Abstract
BackgroundIn recent years, the exciting emergence of circulating miRNAs as stable, reproducible, and consistent among individuals has opened a promising research opportunity for the detection of non-invasive biomarkers. A firm connection has been established between circulating miRNAs and glycaemic as well as metabolic homeostasis, showing that levels of specific miRNAs vary under different physio-pathological conditions.ObjectiveIn this pilot study, we investigated the expression of candidate miRNAs, hsa-miR-191-3p and hsa-miR-375, in relation to biomarkers associated with insulin sensitivity in a subgroup (n=58) of subjects participating to the European I.Family Study, a project aimed to assess the determinants of eating behaviour in children and adolescents and related health outcomes. The sample included overweight/obese children/adolescents since overweight/obesity is a known risk factor for impaired glucose homeostasis and metabolic disorders. Biological targets of candidate miRNAs were also explored in silico.ResultsWe observed a significant association of the two miRNAs and early changes in glycaemic homeostasis, independent of covariates including country of origin, age, BMI z-score, puberty status, highest educational level of parents, total energy intake, energy from fats, energy from carbohydrates, and energy from proteins.ConclusionIdentification of circulating miRNAs associated with insulin impairment may offer novel approaches of assessing early variations in insulin sensitivity and provide evidence about the molecular mechanisms connected to early changes in glycaemic homeostasis.Trial registrationISRCTN, ISRCTN62310987. Retrospectively registered, http://isrctn.com/ISRCTN62310987
Highlights
In recent years, the exciting emergence of circulating miRNAs as stable, reproducible, and consistent among individuals has opened a promising research opportunity for the detection of non-invasive biomarkers
We observed a significant association of the two miRNAs and early changes in glycaemic homeostasis, independent of covariates including country of origin, age, Body mass index (BMI) z-score, puberty status, highest educational level of parents, total energy intake, energy from fats, energy from carbohydrates, and energy from proteins
Identification of circulating miRNAs connected with insulin resistance would have the potential to offer innovative methods of assessing insulin sensitivity to detect prediabetes and provide further evidence about the underlying molecular mechanisms connected to insulin impairment
Summary
The exciting emergence of circulating miRNAs as stable, reproducible, and consistent among individuals has opened a promising research opportunity for the detection of non-invasive biomarkers. Insulin resistance is a pathological condition in which the body’s cells become resistant to the effects of insulin [1] This condition is strictly interconnected to the disruption of the hormone-signalling pathway, which may include either defects in pancreatic insulin secretion or failure of target cells to uptake and metabolize glucose in response to insulin, or both conditions [2]. Dysregulation in insulin signalling is among the typical and earliest metabolic signs predisposing to the development of type 2 diabetes (T2D) [4, 5]. This latter condition is a less defined disorder since clinical features of T2D are not commonly perceived until pancreatic islets start to fail, and clinical diagnosis is delayed until systemic complications start and irreversible damage has already occurred. T2D represents a major health concern since its prevalence has been dramatically increased for the last decade [7], accounting for 90–95% of total diabetes worldwide, in adults and in children [8]
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