prevalence of hypertension and albuminuria in pediatric
TRANSCRIPT
Original Investigation | Pediatrics
Prevalence of Hypertension and Albuminuria in Pediatric Type 2 DiabetesA Systematic Review and Meta-analysisMilena Cioana, BHSc; Jiawen Deng; Maggie Hou, BHSc; Ajantha Nadarajah, BHSc; Yuan Qiu, BHSc; Sondra Song Jie Chen, BHSc; Angelica Rivas, BHSc;Laura Banfield, MLIS, MHSc; Rahul Chanchlani, MD, MSc; Allison Dart, MD, MSc; Brandy Wicklow, MD, MSc; Haifa Alfaraidi, MD; Ahlam Alotaibi, MD;Lehana Thabane, PhD; M. Constantine Samaan, MD, MSc
Abstract
IMPORTANCE Hypertension and albuminuria are markers of diabetes-related nephropathy andimportant factors associated with kidney outcomes in pediatric type 2 diabetes. However, theirprevalence in these patients is unknown.
OBJECTIVE To measure the prevalence of hypertension and albuminuria in pediatric patients withtype 2 diabetes and to evaluate the association of sex and race/ethnicity with these conditions.
DATA SOURCES MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, the gray literature,and references of the screened articles were searched for human studies from date of databaseinception to February 20, 2020.
STUDY SELECTION Observational studies with at least 10 participants reporting the prevalence ofhypertension and/or albuminuria in pediatric patients with type 2 diabetes were included. Threeteams of 2 independent reviewers screened 7614 papers, of which 60 fulfilled the eligibility criteria.
DATA EXTRACTION AND SYNTHESIS Three teams of 2 independent reviewers performed dataextraction, risk of bias analysis, and level of evidence analyses. The meta-analysis was conductedusing a random-effects model and followed the Meta-analysis of Observational Studies inEpidemiology (MOOSE) guidelines.
MAIN OUTCOMES AND MEASURES The primary outcomes included the pooled prevalence rates(percentages with 95% CI) for hypertension and albuminuria. The secondary outcomes assessedpooled prevalence rates by sex and racial/ethnic group.
RESULTS Sixty studies were included in the systematic review. Diabetes duration varied frominclusion at diagnosis to 15.0 years after diagnosis, and the reported mean age at diagnosis rangedfrom 6.5 to 21.0 years. Hypertension prevalence among 3463 participants was 25.33% (95% CI,19.57%-31.53%). Male participants had higher hypertension risk than female participants (odds ratio[OR], 1.42 [95% CI, 1.10-1.83]), with Pacific Islander and Indigenous youth having the highestprevalence of all racial/ethnic groups (Pacific Islander youth: 26.71% [95% CI, 14.54%-40.72%];Indigenous youth: 26.48% [95% CI, 17.34%-36.74%]; White youth: 20.95% [95% CI,12.65%-30.57%]; African American youth: 19.04% [95% CI, 12.01%-27.23%]; Hispanic/Latino youth:15.11% [95% CI, 6.56%-26.30%]; Asian youth: 18.37% [95% CI, 9.49%-29.23%]). Albuminuriaprevalence among 2250 participants was 22.17% (95% CI, 17.34%-27.38%). Pacific Islander youth,Indigenous youth, and Asian youth had higher prevalence rates than White youth (Pacific Islanderyouth: 31.84% [95% CI, 11.90%-55.47%]; Indigenous youth: 24.27% [95% CI, 14.39%-35.73%]; Asianyouth: 23.00% [95% CI, 18.85%-27.41%]; White youth: 12.59% [95% CI, 7.75%-18.33%]), with no
(continued)
Key PointsQuestion What is the prevalence of
hypertension and albuminuria in
children and adolescents with type 2
diabetes?
Findings This systematic review and
meta-analysis of 60 studies found that
25% of children and adolescents with
type 2 diabetes had hypertension and
22% had albuminuria. Pacific Islander
and Indigenous youth had a higher risk
of these conditions than children from
other racial groups.
Meaning In this study, the burden of
hypertension and albuminuria in
pediatric type 2 diabetes was
substantial, especially among Pacific
Islander and Indigenous youth.
+ Supplemental content
Author affiliations and article information arelisted at the end of this article.
Open Access. This is an open access article distributed under the terms of the CC-BY License.
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 1/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Abstract (continued)
sex differences (OR for male vs female participants, 0.68 [95% CI, 0.46-1.01]). Heterogeneity washigh among studies, with a low to moderate risk of bias.
CONCLUSIONS AND RELEVANCE In this study, markers of diabetes-related nephropathy werecommonly detected in pediatric patients with type 2 diabetes, with a disproportionate burden notedamong Pacific Islander and Indigenous youth. Personalized management strategies to target kidneyoutcomes are urgently needed in pediatric patients with type 2 diabetes to alleviate the burden ofthis condition on the kidneys.
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069
Introduction
The global increase in obesity has driven the emergence of type 2 diabetes in children.1,2 Pediatrictype 2 diabetes is an aggressive disease with greater risk of end-organ damage and comorbiditiesthan pediatric type 1 diabetes or adult-onset type 2 diabetes.1-5 The kidneys are notable early targetsof type 2 diabetes–associated organ damage, and diabetes-related nephropathy commonlymanifests as hypertension and albuminuria.6-8 If untreated, hypertension is associated withcardiovascular anomalies, including increased carotid intima-media thickness and left ventricularhypertrophy.9,10 These subclinical adverse outcomes are known risk factors for future cardiovasculardisease and mortality.9,10 Similarly, microalbuminuria is the first sign of diabetes-related nephropathyand can progress to chronic kidney disease and end-stage kidney disease if untreated.11
To ensure early detection and treatment of nephropathy in the pediatric type 2 diabetespopulation, current screening guidelines recommend measuring blood pressure (BP) and urinealbumin-to-creatine ratio (ACR) at type 2 diabetes diagnosis and annually thereafter.9,12,13 Withadequate glycemic and blood pressure control, the onset of end-stage kidney disease can bedelayed, and the risk of microvascular and macrovascular complications can be reduced, making themanagement of hypertension and albuminuria crucial to improving outcomes in patients withpediatric type 2 diabetes.11,14 However, the full burden of diabetes-related nephropathy in pediatricpatients with type 2 diabetes is not well established. There has also been some evidence suggestingthat the rate of type 2 diabetes complications differs by sex and race/ethnicity.15-17 Determining howsex and race/ethnicity are associated with hypertension and albuminuria prevalence is an importantstep toward identifying at-risk groups and can inform future personalized screening and treatmentstrategies.
Thus, this systematic review aimed to determine the prevalence of hypertension andalbuminuria in pediatric patients with type 2 diabetes and to explore the association of sex and race/ethnicity with prevalence.
Methods
Systematic Review Protocol and RegistrationThis systematic review has been registered with PROSPERO (CRD42018091127).18 The study isreported according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE)reporting guideline.19
Search StrategiesSearch strategies were developed by a senior health sciences librarian and conducted in MEDLINE,Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Cochrane Database ofSystematic Reviews from database inception to February 20, 2020, without language restrictions
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 2/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
(eTables 1-5 in the Supplement). The gray literature, including ClinicalTrials.gov and Web of Science:Conference Proceedings Citation Index–Science, was searched. We combined concepts of pediatricsand type 2 diabetes with terms for hypertension, albuminuria, prevalence, and epidemiologic studydesign. We also searched the references of included articles. If a conference abstract was deemedeligible, we sought a full-text publication and contacted the corresponding author if a publishedarticle could not be located or did not report the relevant data set for this analysis.
Eligibility CriteriaWe included studies with observational designs, including retrospective and prospective cohortstudies as well as cross-sectional studies. The eligibility criteria included studies involving humanparticipants with a sample size of at least 10 that reported on hypertension and/or albuminuriaprevalence in patients with type 2 diabetes who were 18 years of age or younger. For studies withserial reporting of data, we included the report with the largest sample size. We excluded studiesreporting participants with gestational diabetes.
To be as comprehensive as possible, we included studies reporting on all definitions ofhypertension and albuminuria for our prevalence estimate. In the meta-analysis, we only pooledstudies with similar definitions. Hypertension was defined as systolic and/or diastolic BP levels in the95th percentile or greater for sex, age, and height.20 Most studies used BP reference values basedon the National Heart, Lung, and Blood Institute data, whereas some used reference values based onthe European guidelines.20-25 Urine ACR of 30 mg/g or greater defined albuminuria.9,12,13,26
Microalbuminuria was defined as an ACR of 30 or greater to 300 mg/g, and macroalbuminuria wasdefined as an ACR of greater than 300 mg/g. Persistent albuminuria, microalbuminuria, ormacroalbuminuria were defined as 2 of 3 samples with levels greater than the corresponding ACRthreshold over 6 months. If not specified, it was assumed that measurements were taken only once.Studies using other definitions of hypertension or albuminuria were removed in the sensitivityanalysis.
Study Selection, Data Abstraction, and Quality AppraisalThree teams of 2 independent reviewers (M.C., M.H., A.N., Y.Q., S.J.J.C., A.R.) screened titles,abstracts, and full-text articles and completed data abstraction, risk of bias assessments, and level ofevidence assessments. Reviewers resolved disagreements through discussion, and a third reviewer(M.C.S.) resolved persistent disagreements.
A data abstraction form was designed and piloted specifically for this study. We extracted dataon study design, age at diabetes diagnosis, age at study enrollment, duration of diabetes, samplesize, sex, and race. We also extracted hypertension and albuminuria definitions and prevalence withsex-specific and race-specific data, if reported.
For longitudinal studies, we extracted the prevalence values closest to the time of type 2diabetes diagnosis because we wanted to define the prevalence closest to the time of hypertensionor albuminuria diagnosis. For unreported data, we contacted the corresponding authors to retrievethe information specific to our study question. Several studies reported on cohorts that includedparticipants older than 18 years. We contacted the study authors to retrieve pediatric-specific data.When we did not receive the data, we included studies if most participants were 18 years or youngerand no participants were older than 25 years.
Risk of bias was evaluated for each study using a validated tool for prevalence studiesdeveloped by Hoy et al.27 The tool assesses methodological quality across 10 items addressingstudies’ external and internal validity.27 Each criterion was given a score of 0 if unaddressed orunclear and 1 if it was met.27 External validity criteria included whether the target population wasrepresentative of the national population, the sampling frame was representative of the targetpopulation, random selection or a census was used, and whether there was limited evidence ofnonresponse bias.27 Internal validity criteria included whether data were collected directly fromparticipants, an acceptable case definition was used, reliable and valid tools were used to assess
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 3/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
prevalence, data were collected using the same method for all participants, the length of the shortestprevalence period for the parameter of interest was appropriate, and, if appropriate, numerators anddenominators were used to assess prevalence.27 The overall risk of bias was rated as low (score >8),moderate (score 6-8), or high (score �5).27 The overall level of evidence was assessed according tothe Oxford Centre for Evidence-Based Medicine criteria (OCEBM).28
Statistical AnalysisA random-effects model meta-analysis was performed when 2 or more studies of similar design,populations, methods, and outcomes were available.29,30 The primary outcomes of this reviewincluded the pooled prevalence of hypertension and albuminuria (reported as a percentage with95% CIs) across all study designs. Because it was expected that some reports would have a smallnumber of events, we transformed all prevalence estimates using the Freeman-Tukey double arcsinemethod30 and converted the results back to prevalence estimates for reporting.31,32 Inconsistencyindex (I2) and χ2 test P values were used to quantify heterogeneity among studies, and an I2 greaterthan 75% and P < .10 defined significant heterogeneity.33 Prespecified subgroup, sensitivity,metaregression, and publication bias assessments were performed if at least 10 studies wereincluded in the meta-analysis for a given outcome.33 Subgroup analyses were performed by sexand race.
We also did a meta-analysis with studies comparing the prevalence between male and femaleparticipants and calculated odds ratios with 95% CIs. We used the National Institutes of Healthdefinitions to categorize racial groups.34 We used the term Indigenous to report data fromIndigenous populations in North America.
We also performed a random-effects metaregression to determine the association of obesityprevalence with hypertension and albuminuria. We performed sensitivity analyses by removingconference abstracts, studies with a sample size smaller than 50 patients, patients older than 18years, or studies that used different or unspecified definitions of hypertension or albuminuria. Afunnel plot was used to investigate publication bias with the Egger test and visual inspection toassess plot asymmetry.35 The prevalence meta-analyses were conducted using the metafor packagein RStudio version 1.1.383, R version 3.4.3 (R Project for Statistical Computing).36-38 The sex-basedforest plots for ORs were generated using Review Manager Version 5.3 (Cochrane Collaboration).39
Results
Search ResultsThe searches yielded 7614 unique records, and 60 eligible studies were included in the review(eFigure 1 in the Supplement). Most articles were removed, as they were irrelevant to the researchquestion, reported on adult type 2 diabetes, or did not assess hypertension and/or albuminuriaprevalence in children and adolescents with type 2 diabetes.
HypertensionStudy CharacteristicsForty-six studies reported hypertension prevalence (Table 1).4,15,17,40-82 The reported age atdiagnosis of type 2 diabetes ranged from 7.1 to 20.0 years,46,47,49,72 and the duration of diabetesranged from inclusion at diagnosis40,41,43,51,52,55,56,60,65,66,75,76,81 to 7.8 years after diagnosis.71 While26 studies (57%) had a cross-sectional design,15,17,40-58,75-78,82 13 (28%) were retrospective cohortstudies,59-69,79,80 and 7 (15%) were prospective cohort studies.4,70-74,81
Pooled Prevalence of HypertensionThirty-one studies including 4363 patients with type 2 diabetes reported on the prevalence ofhypertension defined as BP in the 95th percentile or greater for age, sex, and height or systolic BP130 to 140 mm Hg or greater and diastolic BP of 80 to 90 mm Hg or greater.4,15,17,40-45,51-69,72-74 The
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 4/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e1.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onPr
eval
ence
ofH
yper
tens
ion
inPe
diat
ricTy
pe2
Dia
bete
s
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
aten
rollm
ent,
mea
n(S
D),y
Diab
etes
dura
tion,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
ze,N
o.Se
xdi
strib
utio
nN
o.(%
)Ra
cial
grou
pdi
strib
utio
n,N
o.(%
)
Case
sby
sex
and/
orra
cial
grou
p,N
o.(%
)H
yper
tens
ion
defin
ition
Refe
renc
eva
lues
sour
ce
Prev
alen
ceof
obes
ity,
No.
(%)
Hyp
erte
nsio
n
Pinh
as-
Ham
iel
etal
,40
1996
Unite
dSt
ates
CS13
.8(1
.9)
13.8
(1.9
)0
9(1
7)54
M:2
0(3
7);F
:34
(63)
NH
B:37
(68)
,NH
W:
17(3
2)N
RN
RN
R50
(92)
Scot
teta
l,41
1997
Unite
dSt
ates
CS13
.9(0
.4)a
13.9
(0.4
)a0
14(3
2)44
M:1
7(3
8);F
:27
(62)
AA:3
2(7
4);N
HW
:11
(24)
;H:1
(2)
NR
NR
NR
42(8
5)b
Ettin
ger
etal
,42
2005
Unite
dSt
ates
CSN
R15
.0(1
.9)
1.5
(1.0
)15
(58)
26M
:12
(46)
;F:1
4(5
4)H
:15
(58)
;NH
B:8
(31)
;oth
er:2
(7);
mul
tirac
ial:
1(4
)
NR
BP>9
5th
perc
entil
efo
rsex
and
heig
ht
NH
LBIU
pdat
eon
Seco
ndTa
skFo
rce
Repo
rt2
3
NR
Rein
ehr
etal
,43
2005
Germ
any
CS14
.2(1
3.0-
15.0
)c14
.2(1
3.0-
15.0
)c0
8(5
0)16
M:1
0(6
3);F
:6(3
7)W
hite
:16
(100
)W
hite
:8(5
0)BP
≥95t
hpe
rcen
tile
fora
ge,
gend
er,a
ndhe
ight
USag
e-se
x-he
ight
spec
ific
valu
es2
1
14(8
8)
Eppe
nset
al,4
420
06W
este
rnPa
cific
CS12
.0(1
0.7-
13.5
)b,c
14.9
(13.
2-16
.4)b
,c2.
3(1
.4-3
.6)b
,c64 (2
4.2)
265
M:1
20(4
5.3)
;F:
145
(54.
7)N
RM
:34
(28.
3);F
:30
(20.
7)Sy
stol
ican
ddi
asto
licBP
>95t
hpe
rcen
tile
fora
ge,
sex,
and
heig
ht
NH
LBIU
pdat
eon
Seco
ndTa
skFo
rce
Repo
rt2
3
106
(32.
0)b
Unni
kris
hnan
etal
,45
2008
Indi
aCS
16.2
(2.9
)18
.9(4
.9)
NR
1(3
)36
M:2
1(5
8);F
:15
(42)
Indi
an:3
6(1
00)d
Indi
an:1
(3)
NR
NR
NR
Bell
etal
,46
2009
Unite
dSt
ates
CSra
nge,
10-1
9Ag
e10
-14
y:41
(38.
4%);
age
≥15
y:65
(61.
3%)
NR
17 (16.
0)10
6N
RN
HW
:106
(100
.0)
NH
W:1
7(1
6.0)
BP≥9
5th
perc
entil
efo
rage
,se
x,an
dhe
ight
NH
LBIF
ourt
hRe
port
20
83(7
9.0)
b
Dabe
lea
etal
,47
2009
Unite
dSt
ates
CSAl
lpa
rtic
ipan
ts<2
0
18.0
(2.8
)3.
5(2
.2)
22(3
6)62
NR
Nav
ajo:
62(1
00)
Nav
ajo:
22(3
6)BP
≥95t
hpe
rcen
tile
fora
ge,
sex,
and
heig
ht
NH
LBIF
ourt
hRe
port
20
42(6
8)
Law
renc
eet
al,4
820
09Un
ited
Stat
esCS
Age
10-1
4y:
11.6
(1.5
);ag
e≥1
5y:
14.6
(2.1
)b
Age
10-1
4y:
37(3
0.8%
);ag
e≥1
5y:
83(6
9.2%
)
Age
10-1
4y:
1.2
(0.9
);ag
e≥1
5y:
2.2
(2.0
)b
25 (20.
8)12
0N
RH
:120
(100
.0)
H:2
5(2
0.8)
Syst
olic
and/
ordi
asto
licBP
≥95t
hpe
rcen
tile
fors
ex,
age,
and
heig
ht
NH
LBIF
ourt
hRe
port
20
93(7
3.2)
b,e
Liu
etal
,49
2009
Unite
dSt
ates
CSAl
lpa
rtic
ipan
ts<2
0
NR
Asia
n:1.
6(1
.4);
API:
3.4
(3.1
);PI
:1.
7(1
.7)b
13(2
7)48
NR
Asia
n:29
(60)
;API
:11
(23)
;PI:
8(1
7)As
ian:
8(2
8);A
PI:
4(3
6);P
I:1
(13)
Syst
olic
ordi
asto
licBP
≥95t
hpe
rcen
tile
base
don
age,
sex,
and
heig
ht
NH
LBIF
ourt
hRe
port
20
38(7
6)b
May
er-D
avis
etal
,50
2009
Unite
dSt
ates
CSAg
e10
-14
y:11
.7(1
);ag
e≥1
5y:
15.1
(1.9
)
Age
10-1
4y:
81(3
8.2%
);ag
e≥1
5y:
131
(61.
8%)
Age
10-1
4y:
1.2
(0.7
);ag
e≥1
5y:
2.6
(2.1
)
49 (23.
1)21
2N
RAA
:212
(100
.0)
AA:4
9(2
3.1)
Syst
olic
ordi
asto
licBP
≥95t
hpe
rcen
tile
fora
ge,
heig
ht,a
ndse
x
NH
LBIF
ourt
hRe
port
20
NR
Urak
ami
etal
,51
2009
Japa
nCS
12.9
(1.5
)12
.9(1
.5)
013 (1
1.6)
112
M:4
5(4
0.2)
;F:6
7(5
9.8)
Japa
nese
:112
(100
.0)d
Japa
nese
:13
(11.
6)Sy
stol
icBP
≥130
mm
Hg
and/
ordi
asto
licBP
≥85
mm
Hg
NR
93(8
3.0)
Rodr
igue
zet
al,1
720
10Un
ited
Stat
esCS
12.9
(2.1
)14
.8(2
.0)
1.6
(1.5
)97 (2
3.7)
410
M:1
52(3
7.1)
;F:
258
(62.
9)AA
:130
(31.
7);H
:99
(24.
1);N
HW
:84
(20.
5);A
I:56
(13.
7);
API:
37(9
.0);
othe
r:4
(1.0
)
M:3
8(2
5.0)
;F:
59(2
2.9)
;AA:
36(2
7.7)
;H:2
2(2
2);N
HW
:17
(20)
;AI:
12(2
1);
API:
10(2
7);
othe
r:0
Syst
olic
ordi
asto
licBP
>95t
hpe
rcen
tile
fora
ge,
sex,
and
heig
ht
NH
LBIF
ourt
hRe
port
20
332
(81.
0)
Cope
land
etal
,15
2011
Unite
dSt
ates
CSra
nge,
10-1
714
.0(2
.0)
0.7
(0.5
)96 (1
3.6)
704
M:2
47(3
5.1)
;F:
457
(64.
9)H
:289
(41.
1);N
HB:
222
(31.
5);N
HW
:13
8(1
9.6)
;AI:
43(6
.1);
Asia
n:12
(1.7
)
M:4
4(1
7.8)
;F:
52(1
1.4)
;H:3
1(1
0.7)
;NH
B:34
(15.
3);N
HW
:23
(16.
7);A
I:7
(16)
BP≥9
5th
perc
entil
efo
rage
,se
xan
dhe
ight
NR
NR (c
ontin
ued)
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 5/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e1.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onPr
eval
ence
ofH
yper
tens
ion
inPe
diat
ricTy
pe2
Dia
bete
s(co
ntin
ued)
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
aten
rollm
ent,
mea
n(S
D),y
Diab
etes
dura
tion,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
ze,N
o.Se
xdi
strib
utio
nN
o.(%
)Ra
cial
grou
pdi
strib
utio
n,N
o.(%
)
Case
sby
sex
and/
orra
cial
grou
p,N
o.(%
)H
yper
tens
ion
defin
ition
Refe
renc
eva
lues
sour
ce
Prev
alen
ceof
obes
ity,
No.
(%)
Amed
etal
,52
2012
Cana
daCS
Cana
dian
Abor
igin
al:
12.9
(12.
4-13
.4)f ;
Whi
te:1
4.4
(13.
8-15
.1)f ;
othe
r(A
fric
an/
Carib
bean
,As
ian,
H,
Mid
dle
East
ern)
:14
.3(1
3.7-
14.9
)f
Cana
dian
Abor
igin
al:
12.9
(12.
4-13
.4)f ,
Whi
te:1
4.4
(13.
8-15
.1)f ,
othe
r(A
fric
an/
Carib
bean
,As
ian,
H,
Mid
dle
East
ern)
:14
.3(1
3.7-
14.9
)f
061 (2
7.8)
221
M:9
1(4
1.2)
;F:
130
(58.
8)Ca
nadi
anAb
orig
inal
:10
0(4
5.2)
;Whi
te:5
7(2
5.8)
;oth
er(A
fric
an/C
arib
bean
,As
ian,
H,M
iddl
eEa
ster
n):6
4(2
9.0)
Cana
dian
Abor
igin
al:2
7(2
7.3)
;Whi
te:1
6(2
8);o
ther
(Afr
ican
/Ca
ribbe
an,A
sian
,H
,Mid
dle
East
ern)
:18
(28)
NR
NR
211
(95.
3)
Amut
haet
al,5
320
12In
dia
CSN
R16
.1(2
.5)
22.2
(9.7
)47 (2
3.7)
198
M:8
1(4
0.9)
;F:
117
(59.
1)So
uth
Indi
an:1
98(1
00.0
)dM
:22
(27)
;F:2
5(2
1.4)
;Sou
thIn
dian
:47
(23.
7)
BP≥1
30/8
5m
mH
gN
RN
R
Drut
elan
dPa
ulo,
54
2014
g
Unite
dSt
ates
CSN
Rra
nge,
3-18
NR
73 (27.
8)26
3N
RN
RN
RN
RN
RN
R
Klin
gens
mith
etal
,55
2016
Unite
dSt
ates
CS13
.1(2
.3)b
13.1
(2.3
)b0
44 (29.
3)15
0N
RN
RN
RBP
≥95t
hpe
rcen
tile
fora
gean
dhe
ight
NR
315
(62.
6)b
Zabe
enet
al,5
620
16Ba
ngla
desh
CSAg
e9-
10y:
11(1
4.3%
);ag
e11
-14
y:46
(59.
7%);
age
15-1
7y:
20(2
6.0%
)
Age
9-10
y:11
(14.
3%);
age
11-1
4y:
46(5
9.7%
);ag
e15
-17
y:20
(26.
0%)
025
(32)
77M
:26
(34)
;F:5
1(6
6)Ba
ngla
desh
i:77
(100
)dBa
ngla
desh
i:25
(32)
BP≥9
5th
perc
entil
efo
rage
and
sex
NH
LBIS
econ
dTa
skFo
rce
Repo
rt2
2
45(5
8)
Aulic
het
al,5
720
19Au
stra
liaCS
NR
15.1
(1.9
)1.
8(0
.3-3
.3)c
6(1
9)31
NR
NR
NR
BP≥9
5th
perc
entil
efo
rage
and
sex
for
patie
nts<
18y,
≥140
/90
mm
Hg
forp
atie
nts≥
18y,
orre
leva
ntm
edic
alth
erap
y
NH
LBIS
econ
dTa
skFo
rce
Repo
rt2
2
24(7
5)b
Khal
ilet
al,5
820
19Eg
ypt
CS18
.0(2
.0)
19.8
(1.1
)2.
5(2
.0)
1(8
)13
M:6
(46)
;F:7
(54)
Egyp
tian:
13(1
00)d
M:1
(17)
;F:0
;Eg
yptia
n:0
Syst
olic
BP≥1
40m
mH
gor
dias
tolic
BP≥8
0m
mH
gor
taki
ngan
tihyp
erte
nsiv
em
edic
atio
n
NR
NR
Scot
tet
al,5
920
04N
ewZe
alan
dRC
NR
mea
n,19
.6;
rang
e,14
-23
1.7
5(3
9)13
M:7
(54)
;F:6
(46)
Mao
ri:7
(54)
;Eu
rope
an:4
(30)
;PI:
1(8
);As
ian
Indi
an:1
(8)
NR
Syst
olic
BP>1
30m
mH
gor
dias
tolic
BP>8
0m
mH
g
NR
13(1
00)
Zdra
vkov
icet
al,6
020
04Ca
nada
RC13
.5(2
.2)
[ran
ge,
8.8-
17.5
]
13.5
(2.2
)[r
ange
,8.
8-17
.5]
04
(10)
41M
:15
(37)
;F:2
6(6
3)So
uth/
East
Asia
n:19
(46)
;Afr
ican
Cana
dian
:11
(27)
;N
HW
:6(1
5);H
:4(1
0);F
N:1
(2)
NR
BP≥9
5th
perc
entil
efo
rage
and
sex
NH
LBIU
pdat
eon
Seco
ndTa
skFo
rce
Repo
rt2
3
33(8
0)
Pére
z-Pe
rdom
oet
al,6
120
05
Puer
toRi
coRC
NR
Age
≤17
y:35
(80%
);ag
e18
-19
y:9
(20%
)
NR
5(1
1)44
NR
NR
NR
NR
NR
69(8
0)b
(con
tinue
d)
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 6/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e1.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onPr
eval
ence
ofH
yper
tens
ion
inPe
diat
ricTy
pe2
Dia
bete
s(co
ntin
ued)
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
aten
rollm
ent,
mea
n(S
D),y
Diab
etes
dura
tion,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
ze,N
o.Se
xdi
strib
utio
nN
o.(%
)Ra
cial
grou
pdi
strib
utio
n,N
o.(%
)
Case
sby
sex
and/
orra
cial
grou
p,N
o.(%
)H
yper
tens
ion
defin
ition
Refe
renc
eva
lues
sour
ce
Prev
alen
ceof
obes
ity,
No.
(%)
Scot
tet
al,6
220
06N
ewZe
alan
dRC
NR
20.0
(0.4
)3.
0(0
.3)
21 (20.
0)10
5N
RM
aori/
PI/o
ther
:66
(62.
9);E
urop
ean:
39(3
7.1)
NR
BP>1
30/8
5m
mH
gN
R10
5(1
00)
Bala
sant
hira
net
al,6
320
12Un
ited
King
dom
RC15
.2(3
.3)
21.2
(3.2
)5.
4(3
.1)
9(2
1)44
M:1
7(3
9);F
:27
(61)
Bang
lade
shi:
11(2
5);
Paki
stan
i:9
(20)
;In
dian
:7(1
6);W
hite
Briti
sh:6
(14)
;Bla
ckAf
rican
:4(9
);Bl
ack
Carib
bean
:4(9
);un
clea
r:3
(7)
NR
BPpe
rsis
tent
ly>1
30/8
5m
mH
gN
R23
(59)
b,e
Osm
anet
al,6
420
13Su
dan
RCAg
e<1
1y:
3(8
%);
age
11-1
8y:
35(9
2%)
NR
NR
22(5
8)38
M:1
7(4
5);F
:21
(55)
Arab
:32
(84)
;m
ultir
acia
l:4
(11)
;no
n-Ar
ab:2
(5)
NR
BP≥9
5th
perc
entil
efo
rage
and
sex
on>1
occa
sion
NR
29(7
6)
Dart
etal
,65
2014
Cana
daRC
13.5
(2.2
)13
.5(2
.2)
034
(9.9
)34
2M
:129
(37.
8);F
:21
3(6
2.2)
NR
NR
Elev
ated
BPfo
rag
e,se
x,an
dhe
ight
NH
LBIF
ourt
hRe
port
20
NR
Hay
nes
etal
,66
2014
g
Aust
ralia
RC13
.3(2
.0)b
13.3
(2.0
)b0
15(2
0)75
NR
NR
NR
NR
NR
82(6
0.7)
b
Yafi,
67
2019
gUn
ited
Stat
esRC
rang
e,8-
15N
RN
R1
(5)
25M
:11
(44)
;F:1
4(5
6)H
:15
(60)
;oth
er:1
0(4
0)N
RN
RN
RN
R
Yeow
etal
,68
2019
Mal
aysi
aRC
14.3
(3.5
)20
.7(3
.7)
6.5
(2.8
)3
(13)
24M
:10
(42)
;F:1
4(5
8)M
alay
:12
(50)
;Ch
ines
e:11
(46)
;As
ian
Indi
an:1
(4)
NR
BP≥9
5th
perc
entil
efo
rage
and
sex
for
patie
nts<
17y;
BP≥1
40/9
0m
mH
gfo
rpat
ient
s≥1
7y
NH
LBIF
ourt
hRe
port
20
;N
HLB
ISev
enth
Repo
rt2
4
10(4
2)
Curr
anet
al,6
920
20Au
stra
liaRC
All
part
icip
ants
<10
All
part
icip
ants
,<1
6
NR
3(2
7)11
NR
PI:1
1(1
00)
PI:3
(27)
NR
NR
11(1
00)
Eppe
nset
al,4
2006
Aust
ralia
PC13
.2(1
1.6-
15.0
)b,c
15.3
(13.
6-16
.4)b
,c1.
3(0
.6-3
.1)b
,c21
(36)
58N
RN
RN
RSy
stol
icor
dias
tolic
BP>9
5th
perc
entil
efo
rage
and
sex
NH
LBIU
pdat
eon
Seco
ndTa
skFo
rce
Repo
rt2
3
36(5
6)b
Shie
ldet
al,7
020
09Un
ited
King
dom
and
Repu
blic
ofIr
elan
d
PCm
ean,
13.6
;ra
nge,
9.9-
16.8
b
mea
n,14
.5;
rang
e,10
.8-1
7.8b
mea
n,1b
19(3
2)59
M:2
4(4
1);F
:35
(59)
NR
M:7
(29)
;F:1
2(3
4)Sy
stol
icor
dias
tolic
BP≥9
8th
perc
entil
efo
rage
and
sex
UKRe
fere
nce
Valu
es2
561
(80)
b
Ruha
yel
etal
,71
2010
Aust
ralia
PC13
.4(r
ange
,9.
2-17
.4)a,
cM
:16.
0(1
3.6-
18.2
);F:
15.6
(11.
7-19
.8)a,
c
M:2
.2(0
.0-
7.8)
;F:2
.3(0
.1-7
.4)a,
c
9(3
0)30
NR
NR
NR
BP>9
8th
perc
entil
efo
rage
and
sex
UKRe
fere
nce
Valu
es2
523
(70)
b
Jeff
erie
set
al,7
220
12N
ewZe
alan
dPC
12.9
(1.8
)[r
ange
,7.
1-15
.5]
NR
NR
27(5
2)52
M:1
7(3
3);F
:35
(67)
PI/M
aori:
47(9
0);
othe
r:5
(10)
NR
BP≥9
5th
perc
entil
efo
rsex
and
age
NR
NR
Schm
idt
etal
,73
2012
Germ
any
and
Aust
ria
PC13
.5(3
.4)
15.3
(3.0
)N
R20
2(2
9.5)
684
M:2
61(3
8.2)
;F:
423
(61.
8)Ge
rman
/Aus
tria
n:48
2(7
0.5)
;oth
er:2
02(2
9.5)
NR
BP>9
5th
perc
entil
efo
rage
,se
x,an
dhe
ight
NH
LBIF
ourt
hRe
port
20
NR
Dart
etal
,74
2019
Cana
daPC
All
part
icip
ants
<18
15 (13.
3-16
.8)c
2.3
(0.9
-4.1
)c15
5(8
2.9)
187
M:6
2(3
3.2)
;F:
125
(66.
8)In
dige
nous
:179
(95.
7);o
ther
:8(4
.3)
NR
BP≥9
5th
perc
entil
efo
rage
,se
xan
dhe
ight
NH
LBIF
ourt
hRe
port
20
NR (c
ontin
ued)
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 7/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e1.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onPr
eval
ence
ofH
yper
tens
ion
inPe
diat
ricTy
pe2
Dia
bete
s(co
ntin
ued)
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
aten
rollm
ent,
mea
n(S
D),y
Diab
etes
dura
tion,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
ze,N
o.Se
xdi
strib
utio
nN
o.(%
)Ra
cial
grou
pdi
strib
utio
n,N
o.(%
)
Case
sby
sex
and/
orra
cial
grou
p,N
o.(%
)H
yper
tens
ion
defin
ition
Refe
renc
eva
lues
sour
ce
Prev
alen
ceof
obes
ity,
No.
(%)
Syst
olic
hype
rten
sion
Upch
urch
etal
,75
2003
Unite
dSt
ates
CS13
.6(2
.3)b
13.6
(2.3
)b0
41(4
9)83
NR
NR
NR
Syst
olic
BP≥9
5th
perc
entil
efo
rage
,se
x,an
dhe
ight
NR
91(9
3)b
Wei
etal
,76
2003
Taiw
anCS
M:1
3.7
(2.5
);F:
13.0
(2.5
)a,b
M:1
3.7
(2.5
);F:
13.0
(2.5
)a,b
049 (3
9.2)
125
M:4
7(3
7.6)
;F:7
8(6
2.4)
NR
M:2
3(4
9);F
:26
(33)
Syst
olic
BP≥8
5th
perc
entil
eof
sex
and
age
base
don
popu
latio
nin
the
stud
y
NR
63(4
8.1)
b
Cruz
etal
,77
2004
Mex
ico
CSAl
lpa
rtic
ipan
ts<1
8
13.8
(1.8
)m
ean,
0.9;
rang
e,0.
08-3
2(5
)44
M:2
0(4
6);F
:24
(54)
Mex
ican
:44
(100
)dM
exic
an:2
(5)
NR
NR
NR
Hot
uet
al,7
820
04N
ewZe
alan
dCS
mea
n,15
;ra
nge,
11-1
9N
RN
R5
(28)
18M
:9(5
0);F
:9(5
0)M
aori/
PI:1
8(1
00)
M:3
(33)
;F:2
(22)
;Mao
ri/PI
:5(2
8)
Syst
olic
BP>9
5th
perc
entil
efo
rage
,se
xan
dhe
ight
NH
LBIU
pdat
eon
Seco
ndTa
skFo
rce
Repo
rt2
3
NR
Rodr
igue
zet
al,1
720
10Un
ited
Stat
esCS
12.9
(2.1
)14
.8(2
.0)
1.6
(1.5
)10
6(2
5.9)
410
M:1
52(3
7.1)
;F:
258
(62.
9)AA
:130
(31.
7);H
:99
(24.
1);N
HW
:84
(20.
5);A
I:56
(13.
7);
API:
37(9
.0);
othe
r:4
(1.0
)
NR
Syst
olic
BP>9
5th
perc
entil
efo
rage
,se
xan
dhe
ight
NH
LBIF
ourt
hRe
port
20
332
(81.
0)
Selle
rset
al,7
920
07Ca
nada
RCm
ean,
13.1
;ra
nge,
9-17
mea
n,15
.3;
rang
e,9-
18N
R13
(13)
99M
:42
(42)
;F:5
7(5
8)FN
/Met
is:9
4(9
5);
othe
r:5
(5)
M:5
(12)
;F:8
(14)
Syst
olic
BP>9
5th
perc
entil
efo
rage
and
gend
er
NH
LBIF
ourt
hRe
port
20
38(3
8)
Pelh
amet
al,8
020
18Un
ited
Stat
esRC
NR
15.2
(2.7
)2.
7(1
.7)
34(3
7)93
M:2
7(2
9);F
:66
(71)
NR
NR
Syst
olic
BP≥9
5th
perc
entil
efo
rage
,ge
nder
,and
heig
ht
NH
LBIF
ourt
hRe
port
20
NR
Shie
ldet
al,7
020
09Un
ited
King
dom
and
Repu
blic
ofIr
elan
d
PCm
ean,
13.6
;ra
nge,
9.9-
16.8
b
mea
n,14
.5;
rang
e,10
.8-1
7.8b
mea
n,1b
4(7
)59
M:2
4(4
1);F
:35
(59)
NR
M:1
(4);
F:3
(9)
Syst
olic
BP≥9
8th
perc
entil
efo
rage
and
sex
UKRe
fere
nce
Valu
es2
561
(80)
b
Cand
ler
etal
,81
2018
Unite
dKi
ngdo
man
dRe
publ
icof
Irel
and
PC14
.3(7
.9-1
6.9)
h14
.3(7
.9-1
6.9)
h0
22 (20.
8)10
6M
:35
(33.
0);F
:71
(67.
0)N
HW
:47
(44.
3);
Asia
n/As
ian
Briti
sh:
36(3
4.0)
;BAC
BB:1
4(1
3.2)
;oth
er:5
(4.7
);un
cert
ain:
4(3
.8)
NR
Syst
olic
BP≥9
5th
perc
entil
efo
rsex
,ag
ean
dhe
ight
NH
LBIF
ourt
hRe
port
20
86(8
1.1)
Dias
tolic
hype
rten
sion
Upch
urch
etal
,75
2003
Unite
dSt
ates
CS13
.6(2
.3)b
13.6
(2.3
)b0
9(1
1)83
NR
NR
NR
Dias
tolic
BP≥9
5th
perc
entil
efo
rage
,se
x,an
dhe
ight
NR
91(9
3)b
Wei
etal
,76
2003
Taiw
anCS
M:1
3.7
(2.5
);F:
13.0
(2.5
)a,b
M:1
3.7
(2.5
);F:
13.0
(2.5
)a,b
053 (4
2.4)
125
M:4
7(3
7.6)
;F:7
8(6
2.4)
NR
M:2
4(5
1);F
:29
(37)
Dias
tolic
BP≥8
5th
perc
entil
eof
sex
and
age
base
don
popu
latio
nin
the
stud
y
NR
63(4
8.1)
b
Cruz
etal
,77
2004
Mex
ico
CSN
R13
.8(1
.7)
mea
n,0.
9;ra
nge,
0.08
-3
5(1
1)44
M:2
0(4
6);F
:24
(54)
Mex
ican
:44
(100
)dM
exic
an:5
(11)
NR
NR
NR
Rodr
igue
zet
al,1
720
10Un
ited
Stat
esCS
12.9
(2.1
)14
.8(2
.0)
1.6
(1.5
)75 (1
8.3)
410
M:1
52(3
7.1)
;F:
258
(62.
9)AA
:130
(31.
7);H
:99
(24.
1);N
HW
:84
(20.
5);A
I:56
(13.
7);
API:
37(9
.0);
othe
r:4
(1.0
)
NR
Dias
tolic
BP>9
5th
perc
entil
efo
rage
,se
xan
dhe
ight
NH
LBIF
ourt
hRe
port
20
332
(81.
0)
(con
tinue
d)
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 8/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e1.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onPr
eval
ence
ofH
yper
tens
ion
inPe
diat
ricTy
pe2
Dia
bete
s(co
ntin
ued)
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
aten
rollm
ent,
mea
n(S
D),y
Diab
etes
dura
tion,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
ze,N
o.Se
xdi
strib
utio
nN
o.(%
)Ra
cial
grou
pdi
strib
utio
n,N
o.(%
)
Case
sby
sex
and/
orra
cial
grou
p,N
o.(%
)H
yper
tens
ion
defin
ition
Refe
renc
eva
lues
sour
ce
Prev
alen
ceof
obes
ity,
No.
(%)
Shal
itin
etal
,82
2014
Isra
elCS
NR
15.9
(3.6
)3.
3(2
.1)
4(3
6)11
M:5
(45)
;F:6
(55)
Isra
eli:
11(1
00)d
Isra
eli:
4(3
6)N
RN
R11
(100
)
Selle
rset
al,7
920
07Ca
nada
RCm
ean,
13.1
;ra
nge,
9-17
mea
n,15
.3;
rang
e,9-
18N
R6
(6)
99M
:42
(42)
;F:5
7(5
8)FN
/Met
is:9
4(9
5);
Oth
er:5
(5)
M:3
(7);
F:3
(5)
Dias
tolic
BP>9
5th
perc
entil
efo
rage
and
gend
er
NH
LBIF
ourt
hRe
port
20
38(3
8)
Pelh
amet
al,8
020
18Un
ited
Stat
esRC
NR
15.2
(2.7
)2.
7(1
.7)
7(8
)93
M:2
7(2
9);F
:66
(71)
NR
NR
Dias
tolic
BP≥9
5th
perc
entil
efo
rage
,ge
nder
,and
heig
ht
NH
LBIF
ourt
hRe
port
20
NR
Shie
ldet
al,7
020
09Un
ited
King
dom
and
Repu
blic
ofIr
elan
d
PCm
ean,
13.6
;ra
nge,
9.9-
16.8
b
mea
n,14
.5;
rang
e,10
.8-1
7.8b
mea
n,1b
11(1
9)59
M:2
4(4
1);F
:35
(59)
NR
M:6
(25)
;F:5
(14)
Dias
tolic
BP≥9
8th
perc
entil
efo
rage
and
sex
UKRe
fere
nce
Valu
es2
561
(80)
b
Abbr
evia
tions
:AA,
Afric
anAm
eric
an;A
I,Am
eric
anIn
dian
;API
,Asia
n–Pa
cific
Isla
nder
;BAC
BB,B
lack
/Afr
ican
/Ca
ribbe
an/B
lack
Briti
sh;B
P,bl
ood
pres
sure
;CS,
cros
s-se
ctio
nal;
F,fe
mal
e;FN
,Firs
tNat
ions
;H,H
ispan
ic;M
,mal
e;N
HB,
Non
-Hisp
anic
Blac
k;N
HLB
I,N
atio
nalH
eart
,Lun
g,an
dBl
ood
Inst
itute
;NH
W,N
on-H
ispan
icW
hite
;NR,
not
repo
rted
;PC,
pros
pect
ive
coho
rt;P
I,Pa
cific
Isla
nder
;RC,
retr
ospe
ctiv
eco
hort
.a
Mea
n(S
E).
bBa
sed
onto
tals
tudy
coho
rtin
stea
dof
only
patie
ntse
xam
ined
fort
hesp
ecifi
ccom
orbi
dity
.c
Med
ian
(inte
rqua
rtile
rang
e).
dRa
cial
grou
pdi
strib
utio
nas
sum
edto
mat
chco
untr
yof
orig
in.
eVa
lue
estim
ated
base
don
grap
h.f
Mea
n(C
I).g
Abst
ract
only.
hM
edia
n(r
ange
).
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 9/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
pooled prevalence of hypertension was 25.33% (95% CI, 19.57%-31.53%) (Figure 1). Highheterogeneity was noted across studies (I2 = 94%; P < .001).
Another 15 studies that reported on the prevalence of hypertension were not included in themeta-analysis. Two studies had a higher cutoff for hypertension (BP �98th percentile) and reporteda prevalence of 30% among 30 participants and 32% among 59 participants, respectively.70,71 Fivestudies presented racial subgroup data46-50 of another included study.17 Eight studies were onlyincluded in the analysis of isolated systolic or diastolic hypertension.75-82
When pooling only the studies with hypertension definition of BP in 95th percentile or greaterfor age, sex, and height (2763 participants), the prevalence was significantly higher at 34.00% (95%CI, 24.00%-45.00%; I2 = 97%; P < .001) (eTable 6 in the Supplement).4,15,17,42-44,55-57,60,64,68,72-74
The metaregression analysis revealed no significant association between hypertension prevalenceand obesity prevalence.
Figure 1. Forest Plot Showing Pooled Prevalence of Hypertension in Pediatric Type 2 Diabetes
0 60 10040 80Prevalence, % (95% CI)
20
Weight, %Study
Cross-sectional studies
CasesNo.
TotalPrevalence, %(95% CI)
Khalil et al,58 2019Aulich et al,57 2019Zabeen et al,56 2016Klingensmith et al,55 2016Drutel et al,54 2014Amutha et al,53 2012Amed et al,52 2012Copeland et al,15 2011Rodriguez et al,17 2010Urakami et al,51 2009Unnikrishnan et al,45 2008Eppens et al,44 2006Reinehr et al,43 2005Ettinger et al,42 2005Scott et al,41 1997Pinhas-Hamiel et al,40 1996
162544734761969713164815149
1331771502631982217044101123626516264454
7.69 (0.00-30.13)19.35 (7.05-35.39)32.47 (22.41-43.39)29.33 (22.30-36.90)27.76 (22.50-33.34)23.74 (18.05-29.93)27.60 (21.89-33.70)13.64 (11.20-16.27)23.66 (19.66-27.90)11.61 (6.25-18.27)2.78 (0.00-11.54)24.15 (19.48-29.50)50.00 (25.40-74.60)57.69 (38.07-76.20)31.82 (18.76-46.43)16.67 (7.75-27.93)
2.43.03.43.63.63.63.63.73.73.53.13.62.52.93.23.3
Total (95% CI) 2620 23.14 (18.51-28.10) 52.7Heterogeneity: τ2 = 0.0092; χ2 = 98.16, df = 15 (P < .001); I2 = 85%
Retrospective cohort studies
Curran et al,69 2020Yeow et al,68 2019Yafi,67 2019Haynes et al,66 2014Dart et al,65 2014Osman et al,64 2013Balasanthiran et al,63 2012Scott et al,62 2006Pérez-Perdomo et al,61 2005Zdravkovic et al,60 2004Scott et al,59 2004
331153422921545
112425753423844105444113
27.27 (4.39-57.92)12.50 (1.73-29.28)4.00 (0.00-16.38)20.00 (11.63-29.89)9.94 (6.98-13.35)57.89 (41.76-73.25)20.45 (9.65-33.80)20.00 (12.85-28.24)11.36 (3.37-22.70)9.76 (2.20-21.07)38.46 (13.47-66.73)
2.22.82.93.43.73.13.23.53.23.12.4
Total (95% CI) 762 18.55 (11.35-26.92) 33.4Heterogeneity: τ2 = 0.0192; χ2 = 54.68, df = 10 (P < .001); I2 = 82%
Prospective cohort studies
Dart et al,74 2019Schmidt et al,73 2012Jefferies et al,72 2012Eppens et al,4 2006
1552022721
1876845258
82.89 (77.13-87.97)29.53 (26.17-33.01)51.92 (38.25-65.46)36.21 (24.25-49.06)
3.63.73.33.3
Total (95% CI) 981 50.74 (20.67-80.52) 13.9Heterogeneity: τ2 = 0.1019; χ2 = 192.33, df = 3 (P < .001); I2 = 98%
Total (95% CI) 4363 25.33 (19.57-31.53) 100Heterogeneity: τ2 = 0.0310; χ2 = 527.45, df = 30 (P < .001); I2 = 94%
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 10/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Pooled Prevalence of Systolic and Diastolic Hypertension in Type 2 DiabetesIsolated systolic hypertension prevalence across 6 studies with 747 participants was 24.79% (95%CI, 14.04%-37.31%; I2 = 90%; P < .001) (eFigure 2 in the Supplement).17,75,77-80 Two additionalstudies using different definitions reported a prevalence of 39.2% among 125 participants(hypertension definition, BP �85th percentile)76 and 7% among 59 participants (hypertensiondefinition, BP �98th percentile).70 Another study determined a prevalence of 20.8% among 106participants; because it was the only prospective cohort study, it was not included in themeta-analysis.81
Isolated diastolic hypertension prevalence across 6 studies with 740 participants was 11.65%(95% CI, 6.41%-18.04%; I2 = 75%; P = .001) (eFigure 3 in the Supplement).17,75,77,79,80,82 Twoadditional studies using different definitions reported a prevalence of 42.4% among 125 participants(diastolic hypertension, BP �85th percentile)76 and 19% among 59 participants (diastolichypertension, BP �98th percentile).70
Sex and Race Associations With HypertensionFour studies reported hypertension prevalence in 600 male participants of 23.81% (95% CI, 18.56%-29.47%; I2 = 58%; P = .07) and 977 female participants of 18.56% (95% CI, 12.25%-25.82%;I2 = 85%; P < .001) with an OR of 1.42 (95% CI, 1.10-1.83; I2 = 0%; P for heterogeneity = .65)(eFigure 4 and eFigure 5 in the Supplement).15,17,44,53 In contrast, 1 study with hypertension definitionof BP in the 98th percentile or greater reported a prevalence of 29% in 24 male participants and 34%in 35 female participants.70
When assessing the prevalence of hypertension in different racial groups, Indigenous andPacific Islander youth had the highest rates of hypertension when compared with other groups(Pacific Islander youth17,69: 48 participants; prevalence, 26.71% [95% CI, 14.54%-40.72%]; I2 = 0%;P = .92; Indigenous youth15,47,52: 205 participants; prevalence, 26.48% [95% CI, 17.34%-36.74%];I2 = 58%, P = .09; White youth15,43,46,52,58: 330 participants; prevalence, 20.95% [95% CI, 12.65%-30.57%]; I2 = 66%; P = .02; African American youth15,50: 434 participants; prevalence, 19.04% [95%CI, 12.01%-27.23%]; I2 = 76%; P = .04; Hispanic/Latino youth15,48: 409 participants; prevalence,15.11% [95% CI, 6.56%-26.30%]; I2 = 85%; P < .001; Asian youth45,49,51,53,56: 452 participants;prevalence, 18.37% [95% CI, 9.49%-29.23%]; I2 = 84%, P < .001) (eFigure 6 in the Supplement).
AlbuminuriaStudy CharacteristicsThirty-nine studies reported on albuminuria prevalence(Table 2).4,8,15,16,42,44-46,50,52,53,57-59,62,64-69,71-74,78,81,83-94 The age at type 2 diabetes diagnosisranged from 6.5 to 21.0 years,90,93 and type 2 diabetes duration ranged fromdiagnosis52,65,66,71,81,83,85,89,94 to more than 15.0 years after diagnosis.50,53 Nineteen studies (49%)were cross-sectional studies,15,16,42,44-46,50,52,53,57,58,78,83,84,86-90 14 (36%) were retrospectivecohort studies,8,59,62,64-69,85,91-94 and 6 (15%) were prospective cohort studies.4,71-74,81
Pooled Prevalence of Albuminuria and Persistent Albuminuria in Type 2 DiabetesPooled albuminuria prevalence in 14 studies of 2250 patients with type 2 diabetes was 22.17% (95%CI, 17.34%-27.38%) (Figure 2).16,42,52,53,67-69,71,73,74,78,81,83,85 There were high levels of heterogeneity(I2 = 82%; P < .001).
Four studies were not included in the meta-analysis. One used a definition of albuminuria of24-hour urine protein excretion of greater than 500 mg, and found no patients with this outcome.45
Another study did not report the sample size or the definition of albuminuria but reported aprevalence of 23%.84 Two other studies46,50 reported the prevalence in specific racial groups, andthe data were captured by another included study.16 Removing studies with 678 patients older than18 years lowered the estimate to 17.00% (95% CI, 9.00%-27.00%; I2 = 86%;
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 11/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e2.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onth
ePr
eval
ence
ofAl
bum
inur
iain
Pedi
atric
Type
2D
iabe
tes
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
atst
udy
enro
llmen
tor
mea
sure
men
t,m
ean
(SD)
,y
Dura
tion
ofdi
abet
es,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
zeSe
xdi
strib
utio
n,N
o.(%
)
Raci
algr
oup
dist
ribut
ion,
No.
(%)
Case
sby
sex
orra
cial
grou
p,N
o.(%
)Al
bum
inur
iade
finiti
on
Prev
alen
ceof
obes
ity,
No.
(%)
Albu
min
uria
Hot
uet
al,7
820
04N
ewZe
alan
dCS
mea
n,15
;ra
nge,
11-1
9N
RN
R7
(58)
12M
:6(5
0);F
:6(5
0)M
aori/
PI:1
2(1
00)
M:4
(67)
;F:3
(50)
;M
aori/
PI:7
(58)
ACR
≥30m
g/g
NR
Ettin
ger
etal
,42
2005
Unite
dSt
ates
CSN
R15
.0(1
.9)
1.5
(1.0
)10
(40)
25M
:12
(46)
;F:
14(5
4)a
H:1
5(5
8);N
HB:
8(3
1);o
ther
:2(7
);m
ultir
acia
l:1
(4)a
NR
AER
≥30m
gal
bum
in/2
4h
NR
Maa
hset
al,1
620
07Un
ited
Stat
esCS
All
part
icip
ants
<20
Age
<12
y:19
(5.1
%);
age
≥12
y:35
5(9
4.9%
)
1.9
(0.4
-3.2
)b83
(22.
2)37
4M
:140
(37.
4);
F:23
4(6
2.6)
AA:1
10(2
9.4)
;AI
:92
(24.
6);
NH
W:7
1(1
9.0)
;H
:64
(17.
1);A
PI:
25(6
.8);
mul
tirac
ialo
rot
her:
11(2
.9);
unkn
own:
1(0
.2)
M:2
9(2
0.7)
;F:5
4(2
3.1)
;AA:
18(1
6.4)
;AI
:33
(36)
;NH
W:9
(13)
;H:1
5(2
3);A
PI:
6(2
4);m
ultir
acia
lor
othe
r:2
(18)
;un
know
n:0
(0)
ACR
≥30m
g/g
266
(72.
3)a
Unni
kris
hnan
etal
,45
2008
Indi
aCS
16.2
(2.9
)18
.9(4
.9)
NR
036
M:2
1(5
8);F
:15
(42)
Indi
an:3
6(1
00)c
Indi
an:0
AER
>500
mg
albu
min
/24
hN
R
Bell
etal
,46
2009
Unite
dSt
ates
CSAl
lpa
rtic
ipan
ts<2
0
Age
10-1
4y:
42(4
1.6%
);ag
e≥1
5y:
59(5
8.4%
)
NR
14(1
3.9)
101
NR
NH
W:1
01(1
00)
NH
W:1
4(1
3.9)
ACR
≥30m
g/g
83(7
9.0)
a
May
er-D
avis
etal
,50
2009
Unite
dSt
ates
CS10
-14:
11.7
(1);
≥15:
15.1
(1.9
)
10-1
4:81
(38.
2%);
≥15:
131
(61.
8%)
10-1
4:1.
2(0
.7);
≥15:
2.6
(2.1
)
30(1
4.1)
212
NR
AA:2
12(1
00)
AA:3
0(1
4.1)
ACR
≥30m
g/g
NR
Kim
etal
,83
2010
Unite
dSt
ates
CSN
R14
.5(3
.0)
mea
n,1.
3;ra
nge,
0.0-
2.1
22(2
1.4)
103
M:4
0(3
8.8)
;F:
63(6
1.2)
Pim
aIn
dian
:103
(100
)Pi
ma
Indi
an:2
2(2
1.4)
ACR
≥30m
g/g
NR
Amed
etal
,52
2012
Cana
daCS
Cana
dian
Abor
igin
al:
12.9
(12.
4-13
.4)d
;W
hite
:14.
4(1
3.8-
15.1
)d;
othe
r(A
fric
an/
Carib
bean
,As
ian,
H,
Mid
dle
East
ern)
:14.
3(1
3.7-
14.9
)d
Cana
dian
Abor
igin
al:1
2.9
(12.
4-13
.4)d
;W
hite
:14.
4(1
3.8-
15.1
)d;
othe
r(Af
rican
/Ca
ribbe
an,A
sian
,H
,Mid
dle
East
ern)
:14
.3(1
3.7-
14.9
)d
032
(14.
4)22
1M
:91
(41.
2);F
:13
0(5
8.8)
Cana
dian
Abor
igin
al:1
00(4
5.2)
;Whi
te:5
7(2
5.8)
;oth
er(A
fric
an/
Carib
bean
,Asi
an,
H,M
iddl
eEa
ster
n):6
4(2
9.0)
Cana
dian
Abor
igin
al:
16(1
6.7)
;Whi
te:6
(10)
;oth
er(A
fric
an/
Carib
bean
,Asi
an,H
,M
iddl
eEa
ster
n):9
(14)
NR
211
(95.
3)
Amut
haet
al,5
320
12In
dia
CS16
.1(2
.5)
22.2
(9.7
)Ag
e≤5
y:21
9(5
9.5%
);ag
e>5
to≤1
0y:
67(1
8.2%
);ag
e>1
0to
≤15:
21(5
.7%
);ag
e>1
5y:
61(1
6.6%
)
85(2
3.1)
368
M:1
68(4
5.7)
;F:
200
(54.
3)So
uth
Indi
an:3
68(1
00.0
)cSo
uth
Indi
an:8
5(2
3.1)
ACR
≥30m
g/g
NR
Hol
man
etal
,84
2015
Unite
dKi
ngdo
mCS
All
part
icip
ants
>12
Allp
artic
ipan
ts,
>12
NR
NR
(23)
NR
NR
NR
NR
NR
NR
Selle
rset
al,8
520
09Ca
nada
RCN
RN
R0
26(2
9)90
M:4
0(4
5);F
:50
(55)
FN/M
etis
:88
(98)
;oth
er:2
(2)
NR
ACR
>3m
g/m
mol
NR (c
ontin
ued)
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 12/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e2.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onth
ePr
eval
ence
ofAl
bum
inur
iain
Pedi
atric
Type
2D
iabe
tes(
cont
inue
d)
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
atst
udy
enro
llmen
tor
mea
sure
men
t,m
ean
(SD)
,y
Dura
tion
ofdi
abet
es,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
zeSe
xdi
strib
utio
n,N
o.(%
)
Raci
algr
oup
dist
ribut
ion,
No.
(%)
Case
sby
sex
orra
cial
grou
p,N
o.(%
)Al
bum
inur
iade
finiti
on
Prev
alen
ceof
obes
ity,
No.
(%)
Yafi,
67
2019
eUn
ited
Stat
esRC
rang
e,8-
15N
RN
R3
(12)
25M
:11
(44)
;F:
14(5
6)H
:15
(60)
;oth
er:
10(4
0)N
RN
RN
R
Yeow
etal
,68
2019
Mal
aysi
aRC
14.3
(3.5
)20
.7(3
.7)
6.5
(2.8
)7
(29)
24M
:10
(42)
;F:
14(5
8)M
alay
:12
(50)
;Ch
ines
e:11
(46)
;As
ian
Indi
an:1
(4)
Asia
n:7
(29)
M:A
CR>2
.5m
g/m
mol
,F:
ACR
>3.5
mg/
mm
ol10
(42)
Curr
anet
al,6
920
20Au
stra
liaRC
All
part
icip
ants
<10
Allp
artic
ipan
ts,
<16
NR
2(1
8)11
NR
PI:1
1(1
00)
PI:2
(18)
NR
11(1
00)
Ruha
yel
etal
,71
2010
Aust
ralia
PC13
.4(9
.2-1
7.4)
a,d
M:1
6.0
(13.
6-18
.2;F
:15
.6(1
1.7-
19.8
)a,d
M:2
.2(0
.0-
7.8;
F:2.
3(0
.1-7
.4)a,
d
9(4
5)20
NR
NR
NR
ACR
>3.5
mg/
mm
ol23
(70)
a
Schm
idt
etal
,73
2012
Germ
any
and
Aust
riaPC
13.5
(3.4
)15
.3(3
.0)
NR
170
(24.
9)68
4M
:261
(38.
2);
F:42
3(6
1.8)
Germ
an/A
ustr
ian:
482
(70.
5);
othe
r:20
2(2
9.5)
NR
NR
NR
Cand
ler
etal
,81
2018
Unite
dKi
ngdo
man
dRe
publ
icof
Irel
and
PC14
.3(7
.9-1
6.9)
d14
.3(7
.9-1
6.9)
d0
3(2
.8)
106
M:3
5(3
3.0)
;F:
71(6
7.0)
NH
W:4
7(4
4.3)
;As
ian/
Asia
n-Br
itish
:36
(34.
0);
BACB
B:14
(13.
2);o
ther
:5(4
.7);
unce
rtai
n:4
(3.8
)
NR
NR
86(8
1.1)
Dart
etal
,74
2019
Cana
daPC
All
part
icip
ants
<18
15(1
3.3-
16.8
)b2.
3(0
.9-4
.1)b
47(2
5.1)
187
M:6
2(3
3.2)
;F:
125
(66.
8)In
dige
nous
:179
(95.
7);o
ther
:8(4
.3)
NR
ACR
>2m
g/m
mol
NR
Pers
iste
ntal
bum
inur
ia
Yoo
etal
,86
2004
Kore
aCS
12.8
(1.5
)18
.4(4
.3)
5.5
(3.9
)5
(23)
22M
:8(3
6);M
:14
(64)
Kore
an:2
2(1
00)
Kore
an:5
(23)
AER
>20
μg/m
inon
sam
ples
3m
oap
art
NR
Fara
het
al,8
720
06Un
ited
Stat
esCS
NR
rang
e,10
-21
mea
n,1.
8;ra
nge,
<2-5
9(2
7)33
NR
NR
NR
ACR
>30
mg/
gon
2sa
mpl
esw
ithin
3-6
mo
29(7
3)a
Cope
land
etal
,15
2011
Unite
dSt
ates
CSra
nge,
10-1
714
.0(2
.0)
0.7
(0.5
)92
(13.
0)70
4M
:247
(35.
1);
F:45
7(6
4.9)
H:2
89(4
1.1)
;N
HB:
222
(31.
5);
NH
W:1
38(1
9.6)
;AI
:43
(6.1
);As
ian:
12(1
.7)
M:2
6(1
0.6)
;F:6
5(1
4.3)
;H:4
1(1
4.1)
;N
HB:
25(1
1.2)
;NH
W:
20(1
4.6)
;AI:
3(8
)
ACR
≥30m
g/g
on2
of3
sam
ples
durin
g3-
mo
perio
d
NR
Selle
rset
al,8
820
16Ca
nada
CSAl
lpa
rtic
ipan
ts<1
8
NR
NR
50(5
.1)
976
NR
NR
NR
M:A
CR>2
mg/
mm
ol,F
:AC
R>2
.8m
g/m
mol
on2
occa
sion
sdur
ing
6-m
ope
riod
NR
Aulic
het
al,5
720
19Au
stra
liaCS
NR
15.1
(1.9
)1.
8(0
.3-3
.3)b
6(3
0)20
NR
NR
NR
AER
≥20
μg/m
inin
≥2of
3sa
mpl
esor
mea
nAC
R,M
:≥3.
5m
g/m
mol
;F:≥
4m
g/m
mol
from
3fir
stm
orni
ngco
llect
ions
24(7
5)a
Khal
ilet
al,5
820
19Eg
ypt
CS18
.0(2
.0)
19.8
(1.1
)2.
5(2
.0)
0(0
)13
M:6
(46)
;F:7
(54)
Egyp
tian:
0cEg
yptia
n:0
ACR
≥30m
g/g
on2
sam
ples
with
in3-
6m
oN
R
Scot
tet
al,5
920
04N
ewZe
alan
dRC
NR
mea
n,19
.6;r
ange
,14
-23
1.7
2(1
5)13
M:7
(54)
;F:6
(46)
Mao
ri:7
(54)
;Eu
rope
an:4
(30)
;PI
:1(8
);As
ian
Indi
an:1
(8)
NR
M:A
CR>2
.5m
g/m
mol
;F:
ACR
>3.5
mg/
mm
olon
≥2oc
casi
ons
13(1
00)
(con
tinue
d)
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 13/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e2.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onth
ePr
eval
ence
ofAl
bum
inur
iain
Pedi
atric
Type
2D
iabe
tes(
cont
inue
d)
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
atst
udy
enro
llmen
tor
mea
sure
men
t,m
ean
(SD)
,y
Dura
tion
ofdi
abet
es,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
zeSe
xdi
strib
utio
n,N
o.(%
)
Raci
algr
oup
dist
ribut
ion,
No.
(%)
Case
sby
sex
orra
cial
grou
p,N
o.(%
)Al
bum
inur
iade
finiti
on
Prev
alen
ceof
obes
ity,
No.
(%)
Scot
tet
al,6
220
06N
ewZe
alan
dRC
NR
20.0
(0.4
)3.
0(0
.3)
76(7
2.4)
105
NR
Mao
ri/PI
/oth
er:
66(6
2.9)
;Eu
rope
an:3
9(3
7.1)
NR
M:A
CR>2
.5m
g/m
mol
;F:
ACR
>3.5
mg/
mm
olon
≥2oc
casi
ons
105
(100
)
Dart
etal
,65
2014
Cana
daRC
13.5
(2.2
)13
.5(2
.2)
093
(27.
1)34
2M
:129
(37.
8);
F:21
3(6
2.2)
NR
NR
ACR
>3m
g/m
mol
orAE
R>3
0mg/
24h
on≥2
of3
mea
sure
men
ts1
mo
apar
t
NR
Eppe
nset
al,4
2006
Aust
ralia
PC13
.2(1
1.6-
15.0
)a,b
15.3
(13.
6-16
.4)a,
b1.
3(0
.6-3
.1)a,
b10
(28)
36N
RN
RN
RAE
R≥2
0μg
/min
in≥2
of3
sam
ples
orAC
R≥2
.5m
g/m
mol
36(5
6)a
Jeff
erie
set
al,7
220
12N
ewZe
alan
dPC
mea
n,12
.9;
rang
e,7.
1-15
.5
NR
NR
18(3
5)52
M:1
7(3
3);F
:35
(67)
PI/M
aori:
47(9
0);o
ther
:5(1
0)
NR
ACR
≥2.5
mg/
mm
olon
≥2of
3sa
mpl
esdu
ring
6-m
ope
riod
NR
Dart
etal
,74
2019
Cana
daPC
All
part
icip
ants
<18
15(1
3.3-
16.8
b2.
3(0
.9-4
.1)b
57(3
0.5)
187
M:6
2(3
3.2)
;F:
125
(66.
8)In
dige
nous
:179
(95.
7);o
ther
:8(4
.3)
M:1
5(2
4);F
:42
(33.
6);I
ndig
enou
s:56
(31.
3)
ACR
>2m
g/m
mol
on2
of3
sam
ples
durin
ga
6-m
ope
riod
NR
Mic
roal
bum
inur
ia
Hot
uet
al,7
820
04N
ewZe
alan
dCS
mea
n,15
(11-
19N
RN
R5
(42)
12M
:6(5
0);F
:6(5
0)M
aori/
PI:1
2(1
00)
M:3
(50)
;F:2
(33)
;M
aori/
PI:5
(42)
ACR
≥30-
300m
g/g
NR
Ettin
ger
etal
,42
2005
Unite
dSt
ates
CSN
R15
.0(1
.9)
1.5
(1.0
)10
(40)
25M
:12
(46)
;F:
14(5
4)a
H:1
5(5
8);N
HB:
8(3
1);o
ther
:2(7
);m
ultir
acia
l:1
(4)a
NR
AER
≥30m
gal
bum
in/2
4h
NR
Eppe
nset
al,4
420
06W
este
rnPa
cific
CS12
.0(1
0.7-
13.5
)a,b
14.9
(13.
2-16
.4)a,
b2.
3(1
.4-3
.6)a,
b20
(8.0
)25
1N
RN
RN
RAE
R30
-300
mg/
24h
or>2
0μg
/min
orAC
R>2
.5m
g/m
mol
106
(32.
0)a
Kim
etal
,83
2010
Unite
dSt
ates
CSN
R14
.5(3
.0)
mea
n,1.
3(0
-2.1
19(1
8.5)
103
M:4
0(3
8.8)
;F:
63(6
1.2)
Pim
aIn
dian
:103
(100
.0)
Pim
aIn
dian
:19
(18.
5)AC
R≥3
0-30
0mg/
gN
R
Amut
haet
al,5
320
12In
dia
CS16
.1(2
.5)
22.2
(9.7
)Ag
e≤5
y:21
9(5
9.5%
);ag
e>5
to≤1
0y:
67(1
8.2%
);ag
e>1
0to
≤15
y:21
(5.7
%);
age
>15
y:61
(16.
6%)
54(1
4.7)
368
M:1
68(4
5.7)
;F:
200
(54.
3)So
uth
Indi
an:3
68(1
00)c
Sout
hIn
dian
:54
(14.
7)AC
R≥3
0-29
9mg/
gN
R
Zabe
enet
al,8
920
16e
Bang
lade
shCS
13.0
(11.
0-15
.0)d
13.0
(11.
0-15
.0)d
014
(10.
0)14
4N
RBa
ngla
desh
i:14
4(1
00)c
Bang
lade
shi:
14(1
0.0)
ACR
≥30-
300m
g/g
NR
Nam
bam
etal
,90
2017
Unite
dSt
ates
CSAl
lpa
rtic
ipan
ts<2
1
16.0
(14.
0-17
.7)b
2.0
(0.7
-4.2
)b36
(6.0
)59
8M
:218
(36.
5);
F:38
0(6
3.5)
H:3
29(5
5.0)
;AA
:179
(30.
0);
NH
W:4
8(8
.0);
othe
r/m
ultir
acia
l:42
(7.0
)
NR
NR
472
(85.
0)a
Le etal
,91
2013
Unite
dSt
ates
RC13
.8(2
.4)a
14.2
(2.4
)N
R11
(17)
64M
:20
(31)
;F:
44(6
9)AA
:52
(81)
;N
HW
:12
(19)
AA:1
1(2
1);N
HW
:0f
ACR
≥30-
299
mg/
gN
R
Osm
anet
al,6
420
13Su
dan
RCAg
e<1
1y:
3(7
.9%
);ag
e11
-18
y:35
(92.
1%)
NR
NR
7(1
8)38
M:1
7(4
5);F
:21
(55)
Arab
:32
(84)
;m
ultir
acia
l:4
(11)
;non
-Ara
b:2
(5)
NR
NR
29(7
6)
Hay
nes
etal
,66
2014
eAu
stra
liaRC
13.3
(2.0
)a13
.3(2
.0)a
011
(18)
61N
RN
RN
RN
R82
(60.
7)a
(con
tinue
d)
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 14/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e2.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onth
ePr
eval
ence
ofAl
bum
inur
iain
Pedi
atric
Type
2D
iabe
tes(
cont
inue
d)
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
atst
udy
enro
llmen
tor
mea
sure
men
t,m
ean
(SD)
,y
Dura
tion
ofdi
abet
es,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
zeSe
xdi
strib
utio
n,N
o.(%
)
Raci
algr
oup
dist
ribut
ion,
No.
(%)
Case
sby
sex
orra
cial
grou
p,N
o.(%
)Al
bum
inur
iade
finiti
on
Prev
alen
ceof
obes
ity,
No.
(%)
Cala
gua
Qui
spe
etal
,92
2015
e
Peru
RC12
.6(2
.3)
NR
3.7
(2.4
)9
(43)
20M
:10
(50)
;F:
10(5
0)N
RN
RN
RN
R
New
ton
etal
,93
2015
eN
ewZe
alan
dRC
rang
e,6.
5-17
Allp
artic
ipan
ts,
<17
NR
6(5
5)11
NR
NR
NR
NR
22(9
6)a
Son
etal
,94
2015
Kore
aRC
NR
15.4
(12.
6-17
.4)b
0.9
(0.0
-3.0
)b8
(44)
18M
:4(2
2);F
:14
(78)
Kore
an:1
8(1
00)c
Kore
an:8
(44)
ACR
≥30-
300m
g/g
NR
Yeow
etal
.,68
2019
Mal
aysi
aRC
14.3
(3.5
)20
.7(3
.7)
6.5
(2.8
)7
(29)
24M
:10
(42)
;F:
14(5
8)M
alay
:12
(50)
;Ch
ines
e:11
(46)
;As
ian
Indi
an:1
(4)
Asia
n:7
(29)
M:A
CR>2
.5m
g/m
mol
,F:
ACR
>3.5
mg/
mm
ol10
(42)
Ruha
yel
etal
,71
2010
Aust
ralia
PC13
.4(9
.2-1
7.4)
a,d
M:1
6.0
(13.
6-18
.2);
F:15
.6(1
1.7-
19.8
)a,d
M:2
.2(0
.0-
7.8)
;F:2
.3(0
.1-7
.4)a,
d
9(4
5)20
NR
NR
NR
ACR
>3.5
mg/
mm
ol23
(70)
a
Schm
idt
etal
,73
2012
Germ
any
and
Aust
riaPC
13.5
(3.3
)15
.3(3
.0)
NR
154
(22.
5)68
4M
:261
(38.
2);
F:42
3(6
1.8)
Germ
an/A
ustr
ian:
482
(70.
5);
othe
r:20
2(2
9.5)
NR
NR
NR
Pers
iste
ntm
icro
albu
min
uria
Yoo
etal
,86
2004
Kore
aCS
12.8
(1.5
)18
.4(4
.3)
5.5
(3.9
)4
(18)
22M
:8(3
6);M
:14
(64)
Kore
an:2
2(1
00)
Kore
an:4
(18)
AER
>20
μg/m
inon
sam
ples
3m
oap
art
NR
Fara
het
al,8
720
06Un
ited
Stat
esCS
NR
rang
e,10
-21
mea
n,1.
8;ra
nge,
<2-5
9(2
7)33
NR
NR
NR
ACR
>30m
g/g
on2
sam
ples
with
in3-
6m
o29
(73)
a
Cope
land
etal
,15
2011
Unite
dSt
ates
CSra
nge,
10-1
714
.0(2
.0)
0.7
(0.5
)92
(13.
0)70
4M
:247
(35.
1);
F:45
7(6
4.9)
H:2
89(4
1.1)
;N
HB:
222
(31.
5);
NH
W:1
38(1
9.6)
;AI
:43
(6.1
);As
ian:
12(1
.7)
M:3
5(1
4.3)
;F:4
8(1
0.6)
;H:4
1(1
4.1)
;N
HB:
25(1
1.2)
;NH
W:
20(1
4.6)
;AI:
1(8
)
ACR
≥30m
g/g
on2
of3
sam
ples
durin
g3-
mo
perio
d
NR
Aulic
het
al,5
720
19Au
stra
liaCS
NR
15.1
(1.9
)1.
8(0
.3-3
.3)b
6(3
0)20
NR
NR
NR
AER
≥20
μg/m
inin
≥2of
3sa
mpl
esor
mea
nAC
R,M
:≥3.
5m
g/m
mol
;F:≥
4m
g/m
mol
from
3fir
stm
orni
ngco
llect
ions
24(7
5)a
Scot
tet
al,5
920
04N
ewZe
alan
dRC
NR
19.6
rang
e,14
-23
1.7
2(1
5)13
M:7
(54)
;F:6
(46)
Mao
ri:7
(54)
;Eu
rope
an:4
(30)
;PI
:1(8
);As
ian
Indi
an:1
(8)
NR
M:A
CR>2
.5m
g/m
mol
,F:
ACR
>3.5
mg/
mm
olon
≥2oc
casi
ons
13(1
00)
Scot
tet
al,6
220
06N
ewZe
alan
dRC
NR
20.0
(0.4
)3.
0(0
.3)
76(7
2.4)
105
NR
Mao
ri/PI
/oth
er:
66(6
2.9)
;Eu
rope
an:3
9(3
7.1)
NR
M:A
CR>2
.5m
g/m
mol
,F:
ACR
>3.5
mg/
mm
olon
≥2oc
casi
ons
105
(100
)
Dart
etal
,820
12Ca
nada
RC13
.5(2
.2)
14.9
(2.1
)1.
6(1
.5)
92(2
6.9)
342
M:1
29(3
7.8)
;F:
213
(62.
2)N
RN
RAC
R≥3
mg/
mm
olor
AER
30m
g/24
hon
2of
3sa
mpl
es1
mo
apar
t
NR
Son
etal
,94
2015
Kore
aRC
NR
15.4
(12.
6-17
.4)b
0.9
(0.0
-3.0
)b5
(28)
18M
:4(2
2);F
:14
(78)
Kore
an:1
8(1
00)c
Kore
an:5
(28)
ACR
≥30-
300
mg/
gat
base
line
and
follo
w-u
pN
R
Eppe
nset
al,4
2006
Aust
ralia
PC13
.2(1
1.6-
15.0
)a,b
15.3
(13.
6-16
.4)a,
b1.
3(0
.6-3
.1)a,
b10
(28)
36N
RN
RN
RAE
R≥2
0μg
/min
inat
leas
t2of
3sa
mpl
esor
ACR
≥2.5
mg/
mm
ol
36(5
6)a
Jeff
erie
set
al,7
220
12N
ewZe
alan
dPC
mea
n,12
.9;
rang
e,7.
1-15
.5
NR
NR
18(3
5)52
M:1
7(3
3);F
:35
(67)
PI/M
aori:
47(9
0);o
ther
:5(1
0)
NR
ACR
≥2.5
mg/
mm
olon
≥2of
3sa
mpl
esdu
ring
6-m
ope
riod
NR (c
ontin
ued)
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 15/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Tabl
e2.
Char
acte
ristic
sofI
nclu
ded
Stud
iesR
epor
ting
onth
ePr
eval
ence
ofAl
bum
inur
iain
Pedi
atric
Type
2D
iabe
tes(
cont
inue
d)
Sour
ceCo
untr
ySt
udy
desi
gn
Age
atdi
agno
sis,
mea
n(S
D),y
Age
atst
udy
enro
llmen
tor
mea
sure
men
t,m
ean
(SD)
,y
Dura
tion
ofdi
abet
es,
mea
n(S
D),y
Case
s,N
o.(%
)Sa
mpl
esi
zeSe
xdi
strib
utio
n,N
o.(%
)
Raci
algr
oup
dist
ribut
ion,
No.
(%)
Case
sby
sex
orra
cial
grou
p,N
o.(%
)Al
bum
inur
iade
finiti
on
Prev
alen
ceof
obes
ity,
No.
(%)
Mac
roal
bum
inur
ia
Hot
uet
al,7
820
04N
ewZe
alan
dCS
mea
n,15
;ra
nge,
11-1
9N
RN
R2
(17)
12M
:6(5
0);F
:6(5
0)M
aori/
PI:1
2(1
00)
M:1
(17)
;F:1
(17)
;M
aori/
PI:2
(17)
ACR
>300
mg/
gN
R
Eppe
nset
al,4
420
06W
este
rnPa
cific
CS12
.0(1
0.7-
13.5
)a,b
14.9
(13.
2-16
.4)a,
b2.
3(1
.4-3
.6)a,
b1
(0.6
)24
7N
RN
RN
RAE
R>3
00m
g/24
h10
6(3
2.0)
a
Kim
etal
,83
2010
Unite
dSt
ates
CSN
R14
.5(3
.0)
1.3
(0-2
.1)b
3(2
.9)
103
M:4
0(3
8.8)
;F:
63(6
1.2)
Pim
aIn
dian
:103
(100
)Pi
ma
Indi
ans:
3(2
.9)
ACR
>300
mg/
gN
R
Amut
haet
al,5
320
12In
dia
CS16
.1(2
.5)
22.2
(9.7
)Ag
e≤5
y:21
9(5
9.5%
);ag
e>5
to≤1
0y:
67(1
8.2%
);ag
e>1
0to
≤15:
21(5
.7%
);ag
e>1
5y:
61(1
6.6%
)
31(8
.4)
368
NR
Sout
hIn
dian
:368
(100
)cSo
uth
Indi
an:3
1(8
.4)
ACR
>300
mg/
gN
R
Schm
idt
etal
,73
2012
Germ
any
and
Aust
riaPC
13.5
(3.4
)15
.3(3
.0)
NR
16(2
.4)
684
M:2
61(3
8.2)
;F:
423
(61.
8)Ge
rman
/Aus
tria
n:48
2(7
0.5)
;ot
her:
202
(29.
5)
NR
NR
NR
Pers
iste
ntm
acro
albu
min
uria
Yoo
etal
,86
2004
Kore
aCS
12.8
(1.5
)18
.4(4
.3)
5.5
(3.9
)1
(5)
22M
:8(3
6);F
:14
(64)
Kore
an:2
2(1
00)
Kore
an:1
(5)
AER
>200
μg/m
inon
sam
ples
3m
oap
art
NR
Dart
etal
,820
12Ca
nada
RC13
.5(2
.2)
14.9
(2.1
)1.
6(1
.5)
16(4
.7)
342
M:1
29(3
7.8)
;F:
213
(62.
2)N
RN
RN
RN
R
Abbr
evia
tions
:AA,
Afric
anAm
eric
an;A
CR,a
lbum
in-t
o-cr
eatin
ine
ratio
;AER
,alb
umin
excr
etio
nra
te;A
I,Am
eric
anIn
dian
;API
,Asia
n–Pa
cific
Isla
nder
;BAC
BB,B
lack
/Afr
ican
/Car
ibbe
an/B
lack
Briti
sh;C
S,cr
oss-
sect
iona
l;F,
Fem
ales
;FN
,Firs
tNat
ions
;H,H
ispan
ic;N
R,no
trep
orte
d;M
,Mal
es;N
HB,
Non
-Hisp
anic
Blac
k;N
HW
,Non
-Hisp
anic
Whi
te;
PC,p
rosp
ectiv
eco
hort
;PI,
Paci
ficIs
land
er;R
C,re
tros
pect
ive
coho
rt.
aBa
sed
onto
tals
tudy
coho
rtin
stea
dof
only
patie
ntse
xam
ined
fort
hesp
ecifi
ccom
orbi
dity
.b
Med
ian
(inte
rqua
rtile
rang
e).
cRa
cial
grou
pdi
strib
utio
nas
sum
edto
mat
chco
untr
yof
orig
in.
dM
edia
n(r
ange
).e
Abst
ract
only.
fVa
lue
estim
ated
base
don
grap
h.
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 16/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Figure 2. Forest Plot Showing Pooled Prevalence of Albuminuria and Persistent Albuminuriain Pediatric Type 2 Diabetes
0 60 10040 80Prevalence, % (95% CI)
20
0 60 10040 80Prevalence, % (95% CI)
20
Weight, %Study
Cross-sectional studies
CasesNo.
TotalPrevalence, %(95% CI)
Amutha et al,53 2012Amed et al,52 2012Kim et al,83 2010Maahs et al,16 2007Ettinger et al,42 2005Hotu et al,78 2004
85322283107
3682211033742512
23.10 (18.93-27.55)14.48 (10.12-19.45)21.36 (13.93-29.85)22.19 (18.12-26.55)40.00 (21.46-60.04)58.33 (29.01-85.10)
10.19.68.410.14.93.1
Total (95% CI) 1103 22.91 (17.24-29.09) 46.4Heterogeneity: τ2 = 0.0045; χ2 = 19.41, df = 5 (P < .01); I2 = 74%
Retrospective cohort studies
Curran et al,69 2020Yeow et al,68 2019Yafi,67 2019Sellers et al,85 2009
27326
11242590
18.18 (0.47-47.35)29.17 (12.42-49.17)12.00 (1.65-28.20)28.89 (19.94-38.73)
3.04.84.98.2
Total (95% CI) 150 24.04 (16.36-32.57) 20.9Heterogeneity: τ2 = 0.0012; χ2 = 3.43, df = 3 (P = .33); I2 = 12%
Prospective cohort studies
Dart et al,74 2019Candler et al,81 2018Schmidt et al,73 2012Ruhayel et al,71 2010
4731709
18710668420
25.13 (19.16-31.62)2.83 (0.35-7.05)24.85 (21.68-28.17)45.00 (23.57-67.36)
9.48.510.54.4
Total (95% CI) 997 20.50 (8.85-35.23) 32.7Heterogeneity: τ2 = 0.0240; χ2 = 49.46, df = 3 (P < .001); I2 = 94%
Total (95% CI) 2250 22.17 (17.34-27.38) 100Heterogeneity: τ2 = 0.0081; χ2 = 73.55, df = 13 (P < .001); I2 = 82%
AlbuminuriaA
Weight, %Study
Cross-sectional studies
CasesNo.
TotalPrevalence, %(95% CI)
Khalil et al,58 2019Aulich et al,57 2019Sellers et al,88 2016Copeland et al,15 2011Farah et al,87 2006Yoo et al,86 2004
06509295
13209767043322
0.00 (0.00-12.82)30.00 (11.56-52.18)5.12 (3.82-6.60)13.07 (10.67-15.66)27.27 (13.23-43.91)22.73 (7.22-42.89)
6.87.59.49.48.27.6
Total (95% CI) 1768 13.15 (6.12-22.03) 48.9Heterogeneity: τ2 = 0.0131; χ2 = 54.72, df = 5 (P < .001); I2 = 91%
Retrospective cohort studies
Dart et al,65 2014Scott et al,62 2006Scott et al,59 2004
93762
34210513
27.19 (22.60-32.04)72.38 (63.39-80.55)15.38 (0.37-40.99)
9.39.06.8
Total (95% CI) 460 38.92 (8.35-75.13) 25.1Heterogeneity: τ2 = 0.0966; χ2 = 72.64, df = 2 (P < .001); I2 = 97%
Prospective cohort studies
Dart et al,74 2019Jefferies et al,72 2012Eppens et al,4 2006
571810
1875236
30.48 (24.07-37.29)34.62 (22.20-48.15)27.78 (14.18-43.70)
9.28.68.3
Total (95% CI) 275 30.77 (25.37-36.44) 26.0Heterogeneity: τ2 = 0; χ2 = 0.5, df = 2 (P = .78); I2 = 0%
Total (95% CI) 2503 24.04 (13.50-36.33) 100Heterogeneity: τ2 = 0.0466; χ2 = 358.49, df = 11 (P < .001); I2 = 97%
Persistent albuminuriaB
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 17/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
P < .001),42,52,67,69,74,81,83 suggesting that albuminuria worsens with age in this population (eTable 7in the Supplement).
Pooled prevalence of persistent albuminuria across 12 studies with 2503 participants was24.04% (95% CI, 13.50%-36.33%; I2 = 97%; P < .001) (Figure 2).4,15,57-59,62,65,72,74,86-88 Removingstudies using different definitions of albuminuria lowered the pooled estimate to 17.00% (95% CI,7.00%-29.00%; I2 = 92%; P < .001) (eTable 8 in the Supplement).
Microalbuminuria pooled prevalence across 16 studies with 2441 participants was 21.57% (95%CI, 15.59%-28.16%; I2 = 90%; P < .001) (eFigure 7 in the Supplement).42,44,53,64,66,68,71,73,78,83,89-94
Removing studies with 50 participants or fewer changed the estimate to 14.00% (95% CI,9.00%-20.00%; I2 = 92%; P < .001; 2273 participants),44,53,66,73,83,89-91 as this resulted in theelimination of Pacific Islander group from the analysis; this group had the highest microalbuminuriaprevalence (eTable 9 in the Supplement). Ten studies with 1345 participants reported persistentmicroalbuminuria pooled prevalence of 29.19% (95% CI, 16.85%-43.21%; I2 = 95%; P < .001)(eFigure 8 in the Supplement).4,8,15,57,59,62,72,86,87,94 Similarly, removing studies with patients olderthan 18 years or those using different definitions of microalbuminuria reduced the prevalence andheterogeneity estimates to 23.00% (95% CI, 14.00%-34.00%; I2 = 88%; P < .001) and 24.00%(95% CI, 11.00%-39.00%; I2 = 84%; P < .001), respectively, because this resulted in the exclusion ofa study reporting a very high microalbuminuria prevalence of 72% among 105 participants in asample with a high proportion of Pacific Islander and Indigenous patients (eTable 10 in theSupplement).62
Macroalbuminuria pooled prevalence from 4 studies with 730 participants was 3.85% (95% CI,0.02%-11.63%; P < .001) (eFigure 9 in the Supplement).44,53,78,83 Another study reported aprevalence of 2.4% among 684 participants,73 but it was the only prospective cohort study, so it wasnot included in the meta-analysis. In addition, the prevalence of persistent macroalbuminuria was5% among 22 participants in 1 cross-sectional study86 and 4.7% among 342 participants in anotherretrospective cohort study.8 Metaregression analysis revealed no statistically significant correlationbetween obesity prevalence and albuminuria, persistent albuminuria, microalbuminuria, orpersistent microalbuminuria prevalence.
Sex and Racial Group Associations With AlbuminuriaOne study reported that albuminuria in 140 male participants (20.7%) was lower than in 234 femaleparticipants (23.1%).16 Similarly, persistent microalbuminuria prevalence was higher in 247 maleparticipants (14.3%) than in 457 female participants (10.6%) in another study.15 Persistentalbuminuria prevalence across 2 studies in 309 male participants was 16.14% (95% CI,5.05%-31.65%; I2 = 86%; P < .001) and 22.90% (95% CI, 7.08%-44.22%; I2 = 95%; P < .001) in 582female participants (OR, 0.68 [95% CI, 0.46-1.01]; I2 = 0%; P for heterogeneity = .78) (eFigure 10and eFigure 11 in the Supplement).15,74
Albuminuria prevalence was assessed by racial group, and White youth had lower rates ofalbuminuria than other groups. The pooled prevalence among 158 White participants was 12.59%(95% CI, 7.75%-18.33%; I2 = 0%; P = .58)46,52 compared to 23.00% (95% CI, 18.85%-27.41%;I2 = 0%; P = .46) in 392 Asian participants,53,68 24.27% (95% CI, 14.39%-35.73%; I2 = 79%; P < .01)in 295 Indigenous participants,16,52,83 and 31.84% (95% CI, 11.90%-55.47%; I2 = 58%; P = .09) in 48Pacific Islander participants16,69,78 (eFigure 12 in the Supplement). Single studies found analbuminuria prevalence of 14.1% in 212 African American participants50 and 23% in 64 Hispanic/Latino participants.16
Individual studies reported a prevalence of persistent albuminuria of 11.2% in 222 AfricanAmerican participants,15 14.1% in 289 Hispanic/Latino participants,15 and 23% in 22 Koreanparticipants.86 Two studies reported a prevalence of 6.96% (95% CI, 0.00%-25.91%; I2 = 70%;P = .07) in 150 White participants15,58 and 19.06% (95% CI, 2.27%-45.67%; I2 = 91%; P < .001) in 217Indigenous participants (eFigure 13 in the Supplement).15,74
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 18/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
For microalbuminuria, the pooled prevalence was 18.98% (95% CI, 9.98%-29.87%; I2 = 80%;P = .002) in 554 Asian participants (eFigure 14 in the Supplement).53,68,89,94 Individual studies founda prevalence of microalbuminuria of 0% in 12 White participants,91 21% in 52 African Americanparticipants,91 18.5% in 103 Indigenous participants,83 and 42% in 12 Pacific Islander participants.78
Finally, for persistent microalbuminuria, the pooled prevalence 22.31% (95% CI,10.22%-37.01%; I2 = 0%; P = .48) in 40 Asian participants (eFigure 15 in the Supplement).86,94 Onestudy reported a prevalence of 14.1% in 289 Hispanic/Latino participants, 11.2% in 222 AfricanAmerican participants, 14.6% in 138 White participants, and 8% in 43 Indigenous participants.15
Publication BiasPublication bias was found for the prevalence of microalbuminuria based on the funnel plot andEgger test. It was not found for hypertension, albuminuria, persistent albuminuria, or persistentmicroalbuminuria (eFigures 16-20 in the Supplement).
Risk of Bias and Overall Quality of EvidenceThe included studies had either a low (n = 27)8,15-17,40,44-48,50,53,55,56,60,64,65,69,70,72,76,78,79,81,85,89,90
or moderate (n = 33)4,41-43,49,51,52,54,57-59,61-63,66-68,71,73-75,77,80,82-84,86-88,91-94 risk of bias (eTable 11and eFigure 21 in the Supplement). Some studies did not have a nationally representative sample,which limits their generalizability.4,8,40-43,46-51,53,54,56-60,63-68,71,72,74,75,77-80,82,83,85-87,89,91-94 Thesampling frame of some studies was not representative of their targetpopulation,41,42,44,51,52,54,61,63,67,74,75,77,80,82,86-88,91,92,94 and some did not take a random or censussample.15,41,42,51,52,54,57,67,75,82,86,87,92,94 Some studies also had missing data of greater than 25%,potentially leading to nonresponse bias.4,43,49,57,58,61,62,66,68,71,73,75,83,84,91,93 In 3 studies, thedefinition used to diagnose hypertension or albuminuria was unspecified,67,69,92 and in some studiesit was unclear that all participants were examined using the samemethods.45,52,55,59,61,62,70,73,81,84,88,90
Based on the OCEBM criteria,28 29 studies(48%)8,16,17,40,44,46-48,50,53,55,56,62,65,66,70,72-74,76,79-81,83,85,88-91 had an evidence level of 1; 17 studies(28%)4,43,45,49,58-61,63,64,68,69,71,77,78,84,93, 2; and 14 studies (23%),15,41,42,51,52,54,57,67,75,82,86,87,92,94
3 (eTable 11 in the Supplement). Nearly half of the studies thus provide the highest level of evidenceto answer the prevalence question we posed, although a significant portion of studies did not use arandom sample or census to estimate prevalence.
Discussion
The rates of type 2 diabetes in children and adolescents are increasing globally, and this rise isassociated with the obesity epidemic.95 Type 2 diabetes is associated with rapid progression ofkidney complications, and early detection and treatment are crucial to avoid end-stage kidneydisease, cardiovascular morbidities, and mortality.7,8,11,14 Current clinical guidelines on themanagement of pediatric type 2 diabetes are informed by independent studies with variablesample sizes.9,12,13
This systematic review investigated the prevalence of hypertension and albuminuria, markersof diabetes-related nephropathy and important predictors of kidney outcomes, in pediatric type 2diabetes. Approximately 1 in 4 pediatric patients with type 2 diabetes had hypertension. Althoughmore female patients had type 2 diabetes than male patients,9 male patients appeared to be morelikely to develop hypertension than female patients. Pacific Islander and Indigenous youth had ahigher burden of hypertension than other racial groups.
While most studies followed the National Heart, Lung, and Blood Institute guidelines forassessing hypertension in children and adolescents4,17,42,44,46-50,56,57,60,68,73,74 (ie, BP �95thpercentile for age, sex, and height20), 6 studies used the adult definition of hypertension of systolicBP level of 130 to 140 mm Hg or greater and diastolic BP level of 80 to 90 mm Hg or
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 19/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
greater.51,53,58,59,62,63 The different definitions of hypertension across studies were partlyresponsible for the noted heterogeneity, and using adult definitions might underestimatehypertension prevalence in children and adolescents.
Updated National Heart, Lung, and Blood Institute guidelines were released in 2017 thatlowered BP thresholds for hypertension, as they were based on only children with weight in thereference range, whereas older guidelines also included children with overweight and obesity.96
While no studies reported using the 2017 guidelines, it is possible that hypertension prevalence willbe higher if assessing data from existing studies against the 2017 guidelines.
Obesity is an important contributor to hypertension risk, with an estimated 6% increased riskof hypertension per unit of body mass index increase.6 Conversely, the metaregression analysisrevealed that obesity was not associated with the prevalence of hypertension. However, obesityprevalence and severity were not available in all studies, and it is probable that obesity maycontribute indirectly to the risk of hypertension in pediatric type 2 diabetes. On a mechanistic level,obesity-driven insulin resistance and hyperinsulinemia increases sodium reabsorption from the renaltubules.97 In addition, hyperglycemia can lead to hypervolemia, increased sympathetic activity,97
and the activation of the renin-angiotensin-aldosterone system, which increases cardiac output andperipheral vascular resistance, leading to hypertension.97 The associations between obesity andhypertension in pediatric type 2 diabetes require further study.
This review also demonstrated that between 1 in 5 and 1 in 4 pediatric patients with type 2diabetes had albuminuria. While no sex differences were identified, Pacific Islander, Indigenous, andAsian youth had higher rates of albuminuria than White youth. While macroalbuminuria occurred in4% of participants, fewer studies reported the persistence of albuminuria, despite the need forconfirmation of persistence being a key criterion for albuminuria diagnosis.9,12,13 Persistentalbuminuria is associated with macrovascular disease98 and predicts the progression to end-stagekidney disease.9,99 Prospective studies are needed to assess persistent albuminuria in pediatric type2 diabetes. When studies of adult patients with type 2 diabetes were excluded, the albuminuriapooled prevalence estimate decreased from 22.17% (95% CI, 17.34%-27.38%) to 17.00% (95% CI,9.00%-27.00%), and these results corroborate current evidence that albuminuria increases with ageand duration of diabetes.6,53
These data have several important implications. Type 2 diabetes–related nephropathy exerts amuch higher burden than that seen in children with type 1 diabetes.16,100 For example, the SEARCHfor Diabetes in Youth study reported elevated urine ACR of 9.2% in children with type 1 diabetes vs22.2% in those with type 2 diabetes,16 and youth with type 2 diabetes had 4-fold higher rates ofkidney failure compared with youth with type 1 diabetes.8 In addition, a study including Pima Indians,an Indigenous group with high rates of type 2 diabetes, found that those who developed type 2diabetes before 20 years of age had a 5-fold increased risk of end-stage kidney disease by middle ageand higher mortality rates compared with patients with adult-onset type 2 diabetes.7 Ongoingintensive screening and intervention strategies are warranted to reduce mortality and end-stagekidney disease in pediatric patients with type 2 diabetes.
The specific renal pathology that drives proteinuria and hypertension in pediatric type 2diabetes is unknown. While studies of kidney biopsies in youth with type 2 diabetes are limited, mostanomalies found on kidney ultrasounds have been classified as congenital.88 Kidney biopsies frompatients describe immune complex disease and glomerulosclerosis, findings that are notcharacteristic of typical diabetes-related nephropathy, which are considered non–diabetes-drivenpathologies.85 However, these observations are based on a small sample of Indigenous youth andmay not be generalizable to all children and adolescents with type 2 diabetes. Further studies areurgently needed to assess renal histopathology in type 2 diabetes across different sexes and racialgroups to define the exact mechanisms of nephropathy in this population.
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 20/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
LimitationsThis study has limitations, including the high heterogeneity among studies. Some studies did notachieve a high quality rating (n = 31) because of small sample sizes (n = 17) or the lack of clarity as towhether the results were based on a randomized sample or census (n = 14). Moreover, a largeproportion of the studies did not have a nationally representative sample, as they were based in asingle center or clinic. As such, larger studies across multiple centers are needed to assessprevalence. In addition, obesity severity data, which could confound hypertension and proteinuriaprevalence, were also not available. While the results should be interpreted with this information inmind, this report presents all current data available to assess hypertension and albuminuria inpediatric patients with type 2 diabetes.
Conclusions
In this study, hypertension and albuminuria were frequent comorbidities of pediatric type 2 diabetes,and Pacific Islander and Indigenous youth had a disproportionately higher burden of these conditionsthan youth from other racial groups. There is a critical need for personalized screening and treatmentstrategies to provide renoprotection from prolonged hyperglycemia and obesity to preventend-stage kidney disease, future cardiovascular disease, and improve life expectancy. The exactetiopathogenetic mechanisms driving nephropathy in youth with type 2 diabetes need to beelucidated. These data are relevant for health care professionals and policy makers, as clinicalservices treating pediatric patients with type 2 diabetes need to be resourced to track kidneyscreening and treatments to improve outcomes.
ARTICLE INFORMATIONAccepted for Publication: February 24, 2021.
Published: April 30, 2021. doi:10.1001/jamanetworkopen.2021.6069
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Cioana Met al. JAMA Network Open.
Corresponding Author: M. Constantine Samaan, MD, MSc, Department of Pediatrics, McMaster University,1200 Main St W, 3A-57, Hamilton, ON L8N 3Z5, Canada ([email protected]).
Author Affiliations: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada (Cioana, Deng,Hou, Nadarajah, Qiu, Chen, Rivas, Chanchlani, Samaan); Division of Pediatric Endocrinology, McMaster Children’sHospital, Hamilton, Ontario, Canada (Cioana, Deng, Hou, Nadarajah, Qiu, Chen, Rivas, Samaan); Health SciencesLibrary, McMaster University, Hamilton, Ontario, Canada (Banfield); Division of Pediatric Nephrology, McMasterChildren’s Hospital, Hamilton, Ontario, Canada (Chanchlani); Department of Pediatrics and Child Health, Universityof Manitoba, Winnipeg, Manitoba, Canada (Dart, Wicklow); Children’s Hospital Research Institute of Manitoba,University of Manitoba, Winnipeg, Manitoba, Canada (Dart, Wicklow); College of Medicine, King Saud binAbdulaziz University for Health Sciences, Division of Endocrinology, Department of Pediatrics, Ministry of theNational Guard Health Affairs, Riyadh, Saudi Arabia (Alfaraidi); Department of Pediatrics, Division of PediatricEndocrinology, King Abdullah bin Abdulaziz University Hospital, Princess Noura University, Riyadh, Saudi Arabia(Alotaibi); Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton,Ontario, Canada (Thabane, Samaan); Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada(Thabane); Centre for Evaluation of Medicines, St Joseph’s Health Care, Hamilton, Ontario, Canada (Thabane);Biostatistics Unit, St Joseph’s Healthcare, Hamilton, Ontario, Canada (Thabane); Michael G. De Groote School ofMedicine, McMaster University, Hamilton, Ontario, Canada (Qiu, Rivas, Samaan).
Author Contributions: Ms Cioana and Dr Samaan had full access to all of the data in the study and takeresponsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Cioana, Dart, Thabane, Samaan.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Cioana, Thabane, Samaan.
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 21/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
Critical revision of the manuscript for important intellectual content: Cioana, Deng, Hou, Nadarajah, Qiu, Chen,Rivas, Banfield, Chanchlani, Dart, Wicklow, Alfaraidi, Alotaibi, Samaan.
Statistical analysis: Cioana, Deng, Dart, Thabane, Samaan.
Administrative, technical, or material support: Hou, Qiu, Banfield, Wicklow, Samaan.
Supervision: Chanchlani, Thabane, Samaan.
Conflict of Interest Disclosures: None reported.
Meeting Presentation: Data were presented as an oral presentation at the Diabetes Canada Meeting; October29, 2020.
REFERENCES1. Reinehr T. Type 2 diabetes mellitus in children and adolescents. World J Diabetes. 2013;4(6):270-281. doi:10.4239/wjd.v4.i6.270
2. Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus—present and futureperspectives. Nat Rev Endocrinol. 2011;8(4):228-236. doi:10.1038/nrendo.2011.183
3. Hillier TA, Pedula KL. Complications in young adults with early-onset type 2 diabetes: losing the relativeprotection of youth. Diabetes Care. 2003;26(11):2999-3005. doi:10.2337/diacare.26.11.2999
4. Eppens MC, Craig ME, Cusumano J, et al. Prevalence of diabetes complications in adolescents with type 2compared with type 1 diabetes. Diabetes Care. 2006;29(6):1300-1306. doi:10.2337/dc05-2470
5. Song SH, Hardisty CA. Early onset type 2 diabetes mellitus: a harbinger for complications in later years—clinicalobservation from a secondary care cohort. QJM. 2009;102(11):799-806. doi:10.1093/qjmed/hcp121
6. TODAY Study Group. Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: the TODAYclinical trial. Diabetes Care. 2013;36(6):1735-1741. doi:10.2337/dc12-2420
7. Pavkov ME, Bennett PH, Knowler WC, Krakoff J, Sievers ML, Nelson RG. Effect of youth-onset type 2 diabetesmellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians. JAMA.2006;296(4):421-426. doi:10.1001/jama.296.4.421
8. Dart AB, Sellers EA, Martens PJ, Rigatto C, Brownell MD, Dean HJ. High burden of kidney disease in youth-onsettype 2 diabetes. Diabetes Care. 2012;35(6):1265-1271. doi:10.2337/dc11-2312
9. Zeitler P, Arslanian S, Fu J, et al. ISPAD clinical practice consensus guidelines 2018: type 2 diabetes mellitus inyouth. Pediatr Diabetes. 2018;19(S27)(suppl 27):28-46. doi:10.1111/pedi.12719
10. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children andAdolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascularhealth and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128(suppl 5):S213-S256.doi:10.1542/peds.2009-2107C
11. Remuzzi G, Schieppati A, Ruggenenti P. Clinical practice. Nephropathy in patients with type 2 diabetes. N EnglJ Med. 2002;346(15):1145-1151. doi:10.1056/NEJMcp011773
12. American Diabetes Association. 13. Children and adolescents: Standards of Medical Care in Diabetes-2019.Diabetes Care. 2019;42(suppl 1):S148-S164. doi:10.2337/dc19-S013
13. Panagiotopoulos C, Hadjiyannakis S, Henderson M; Diabetes Canada Clinical Practice Guidelines ExpertCommittee. Type 2 diabetes in children and adolescents. Can J Diabetes. 2018;42(suppl 1):S247-S254. doi:10.1016/j.jcjd.2017.10.037
14. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular andmicrovascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317(7160):703-713. doi:10.1136/bmj.317.7160.703
15. Copeland KC, Zeitler P, Geffner M, et al; TODAY Study Group. Characteristics of adolescents and youth withrecent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011;96(1):159-167. doi:10.1210/jc.2010-1642
16. Maahs DM, Snively BM, Bell RA, et al. Higher prevalence of elevated albumin excretion in youth with type 2than type 1 diabetes: the SEARCH for Diabetes in Youth study. Diabetes Care. 2007;30(10):2593-2598. doi:10.2337/dc07-0450
17. Rodriguez BL, Dabelea D, Liese AD, et al; SEARCH Study Group. Prevalence and correlates of elevated bloodpressure in youth with diabetes mellitus: the SEARCH for diabetes in youth study. J Pediatr. 2010;157(2):245-251.e1. doi:10.1016/j.jpeds.2010.02.021
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 22/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
18. Samaan MC, Cioana M, Banfield L, et al. The prevalence of comorbidities in pediatric type 2 diabetes mellitus:a systematic review. PROSPERO. Published March 19, 2018. Accessed April 5, 2021. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=91127
19. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal forreporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008
20. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children andAdolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children andadolescents. Pediatrics. 2004;114(2)(Suppl 4th Report):555-576.
21. Rosner B, Prineas RJ, Loggie JM, Daniels SR. Blood pressure nomograms for children and adolescents, byheight, sex, and age, in the United States. J Pediatr. 1993;123(6):871-886. doi:10.1016/S0022-3476(05)80382-8
22. Report of the Second Task Force on Blood Pressure Control in Children—1987: Task Force on Blood PressureControl in Children, National Heart, Lung, and Blood Institute, Bethesda, Maryland. Pediatrics. 1987;79(1):1-25.
23. National High Blood Pressure Education Program Working Group on Hypertension Control in Children andAdolescents. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents:a working group report from the National High Blood Pressure Education Program. Pediatrics. 1996;98(4 Pt 1):649-658.
24. Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation, andTreatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood PressureEducation Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention,Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-1252. doi:10.1161/01.HYP.0000107251.49515.c2
25. Jackson LV, Thalange NKS, Cole TJ. Blood pressure centiles for Great Britain. Arch Dis Child. 2007;92(4):298-303. doi:10.1136/adc.2005.081216
26. Levin A, Stevens PE. Summary of KDIGO 2012 CKD guideline: behind the scenes, need for guidance, and aframework for moving forward. Kidney Int. 2014;85(1):49-61. doi:10.1038/ki.2013.444
27. Hoy D, Brooks P, Woolf A, et al. Assessing risk of bias in prevalence studies: modification of an existing tool andevidence of interrater agreement. J Clin Epidemiol. 2012;65(9):934-939. doi:10.1016/j.jclinepi.2011.11.014
28. OCEBM Levels of Evidence Working Group. The Oxford 2011 Levels of Evidence. Oxford Center for Evidence-Based Medicine. Accessed July 20, 2020. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence
29. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effectsmodels for meta-analysis. Res Synth Methods. 2010;1(2):97-111. doi:10.1002/jrsm.12
30. Barendregt JJ, Doi SA, Lee YY, Norman RE, Vos T. Meta-analysis of prevalence. J Epidemiol Community Health.2013;67(11):974-978. doi:10.1136/jech-2013-203104
31. Freeman MF, Tukey JW. Transformations related to the angular and the square root. Ann Math Stat. 1950:607-611. doi:10.1214/aoms/1177729756
32. Miller JJ. The inverse of the Freeman–Tukey double arcsine transformation. Am Stat. 1978;32(4):138. doi:10.1080/00031305.1978.10479283
33. Deeks JJ, Higgins JPT, Altman DG. Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J,Chandler J, et al, eds. Cochrane Handbook for Systematic Reviews of Interventions. Cochrane; 2019. doi:10.1002/9781119536604.ch10
34. National Institutes of Health. Racial and ethnic categories and definitions for NIH diversity programs and forother reporting purposes. Published April 8, 2015. Accessed March 17, 2021. https://grants.nih.gov/grants/guide/notice-files/not-od-15-089.html
35. Page MJ, Higgins JPT, Sterne JAC. Assessing risk of bias due to missing results in a synthesis. In: Higgins JPT,Thomas J, Chandler J, et al, eds. Cochrane Handbook for Systematic Reviews of Interventions. Cochrane; 2019. doi:10.1002/9781119536604.ch13
36. Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Soft. 2010;36(3):1-48. doi:10.18637/jss.v036.i03
37. RStudio. Accessed March 17, 2021. https://www.rstudio.com/
38. The R Project for Statistical Computing. Accessed March 17, 2021. https://www.r-project.org/
39. The Cochrane Collaboration. Review Manager version 5. Accessed March 17, 2021. https://training.cochrane.org/online-learning/core-software-cochrane-reviews/revman/revman-5-download
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 23/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
40. Pinhas-Hamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P. Increased incidence ofnon-insulin-dependent diabetes mellitus among adolescents. J Pediatr. 1996;128(5 Pt 1):608-615. doi:10.1016/S0022-3476(96)80124-7
41. Scott CR, Smith JM, Cradock MM, Pihoker C. Characteristics of youth-onset noninsulin-dependent diabetesmellitus and insulin-dependent diabetes mellitus at diagnosis. Pediatrics. 1997;100(1):84-91. doi:10.1542/peds.100.1.84
42. Ettinger LM, Freeman K, DiMartino-Nardi JR, Flynn JT. Microalbuminuria and abnormal ambulatory bloodpressure in adolescents with type 2 diabetes mellitus. J Pediatr. 2005;147(1):67-73. doi:10.1016/j.jpeds.2005.02.003
43. Reinehr T, Andler W, Kapellen T, et al. Clinical characteristics of type 2 diabetes mellitus in overweightEuropean Caucasian adolescents. Exp Clin Endocrinol Diabetes. 2005;113(3):167-170. doi:10.1055/s-2005-837522
44. Eppens MC, Craig ME, Jones TW, Silink M, Ong S, Ping YJ; International Diabetes Federation Western PacificRegion Steering Committee. Type 2 diabetes in youth from the Western Pacific region: glycaemic control, diabetescare and complications. Curr Med Res Opin. 2006;22(5):1013-1020. doi:10.1185/030079906X104795
45. Unnikrishnan AG, Bhatia E, Bhatia V, et al. Type 1 diabetes versus type 2 diabetes with onset in personsyounger than 20 years of age. Ann N Y Acad Sci. 2008;1150(1):239-244. doi:10.1196/annals.1447.056
46. Bell RA, Mayer-Davis EJ, Beyer JW, et al; SEARCH for Diabetes in Youth Study Group. Diabetes in non-HispanicWhite youth: prevalence, incidence, and clinical characteristics: the SEARCH for Diabetes in Youth Study. DiabetesCare. 2009;32(suppl 2):S102-S111. doi:10.2337/dc09-S202
47. Dabelea D, DeGroat J, Sorrelman C, et al; SEARCH for Diabetes in Youth Study Group. Diabetes in Navajoyouth: prevalence, incidence, and clinical characteristics: the SEARCH for Diabetes in Youth Study. Diabetes Care.2009;32(suppl 2):S141-S147. doi:10.2337/dc09-S206
48. Lawrence JM, Mayer-Davis EJ, Reynolds K, et al; SEARCH for Diabetes in Youth Study Group. Diabetes inHispanic American youth: prevalence, incidence, demographics, and clinical characteristics: the SEARCH forDiabetes in Youth Study. Diabetes Care. 2009;32(suppl 2):S123-S132. doi:10.2337/dc09-S204
49. Liu LL, Yi JP, Beyer J, et al; SEARCH for Diabetes in Youth Study Group. Type 1 and type 2 diabetes in Asian andPacific Islander U.S. youth: the SEARCH for Diabetes in Youth Study. Diabetes Care. 2009;32(suppl 2):S133-S140.doi:10.2337/dc09-S205
50. Mayer-Davis EJ, Beyer J, Bell RA, et al; SEARCH for Diabetes in Youth Study Group. Diabetes in AfricanAmerican youth: prevalence, incidence, and clinical characteristics: the SEARCH for Diabetes in Youth Study.Diabetes Care. 2009;32(suppl 2):S112-S122. doi:10.2337/dc09-S203
51. Urakami T, Suzuki J, Yoshida A, et al. Prevalence of components of the metabolic syndrome in schoolchildrenwith newly diagnosed type 2 diabetes mellitus. Pediatr Diabetes. 2009;10(8):508-512. doi:10.1111/j.1399-5448.2009.00533.x
52. Amed S, Hamilton JK, Sellers EAC, et al. Differing clinical features in Aboriginal vs. non-Aboriginal childrenpresenting with type 2 diabetes. Pediatr Diabetes. 2012;13(6):470-475. doi:10.1111/j.1399-5448.2012.00859.x
53. Amutha A, Datta M, Unnikrishnan R, Anjana RM, Mohan V. Clinical profile and complications of childhood- andadolescent-onset type 2 diabetes seen at a diabetes center in south India. Diabetes Technol Ther. 2012;14(6):497-504. doi:10.1089/dia.2011.0283
54. Drutel RO, Paulo R. Abstract 660: prevalence of hypertension among children with diabetes mellitus.Hypertension. 2014;64(suppl_1):A660. Accessed April 5, 2020. https://www.ahajournals.org/doi/10.1161/hyp.64.suppl_1.660
55. Klingensmith GJ, Connor CG, Ruedy KJ, et al; Pediatric Diabetes Consortium. Presentation of youth with type2 diabetes in the Pediatric Diabetes Consortium. Pediatr Diabetes. 2016;17(4):266-273. doi:10.1111/pedi.12281
56. Zabeen B, Nahar J, Tayyeb S, Mohsin F, Nahar N, Azad K. Characteristics of children and adolescents at onsetof type 2 diabetes in a tertiary hospital in Bangladesh. Indian J Endocrinol Metab. 2016;20(5):638-642. doi:10.4103/2230-8210.190544
57. Aulich J, Cho YH, Januszewski AS, et al. Associations between circulating inflammatory markers, diabetes typeand complications in youth. Pediatr Diabetes. 2019;20(8):1118-1127. doi:10.1111/pedi.12913
58. Khalil SA, Megallaa MH, Rohoma KH, et al. Prevalence of chronic diabetic complications in newly diagnosedversus known type 2 diabetic subjects in a sample of Alexandria population, Egypt. Curr Diabetes Rev. 2019;15(1):74-83. doi:10.2174/1573399814666180125100917
59. Scott A, Whitcombe S, Bouchier D, Dunn P. Diabetes in children and young adults in Waikato Province, NewZealand: outcomes of care. N Z Med J. 2004;117(1207):U1219.
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 24/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
60. Zdravkovic V, Daneman D, Hamilton J. Presentation and course of Type 2 diabetes in youth in a large multi-ethnic city. Diabet Med. 2004;21(10):1144-1148. doi:10.1111/j.1464-5491.2004.01297.x
61. Pérez-Perdomo R, Pérez-Cardona CM, Allende-Vigo M, Rivera-Rodríguez MI, Rodríguez-Lugo LA. Type 2diabetes mellitus among youth in Puerto Rico, 2003. P R Health Sci J. 2005;24(2):111-117.
62. Scott A, Toomath R, Bouchier D, et al. First national audit of the outcomes of care in young people withdiabetes in New Zealand: high prevalence of nephropathy in Maori and Pacific Islanders. N Z Med J. 2006;119(1235):U2015.
63. Balasanthiran A, O'Shea T, Moodambail A, et al. Type 2 diabetes in children and young adults in East London:an alarmingly high prevalence. Practical Diabetes. 2012;29(5):193-198a. doi:10.1002/pdi.1689
64. Osman HAM, Elsadek N, Abdullah MA. Type 2 diabetes in Sudanese children and adolescents. Sudan JPaediatr. 2013;13(2):17-23.
65. Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA. Earlier onset of complications in youth withtype 2 diabetes. Diabetes Care. 2014;37(2):436-443. doi:10.2337/dc13-0954
66. Haynes A, Kalic R, Curran J, et al. Type 2 diabetes and associated complications in Western Australian children:a population-based study (1990-2012). Diabetologia. 2014;57(Suppl 1):S510-S510.
67. Yafi M. The prevalence of microalbuminuria in children with type 2 diabetes mellitus (T2DM). Arch Dis Child.2019;104:A250. doi:10.1136/archdischild-2019-epa.585
68. Yeow TP, Aun ES-Y, Hor CP, Lim SL, Khaw CH, Aziz NA. Challenges in the classification and management ofAsian youth-onset diabetes mellitus—lessons learned from a single centre study. PLoS One. 2019;14(1):e0211210.doi:10.1371/journal.pone.0211210
69. Curran JA, Haynes A, Davis EA. Clinical characteristics of Western Australian children diagnosed with type 2diabetes before 10 years of age. Med J Aust. 2020;212(2):95-95.e1. doi:10.5694/mja2.50451
70. Shield JPH, Lynn R, Wan KC, Haines L, Barrett TG. Management and 1 year outcome for UK children with type2 diabetes. Arch Dis Child. 2009;94(3):206-209. doi:10.1136/adc.2008.143313
71. Ruhayel SD, James RA, Ehtisham S, Cameron FJ, Werther GA, Sabin MA. An observational study of type 2diabetes within a large Australian tertiary hospital pediatric diabetes service. Pediatr Diabetes. 2010;11(8):544-551. doi:10.1111/j.1399-5448.2010.00647.x
72. Jefferies C, Carter P, Reed PW, et al. The incidence, clinical features, and treatment of type 2 diabetes inchildren <15 yr in a population-based cohort from Auckland, New Zealand, 1995–2007. Pediatr Diabetes. 2012;13(4):294-300. doi:10.1111/j.1399-5448.2011.00851.x
73. Schmidt F, Kapellen TM, Wiegand S, et al; DPV-Wiss Study Group; BMBF Competence Network Diabetes.Diabetes mellitus in children and adolescents with genetic syndromes. Exp Clin Endocrinol Diabetes. 2012;120(10):579-585. doi:10.1055/s-0032-1306330
74. Dart AB, Wicklow B, Blydt-Hansen TD, et al. A holistic approach to risk for early kidney injury in Indigenousyouth with type 2 diabetes: a proof of concept paper from the iCARE Cohort. Can J Kidney Health Dis. 2019;6:2054358119838836. doi:10.1177/2054358119838836
75. Upchurch SL, Brosnan CA, Meininger JC, et al. Characteristics of 98 children and adolescents diagnosed withtype 2 diabetes by their health care provider at initial presentation. Diabetes Care. 2003;26(7):2209-2209. doi:10.2337/diacare.26.7.2209
76. Wei J-N, Sung F-C, Lin C-C, Lin R-S, Chiang C-C, Chuang L-M. National surveillance for type 2 diabetes mellitusin Taiwanese children. JAMA. 2003;290(10):1345-1350. doi:10.1001/jama.290.10.1345
77. Cruz M, Torres M, Aguilar-Herrera B, et al. Type 2 diabetes mellitus in children—an increasing health problemin Mexico. J Pediatr Endocrinol Metab. 2004;17(2):183-190. doi:10.1515/JPEM.2004.17.2.183
78. Hotu S, Carter B, Watson PD, Cutfield WS, Cundy T. Increasing prevalence of type 2 diabetes in adolescents.J Paediatr Child Health. 2004;40(4):201-204. doi:10.1111/j.1440-1754.2004.00337.x
79. Sellers EAC, Yung G, Dean HJ. Dyslipidemia and other cardiovascular risk factors in a Canadian First Nationpediatric population with type 2 diabetes mellitus. Pediatr Diabetes. 2007;8(6):384-390. doi:10.1111/j.1399-5448.2007.00284.x
80. Pelham JH, Hanks L, Aslibekyan S, Dowla S, Ashraf AP. Higher hemoglobin A1c and atherogenic lipoproteinprofiles in children and adolescents with type 2 diabetes mellitus. J Clin Transl Endocrinol. 2018;15:30-34. doi:10.1016/j.jcte.2018.11.006
81. Candler TP, Mahmoud O, Lynn RM, Majbar AA, Barrett TG, Shield JPH. Continuing rise of type 2 diabetesincidence in children and young people in the UK. Diabet Med. 2018;35(6):737-744. doi:10.1111/dme.13609
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 25/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
82. Shalitin S, Tauman R, Meyerovitch J, Sivan Y. Are frequency and severity of sleep-disordered breathing inobese children and youth with and without type 2 diabetes mellitus different? Acta Diabetol. 2014;51(5):757-764.doi:10.1007/s00592-014-0583-1
83. Kim NH, Pavkov ME, Knowler WC, et al. Predictive value of albuminuria in American Indian youth with orwithout type 2 diabetes. Pediatrics. 2010;125(4):e844-e851. doi:10.1542/peds.2009-1230
84. Holman N, Campbell F, Sattar N, Warner J. Microvascular disease among young people with diabetes. DiabeticMedicine. 2015;32(Supplement 1):16. doi:10.1111/dme.12665_8
85. Sellers EAC, Blydt-Hansen TD, Dean HJ, Gibson IW, Birk PE, Ogborn M. Macroalbuminuria and renal pathologyin First Nation youth with type 2 diabetes. Diabetes Care. 2009;32(5):786-790. doi:10.2337/dc08-1828
86. Yoo EG, Choi IK, Kim DH. Prevalence of microalbuminuria in young patients with type 1 and type 2 diabetesmellitus. J Pediatr Endocrinol Metab. 2004;17(10):1423-1427. doi:10.1515/JPEM.2004.17.10.1423
87. Farah SE, Wals KT, Friedman IB, Pisacano MA, DiMartino-Nardi J. Prevalence of retinopathy andmicroalbuminuria in pediatric type 2 diabetes mellitus. J Pediatr Endocrinol Metab. 2006;19(7):937-942. doi:10.1515/JPEM.2006.19.7.937
88. Sellers EAC, Hadjiyannakis S, Amed S, et al. Persistent albuminuria in children with type 2 diabetes: a CanadianPaediatric Surveillance Program Study. J Pediatr. 2016;168:112-117. doi:10.1016/j.jpeds.2015.09.042
89. Zabeen B, Nahar J, Tayyeb S, Nhar N, Azad K. Type 2 diabetes in Bangladeshi children and adolescents—anemerging problem. Pediatr Diabetes. 2016;17(Suppl 24):36-164.
90. Nambam B, Silverstein J, Cheng P, et al; Pediatric Diabetes Consortium. A cross-sectional view of the currentstate of treatment of youth with type 2 diabetes in the USA: enrollment data from the Pediatric DiabetesConsortium Type 2 Diabetes Registry. Pediatr Diabetes. 2017;18(3):222-229. doi:10.1111/pedi.12377
91. Le PT, Huisingh CE, Ashraf AP. Glycemic control and diabetic dyslipidemia in adolescents with type 2 diabetes.Endocr Pract. 2013;19(6):972-979. doi:10.4158/EP13016.OR
92. Calagua Quispe M, Del Aguila Villar C, Nuñez Almache O, et al. Clinical features and course of pediatric patientswith type 1 and type 2 diabetes mellitus. Horm Res Paed. 2015;84(Suppl 2):39.
93. Newton K, Stanley J, Wiltshire E. Audit of type 2 diabetes in youth in Wellington, New Zealand 2001–2013.Pediatric Diabetes. 2015;16:147. doi:10.1111/pedi.12309
94. Son MK, Yoo HY, Kwak BO, et al. Regression and progression of microalbuminuria in adolescents withchildhood onset diabetes mellitus. Ann Pediatr Endocrinol Metab. 2015;20(1):13-20. doi:10.6065/apem.2015.20.1.13
95. Fazeli Farsani S, van der Aa MP, van der Vorst MMJ, Knibbe CAJ, de Boer A. Global trends in the incidence andprevalence of type 2 diabetes in children and adolescents: a systematic review and evaluation of methodologicalapproaches. Diabetologia. 2013;56(7):1471-1488. doi:10.1007/s00125-013-2915-z
96. Flynn JT, Kaelber DC, Baker-Smith CM, et al; Subcommittee on Screening and Management of High BloodPressure in Children. Clinical practice guideline for screening and management of high blood pressure in childrenand adolescents. Pediatrics. 2017;140(3):e20171904. doi:10.1542/peds.2017-1904
97. Ohishi M. Hypertension with diabetes mellitus: physiology and pathology. Hypertens Res. 2018;41(6):389-393. doi:10.1038/s41440-018-0034-4
98. Fox CS, Matsushita K, Woodward M, et al; Chronic Kidney Disease Prognosis Consortium. Associations ofkidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes:a meta-analysis. Lancet. 2012;380(9854):1662-1673. doi:10.1016/S0140-6736(12)61350-6
99. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes.N Engl J Med. 1984;310(6):356-360. doi:10.1056/NEJM198402093100605
100. Constantino MI, Molyneaux L, Limacher-Gisler F, et al. Long-term complications and mortality in young-onsetdiabetes: type 2 diabetes is more hazardous and lethal than type 1 diabetes. Diabetes Care. 2013;36(12):3863-3869. doi:10.2337/dc12-2455
SUPPLEMENT.eTable 1. Search Strategy, MEDLINEeTable 2. Search Strategy, EmbaseeTable 3. Search Strategy, CINAHLeTable 4. Search Strategy, Cochrane Library: Cochrane Central Register of Controlled Trials and Cochrane Databaseof Systematic ReviewseTable 5. Search Strategy, Web of Science: Conference Proceedings Citation Index-ScienceeTable 6. Results of Sensitivity Analysis for Prevalence of Hypertension in Pediatric Type 2 Diabetes Meta-analysis
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 26/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022
eTable 7. Results of Sensitivity Analysis for Prevalence of Albuminuria in Pediatric Type 2 Diabetes Meta-analysiseTable 8. Results of Sensitivity Analysis for Prevalence of Persistent Albuminuria in Pediatric Type 2 DiabetesMeta-analysiseTable 9. Results of Sensitivity Analysis for Prevalence of Microalbuminuria in Pediatric Type 2 Diabetes Meta-analysiseTable 10. Results of Sensitivity Analysis for Prevalence of Persistent Microalbuminuria in Pediatric Type 2Diabetes Meta-analysiseTable 11. Risk of Bias and OCEBM Level of Evidence of Included StudieseFigure 1. Study Flow DiagrameFigure 2. Forest Plot Showing Pooled Prevalence of Systolic Hypertension in Pediatric Type 2 DiabeteseFigure 3. Forest Plot Showing Pooled Prevalence of Diastolic Hypertension in Pediatric Type 2 DiabeteseFigure 4. Forest Plot Showing Pooled Prevalence of Hypertension in Pediatric Type 2 Diabetes by SexeFigure 5. Forest Plot Showing Pooled Odds Ratio of Hypertension in Male vs Female Participants with PediatricType 2 DiabeteseFigure 6. Forest Plot Showing Pooled Prevalence of Hypertension Across Different Racial Groups with PediatricType 2 DiabeteseFigure 7. Forest Plot Showing Pooled Prevalence of Microalbuminuria in Pediatric Type 2 DiabeteseFigure 8. Forest Plot Showing Pooled Prevalence of Persistent Microalbuminuria in Pediatric Type 2 DiabeteseFigure 9. Forest Plot Showing Pooled Prevalence of Macroalbuminuria in Pediatric Type 2 DiabeteseFigure 10. Forest Plot Showing Pooled Prevalence of Persistent Albuminuria in Pediatric Type 2 Diabetes by SexeFigure 11. Forest Plot Showing Pooled Odds Ratio of Persistent Albuminuria in Male vs Female Participants withPediatric Type 2 DiabeteseFigure 12. Forest Plot Showing Pooled Prevalence of Albuminuria across Different Racial Groups with PediatricType 2 DiabeteseFigure 13. Forest Plot Showing Pooled Prevalence of Persistent Albuminuria across Different Racial Groups withPediatric Type 2 DiabeteseFigure 14. Forest Plot Showing Pooled Prevalence of Microalbuminuria in Asian Patients with Pediatric Type 2DiabeteseFigure 15. Forest Plot Showing Pooled Prevalence of Persistent Microalbuminuria in Asian Patients with PediatricType 2 DiabeteseFigure 16. Funnel Plot Examining Publication Bias for Pooled Prevalence of Hypertension OutcomeeFigure 17. Funnel Plot Examining Publication Bias for Pooled Prevalence of Albuminuria OutcomeeFigure 18. Funnel Plot Examining Publication Bias for Pooled Prevalence of Persistent Albuminuria OutcomeeFigure 19. Funnel Plot Examining Publication Bias for Pooled Prevalence of Microalbuminuria OutcomeeFigure 20. Funnel Plot Examining Publication Bias for Pooled Prevalence of Persistent MicroalbuminuriaOutcomeeFigure 21. Distribution of Risk of Bias Sources in the Included StudieseAppendix. List of Studies Excluded at the Full-Text Screening StageeReferences.
JAMA Network Open | Pediatrics Prevalence of Hypertension and Albuminuria in Pediatric Type 2 Diabetes
JAMA Network Open. 2021;4(4):e216069. doi:10.1001/jamanetworkopen.2021.6069 (Reprinted) April 30, 2021 27/27
Downloaded From: https://jamanetwork.com/ on 05/19/2022