Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome

Background: Ghrelin. a peptide mainly derived from the stomach, plays a pivotal role in the regulation of food intake, energy metabolism, and storage, as well as in insulin sensitivity Ghrelin circulates in acylated (A-Ghr) and nonacylated (NA-Ghr) forms. and their potential differential associations with insulin resistance (IR) in childhood obesity remain undefined. Objective: We investigated the associations of ghrelin forms with IR in normal weight and obese children and the impact of metabolic syndrome (MS) on their plasma values. Design. A total of 210 children in four subgroups of normal weight/obese children with and without components of MS were studied. Fasting blood glucose, insulin, lipid profile, and acylated and total ghrelin were examined IR was determined by a homeostasis model assessment (HOMA) of IR. Results: In the entire population, plasma insulin and HOMA-IR were associated negatively with T-Ghr and NA-Ghr, but positively with the ratio of A/NA-Ghr after adjustment for age, gender, and Tanner stage. Obese metabolically abnormal children had lower T-Ghr and NA-Ghr, but comparable A-Ghr and a higher A/NA-Ghr ratio than obese metabolically normal subjects Compared with lean healthy children. lean metabolically abnormal subjects had higher A-Ghr and the A/NA-Ghr ratio, but comparable T-Ghr and NA-Ghr. A multiple regression analysis showed that A-Ghr and the A/NA-Ghr ratios were positively associated with HOMA-IR, independent of age, gender, Tanner stage, and body mass index (or waist circumference) and other components of MS. Conclusions: A-Ghr excess may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of IR and MS.