Open Journal of Pediatrics, 2011, 1, 4-8
doi:10.4236/ojped.2011.11002 Published Online March 2011 (http://www.SciRP.org/journal/OJPed/
OJPed
).
Published Online March 2011 in SciRes. http://www.scirp.org/journal/OJPed
Chronic Low-grade Inflammation and Haematological,
Circulatory, Metabolic, and Hepatic Abnormalities in
Childhood Obesity
Reizo Baba, M.D., Osaaki Ando, M.D. Reizo Baba, M.D., Ph.D.1,2, Kyoko Shinohara, M.D.,3 Osaaki
Ando, M.D., Ph.D.1, Jun Tanaka, M.D., Ph.D.1
1Committee for Health Promotion, Board of Education, Toyota City.
2Department of Neonatal and Perinatal Medicine, Aichi Medical University
3Department of Paediatrics, Ikeda Municipal Hospital.
E-mail : [e-mail]
ABSTRACT
Background: Little is known as to the associations
between childhood obesity and chronic low-grade
inflammation, circulatory, hepatic, metabolic and
haematological abnormalities. Methods and Results:
A total of 1,871 boys and 1,810 girls were measured
anthropometric data, white blood cell (WBCC),
platelet count, blood pressure, plasma concentrations
of aspartate aminotransferase (AST), alanine ami-
notransferase (ALT), triglyceride (TG), and high-
density (HDL) lipoprotein cholesterol,. The subjects
were classified into three body mass index categories
depending on the international standard definition
for child overweight and obesity. WBCC, platelet
counts, systolic blood pressure, serum levels of ami-
notransferases,TG and HDL-cholesterol were related
with body composition in both boys and girls. Obese
girls had high risks of having abnormal levels of
WBCC, platelet count, systolic blood pressure (SBP),
ALT, TG, HDL-cholesterol. Obese boys had high
risks of having abnormal levels of WBCC, haemobo-
bin concentration, platelet count, SBP, diastolic blood
pressure, AST, ALT, TG, and HDL-cholesterol. Con-
clusions: Childhood obesity is related with chronic
inflammation, hypercoagulability, as well as circula-
tory, metabolic, and hepatic abnormalities.
Keywords: Obesity; Metabolic Syndrome; Inflammation;
Platelet; Children
1. INTRODUCTION
The prevalence of childhood obesity and metabolic syn-
drome are increasing in the western countries[1-5] as
well as in Asia.[6-8] These conditions are known to be
associated with hypertension,[10-12] abnormal lipid and
glucose metabolism,[10] liver dysfunction,[13-16]
chronic low-grade inflammation[17,18] and hyperco-
agulability[19-21] in the adult populations. However,
little is known as to the association of obesity and these
abnormalities in the paediatric populations.[22] There-
fore, we aimed to investigate whether childhood obesity
is related with these circulatory, metabolic and hepatic
abnormalities, as well as with chronic low-grade in-
flammation.
2. METHODS
2.1. Study Subjects and Measurements
The subjects in the present study were all first-year jun-
ior high school students who had been admitted to Toy-
ota municipal public junior high schools in the 2009
academic year. Their mean age is 12.5(SD = 0.3) years
old in both boys and girls. We utilized the database of
the results of the medical checkups performed by us and
possessed by Toyota Municipal Board of Education.
Information that could be used to identify individual
subjects had been deleted before the Board of Education
had provided us with the data.
At the medical check-up, experienced nurses meas-
ured the subject’s body weight to the nearest 0.1 kg and
height to the nearest 0.1 cm. Blood pressure was meas-
ured with an automatic oscillometric sphygmomanome-
ter (BP-103iII, Colin, Nagoya, Japan) after the student
had been resting on a chair for more than 5 minutes. A
second measurement was performed 2 minutes later, and
the lower of the two measurements was used in the
analysis. After an overnight fast, blood samples (6ml)
were drawn from the peripheral veins for the measure-
ments of complete blood cell counts, plasma concentra-
tions of aspartate aminotransferase (AST), alanine ami-
notransferase (ALT), triglyceride, high-density lipopro-

R. Baba et al. / Open Journal of Pediatrics 1 (2011) 4-8 5
tein (HDL) cholesterol (Hitachi 917 Biochemical Ana-
lyzer, Tokyo, Japan). Valid measurements obtained from
1,871 boys and 1,810 girls were used in the analysis.
The characteristics of the subjects are summarised in
Table 1. The number of subjects included in the present
study represented 95% of the peers in the 2009 academic
year in Toyota city. Therefore, the subjects in the present
study were considered to be valid and unbiased samples.
This study conformed with the Ethical Guidelines for
Epidemiological Research of the Japanese Ministry of
Education, Culture, Sports, Science and Technology,
Ministry of Health, Labour and Welfare. We obtained
permission to use and analyse these data from the mu-
nicipal board of education on the condition with confi-
dentiality of personal data.
2.2. Definitions of Overweight and Obesity, and
Abnormal Values
The subjects were classified into three body mass index
(BMI) categories depending on the international stan-
dard definition for childhood overweight and obesity[23]:
nonobese defined by a BMI<21.56 kg/m2 in boys and
<22.14 kg/m2 in girls, overweight defined by a BMI be-
tween 21.56 to 26.43 kg/m2 in boys and 22.14 to 27.24
kg/m2 in girls, and obese defined by a BMI ≥ 26.84
kg/m2 in boys and ≥ 27.24 kg/m2 in girls. A high systolic
blood pressure was defined as a systolic blood pressure
greater than or equal to the 95th percentile (≥132 mmHg
in both boys and girls). A high diastolic blood pressure
was defined as a diastolic blood pressure equal to or
greater than 95th percentile (≥78 mmHg in boys and ≥79
mmHg in girls). High AST, high ALT, high TG, high
white blood cell count (WBCC), high hemoglobin con-
centration(Hb), and high platelet count are defined by
levels ≥ 95th percentile (AST: ≥ 33 IU/l in boys and ≥ 28
IU/l in girls; ALT ≥ 24 IU/l in boys and ≥ 18 IU/l in girls;
TG: ≥ 188 mg/dl in boys and ≥ 190 mg/dl in girls;
WBCC ≥ 8.3×103 in boys and ≥ 8.8×103 in girls; Hb ≥
15.2 g/dl in boys and ≥ 14.6 g/dl in girls; platelet count
4.48×105 /mm3 in boys and ≥ 3.49×105 /mm3 in girls).
Low HDL level was defined by a serum concentration ≤
5th percentile, or ≤ 43 mg/dl in boys and ≤ 45 mg/dl in
girls.
2.3. Statistics
A probability value of p<0.05 was considered to be sta-
tistically significant. Mean values were compared using
Student’s t-test. All statistical analyses were performed
with the Japanese edition of SPSS version 15.0 (Tokyo,
Japan).
3. RESULTS
Mean values of the measurements as classified by body
composition are listed in Table 1. The odds ratios of
having abnormal measurements are listed in Table 2.
3.1. Blood Pressure
In both boys and girls, systolic blood pressure was re-
lated with body composition. Also, the risk of having
abnormally high systolic blood pressure was greater in
Table 1. Mean values of the measurements as classified by body composition.
girls boys
obese overweight normal p obese overweight normal p
n = 20 n = 177 n = 1613 n = 39 n = 189 n = 1643
Height (cm) 154.1 (5.8) 152.6 (5.7) 151.0 (6.0)<0.001 157.4 (5.6) 154.7 (7.7) 150.6 (7.8) <0.001
Weight (kg) 71.1 (8.1) 56.9 (5.7) 41.1 (6.1) <0.001 72.7 (10.4) 56.2 (6.4) 40.1 (6.7) <0.001
BMI (kg/m2) 29.9 (2.4) 24.0 (1.5) 18.0 (1.9) <0.001 29.3 (3.4) 23.4 (1.3) 17.6 (1.8) <0.001
SBP (mmHg) 122 (14) 117 (11) 113 (11) <0.001 124 (9) 119 (11) 114 (12) <0.001
DBP (mmHg) 66 (9) 64 (9) 64 (9) 0.34 67 (9) 63 (9) 62 (9) 0.013
AST (IU/l) 19 (9) 18 (6) 20 (5) 0.001 30 (25) 23 (6) 23 (6) <0.001
ALT (IU/l) 17 (9) 12 (10) 11 (4) <0.001 39 (58) 19 (11) 13 (5) <0.001
TG (mg/dl) 141 (70) 101 (69) 86 (51) <0.001 139 (73) 110 (74) 77 (47) <0.001
HDL-cholesterol (mg/dl) 49 (9) 56 (12) 65 (13) <0.001 51 (10) 55 (12) 65 (13) <0.001
WBCC (×103/μl) 8.1 (1.8) 7.1 (1.3) 6.2 (1.4) <0.001 7.5 (1.8) 6.5 (1.4) 5.8 (1.2) <0.001
Hb (g/dl) 13.6 (0.8) 13.4 (0.8) 13.4 (0.8) 0.71 14.4 (1.0) 13.9 (0.7) 13.7 (0.8) <0.001
Platelet (×105/μl) 3.1 (0.6) 2.8 (0.5) 2.6 (0.5) <0.001 3.1 (0.6) 2.8 (0.5) 2.6 (0.5) <0.001
Data are mean (SD) values. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; AST, aspartate aminotransferase; ALT,
alanine aminotransferase; TG, triglyceride; HDL, high-density lipoprotein; WBCC, white blood cell count; Hb, haemoglobin.
C
opyright © 2011 SciRes. OJPed

6 R. Baba et al. / Open Journal of Pediatrics 1 (2011) 4-8
Table 2. The odds ratio of having abnormal circulatory, hepatic, metabolic and haematological abnormalities in obese and over-
weight children.
Girls Boys
obese overweight normal obese overweight normal
prevalence 35.0% 8.5% 4.9% 20.5% 8.5% 5.0%
High SBP
OR (95% CI) 10.3 (4.1-26.5)1.8 (0.99-3.2)1 4.4 (2.0-10.0) 1.6 (0.9-2.8)1
prevalence 5.0% 6.9% 5.0% 12.8% 7.9% 4.6%
High DBP
OR (95% CI) 1.1 (0.6-2.1) 0.83(0.1-6.3) 1 3.0 (1.1-8.0) 1.8 (1.0-3.2)1
prevalence 10.0% 4.0% 5.0% 20.5% 5.3% 4.8%
High AST
OR (95% CI) 1.9 (0.4-8.4) 0.7(0.3-1.6) 1 5.1(2.3-11.5) 1.1 (0.6-2.2)1
prevalence 40.0% 9.0% 4.1% 46.2% 20.6% 2.5%
High ALT
OR (95% CI) 15.6 (6.2-39.5)2.3(1.3-4.1) 1 33.4(16.6-67.5) 10.1 (6.3-16.2)1
prevalence 20.0% 7.9% 4.6% 17.9% 14.3% 3.6%
High TG
OR (95% CI) 5.2 (1.7-15.9)1.8(0.9-3.2) 1 5.9(2.5-13.8) 4.5 (2.8-7.3)1
prevalence 55.0% 15.3% 4.9% 25.6% 15.9% 4.1%
Low HDL
OR (95% CI) 16.8 (6.7-41.7)3.7(2.3-5.9) 1 7.5(3.4-16.6) 5.0 (3.2-8.0)1
prevalence 35.0% 10.7% 4.6% 25.6% 10.1% 4.3%
High WBCC
OR (95% CI) 11.5 (4.5-29.8)2.6(1.5-4.4) 1 7.7(3.6-16.5) 2.5 (1.5-4.3)1
prevalence 10.0% 6.8% 5.0% 25.6% 6.3% 4.7%
High Hb OR (95% CI) 1.7 (0.4-7.3) 1.1(0.6-2.0) 1 7.0 (3.3-14.9) 1.4 (0.7-2.6)1
prevalence 40.0% 7.9% 4.6% 17.9% 8.9% 4.3%
High platelet count OR (95% CI) 13.9 (5.5-34.9)1.8(1.1-3.2) 1 5.0 (2.1-11.7) 2.3 (1.3-3.9)1
OR, odds ratio, CI, confidence interval; SBP, systolic blood pressure; DBP, diastolic blood pressure; AST, aspartate aminotransferase; ALT, alanine ami-
notransferase; TG, triglyceride; HDL, high-density lipoprotein; WBCC, white blood cell count; Hb, haemoglobin.
obese boys and girls. Diastolic blood pressure was re-
lated with body composition only in boys, not in girls.
The risk of having abnormally high diastolic blood
pressure was found in overweight and obese boys, but
not in girls.
3.2. Aminotransferases
In both boys and girls, aminotransfereses (AST and ALT)
were related with body composition. The odds ratio for
having abnormally high serum AST was greater in obese
boys. The odds ratio for having abnormally high serum
ALT was greater in both obese and overweight boys and
girls.
3.3. Serum Lipid Levels
Serum TG level was related with body composition in
both boys and girls. The odds ratio for having abnor-
mally high TG level was greater in obese girls and in
obese and overweight boys. Serum HDL level was asso-
ciated with body composition in both boys and girls. The
odds ratios for having abnormally low HDL level were
greater in obese and overweight boys and girls.
3.4. Blood Cell Counts
WBCC was related with body composition in both boys
and girls. The risk for having abnormally high WBCC
was observed in both obese and overweight boys and
girls. Hb was related with body composition in boys, but
not in girls. The risk of having abnormally high Hb lev-
els was found in obese boys. Platelet count was related
with body composition in both bys and girls. The risk of
having abnormally high platelet counts was found in
both obese and overweight boys and girls.
4. DISCUSSION
The most striking finding of the present study is that
childhood obesity is related with WBCC, a marker of
chronic inflammation, as well as with platelet count,
possible marker of hypercoagulability. Also, the present
study has revealed that childhood obesity is related with
circulatory, metabolic, and hepatic abnormalities.
Obesity and metabolic syndrome are known to be re-
lated with chronic inflammation not only in adults[17-21]
but also in children.[22] WBCC is a marker of chronic
inflammation[24] and is known to correlate with the
amount of body fat in adults.[25] To our knowledge, this
study is the first one that has revealed the association
between childhood obesity and increased WBCC. This
finding confirms the relation of chronic inflammation
with childhood obesity.[22] Childhood obesity may be
C
opyright © 2011 SciRes. OJPed

R. Baba et al. / Open Journal of Pediatrics 1 (2011) 4-8 7
more dangerous than adult obesity, as the patients with
childhood obesity have longer history of having chronic
inflammation than adulthood obesity patients, which can
cause early development of cardiovascular diseases.
The present study is also the first one that has shown
the relation of childhood obesity with increased platelet
counts, a well-known risk factor for fatal coronary heart
disease in adult population.[26] Taniguchi et al. showed
a relationship between platelet count and insulin resis-
tance in non-obese adult Japanese type 2 diabetic pa-
tients.[27] Thus, increased platelet count may be related
with impaired insulin sensitivity in obese children. The
mechanisms for the increase in platelet counts are un-
known. But, it seems interesting that insulin is thought to
reduce platelet sensitivity to aggregating agents such as
adenosine diphosphate.[28]
The present study shows that body composition is
closely related with systolic blood pressure and that
obese boys and girls have high risks of having abnor-
mally high systolic blood pressure. These findings con-
firm the findings of previous studies that childhood and
adolescent obesity is related with hyperkinetic circula-
tion.[7,29] The close and early association of systolic
hypertension with adiposity suggests the role of im-
paired autonomic function in the pathogenesis of adipos-
ity-associated hypertension.
The present study has some limitations. We did not
measure blood glucose or insulin activity. Also, the data
of waist circumference is lacking. These measurements
are essential for the diagnosis of metabolic syndrome.
Therefore, addition of these data may provide us further
knowledge as to the understanding of childhood obesity
or metabolic syndrome and their associations with hae-
matological, hepatic and circulatory disorders, which
awaits further investigations.
REFERENCES
[1] Hayman LL, Meininger JC, Daniels SR, McCrindle BW,
Helden L, Ross J, et al. Primary prevention of cardio-
vascular disease in nursing practice: Focus on children
and youth: A scientific statement from the American
Heart Association Committee on Atherosclerosis, Hyper-
tension, and Obesity in Youth of the Council on Cardio-
vascular Disease in the Young, Council on Cardiovascu-
lar Nursing, Council on Epidemiology and Prevention,
and Council on Nutrition, Physical Activity, and Metabo-
lism. Circulation 2007; 116: 344-57.
[2] Weiss R, Dziura J, Burgert TS. Obesity and the metabolic
syndrome in children and adolescents. N Engl J Med
2004; 350: 2362-74.
[3] Rocchini AP. Childhood obesity and a diabetes epidemic.
N Engl J Med 2002; 346: 854-5.
[4] Strauss RS, Pollack HA. Epidemic increase in childhood
overweight. 1986–1998. JAMA 2001; 286: 2845-48.
[5] Reilly JJ, Dorosty AR. Epidemic of obesity in UK chil-
dren. Lancet 1999; 354: 1874-5.
[6] Baba R, Nagashima M, Asai T, Kato Y. Effect of physical
activity and readiness for exercise on the development of
obesity in adolescents (in Japanese). Jpn J Clin Sports
Med 2004; 12: 346-51.
[7] Baba R, Koketsu M, Nagashima M, Inasaka H, Yoshi-
naga M, Yokota M. Adolescent obesity adversely affects
blood pressure and resting heart rate. Circ J 2007; 71:
722-6.
[8] Baba R, Iwao N, Iwao S, Koketsu M, Nagashima M,
Inasaka H. Risk of obesity enhanced by poor physical ac-
tivity in high school students. Pediatr Int 2006; 48:
268-73.
[9] DeFronzo RA, Ferrannini E. Insulin resistance. A multi-
faceted syndrome responsible for NIDDM, obesity, hy-
pertension, dyslipidemia, and atherosclerotic cardiovas-
cular disease. Diabetes Care 1991; 14: 173-94.
[10] Nguyen NT, Magno CP, Lane KT, Hinojosa MW, Lane
JS. Association of hypertension, diabetes, dyslipidemia,
and metabolic syndrome with obesity: findings from the
National Health and Nutrition Examination Survey, 1999
to 2004. J Clin Endocrinol Metab 2002; 87: 3023-8.
[11] Rahmouni K, Correia MLG, Haynes WG, Mark AL. Obe-
sity-associated hypertension: new insights into mecha-
nisms. Hypertension 2005; 45: 9-14.
[12] Hall JE, Hildebrandta DA, Kuo J. Obesity hypertension:
role of leptin and sympathetic nervous system. Am J Hy-
pertens 2001; 14 (suppl 1): S103-15.
[13] Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepati-
tis) and obesity: An autopsy study with analysis of risk
factors. Hepatology 2005; 12: 1106-10.
[14] Marceau P, Biron S, Hould FS, Marceau S, Simard S,
Thung SN, et al. Liver pathology and the metabolic syn-
drome X in severe obesity. J Clin Endocrinol Metab
1999; 84:1513-7.
[15] Marchesini G, Brizi M, Bianchi G, Tomassetti S,
Bugianesi E, Lenzi M, et al. Nonalcoholic fatty liver dis-
ease: a feature of the metabolic syndrome. Diabetes 2001;
50: 1844-50.
[16] Pagano G, Pacini G, Musso G, Gambino R, Mecca F,
Depetris N, et al. Nonalcoholic steatohepatitis, insulin
resistance, and metabolic syndrome: further evidence for
an etiologic association. Hepatology 2002; 35: 367-72.
[17] Wellen KE, Hotamisligil GS.Obesity-induced inflamma-
tory changes in adipose tissue. J Clin Invest 2003; 112:
1785-8.
[18] Lee YH, Pratley RE, The evolving role of inflammation
in obesity and the metabolic syndrome. Curr Diab Rep
2005; 5: 70-5.
[19] Falcon C, Pfliegler G, Deckmyn H, Vermylen J. The
platelet insulin receptor: Detection, partial characteriza-
tion, and search for a function. Biochem Biophys Res
Commun 1988; 157: 1190-6.
[20] Trovati M, Anfossi G, Cavalot F, Massucco P, Mularoni E,
Emanuelli G. Insulin directly reduces platelet sensitivity
to aggregating agents: Studies in vitro and in vivo. Dia-
betes 1988; 37: 780-6.
[21] Westerbacka J, Yki-Järvinen H, Turpeinen A, Rissanen A,
Vehkavaara S, Syrjälä M, et al. Inhibition of plate-
let-collagen interaction: An in vivo action of insulin abol-
ished by insulin resistance in obesity. Arterioscler
Thr omb Vasc Biol 2002; 22: 167-72.
C
opyright © 2011 SciRes. OJPed

8 R. Baba et al. / Open Journal of Pediatrics 1 (2011) 4-8
[22] Herder C, Schneitler S, Rathmann W, Haastert B,
Schneitler H, Winkler H, et al. Low-grade inflammation,
obesity, and insulin resistance in adolescents. Clin Endo-
crinol Metab 2007; 92: 4569-74.
[23] Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establish-
ing a standard definition for child overweight and obesity
worldwide: international survey. BMJ 2000; 320:1240-3.
[24] Festa A, D'Agostino R Jr, Howard G, Mykkänen L, Tracy
RP, Haffner SM. Chronic subclinical inflammation as
part of the insulin resistance syndrome: the Insulin Re-
sistance Atherosclerosis Study (IRAS). Circulation 2000;
102: 42-7.
[25] Wilson CA, Bekele G, Nicolson M, Ravussin E, Prat-
leyRE. Relationship of the white blood cell count to body
fat: role of leptin. Br J Haematol 2003; 99: 447-51.
[26] Thaulow E, Erikssen J, Sandvik L, Stormorken H, Cohn
PF. Blood platelet count and function are related to total
and cardiovascular death in apparently healthy men. Cir-
culation 1991; 84: 613-7.
[27] Taniguchi A, Fukushima M, Seino Y, Sakai M, Yoshii S,
Nagasaka S, et al. Platelet count is independently associ-
ated with insulin resistance in non-obese Japanese type 2
diabetic patients. Metabolism 2003; 52: 1246-9.
[28] Falcon CR, Cattaneo M, Ghidoni A, Mannucci PM. The
in vitro production of thromboxane B2 by platelets of
diabetic patients is normal at physiological concentra-
tions of ionized calcium. Thromb Haemost 1993; 70:
389-92.
[29] Sorof JM, Poffenbarger T, Franco K, Bernard L, Portman
RJ. Isolated systolic hypertension, obesity, and
hyperkinetic hemodynamic states in children. J Pediatr
2002; 140: 660-6.