Received: 20 June 2016 Revised: 20 September 2016 Accepted: 22 September 2016

DOI 10.1111/pedi.12463

CASE REPORT

Type 2 diabetes in a 5-year-old and single center experience

of type 2 diabetes in youth under 10
Jessica Hutchins | Rose Ann Barajas | Daniel Hale | Elia Escaname | Jane Lynch

Department of Pediatrics, Division of

Endocrinology & Diabetes & Genetics, The
University of Texas Health Science Center at
San Antonio, San Antonio, Texas
Corresponding Author: Jane L. Lynch,
Department of Pediatrics, Division of
Endocrinology, Diabetes & Genetics, The
University of Texas Health Science Center at
San Antonio, 7703 Floyd Curl Drive San
Antonio, TX 78229 (lynchj2@uthscsa.edu)
The worrisome rise in pediatric type 2 diabetes (T2DM) is most prevalent among minority eth-
nic/racial populations. Typically, T2DM occurs during puberty in high risk obese adolescents
with evidence of insulin resistance. Screening for T2DM in obese youth can be a daunting task
for pediatricians and differentiating between pediatric T1DM and T2DM in obese youth can be
challenging for pediatric endocrinologists. There is very limited data regarding the prevalence
of T2DM among youth < 10 years of age. Here we present the case of a 5-year-old Hispanic
male diagnosed with T2DM after referral by his pediatrician for abnormal weight gain, acantho-
sis nigricans and an elevated HbgA1c. He subsequently became symptomatic for diabetes with
conrmed hyperglycemia and HbgA1c of 9.7% (83 mmol/mol) at the time of formal diagnosis.
Type 1 diabetes autoantibodies (GAD65, Islet, and ZincT8) and monogenic diabetes genetic
tests were negative. Due to elevated liver enzymes and baseline HbgA1c, he received basal
insulin as his initial therapy. In this paper, we will discuss this case and present an IRB approved
retrospective review of the characteristics of the 20 T2DM patients <10 years of age identied
to date in our pediatric diabetes center. This review highlights that while uncommon, the diag-
nosis of T2DM merits consideration even in prepubertal children. This is especially true when
working with a high risk population, such as our Hispanic South Texas youth.

KEYWORDS

early onset type 2 diabetes, pediatric diabetes, type 2 diabetes mellitus

1 | I N T RO D UC T I O N prevalence. The SEARCH 2009 database reported a highest T2DM

The rise of obesity in youth over the past several decades has con-
tributed to the observed increase in the rates of type 2 diabetes mel-
litus (T2DM) in youth. Type 2 diabetes rates are disproportionately
increasing in minority race/ethnic youth and thus vary per region
1
based on population demographics. Begun in 2000, the SEARCH for
Diabetes in Youth study currently provides the largest ongoing regis-
try of incidence and prevalence of all forms of diabetes in US youth
less than 20 years of age. Incident cases of diabetes in geographically
diverse regions of the United States are categorized by pediatric dia-
betes experts into four SEARCH categories: type 1 diabetes (T1DM),
T2DM, suspected monogenic diabetes and uncertain type based on
clinical algorithms which include autoimmunity and insulin resistance
24
measures. Comparisons of T1DM and T2DM data for youth aged
10 to 19 years from SEARCH 2001 and 2009 diabetes databases
estimated a signicant relative overall increase of 30.5% in T2DM
prevalence of 1.20/1000 among American Indian youth, followed by
1.06/1000 among black youth, 0.79/1000 among Hispanic youth,
and 0.17/1000 among white youth.1 Estimates of initial T2DM preva-
lence for youth aged 0 to 9 years ranged from 0.18% to 1.03% in the
2001 baseline SEARCH database.2 Similarly, of the 819 T2DM youth
in the 2009 SEARCH database, only 19 (2.3%) overall were < 10
years of age. 4
The 2016 ADA diabetes care guidelines recommend that youth
with a BMI 85% and two risk factors for T2DM (positive family his-
tory, at-risk ethnicity, mother with gestational diabetes, or signs of
insulin resistance) be screened beginning at age 10 or earlier depend-
ing on when puberty starts and then screened every 3 years thereaf-
ter or immediately if they develop symptoms of diabetes.5 The 2013
AAP Pediatric Guidelines for T2DM only address management guide-
lines for patients > age 10 which reect the paucity of patients
described at a young age to date.6

Pediatr Diabetes 2016; wileyonlinelibrary.com/journal/pedi 2016 John Wiley & Sons A/S. 1
Published by John Wiley & Sons Ltd
2 HUTCHINS ET AL

Here we present one of our youngest conrmed cases of T2DM. genetics panel that includes HNF1A, HNF1B, HNF4A, and GCK
We describe our patients pertinent laboratory ndings and manage- testing.
ment. This individual case is followed by an IRB approved retrospec-
tive review of clinical chart data for a cohort of 20 primarily Hispanic
children diagnosed with T2DM at < 10 years of age between the 3 | SINGLE CENTER EXPERIENCE
years of 2000 and 2015. All cases of T2DM were diagnosed by pedi-
atric endocrinologists within our institution using ADA criteria. Clini- This retrospective review describes our South Texas pediatric diabe-

cal ndings, c-peptide, OGTT results and/or genetic testing were tes experience where the majority of our patients with T2DM are

reviewed to eliminate suspected monogenic diabetes patients. Seven- Hispanic. We began carefully tracking our diabetes population before

teen out of 20 patients in this cohort had negative GAD and IA2 anti- 2000 in anticipation of recruitment for the TODAY study. Six of our

bodies at diagnosis with clinical ndings consistent with T2DM. The 20 described youth were diagnosed with T2DM at age <10 years

3 patients without initial titers were diagnosed before 2003 and were prior to 2003 when the TODAY study screening allowed for antibody

treated without insulin for at least 7 years. 5,7

To our knowledge this conrmation of their diagnosis. The majority of our cohort has had

report is unique for looking specically at clinical experience with conrmed negative NIH standardized diabetes antibody testing and

T2DM in children <10 years of age. all continue to have clinical courses consistent with T2DM.
We describe 20 youth diagnosed with T2DM at <10 years of age
between 2000 and 2015. This cohort of 20 youth represents approxi-
mately 2.5% of our total number of youth who were diagnosed with
2 | CAS E
T2DM at 18 years of age during this same time frame within our

This Hispanic boy was initially referred to our pediatric diabetes cen- institution. Almost 2900 youth < 18 years of age have been diag-

ter at age 4 2/12 for severe acanthosis nigricans, morbid obesity and nosed with diabetes in our South Texas pediatric diabetes clinic since

elevated HbgA1c. Referral labs included an HbgA1c of 7.6% 2000. Of these, 1125 were diagnosed with T1DM at <10 years of

(60 mmol/mol), slightly elevated liver enzymes and liver ultrasound age with approximately equal gender distribution. An additional

report suggesting non-alcoholic fatty liver disease (NAFLD). On 15 were diagnosed clinically with monogenetic diabetes. About 30%

review, his mother denied any symptoms of polyuria, polydipsia or of our <10-year-old patients with T1DM were Hispanic, in contrast

nocturia but did report symptoms suggestive of sleep apnea. He had to 80% within our <10 year T2DM cohort. Thus, our described

a family history of T2DM which included his father diagnosed as an cohort represents only 1.7% of our overall patients who were <10

adult, sister at 12 years and brother at 16 years. There was also a years of age at diagnosis.

strong family history of obesity. At this initial visit, he weighed 42 kg Our cohort of 20 youth < age 10 with T2DM were diagnosed
2
(>97%) with BMI of 35.03 kg/m (>97%) and his blood pressure was between the ages 4 to 9 years with the mean age of 8.13 years for

elevated to >95% at 117/60. On physical examination he had severe girls and 8.2 years for boys (Figure 1). Within this cohort, 75% were

acanthosis nigricans, no dysmorphic features, and was prepubertal. female. Initial BMI Z scores for this cohort ranged from +1.68 to

Initial dietary and lifestyle interventions initiated by his pediatrician 5.02 (average 2.72) and all were >97% for age and gender at diagno-

likely accounted for a fall in HbgA1c from 7.6% (60 mmol/mol) to sis. Seventeen had documented rst degree relatives, and all had

6.3% (45 mmol/mol) at this rst endocrine clinic visit. Therefore, this second degree relatives with T2DM. Our South Texas diabetes cen-

child did not initially meet criteria for diagnosis of T2DM and no ter has a high proportion of Hispanic patients and our region has

medications were initiated at this visit. Lifestyle interventions were high rates of childhood obesity. Thus, it is not surprising that 80% of

reinforced with close follow-up scheduled in our clinic. this cohort with T2DM < age 10 years were Hispanic and overall

Unfortunately, this patient subsequently missed multiple endo- 100% of these youth had a racial/ethnic minority background

crine follow-up appointments and returned 11 months later at 5 years (Figure 2).

1 month. At this visit, he was formally diagnosed with diabetes meet-

ing ADA criteria with a HbgA1c of 9.7% (83 mmol/mol), conrmatory
8
home glucose values of >200 mg/dL and symptoms of polyuria and Male Female
polydipsia. Additional labs included >3x elevations of liver enzymes 7
Number of Patients Diagnosed

and normal thyroid function tests. He was negative for GAD 65, islet 6

cell and ZincT8 antibodies which conrmed his suspected diagnosis 5

of T2DM. Due to his elevated liver enzymes and HbgA1c >9%, glar-
4
gine insulin at 0.1 mg/kg/day was initiated and his family was edu-
3
cated on home T2DM management.
Our patient is now 7 years of age and he requires 9 units/day of 2

glargine insulin (0.15 units/kg/day) to maintain a 7% (53 mmol/mol) 1

range HbgA1c. He continues to be obese despite lifestyle interven- 0
4 yrs.old 5 yrs old 6 yrs old 7 yrs old 8 yrs old 9 yrs old
tions and has continued evidence for NAFLD, sleep apnea, and inter-
Gender/Age of Patients at Diagnosis
mittent elevation of blood pressure. His genetic testing was negative
for all 56 diabetes-obesity gene mutations in the Fulgent Diagnostics FIGURE 1 Age and gender of T2DM < age 10 years cohort.
HUTCHINS ET AL
12
W non-H H AA AI
10
Number of Patients Diagnosed
8
6 17
4
2 history, and a clinical course which is not consistent with T2DM. Lim-
0 endocrinologists miscategorized the type of diabetes. This differentia-
4 yrs old 5 yrs old 6 yrs old 7 yrs old 8 yrs old
Age of Patients at Diagnosis
FIGURE 2 Age and racial/ethnic distribution of T2DM < age
10 years cohort.
4 | DISCUSSION
T2DM is rapidly becoming more prevalent in youth. Projections sug-
gest that the number of youth in the United States with type 2 diabe-
tes will increase from 22 820 in 2010 to 84 131 in 2050.8 In review
of existing literature, there is limited discussion or data regarding the
occurrence of T2DM in youth under the age of 10. Although the
diagnosis of T2DM in youth <10 years of age is rare, it still must be
considered, especially among at risk racial/ethnic populations. Our
reviewed data was incomplete for initial pubertal status at diagnosis.
Therefore, we cannot hypothesize if this is comparable to the
increased female T2DM incidence rates during adolescence which is
attributed to earlier and higher peaks of insulin resistance during
911
puberty.
Accurate classication of diabetes type in youth can be difcult
due to overlapping phenotypic ndings. It is estimated that 35% to
50% of youth with type 1 autoimmune diabetes are overweight or
obese across all racial/ethnic groups. Furthermore, type 2 diabetes
accounts for 9.7% of the approximately 30% of new onset pediatric
diabetes presenting with ketoacidosis.3 In SEARCH, 21.5% of children
10 to 19 years of age with physician identied type 2 diabetes were
found to be positive for GAD-65 antibodies when using the non
NIDDK standardized assays.12 Likewise, 9.8% of youth aged 10 to
18 years of age with physician diagnosis of T2DM screened for the
TODAY study were antibody positive with 5.9% positive for a single
antibody and 3.9% positive for both GAD-65 and insulinoma-
associated protein 2 autoantibodies using the NIDDK standardized
13
assay. Accurately diagnosing T2DM is further complicated by tran-
sient secretion alterations of c-peptide and insulin in youth newly
diagnosed with diabetes. 1416
In light of these challenges it is appro-
priate to screen symptomatic children as young as age 7 to 8 for
T2DM who present as VERY obese, in a high risk ethnic racial group
and with a strong family history.6
As discussed in our individual case, genetic testing for MODY
can be helpful to identify patients with monogenic mutations to con-
rm diagnosis and guide management. 17 Genetic testing may be con-
sidered in children <10 with new onset diabetes which does not
appear to be either type 1 or type 2. Our cohort excluded patients
who were suspected to have monogenic diabetes based on their
3
biochemical and clinical phenotypes. The criteria we used to diagnose
MODY is similar to SEARCH study reports. It was based on clinical
phenotypes with no ndings of insulin resistance and biochemical
results which included a combination of negative diabetes autoanti-
bodies, low levels of fasting insulin and fasting c-peptide response of
>0.8 ng/mL. When genetic testing is not affordable, clinical judge-
ment is required to best categorize between T2DM and MODY in
youth with diabetes and negative autoantibodies, a positive family
itations of this report include a risk that our experienced pediatric
9 yrs old
tion can be especially challenging in obese children with negative
autoantibodies which we often encountered in our South Texas
population.
Data shows that youth with T2DM are at risk for earlier onset
and more aggressive progression of diabetes related complications
1823
when compared to T1DM in youth or T2DM in adults. There-
fore, aggressive attention to accurate diagnosis of T2DM in this
<10 year age range will allow for aggressive surveillance to inform
the risks for diabetes comorbidities in this unique subset of youth
with T2DM.
5 | CONC LU SION
With the increasing prevalence of T2DM diabetes in youth, the gen-
eral pediatrician needs to recognize the early ndings of diabetes and
perform appropriate screening tests. If the diagnosis is conrmed,
then prompt referral to a pediatric endocrinologist for further diag-
nostic testing and diabetes management is warranted. The diagnosis
of T2DM in high risk youth <10 years of age cannot be excluded
solely based on young age. The patients described in this report could
have potentially been undiagnosed if not screened at an early age
and/or miscategorized if the diagnosis of T1DM and other forms of
diabetes were not carefully excluded. There is no current data to pre-
dict the rates of progression of diabetes complications in youth with
such early onset of T2DM. Accurate identication, surveillance and
inclusion of this population in prospective future clinical trial will bet-
ter inform clinicians on risks for comorbidities and outcomes for
these patients.
Author contributions
J.H. managed the genetic testing for the case patient, assisted in the
initial analyses, reviewed and revised the manuscript, and approved
the nal manuscript as submitted. R.A.B. coordinated and supervised
data collection, assisted in the data analyses, reviewed the manu-
script, and approved the nal manuscript as submitted. D.H. managed
the case patients care, assisted in the manuscript, and approved the
nal manuscript as submitted. E.E. managed the case patients care,
assisted in the manuscript, and approved the nal manuscript as sub-
mitted. J.L. conceptualized and designed the study, drafted the initial
manuscript, and approved the nal manuscript as submitted. All
authors approved the nal manuscript as submitted and agree to be
accountable for all aspects of the work.
4 HUTCHINS ET AL

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