Discussion
The prevalence of IR observed in our study (42.3%) is very close to
that reported by Arshi et al (42.9%) in an Australian population, using
the same cut off of HOMA-IR ≥1.77 9. Literature on IR
in Indian children is scarce. A recent study reporting on Indian
children with asthma, aged 6-18 years, estimated the prevalence to be
15.5% 24. The study had used a HOMA-IR value of 2.5,
which has been suggested to be more accurate for the Indian population23. Applying the same threshold, the prevalence of IR
in our population comes to 20.5%, which is comparable. Unfortunately,
our study did not include a control group. Overall, the median HOMA-IR
in our cohort of children with asthma was lower than the average
reported in a study conducted in schoolchildren aged 6 to 16 years, in
the eastern part of the country 25. However, in the
latter study, 28.2% participants were overweight and obese, compared to
only 10.8% in our population. In addition, there might be other factors
accounting for the difference, like a differential distribution of
post-pubertal children, as HOMA-IR values have been shown to increase
with increase in sexual maturation 23.
IR has been suggested to be an early biochemical marker of MS,
developing at age 18-19 years 26. We, therefore,
believe our result to be significant because relying on anthropometry
alone, the risk of developing MS in our population would appear to be
lower. If the prevalence of IR in Indian children with asthma is
confirmed to be as high in larger studies, this might indicate the need
to adopt stricter lifestyle measures in early adolescence.
The prevalence of dyslipidemia in our study was 86.7% (79.4-94.0%).
The high prevalence was predominantly because of commonly observed low
HDL-C in our study subjects, seen in 80.7% (72.2-89.2%). In a
population of 695 Indian urban adolescents, in the age group of 10-18
years, low HDL-C was reported in 27.3% 27. One reason
for our group to have a low HDL-C could be the higher proportion of
males, as it has been shown that boys typically show a sudden decline
the HDL-C levels around the pubertal age, compared to females28. We believe it is extremely unlikely that asthma
alone would be responsible for such a drastic abnormality.
Only one child in our study fulfilled the criteria for MS. Similarly, in
another Indian cohort of 90 children, only two had MS24. Ross et al found 12 children to qualify for
presence of MS in a group of 116 children with asthma12. However, contrary to Ross’s study where 52
children (44.8%) were obese, none of the children sampled in our study
were obese. This might possibly explain the observed low prevalence of
MS in our study. However, as previously stated, we believe that a higher
proportion of children, who have IR currently might be at risk for
developing MS later.
Studies have shown that among children & adolescents with asthma, IR
and MS are associated with higher bronchial hyperresponsiveness and
severe asthma 7,29. Also, dyslipidemia has been shown
to be associated with higher airway resistance measured by forced
oscillation technique 30. We hypothesized that it
might be possible to demonstrate an association between metabolic
parameters and asthma symptom control. To test this, we compared the
groups with controlled, partly controlled, and uncontrolled asthma.
While there was no statistically significant difference in median
HOMA-IR of the groups, there was a significant increasing trend in serum
insulin level, associated with poorer asthma control. There was a
similar association seen with presence of IR, defined as HOMA-IR ≥2.5.
Further, we performed a similar comparison for lipid levels and there
was a significant increase in serum TG and LDL-C with poorer control.
The association of poor asthma control with fasting serum insulin,
presence of insulin resistance (HOMA-IR ≥2.5) and serum TG persisted
after adjusting for BMI. Simply put, children with asthma who had higher
fasting serum insulin, higher serum TG or HOMA-IR ≥2.5 were at a higher
risk of having a poorer asthma control, irrespective of their BMI.
These results show that metabolic derangements are directly associated
with clinically relevant outcomes like asthma symptom control. To the
best of our knowledge, this is the first study demonstrating a
correlation between lipid profile and asthma control in children.
Unfortunately, the current study design doesn’t permit further
delineation between association and causality. It might be worthwhile to
explore these metabolic parameters in children with poor asthma control
and see if treatment addressing these has a beneficial effect on asthma
symptoms.
We also explored correlations between metabolic parameters and
spirometry indices (table 3) and found a weak negative correlation
between lipid levels and PEFR. The correlation was not significant
statistically on adjusting for height. Similar negative correlations
with metabolic markers have been reported by a few pediatric studies but
the results are not consistent and have often lacked confidence24,31,32. The most likely explanation for the same is
that there are several mechanical and non-mechanical factors influencing
lung function, and consequently the effect of a single metabolic
parameter might not be very strong.
Our study is unique because we have focused on the relationship between
metabolic derangements and clinically useful outcomes like symptom
control, which are helpful in clinical decision making. Our group
included children with physician diagnosed asthma rather than relying on
self-reported symptoms. We used population specific standards for
anthropometry, blood pressure centiles and spirometry indices.
We acknowledge a few limitations in our study. Of the initially enrolled
97 children, only 83 reported for sampling. There was disproportionate
representation of the genders with boys predominating. As there was no
control population, prevalence of metabolic derangements could not be
compared to that in healthy children. Also, the cross-sectional design
prevents us from exploring the temporal association and hence, causality
between poor symptom control and metabolic abnormalities.