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Indian Pediatr 2017;54:848-850 |
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Adiponectin,
Interleukin-6 and High-sensitivity C-reactive Protein Levels in
Overweight/Obese Indian children
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Vandana Jain, Ajay Kumar, Anuja Agarwala, *Naval
Vikram and #Lakshmy
Ramakrishnan
From Departments of Pediatrics, *Medicine and
#Cardiac Biochemistry, All India Institute of Medical Sciences, New
Delhi, India.
Correspondence to: Dr Vandana Jain, Professor,
Division of Pediatric Endocrinology, Department of Pediatrics, All India
Institute of Medical Sciences, New Delhi 110 029, India.
Email: [email protected]
Received: July 08, 2016;
Initial Review: December 09, 2016;
Accepted: June 13, 2017.
Published online: July 11, 2017.
PII:S097475591600076
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Objective: The aim of our study was to assess serum Adiponectin,
Interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP)
levels and their correlation with conventional risk factors for
cardiovascular disease and diabetes in overweight/obese Indian children.
Methods: Body mass index (BMI), waist circumference, blood
pressure, fasting serum adiponectin, IL-6, hsCRP, blood glucose,
triglycerides, and total and high density lipoprotein cholesterol were
measured in children aged 7-15 years with BMI >85th centile. Results:
84 overweight/obese children (48 boys) with mean (SD) age 10.2 (1.9)
years were enrolled. Mean (SD) adiponectin, hsCRP and median (IQR) IL-6
levels were 6.0 (3.1) µg/mL, 3.4 (2.4) mg/L and 12.7 (5.0-90.0) pg/mL,
respectively. Low adiponectin, high hsCRP and high IL-6 were noted in
16.5%, 49.4% and 54.4% participants, respectively. Adiponectin was
inversely correlated with waist circumference, and IL-6 positively with
BMI and blood glucose. Conclusion: Inflammatory mediators, hsCRP
and IL-6 were elevated in half of the overweight children. Adiponectin
and IL-6 correlated well with traditional risk markers.
Keywords: Cytokines, Inflammation, Metabolic syndrome.
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O ver the last decade, several studies have
indicated that inflammatory markers and adipocytokines mediate the
evolution of the cardiovascular and metabolic complications of obesity.
Low-grade chronic inflammation in association with obesity plays a major
role in the pathogenesis of atherosclerosis and insulin resistance
[1,2]. Adipose-tissue macrophages and adipocytes secrete interleukin-6
(IL-6), an inflammatory mediator postulated to affect lipid and glucose
metabolism through several mechanisms [2].
C-reactive protein (CRP) is another inflammatory
biomarker, associated with impaired insulin sensitivity and the
development of cardiometabolic syndrome [3]. It is considered to play an
important role in vascular remodeling and plaque deposition [4].
High-sensitivity CRP (hsCRP) test measures low levels of CRP. Values
above 3 mg/L are indicative of high risk for cardiovascular disease [4].
Adiponectin is a collagen-like plasma protein secreted exclusively by
adipocytes. This protein has anti-inflammatory, anti-atherogenic, and
potent insulin-sensitizing effects, which may be partially mediated by
suppression of TNF- a
and IL-6 [3]. Low levels of adiponectin have been associated with
metabolic syndrome, insulin resistance and type 2 diabetes [3,5].
Majority of the studies on these adipocytokines and
inflammatory markers have been done in adults. The aim of our study was
to assess serum IL-6, hsCRP and Adiponectin levels and their correlation
with conventional risk factors for cardiovascular disease and diabetes
in overweight/obese Indian children.
Methods
This cross-sectional study was conducted at All India
Institute of Medical Sciences, New Delhi after obtaining ethical
approval from the Institute ethics committee. Children between 7-15
years, with BMI >85th
centile according to Indian reference curves were enrolled from
Pediatric outpatient department. Children with genetic, syndromic,
endocrine or medication-related obesity were excluded. Informed consent
was obtained from the parents, and assent from the children.
Weight, height, waist circumference and blood
pressure (BP) were measured. BMI was calculated and pubertal staging was
done. Fasting blood sample was collected for adiponectin, IL-6, hsCRP,
glucose, total cholesterol, HDL cholesterol and triglycerides.
Adiponectin, IL-6 and hsCRP were measured using quantitative
colorimetric sandwich ELISA kits. Glucose was measured in the fresh
sample by glucose oxidase method, total and HDL cholesterol and
triglycerides were measured by Randox kits (Randox Ltd, Antrim, UK). LDL
cholesterol was estimated using Friedewald’s formula as total
cholesterol – HDL cholesterol – (triglyceride/ 5) mg/dL.
The following cut-offs were considered abnormal:
Adiponectin <3 µg/mL [7], hsCRP >3 mg/L [5], IL-6 >10 pg/mL [8], fasting
blood glucose ³100
mg/dL, Total cholesterol ³200
mg/dL, LDL cholesterol ³130
mg/dL, HDL cholesterol <40 mg/dL and Triglyceride>150 mg/dL [9].
Abdominal obesity was considered present if waist circumference was
above 95th percentile for age or >90 cm in boys/ >80 cm in girls [9].
Spearman test was applied to check for correlation
between adiponectin, IL-6, hsCRP, BMI, waist circumference and fasting
blood glucose. Wilcoxon rank-sum (Mann-Whitney) test was applied to test
for difference in adiponectin, IL-6 and hsCRP in children with and
without abdominal obesity and impaired fasting glucose.
Results
Eighty-four children (48 boys) with a mean (SD) age
of 10.2 (1.9) years were enrolled. Two-thirds of the children were
prepubertal, and 87% were obese. The mean (SD) BMI Z-score was 2.7
(0.8). Mean (SD) waist circumference was 82.4 (10.3) cm, with abdominal
obesity in 67.3%. Mean (SD) systolic and diastolic BP was 113 (10) and
74 (10) mm Hg, respectively with hypertension present in 15.5%.
The biochemical parameters are summarized in
Table I. Values of lipid profile and fasting blood glucose could
not be traced from the central laboratory for some patients. Elevation
of inflammatory mediators constituted the commonest abnormality, with
IL-6 being elevated in 54.4% and hsCRP in 49.4%. Low HDL was the
commonest dyslipidemia, noted in 35.1%. Impaired fasting glucose was
seen in 10.7% and low adiponectin levels in 16.5%.
TABLE I Summary of Biochemical Parameters in Overweight/Obese Indian Children
S.No. |
Parameter |
Value |
1. |
Adiponectin* (µg/mL) |
6.0
(3.1) |
|
<3 |
13
(16.5) |
2. |
high-sensitivity C-reactive protein*(mg/L) |
3.4
(2.4) |
|
>3 |
39
(49.4) |
3. |
Interleukin-6# (pg/mL) |
12.7 (5.0-90.0) |
|
>10
|
43
(54.4) |
4. |
Total cholesterol* (mg/dL) |
153.0 (33.0) |
|
≥200 |
5
(8.8) |
5. |
HDL
cholesterol* (mg/dL) |
43.9 (8.6) |
|
<40
|
20
(35.1) |
6. |
Triglycerides* (mg/dL) |
105.6 (39.4) |
|
>150 |
7
(12.3) |
7. |
LDL
cholesterol* (mg/dL) |
88.0 (33.0) |
|
≥130 |
4
(7.0) |
8. |
Fasting blood glucose* (mg/dL) |
85.0 (15.4) |
|
≥100 |
6
(10.7) |
Value in No. (%), *mean
(SD) or #median (IQR). N = 79 for S.No.1-3, 57 for S.No. 4-7,
and 56 for S.No. 8. |
Serum adiponectin was noted to have a significant
inverse correlation with waist circumference (r= -0.28, P=0.047).
Serum IL-6 had a positive correlation with BMI (r= 0.23, P=
0.09), and blood glucose (r= 0.24, P= 0.08), but was not
statistically significant. Median (IQR) serum IL-6 in children with
abdominal obesity was 45.2 (6.3-31.2) pg/mL as compared to 6.6
(4.5-22.5) pg/mL in those without abdominal obesity (P=0.047).
Median (IQR) serum IL-6 was higher in the children with impaired fasting
glucose as compared to those with normal levels (107.0 (22.5-197.5)
vs 8.5 (5.0-116.0) pg/mL, P=0.06). There was no significant
correlation between the serum levels of IL-6, hsCRP and adiponectin. No
correlation was observed between hsCRP and BMI, waist circumference or
blood glucose.
Discussion
We noted a high prevalence of traditional risk
markers of later cardiovascular disease and diabetes in our young study
population. Half of our study group had elevated levels of inflammatory
mediators IL-6 and hsCRP. To the best of our knowledge, no previous
Indian study has reported IL-6 levels in obese children. However, higher
levels of hsCRP and lower levels of adiponectin in obese post-pubertal
adolescents as compared to lean have been reported by Vikram, et al.
[9].
A limitation of our study is the lack of lean
controls. Another limitation is that as a majority of our study
participants were either pre- or early-pubertal, and only 10% were in
pubertal stage 3 or above; thus, we could not ascertain the effect of
puberty on the levels of IL-6, hsCRP and adiponectin.
In another study by our group (unpublished), serum
adiponectin in 29 lean children, (mean (SD) age 11.5 (1.6) y, mean (SD)
BMI z-score -0.4 (0.5)) was 8.7 (5.3) µg/mL, which is significantly
higher as compared to the level in the overweight/obese children in the
present study. In a study in Austrian children with mean (SD) age of 12
(4) years, the mean (SD) hsCRP in the obese group was 4.1(4.8) mg/L
[10]; and in another study in Caucasian pre-pubertal children with mean
(SD) age of 8.0 (0.1) years, the median (IQR) hsCRP levels in the obese
group were 2.5 (1.4-5.3) mg/L, [11], which were similar to the levels
noted in our study. In these two studies, the levels in lean children
were significantly lower at 0.9 (1.5) mg/L and 0.5 (0.2-1.7) mg/L,
respectively [10,11]. In a Spanish study, mean (SD) serum IL-6 in obese
children aged 4-15 years was 7.5 (3.8) pg/mL, similar to our study [12].
We noted an inverse association of adiponectin with
waist circumference, indicating that the association between abdominal
obesity and insulin resistance may be mediated by lowered adiponectin.
Similar observations of inverse association of adiponectin with obesity
have been made in Taiwanese and Japanese children [13,14]. We also
observed a positive correlation of IL-6 with BMI and fasting blood
glucose, as has been reported previously in adults [15].
To conclude, our study showed that inflammatory
mediators hsCRP and IL-6 were elevated in half of the obese/overweight
children and adiponectin was low in 16.5%. Inverse correlation of
adiponectin with waist circumference, and positive correlation of IL-6
with BMI and fasting blood glucose indicated the utility of these
parameters as markers of metabolic risk in children.
Contributors: VJ conceptualized and
conducted the study and drafted the manuscript. AK helped in conducting
the study, AA, NV and RK were co-investigators, AA helped in patient
enrolment, NV and RK supervised the biochemical assays. All authors have
given their inputs and approved the final manuscript.
Funding: All India Institute of Medical Sciences,
New Delhi.
Competing interest: None stated.
What This Study Adds?
•
Serum adiponectin has a
significant inverse correlation with waist circumference, and
serum IL-6 was significantly higher in children with abdominal
obesity as compared to those without.
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