Asthma and insulin resistance in children

Arshi, Mandana; Cardinal, John; Hill, Rebecca J.; Davies, Peter S. W.; Wainwright, Claire

doi:10.1111/j.1440-1843.2010.01767.x

Cited by 83 publications

(70 citation statements)

References 37 publications

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“…122 Our review of the recent literature highlights that metabolic dysregulation plays a role in pediatric obesity-related asthma (Table 3). Higher prevalence 124 and degree of insulin resistance 22 and higher prevalence of its surrogate marker, acanthosis nigricans, 23 and metabolic syndrome, 25 have been reported among children with asthma compared with their nonasthmatic counterparts. Insulin resistance correlates with the proinflammatory markers leptin and IL-6 124 and is found to be a predictor of both lower airway obstruction and reduced lung volumes, 2 distinct measures of lung function deficits, independent of general and truncal adiposity.…”

Section: Association With Insulin Resistancementioning

confidence: 99%

“…Higher prevalence 124 and degree of insulin resistance 22 and higher prevalence of its surrogate marker, acanthosis nigricans, 23 and metabolic syndrome, 25 have been reported among children with asthma compared with their nonasthmatic counterparts. Insulin resistance correlates with the proinflammatory markers leptin and IL-6 124 and is found to be a predictor of both lower airway obstruction and reduced lung volumes, 2 distinct measures of lung function deficits, independent of general and truncal adiposity. 34 Systemic inflammation, associated with insulin resistance, may be one of the mechanisms through which insulin resistance contributes to impaired lung function and asthma phenotype.…”

Section: Association With Insulin Resistancementioning

confidence: 99%

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Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

2016

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The burden of obesity-related asthma among children, particularly among ethnic minorities, necessitates an improved understanding of the underlying disease mechanisms. Although obesity is an independent risk factor for asthma, not all obese children develop asthma. Several recent studies have elucidated mechanisms, including the role of diet, sedentary lifestyle, mechanical fat load, and adiposity-mediated inflammation that may underlie the obese asthma pathophysiology. Here, we review these recent studies and emerging scientific evidence that suggest metabolic dysregulation may play a role in pediatric obesity-related asthma. We also review the genetic and epigenetic factors that may underlie susceptibility to metabolic dysregulation and associated pulmonary morbidity among children. Lastly, we identify knowledge gaps that need further exploration to better define pathways that will allow development of primary preventive strategies for obesity-related asthma in children.

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Section: Association With Insulin Resistancementioning

confidence: 99%

Section: Association With Insulin Resistancementioning

confidence: 99%

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

2016

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“…However, insulin resistance may also predispose to asthma independent of body mass index (5,(8)(9)(10)(11)(12). The frequency of asthma increases with increasing insulin resistance (as reflected by acanthosis nigricans [10] or by homeostatic model assessment of insulin resistance [11,12]) in children independent of body mass. Thus, insulin resistance and compensatory hyperinsulinemia may be one of the mechanisms that increase asthmatic symptoms in obese individuals.…”

mentioning

confidence: 99%

Hyperinsulinemia Potentiates Airway Responsiveness to Parasympathetic Nerve Stimulation in Obese Rats

Nie

Jacoby

Fryer

2014

Am J Respir Cell Mol Biol

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Obesity is a substantial risk factor for developing asthma, but the molecular mechanisms underlying this relationship are unclear. We tested the role of insulin in airway responsiveness to nerve stimulation using rats genetically prone or resistant to diet-induced obesity. Airway response to vagus nerve stimulation and airway M 2 and M 3 muscarinic receptor function were measured in obeseprone and -resistant rats with high or low circulating insulin. The effects of insulin on nerve-mediated human airway smooth muscle contraction and human M 2 muscarinic receptor function were tested in vitro. Our data show that increased vagally mediated bronchoconstriction in obesity is associated with hyperinsulinemia and loss of inhibitory M 2 muscarinic receptor function on parasympathetic nerves. Obesity did not induce airway inflammation or increase airway wall thickness. Smooth muscle contraction to acetylcholine was not increased, indicating that hyperresponsiveness is mediated at the level of airway nerves. Reducing serum insulin with streptozotocin protected neuronal M 2 receptor function and prevented airway hyperresponsiveness to vagus nerve stimulation in obese rats. Replacing insulin restored dysfunction of neuronal M 2 receptors and airway hyperresponsiveness to vagus nerve stimulation in streptozotocintreated obese rats. Treatment with insulin caused loss of M 2 receptor function, resulting in airway hyperresponsiveness to vagus nerve stimulation in obese-resistant rats, and inhibited human neuronal M 2 receptor function in vitro. This study shows that it is not obesity per se but hyperinsulinemia accompanying obesity that potentiates vagally induced bronchoconstriction by inhibiting neuronal M 2 muscarinic receptors and increasing acetylcholine release from airway parasympathetic nerves.Keywords: hyperinsulinemia; obesity; asthma; airway responsiveness; neural M 2 muscarinic receptor Clinical RelevanceObesity-induced asthma does not respond well to traditional anti-inflammatory therapies, suggesting that it is a unique asthma phenotype. Here we show that hyperinsulinemia causes airway hyperresponsiveness to vagus nerve stimulation in obese rats. In human trachea and in rats, we demonstrate that insulin inhibits M 2 muscarinic receptors on airway parasympathetic nerves, resulting in increased acetylcholine release and increased airway contraction. Because hyperinsulinemia is greater and more prevalent in obese individuals, these data may explain why obese individuals are prone to asthma exacerbations and suggest that anticholinergic drugs may be effective in this specific phenotype of asthma.In the United States, 31% of adults and 15% of children are obese. In obese and overweight individuals, the prevalence of asthma (1-3) and the rate of new-onset asthma have increased (4-6). Obese patients with asthma also have increased severity of illness and reduced effectiveness of steroids compared with nonobese patients with asthma (1, 6, 7). The mechanisms by which obesity predisposes to asthma are unclear, limi...

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“…Conversely, atopic asthmatic children have lower resistin levels as compared to the nonatopic asthma and control groups (Kim et al, 2008). However, in a recent study (Arshi et al, 2010) in children of a similar age to those in the previous study (11 years) resistin levels were not different between a group of atopic asthmatics and a control group. In fact, its levels in the former study were about double than in the latter both in the control and in the atopic asthmatic groups.…”

Section: Resistinmentioning

confidence: 47%