-LABS) and Treatment Options of Type 2 2015;100:3393–3399
127. Rubino F, Nathan DM, Eckel RH, et al.; Diabetes in Adolescents and Youth (TODAY) 158. Krakoff J, Lindsay RS, Looker HC, Nelson RG,
Delegates of the 2nd Diabetes Surgery Summit. Consortia. Comparison of surgical and medical Hanson RL, Knowler WC. Incidence of retinop-
Metabolic surgery in the treatment algorithm for therapy for type 2 diabetes in severely obese athy and nephropathy in youth-onset compared
type 2 diabetes: a joint statement by interna- adolescents. JAMA Pediatr 2018;172:452–460 with adult-onset type 2 diabetes. Diabetes Care
tional diabetes organizations. Diabetes Care 143. Beamish AJ, D’Alessio DA, Inge TH. Con- 2003;26:76–81
2016;39:861–877 troversial issues: when the drugs don’t work, can 159. Dyck RF, Jiang Y, Osgood ND. The long-term
128. Cummings DE, Cohen RV. Bariatric/ surgery provide a different outcome for dia- risks of end stage renal disease and mortality
metabolic surgery to treat type 2 diabetes in betic adolescents? Surg Obes Relat Dis 2015; among First Nations and non-First Nations peo-
patients with a BMI ,35 kg/m2. Diabetes Care 11:946–948 ple with youth-onset diabetes. Can J Diabetes
2016;39:924–933 144. Shah AS, D’Alessio D, Ford-Adams ME, 2014;38:237–243
129. Schauer PR, Mingrone G, Ikramuddin S, Desai AP, Inge TH. Bariatric surgery: a potential 160. Dart AB, Sellers EA, Martens PJ, Rigatto C,
Wolfe B. Clinical outcomes of metabolic surgery: treatment for type 2 diabetes in youth. Diabetes Brownell MD, Dean HJ. High burden of kidney
efficacy of glycemic control, weight loss, and Care 2016;39:934–940 disease in youth-onset type 2 diabetes. Diabetes
remission of diabetes. Diabetes Care 2016;39: 145. Inge TH, Jenkins TM, Xanthakos SA, et al. Care 2012;35:1265–1271
902–911 Long-term outcomes of bariatric surgery in ado- 161. Nelson RG, Newman JM, Knowler WC,
130. Pratt JSA, Lenders CM, Dionne EA, et al. lescents with severe obesity (FABS-51): a pro- et al. Incidence of end-stage renal disease in
Best practice updates for pediatric/adolescent spective follow-up analysis. Lancet Diabetes type 2 (non-insulin-dependent) diabetes mel-
weight loss surgery. Obesity (Silver Spring) 2009; Endocrinol 2017;5:165–173 litus in Pima Indians. Diabetologia 1988;31:
17:901–910 146. Rubin JK, Hinrichs-Krapels S, Hesketh R, 730–736
131. Dolan K, Creighton L, Hopkins G, Fielding G. Martin A, Herman WH, Rubino F. Identifying 162. Bjornstad P, Škrtić M, Lytvyn Y, Maahs DM,
Laparoscopic gastric banding in morbidly obese barriers to appropriate use of metabolic/ Johnson RJ, Cherney DZ. The Gomez’ equations
adolescents. Obes Surg 2003;13:101–104 bariatric surgery for type 2 diabetes treatment: and renal hemodynamic function in kidney
disease research. Am J Physiol Renal Physiol diabetes in children with nonalcoholic fatty liver 191. Buxton OM, Pavlova M, Reid EW, Wang W,
2016;311:F967–F975 disease. JAMA Pediatr 2016;170:e161971 Simonson DC, Adler GK. Sleep restriction for
163. Salardi S, Balsamo C, Zucchini S, et al. High 177. Xanthakos SA, Jenkins TM, Kleiner DE, et al.; 1 week reduces insulin sensitivity in healthy
rate of regression from micro-macroalbuminuria Teen-LABS Consortium. High prevalence of non- men. Diabetes 2010;59:2126–2133
to normoalbuminuria in children and adoles- alcoholic fatty liver disease in adolescents un- 192. Tasali E, Leproult R, Ehrmann DA, Van
cents with type 1 diabetes treated or not dergoing bariatric surgery. Gastroenterology Cauter E. Slow-wave sleep and the risk of
with enalapril: the influence of HDL cholesterol. 2015;149:623–634.e8 type 2 diabetes in humans. Proc Natl Acad Sci
Diabetes Care 2011;34:424–429 178. Chan W-K, Sthaneshwar P, Nik Mustapha U S A 2008;105:1044–1049
164. Solis-Herrera C, Triplitt CL, Lynch JL. Ne- NR, Mahadeva S. Limited utility of plasma M30 193. Spiegel K, Leproult R, Van Cauter E. Impact
phropathy in youth and young adults with type 2 in discriminating non-alcoholic steatohepatitis of sleep debt on metabolic and endocrine func-
diabetes. Curr Diab Rep 2014;14:456 from steatosisda comparison with routine tion. Lancet 1999;354:1435–1439
165. Heart Outcomes Prevention Evaluation biochemical markers. PLoS One 2014;9: 194. Javaheri S, Storfer-Isser A, Rosen CL,
Study Investigators. Effects of ramipril on car- e105903 Redline S. Association of short and long sleep
diovascular and microvascular outcomes in peo- 179. Loomba R, Sirlin CB, Schwimmer JB, Lavine durations with insulin sensitivity in adolescents.
ple with diabetes mellitus: results of the HOPE JE. Advances in pediatric nonalcoholic fatty liver J Pediatr 2011;158:617–623
study and MICRO-HOPE substudy. Lancet 2000; disease. Hepatology 2009;50:1282–1293 195. Watson SE, Li Z, Tu W, et al. Obstructive
355:253–259 180. Kohli R, Sunduram S, Mouzaki M, et al. sleep apnoea in obese adolescents and cardio-
166. Herman WH, Pop-Busui R, Braffett BH, Pediatric nonalcoholic fatty liver disease: a report metabolic risk markers. Pediatr Obes 2014;9:
et al.; DCCT/EDIC Research Group. Use of the from the Expert Committee on Nonalcoholic 471–477
Michigan Neuropathy Screening Instrument as Fatty Liver Disease (ECON). J Pediatr 2016; 196. Ayas NT, White DP, Al-Delaimy WK, et al. A
a measure of distal symmetrical peripheral 172:9–13 prospective study of self-reported sleep duration
neuropathy in type 1 diabetes: results from 181. Tsai E, Lee T-P. Diagnosis and evaluation of and incident diabetes in women. Diabetes Care
the Diabetes Control and Complications Trial/ nonalcoholic fatty liver disease/nonalcoholic 2003;26:380–384
Epidemiology of Diabetes Interventions and steatohepatitis, including noninvasive biomark- 197. Gangwisch JE, Heymsfield SB, Boden-Albala
Complications. Diabet Med 2012;29:937–944 ers and transient elastography. Clin Liver Dis B, et al. Sleep duration as a risk factor for diabe-
167. Moghtaderi A, Bakhshipour A, Rashidi H. 2018;22:73–92 tes incidence in a large U.S. sample. Sleep 2007;
Validation of Michigan Neuropathy Screening 182. Lavine JE, Schwimmer JB, Van Natta ML, 30:1667–1673
Instrument for diabetic peripheral neuropathy. et al.; Nonalcoholic Steatohepatitis Clinical Re- 198. Tasali E, Mokhlesi B, Van Cauter E. Ob-
Clin Neurol Neurosurg 2006;108:477–481 search Network. Effect of vitamin E or metformin structive sleep apnea and type 2 diabetes: in-
168. Jaiswal M, Lauer A, Martin CL, et al.; for treatment of nonalcoholic fatty liver disease teracting epidemics. Chest 2008;133:496–506
SEARCH for Diabetes in Youth Study Group. in children and adolescents: the TONIC ran- 199. Chaput J-P, Després J-P, Bouchard C,
Peripheral neuropathy in adolescents and domized controlled trial. JAMA 2011;305: Tremblay A. Association of sleep duration
young adults with type 1 and type 2 diabetes 1659–1668 with type 2 diabetes and impaired glucose
from the SEARCH for Diabetes in Youth follow-up 183. Corey KE, Vuppalanchi R, Vos M, et al.; tolerance. Diabetologia 2007;50:2298–2304
cohort: a pilot study. Diabetes Care 2013;36: Nonalcoholic Steatohepatitis Clinical Research 200. Jean-Louis G, Zizi F, Clark LT, Brown CD,
3903–3908 Network. Improvement in liver histology is as- McFarlane SI. Obstructive sleep apnea and car-
169. Mueller MJ. Identifying patients with sociated with reduction in dyslipidemia in chil- diovascular disease: role of the metabolic syn-
diabetes mellitus who are at risk for lower- dren with nonalcoholic fatty liver disease. J drome and its components. J Clin Sleep Med
extremity complications: use of Semmes- Pediatr Gastroenterol Nutr 2015;60:360–367 2008;4:261–272
Weinstein monofilaments. Phys Ther 1996;76: 184. Schwimmer JB, Lavine JE, Wilson LA, et al.; 201. Buxton OM, Cain SW, O’Connor SP, et al.
68–71 NASH CRN. In children with nonalcoholic fatty Adverse metabolic consequences in humans
170. Amutha A, Datta M, Unnikrishnan R, Anjana liver disease, cysteamine bitartrate delayed re- of prolonged sleep restriction combined with
RM, Mohan V. Clinical profile and complications lease improves liver enzymes but does not re- circadian disruption. Sci Transl Med 2012;4:
of childhood- and adolescent-onset type 2 di- duce disease activity scores. Gastroenterology 129ra43
abetes seen at a diabetes center in south India. 2016;151:1141–1154.e9 202. Shaw ND, McHill AW, Schiavon M, et al.
Diabetes Technol Ther 2012;14:497–504 185. Cappuccio FP, Taggart FM, Kandala N-B, Effect of slow wave sleep disruption on metabolic
171. Diabetes Control and Complications Trial et al. Meta-analysis of short sleep duration and parameters in adolescents. Sleep (Basel) 2016;
Research Group. Effect of intensive diabetes obesity in children and adults. Sleep 2008;31: 39:1591–1599
treatment on the development and progression 619–626 203. Mokhlesi B, Grimaldi D, Beccuti G, et al.
of long-term complications in adolescents with 186. Broussard JL, Van Cauter E. Disturbances of Effect of one week of 8-hour nightly continuous
insulin-dependent diabetes mellitus: Diabetes sleep and circadian rhythms: novel risk factors positive airway pressure treatment of obstruc-
Control and Complications Trial. J Pediatr 1994; for obesity. Curr Opin Endocrinol Diabetes tive sleep apnea on glycemic control in type 2
125:177–188 Obes 2016;23:353–359 diabetes: a proof-of-concept study. Am J Respir
172. White NH. Long-term outcomes in youths 187. Reutrakul S, Van Cauter E. Interactions Crit Care Med 2016;194:516–519
with diabetes mellitus. Pediatr Clin North Am between sleep, circadian function, and glucose 204. Martı́nez-Cerón E, Barquiel B, Bezos A-M,
2015;62:889–909 metabolism: implications for risk and severity of et al. Effect of continuous positive airway pres-
173. American Diabetes Association. 10. Micro- diabetes. Ann N Y Acad Sci 2014;1311:151–173 sure on glycemic control in patients with ob-
vascular complications and foot care: Standards 188. Chen X, Beydoun MA, Wang Y. Is sleep structive sleep apnea and type 2 diabetes. a
of Medical Care in Diabetesd2018. Diabetes duration associated with childhood obesity? A randomized clinical trial. Am J Respir Crit Care
Care 2018;41(Suppl. 1):S105–S118 systematic review and meta-analysis. Obesity Med 2016;194:476–485
174. Yokoyama H, Okudaira M, Otani T, et al. (Silver Spring) 2008;16:265–274 205. Zychowski KE, Sanchez B, Pedrosa RP, et al.
Existence of early-onset NIDDM Japanese dem- 189. Rutters F, Gerver WJ, Nieuwenhuizen AG, Serum from obstructive sleep apnea patients
onstrating severe diabetic complications. Diabe- Verhoef SPM, Westerterp-Plantenga MS. Sleep induces inflammatory responses in coronary
tes Care 1997;20:844–847 duration and body-weight development during artery endothelial cells. Atherosclerosis 2016;
175. Mayer-Davis EJ, Davis C, Saadine J, et al.; puberty in a Dutch children cohort. Int J Obes 254:59–66
SEARCH for Diabetes in Youth Study Group. (Lond) 2010;34:1508–1514 206. Ehrmann DA. Polycystic ovary syndrome.
Diabetic retinopathy in the SEARCH for Diabetes 190. Nedeltcheva AV, Kessler L, Imperial J, Penev N Engl J Med 2005;352:1223–1236
in Youth cohort: a pilot study. Diabet Med 2012; PD. Exposure to recurrent sleep restriction in 207. Azziz R, Woods KS, Reyna R, Key TJ,
29:1148–1152 the setting of high caloric intake and physical Knochenhauer ES, Yildiz BO. The prevalence
176. Newton KP, Hou J, Crimmins NA, et al.; inactivity results in increased insulin resistance and features of the polycystic ovary syndrome
Nonalcoholic Steatohepatitis Clinical Research and reduced glucose tolerance. J Clin Endocrinol in an unselected population. J Clin Endocrinol
Network. Prevalence of prediabetes and type 2 Metab 2009;94:3242–3250 Metab 2004;89:2745–2749
208. Christensen SB, Black MH, Smith N, et al. response to adrenocorticotropin with reduction heart disease in adulthood. N Engl J Med 2007;
Prevalence of polycystic ovary syndrome in of insulinemia/insulin resistance. J Clin Endocri- 357:2329–2337
adolescents. Fertil Steril 2013;100:470–477 nol Metab 2002;87:1555–1559 233. Tirosh A, Shai I, Afek A, et al. Adolescent
209. Dunaif A. Insulin action in the polycystic 223. Vuorio A, Kuoppala J, Kovanen PT, et al. BMI trajectory and risk of diabetes versus cor-
ovary syndrome. Endocrinol Metab Clin North Statins for children with familial hypercholester- onary disease. N Engl J Med 2011;364:1315–1325
Am 1999;28:341–359 olemia. Cochrane Database Syst Rev 2017;7: 234. Mahoney LT, Burns TL, Stanford W, et al.
210. Lewy VD, Danadian K, Witchel SF, Arslanian CD006401 Coronary risk factors measured in childhood and
S. Early metabolic abnormalities in adolescent 224. Expert Panel on Integrated Guidelines for young adult life are associated with coronary
girls with polycystic ovarian syndrome. J Pediatr Cardiovascular Health and Risk Reduction in artery calcification in young adults: the Mus-
2001;138:38–44 Children and Adolescents; National Heart, catine Study. J Am Coll Cardiol 1996;27:277–
211. Arslanian SA, Lewy VD, Danadian K. Glucose Lung, and Blood Institute. Expert Panel on In- 284
intolerance in obese adolescents with polycystic tegrated Guidelines for Cardiovascular Health 235. Juonala M, Magnussen CG, Venn A, et al.
ovary syndrome: roles of insulin resistance and and Risk Reduction in Children and Adolescents: Influence of age on associations between child-
b-cell dysfunction and risk of cardiovascular summary report. Pediatrics 2011;128(Suppl. 5): hood risk factors and carotid intima-media thick-
disease. J Clin Endocrinol Metab 2001;86:66–71 S213–S256 ness in adulthood: the Cardiovascular Risk in
212. Palmert MR, Gordon CM, Kartashov AI, 225. Marcovecchio ML, Chiesa ST, Bond S, et al.; Young Finns Study, the Childhood Determinants
Legro RS, Emans SJ, Dunaif A. Screening for AdDIT Study Group. ACE inhibitors and statins in of Adult Health Study, the Bogalusa Heart Study,
abnormal glucose tolerance in adolescents adolescents with type 1 diabetes. N Engl J Med and the Muscatine Study for the International
with polycystic ovary syndrome. J Clin Endocrinol 2017;377:1733–1745 Childhood Cardiovascular Cohort (i3C) Consor-
Metab 2002;87:1017–1023 226. Kavey R-EW, Allada V, Daniels SR, et al.; tium. Circulation 2010;122:2514–2520
213. Legro RS, Arslanian SA, Ehrmann DA, et al.; American Heart Association Expert Panel on 236. Gungor N, Thompson T, Sutton-Tyrrell K,
Endocrine Society. Diagnosis and treatment of Population and Prevention Science; American Janosky J, Arslanian S. Early signs of cardiovas-
polycystic ovary syndrome: an Endocrine Society Heart Association Council on Cardiovascular cular disease in youth with obesity and type 2
clinical practice guideline. J Clin Endocrinol Disease in the Young; American Heart Associa- diabetes. Diabetes Care 2005;28:1219–1221
Metab 2013;98:4565–4592 tion Council on Epidemiology and Prevention; 237. Shah AS, Dolan LM, Kimball TR, et al. In-
214. Witchel SF, Oberfield S, Rosenfield RL, et al. American Heart Association Council on Nutrition, fluence of duration of diabetes, glycemic control,
The diagnosis of polycystic ovary syndrome Physical Activity and Metabolism; American and traditional cardiovascular risk factors on
during adolescence. Horm Res Paediatr 2015; Heart Association Council on High Blood Pressure early atherosclerotic vascular changes in adoles-
83:376–389 Research; American Heart Association Council on cents and young adults with type 2 diabetes
215. Kelsey MM, Braffett BH, Geffner ME, et al.; Cardiovascular Nursing; American Heart Associ- mellitus. J Clin Endocrinol Metab 2009;94:3740–
TODAY Study Group. Menstrual dysfunction in ation Council on the Kidney in Heart Disease; 3745
girls From the Treatment Options for Type 2 Interdisciplinary Working Group on Quality of 238. Wadwa RP, Urbina EM, Anderson AM,
Diabetes in Adolescents and Youth (TODAY) Care and Outcomes Research. Cardiovascular et al.; SEARCH Study Group. Measures of arterial
study. J Clin Endocrinol Metab 2018;103: risk reduction in high-risk pediatric patients: stiffness in youth with type 1 and type 2 diabe-
2309–2318 a scientific statement from the American Heart tes: the SEARCH for Diabetes in Youth study.
216. Hoeger K, Davidson K, Kochman L, Cherry T, Association Expert Panel on Population and Diabetes Care 2010;33:881–886
Kopin L, Guzick DS. The impact of metformin, oral Prevention Science; the Councils on Cardiovas- 239. Bacha F, Edmundowicz D, Sutton-Tyrell K,
contraceptives, and lifestyle modification on cular Disease in the Young, Epidemiology and Lee S, Tfayli H, Arslanian SA. Coronary artery
polycystic ovary syndrome in obese adolescent Prevention, Nutrition, Physical Activity and Me- calcification in obese youth: what are the phe-
women in two randomized, placebo-controlled tabolism, High Blood Pressure Research, Cardio- notypic and metabolic determinants? Diabetes
clinical trials. J Clin Endocrinol Metab 2008;93: vascular Nursing, and the Kidney in Heart Care 2014;37:2632–2639
4299–4306 Disease; and the Interdisciplinary Working Group 240. Levitt Katz L, Gidding SS, Bacha F, et al.;
217. Ornstein RM, Copperman NM, Jacobson on Quality of Care and Outcomes Research: TODAY Study Group. Alterations in left ventric-
MS. Effect of weight loss on menstrual function endorsed by the American Academy of Pediat- ular, left atrial, and right ventricular structure and
in adolescents with polycystic ovary syndrome. rics. Circulation 2006;114:2710–2738 function to cardiovascular risk factors in adoles-
J Pediatr Adolesc Gynecol 2011;24:161–165 227. Sarwar N, Gao P, Seshasai SR, et al.; Emerg- cents with type 2 diabetes participating in the
218. Lass N, Kleber M, Winkel K, Wunsch R, ing Risk Factors Collaboration. Diabetes mellitus, TODAY clinical trial. Pediatr Diabetes 2015;16:
Reinehr T. Effect of lifestyle intervention on fasting blood glucose concentration, and risk of 39–47
features of polycystic ovarian syndrome, meta- vascular disease: a collaborative meta-analysis of 241. Bacha F, Gidding SS, Pyle L, et al.; Treatment
bolic syndrome, and intima-media thickness in 102 prospective studies [published correction Options for Type 2 Diabetes in Adolescents and
obese adolescent girls. J Clin Endocrinol Metab appears in Lancet 2010;376:958]. Lancet 2010; Youth (TODAY) Study Group. Relationship of
2011;96:3533–3540 375:2215–2222 cardiac structure and function to cardiorespira-
219. Mastorakos G, Koliopoulos C, 228. Huo X, Gao L, Guo L, et al. Risk of non-fatal tory fitness and lean body mass in adolescents
Deligeoroglou E, Diamanti-Kandarakis E, cardiovascular diseases in early-onset versus and young adults with type 2 diabetes. J Pediatr
Creatsas G. Effects of two forms of combined late-onset type 2 diabetes in China: a cross- 2016;177:159–166.e1
oral contraceptives on carbohydrate metabolism sectional study. Lancet Diabetes Endocrinol 242. Juutilainen A, Lehto S, Rönnemaa T, Pyörälä
in adolescents with polycystic ovary syndrome. 2016;4:115–124 K, Laakso M. Type 2 diabetes as a “coronary heart
Fertil Steril 2006;85:420–427 229. Yang W, Cai X, Han X, Ji L. Clinical character- disease equivalent”: an 18-year prospective pop-
220. Mastorakos G, Koliopoulos C, Creatsas G. istics of young type 2 diabetes patients with ulation-based study in Finnish subjects. Diabetes
Androgen and lipid profiles in adolescents with atherosclerosis. PLoS One 2016;11:e0159055 Care 2005;28:2901–2907
polycystic ovary syndrome who were treated 230. Hillier TA, Pedula KL. Complications in 243. Tancredi M, Rosengren A, Svensson A-M,
with two forms of combined oral contraceptives. young adults with early-onset type 2 diabetes: et al. Excess mortality among persons with type 2
Fertil Steril 2002;77:919–927 losing the relative protection of youth. Diabetes diabetes. N Engl J Med 2015;373:1720–1732
221. Bridger T, MacDonald S, Baltzer F, Rodd C. Care 2003;26:2999–3005 244. Waernbaum I, Blohmé G, Ostman J, et al.
Randomized placebo-controlled trial of metfor- 231. McGill HC Jr, McMahan CA, Herderick EE, Excess mortality in incident cases of diabetes
min for adolescents with polycystic ovary syn- et al.; Pathobiological Determinants of Athero- mellitus aged 15 to 34 years at diagnosis: a pop-
drome. Arch Pediatr Adolesc Med 2006;160: sclerosis in Youth (PDAY) Research Group. Obe- ulation-based study (DISS) in Sweden. Diabeto-
241–246 sity accelerates the progression of coronary logia 2006;49:653–659
222. Arslanian SA, Lewy V, Danadian K, Saad R. atherosclerosis in young men. Circulation 245. Dart AB, Martens PJ, Rigatto C, Brownell
Metformin therapy in obese adolescents with 2002;105:2712–2718 MD, Dean HJ, Sellers EA. Earlier onset of com-
polycystic ovary syndrome and impaired glucose 232. Baker JL, Olsen LW, Sørensen TIA. Child- plications in youth with type 2 diabetes. Diabetes
tolerance: amelioration of exaggerated adrenal hood body-mass index and the risk of coronary Care 2014;37:436–443
246. Al-Saeed AH, Constantino MI, Molyneaux L, care for emerging adults: recommendations for 256. Van Walleghem N, MacDonald CA, Dean HJ.
et al. An inverse relationship between age of transition from pediatric to adult diabetes care Building connections for young adults with
type 2 diabetes onset and complication risk and systems. A position statement of the American type 1 diabetes mellitus in Manitoba: feasibil-
mortality: the impact of youth-onset type 2 Diabetes Association, with representation by the ity and acceptability of a transition initiative.
diabetes. Diabetes Care 2016;39:823–829 American College of Osteopathic Family Physi- Chronic Dis Can 2006;27:130–134
247. Reid GJ, Irvine MJ, McCrindle BW, et al. cians, the American Academy of Pediatrics, the 257. Van Walleghem N, MacDonald CA, Dean
Prevalence and correlates of successful transfer American Association of Clinical Endocrinolo- HJ. Evaluation of a systems navigator model for
from pediatric to adult health care among a gists, the American Osteopathic Association, transition from pediatric to adult care for young
cohort of young adults with complex congenital the Centers for Disease Control and Prevention, adults with type 1 diabetes. Diabetes Care 2008;
heart defects. Pediatrics 2004;113:e197–e205 Children with Diabetes, The Endocrine Society, 31:1529–1530
248. Blum RW, Garell D, Hodgman CH, et al. the International Society for Pediatric and Ad- 258. Van Walleghem N, MacDonald CA, Dean HJ.
Transition from child-centered to adult health- olescent Diabetes, Juvenile Diabetes Research The Maestro Project: a patient navigator for the
care systems for adolescents with chronic con- Foundation International, the National Diabetes transition of care for youth with type 1 diabetes.
ditions. A position paper of the Society for Education Program, and the Pediatric Endocrine Diabetes Spectr 2011;24:9–13
Adolescent Medicine. J Adolesc Health 1993; Society (formerly Lawson Wilkins Pediatric En- 259. Salamon KS, Brouwer AM, Fox MM, et al.
14:570–576 docrine Society). Diabetes Care 2011;34:2477– Experiencing type 2 diabetes mellitus: qualita-
249. American Academy of Pediatrics; American 2485 tive analysis of adolescents’ concept of illness,
Academy of Family Physicians; American College 253. Chiang JL, Kirkman MS, Laffel LMB, Peters adjustment, and motivation to engage in self-
of Physicians–American Society of Internal Med- AL; Type 1 Diabetes Sourcebook Authors. Type care behaviors. Diabetes Educ 2012;38:543–
icine. A consensus statement on health care 1 diabetes through the life span: a position 551
transitions for young adults with special health statement of the American Diabetes Associa- 260. Arslanian S, Kim JY, Nasr A, et al. Insulin
care needs. Pediatrics 2002;110:1304–1306 tion. Diabetes Care 2014;37:2034–2054 sensitivity across the lifespan from obese ado-
250. Turner JR, Schatz DA, Cusi K, Strumph P. 254. Chiang JL, Maahs DM, Garvey KC, et al. Type lescents to obese adults with impaired glucose
Healthcare transition from pediatric to adult 1 diabetes in children and adolescents: a posi- tolerance: who is worse off? Pediatr Diabetes
medical homes in diabetes mellitus. Endocr Pract tion statement by the American Diabetes Asso- 2018;19:205–211
2014;20:715–721 ciation. Diabetes Care 2018;41:2026–2044 261. Chen ME, Chandramouli AG, Considine
251. Reiss J, Gibson R. Health care transition: 255. Lotstein DS, Seid M, Klingensmith G, et al.; RV, Hannon TS, Mather KJ. Comparison of
destinations unknown. Pediatrics 2002;110: SEARCH for Diabetes in Youth Study Group. b-cell function between overweight/obese
1307–1314 Transition from pediatric to adult care for youth adults and adolescents across the spec-
252. Peters A, Laffel L; American Diabetes As- diagnosed with type 1 diabetes in adolescence. trum of glycemia. Diabetes Care 2018;41:318–
sociation Transitions Working Group. Diabetes Pediatrics 2013;131:e1062–e1070 325

Evaluation and Management of Youth-Onset Type 2 Diabetes: A Position Statement by The American Diabetes Association

Uploaded by

Copyright:

Available Formats

Evaluation and Management of Youth-Onset Type 2 Diabetes: A Position Statement by The American Diabetes Association

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Evaluation and Management of Youth-Onset Type 2 Diabetes: A Position Statement by The American Diabetes Association

Uploaded by

Copyright:

Available Formats

2648 Diabetes Care Volume 41, December 2018

Silva Arslanian,1,2 Fida Bacha,3

Although all types of diabetes result in hyperglycemia, the pathophysiology of each

risk of nephropathy is much higher in myelinated ﬁbers with numbness, tin-

You might also like