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Indian Pediatr 2012;49: 109 -112 |
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Serum Magnesium in Overweight Children
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Bipin Jose, Vandana Jain, *Naval Kishore Vikram, Anuja Agarwala and
Savita Saini
From the Department of Pediatrics and
*Medicine, All India Institute of Medical Sciences, New Delhi, India.
Correspondence to: Dr Vandana Jain, Associate
Professor, Division of Pediatric Endocrinology, Department of Pediatrics,
All India Institute of Medical Sciences, New Delhi 110 029, India.
Email: [email protected]
Received: January 17, 2011;
Initial review: February 02, 2011;
Accepted: March 03, 2011.
Published online: 2011 January, 30
PII: S097475591100061-1
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Objective: To determine whether overweight children and adolescents
have lower serum concentration and lower dietary intake of magnesium
compared to those with normal weight; and to study the correlation of
serum magnesium levels with components of metabolic syndrome in children
and adolescents.
Design: Cross-sectional, comparative study.
Setting: General/Pediatric Endocrinolgy OPD
tertiary care medical centre. Study done from July 2007 to March 2009
Participants: 55 overweight and 53 normal weight
children and adolescents aged 4 years to 14 years.
Methods: We compared fasting levels of serum
magnesium, insulin, glucose, total and HDL-cholesterol, triglycerides
and dietary magnesium intake.
Results: The serum magnesium levels were
significantly lower in overweight (2.12 ± 0.33 mg/dL) compared to normal
weight group (2.56 ± 0.24 mg/dL, P<0.001), while the dietary
intake of magnesium (adjusted for calorie intake) was higher in
overweight group (0.20 ± 0.06 mg/kcal) compared to normal weight (0.17 ±
0.05 mg/kcal; P= 0.005). Serum magnesium levels were inversely
correlated with body mass index, systolic blood pressure, diastolic
blood pressure, waist circumference and fasting insulin levels.
Conclusions: Serum magnesium levels were
significantly lower in overweight children compared to those with normal
weight in spite of a higher dietary intake.
Key words: Child, India, Magnesium, Metabolic syndrome,
Overweight.
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Overweight adults have lower serum and
intracellular magnesium compared to healthy normal weight controls
[1-3]. An association is also reported between lower serum/
intracellular magnesium and insulin resistance (IR), type 2 diabetes
mellitus (DM), hypertension and metabolic syndrome (MS) [1-3]. This
association is biologically plausible because magnesium containing
ATPases are important co-factors for many of the enzymes of the
carbohydrate metabolism pathway [4]. Impaired cellular glucose uptake,
impaired action of insulin at receptor level, and impaired tyrosine
kinase activity are other mechanisms by which magnesium deficiency
impairs insulin action at cellular level [5-7].
It is being increasingly recognized that the
foundations for obesity and metabolic syndrome are laid down in
childhood with subsequent tracking into adulthood [8]. We conducted this
study to test the hypothesis that the association of lower serum
magnesium with obesity and metabolic syndrome develops in childhood
itself. The objectives of the study were to determine whether serum
magnesium and dietary intake of magnesium were lower in overweight
children compared to normal weight and to assess the correlation of
serum magnesium with parameters of metabolic syndrome.
Methods
Subjects included 55 overweight children (BMI
>85th centile for age
and gender as per Agarwal’s growth charts for Indian children) and 53
normal weight children, aged between 4 to 14 years enrolled from the
general pediatric outpatient or Pediatric endocrinology clinic. Children
with genetic/endocrine/syndromic causes of obesity, diabetes mellitus,
medical conditions predisposing to hypomagnesemia (gastroenteritis,
chronic kidney disease and chronic liver disease) or on medications
predisposing to hypomagnesemia (e.g. diuretics, amphotericin were
excluded. The study was approved by the institutional ethics committee.
Written informed consent from all parents and assent from subjects,
wherever appropriate, were obtained.
Detailed dietary history was obtained in both groups
using a validated food frequency question-naire (based on 24-hour as
well as a monthly recall) by an experienced pediatric dietician.
Enrolment of cases and controls was done simultaneously to avoid
seasonal bias in dietary characteristics. A detailed clinical
examination including anthropometry (height, weight and waist
circumference (WC)), markers of insulin resistance (acanthosis nigricans
and skin tags), and blood pressure (BP) was performed in all subjects.
Sexual maturity rating (SMR) was evaluated in all subjects and they were
grouped into pre (Tanner 1), early (Tanner 2, 3) and advanced puberty ( ³Tanner
4) [9]. Weight was measured with an accuracy of 0.1 kg and height to the
nearest 0.5 cm using a calibrated digital weighing scale with a
stadiometer (Seca, Germany, model no: 7892317109) and BMI was
calculated. WC was measured to an accuracy of 0.5 cm, using a non
elastic tape at the midpoint of iliac crest and the lower border of rib
cage. BP was measured in duplicate using mercury sphygmomanometer
(Elkometer-300, India) in sitting position in the right arm with
appropriate sized cuffs after the child had rested for five minutes.
Venous blood samples were obtained after an overnight
fast of at least 10 hours for estimation of serum magnesium, insulin,
total and HDL-cholesterol (HDL-C) and triglycerides in all subjects.
Serum was separated and stored at -80 °C
until analysis. An oral glucose tolerance test was also performed in
overweight children by measuring fasting and 2 hour plasma glucose after
loading with 1.75 g/kg of glucose. Serum magnesium was analyzed using
flame atomic absorption spectrometer (Avanta M, GBC, Australia).
Standard curves were prepared using international magnesium standards
(Merck, Germany). The validation of these curves was done using two
different seronorms (Sero, A/S, Norway) of known concentrations.
Intra-assay quality control was ensured by repeating the pooled serum
magnesium analysis after every 10 samples. The maximum accepted
intra-assay variation was 10%. Serum insulin was measured using a
commercially available radioimmuno-assay kit (Medicorp, Montreal,
Canada). Total cholesterol, triglyceride and HDL-C were measured by
enzymatic end point method using the principle of enzymatic hydrolysis
and oxidation using a commercially available kit (Randox, UK). LDL
cholesterol was calculated using ‘Friedewald’s formula [10] [LDL = total
cholesterol – (triglyceride/5 + HDL)] and non-HDL cholesterol
(non-HDL-C) was calculated as total cholesterol –HDL-C.
The daily magnesium and calorie intake of each
subject was calculated by entering the dietary record into nutrient
calculator software (Diet soft), which has data on the calorie content,
micro and macro-nutrient composition of most Indian foods as per
National Institute of Nutrition, Hyderabad, guidelines [11]. The daily
magnesium intake was expressed as mg/kcal to factor in the higher
calorie intake in the overweight group.
Metabolic syndrome was defined according to the
International Diabetes Federation criteria for children and adolescents
as abdominal obesity (waist circumference ≥90th percentile for
age and gender or adult cut off) and the presence of 2 or more other
features (triglycerides ≥1.7
mmol/L (150 mg/dL); HDL-C <1.03 mmol/L (40 mg/dl); BP
≥130 mm Hg systolic
or ³85 mm Hg
diastolic; fasting glucose ≥5.6
mmol/L (100 mg/dL) or type 2 DM [12].
Data were recorded in a predesigned proforma and
managed in an Excel spread sheet. Comparison of physical, biochemical
parameters and dietary magnesium intake between the overweight and
normal weight groups was done using either Student’s t-test or Wilcoxon
rank sum test. Bivariate (unadjusted) correlations of serum magnesium
with BP, WC, serum HDL-C, non-HDL-C and insulin were examined using
Spearman’s rank correlation. Log transformed values of variables not
normally distributed (fasting insulin and lipid parameters) were used to
examine the BMI adjusted linear correlations between serum magnesium and
the variables found to be significant in unadjusted comparison. STATA
9.0 statistical software was used for data analysis. P <0.05 was
considered significant.
Results
Table I compares the baseline anthropometric
and biochemical variables in two groups. Table II compares
the outcome variables between overweight and normal weight children.
Lower serum magnesium levels in the overweight group persisted even when
subgroup analysis was done for children
≤10 years and >10
years.
TABLE I Comparison of+9 Baseline Characteristics of Overweight and Normal Weight Subjects
Characteristic |
Overweight (n=55) |
Normal weight (n=53) |
P value |
Gender (M/F) |
44/11 |
37/16 |
0.36 |
Age (years) |
10.6 ± 2.7 |
10.2 ± 2.1 |
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SMR stage |
|
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|
Tanner 1 (males) |
28 (18) |
27 (17) |
|
Tanner 2,3 (males) |
21(20) |
21(17) |
0.56 |
>Tanner 4 (males) |
6 (6) |
5 (3) |
|
BMI (kg/m2 )
|
24.8 ± 5.0 |
14.8 ± 2.2 |
<0.001 |
Waist circumference (cm)
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85 ± 8.9 |
58.3 ± 6.8 |
<0.001 |
Systolic BP (mm Hg)
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118 ± 16 |
102 ± 10 |
<0.001 |
Diastolic BP (mm Hg)
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78 ± 12 |
68 ± 7 |
<0.001 |
Total cholesterol (mg/dL)
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137 (117-170) |
130.4(119-140) |
0.127 |
Triglycerides (mg/dL)
|
107 (90 - 144) |
94 (69 -116) |
0.037 |
HDL cholesterol (mg/dL)
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36 (31-41) |
29 (24-39) |
0.001 |
Non-HDL cholesterol(mg/dL)
|
103 (126) |
99 (86-112) |
0.28 |
Serum insulin (µIU/mL)
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6.5 (4.1-11.9) |
3.2 (2.2-5.6) |
<0.001 |
* Data presented as mean ± S.D or median (inter-quartile
range). |
TABLE II Serum and Dietary Magnesium in Overweight and Normal Weight Children
Variable |
Overweight
|
Normal weight |
P |
|
(n=55) |
(n=53) |
value |
Serum Mg (mg/dL) |
2.12 ± 0.33 |
2.56 ± 0.24 |
<0.001 |
age ≤10 y |
2.14 ± 0.37 |
2.58 ± 0.21 |
<0.001 |
age >10 y
|
2.10 ± 0.29 |
2.56 ± 0.26 |
<0.001 |
Dietary Mg (mg/Cal) |
0.20 ± 0.06
|
0.17 ± 0.05 |
0.005 |
Unadjusted Mg
intake (mg/day) |
303 ± 15
|
192 ± 8.5 |
<0.005
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Prevalence of metabolic syndrome in overweight
adolescents (≥10
years of age) was 45%. Systolic hypertension was seen in 20%, diastolic
hypertension in 35%, low HDL-C in 75%, hypertriglyceridemia in 10% and
deranged oral glucose tolerance test in 17.5% of the overweight
adolescents.
Among the components of metabolic syndrome, a
significant inverse correlation of serum magnesium was observed with
serum insulin (P<0.005), BMI (P<0.0001), WC (P<0.001),
systolic BP (P=0.001) and diastolic BP (P=0.0009). After
adjusting for BMI, the correlation of serum magnesium with WC remained
significant (P< 0.001) while all others became non-significant.
Discussion
Our study has shown that overweight children, even
those ≤10
years of age have significantly lower serum magnesium levels as compared
to normal weight children. We speculate that the lower serum magnesium
levels further aggravate the insulin resistant state in overweight
children and predispose them to type 2 diabetes and cardiovascular
diseases in adulthood.
Human and animal studies suggest that
supplementation with magnesium improves
insulin-mediated glucose
disposal and insulin secretion [13-15]. In one small (n=25)
pediatric study by Huerta, et al. [16], overweight children had
lower serum levels as well as lower calorie-adjusted intake of magnesium
compared to normal weight children. However, we found the unadjusted as
well as calorie-adjusted dietary intake of magnesium to be higher in the
overweight group, which was even greater than the RDA for magnesium
(140-290 mg/day).We postulate that the lower serum levels of magnesium
in our overweight group in spite of a higher dietary intake might be due
to either decreased absorption or increased excretion of magnesium.
Increased fractional excretion of magnesium in urine in patients with
type 2 DM, hypertension and obesity has been previously reported in
adults [17]. Association of lower serum magnesium levels with BMI,
systolic and diastolic BP, WC and serum insulin level in our study
suggests that the origin of the association of insulin resistant state
with low serum magnesium starts in childhood itself.
Acknowledgments: Dr Arvind Bagga and Dr
Shinjini Bhatnagar for critical evaluation and suggestions. Mrs M
Kalaivani for statistical analysis.
Contributors: BJ: patient enrolment, data
acquisition, data analysis and drafting of manuscript; VJ:
concept and design, data acquisition, analysis, drafting and critical
review of the manuscript. She will serve as guarantor of the study; NV:
data analysis and interpretation, laboratory analysis and critical
revision of the manuscript; AA: data acquisition, data analysis
and interpretation; SS: laboratory analysis and interpretation of
lab results.
Funding: ICMR, New Delhi and International Atomic
Energy Agency, Vienna;
Competing interests: None stated.
What is Already Known
• Serum and intracellular magnesium is low in
obese and hypertensive adults.
What This Study Adds?
• Overweight children have lower serum
magnesium levels compared to normal weight children.
• Serum magnesium has a significant inverse
correlation with waist circumference.
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