Our study identifies circulating miR-200c-3p, miR-190a and miR-95 as biomarkers of insulin resistance in obese preschoolers, being differentially regulated in IR patients both in fasting condition and after the OGTT. Expression of some circulating miRNAs seems reflecting glucose and insulin excursion following the OGTT differently in controls and IR obese preschoolers.

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IMPORTANCETo date, the relationship among adiposity, insulin resistance, and cardiovascular risk factors at the onset of overweight or obesity has been unexplored.OBJECTIVES To assess whether insulin resistance and metabolic abnormalities are detectable at the onset of obesity and to unravel the interplay among adiposity, insulin resistance, and other such abnormalities. DESIGN, SETTING, AND PARTICIPANTSThe Origin of Cardiovascular Risk in Overweight Preschool Children cohort study aimed to evaluate at the onset of obesity in preschool children the prevalence of metabolic abnormalities, including hypertension, dyslipidemia, impaired carbohydrate metabolism, and nonalcoholic fatty liver disease. Between July 1, 2011, and July 30, 2012, in the Rome municipality, 13 family pediatricians enrolled healthy children (age range, 2.0-5.8 years) in the study during their routine practice of growth monitoring. Clinical medical records of 5729 children were reviewed; 597 children manifested new-onset overweight or obesity as their body mass index changed from normal weight to overweight or obesity in the previous 12 months according to the International Obesity Task Force classification. Of them, 219 were studied. MAIN OUTCOMES AND MEASURESPatients with new-onset overweight or obesity underwent clinical laboratory testing, including oral glucose tolerance test, and ultrasonographic investigations of fatty liver and intimal medial thickness of the common carotid arteries, subcutaneous adipose tissue, and visceral adipose tissue. The homeostatic assessment model algorithm-insulin resistance was calculated. RESULTS Among the entire population (n = 5729), overweight increased from 7.0% at 2.0 years to 16.9% at 5.8 years, with corresponding figures of 1.1% to 2.9% for obesity. In total, 597 overweight or obese children (10.4%) were identified, and 219 of them (36.7%) were studied. Among the latter, 86 patients (39.3%) had at least 1 metabolic abnormality. Hypertension was diagnosed in 29 patients (13.2%), dyslipidemia in 55 patients (25.1%), impaired fasting glucose level in 7 patients (3.2%), and glucose intolerance in 6 patients (2.7%). Nonalcoholic fatty liver disease was diagnosed in 68 patients (31.1%).CONCLUSIONS AND RELEVANCE Cardiometabolic risk factors, including fatty liver, are detectable in preschoolers at the onset of overweight or obesity, despite short-term exposure to excess weight and reduced insulin sensitivity. Our findings suggest the need to screen for cardiometabolic abnormalities at an earlier age than is now recommended.

Though exclusive formula or mixed feeding represents an age-specific risk factor for overweight/obesity, lifestyle factors associated with increased risk in Italian preschoolers include habits that are common to school-age children, such as skipping breakfast and consumption of sugar-sweetened beverages. The reduced consumption of meat emerged as a risk factor for overweight/obesity, but future research is required to better understand this relationship. Our data suggest, on the whole, that prevention of such unhealthy behaviors must be pursued in preschoolers by means of age-specific interventions.