Insulin and Insulin Resistance Index are Not Independent Determinants for the Variation in Leptin in Obese Children and Adolescents

Abstract

Recent findings have questioned the independent influence of insulin on leptin. We studied whether insulin contributes to leptin in obese children, independent of confounding parameters, such as total adiposity, fasting insulin resistance index, and fat free mass. In 100 obese boys and 103 obese girls, blood levels of leptin, insulin, glucose, and triglycerides were determined. The fasting insulin resistance index (FIRI) was calculated, and body composition was assessed by means of impedance. Leptin and glucose were higher in girls, and all estimates of adiposity were significantly associated with leptin. However, when adjusted for adiposity, the relationship between insulin and leptin, and also between FIRI and leptin, remained significant in boys and girls (p<0.05). Although several regression models were tested, neither insulin nor FIRI were found to contribute significantly and independently to leptin. BMI together with triglycerides and FFM were the main determinants for the variation in leptin in boys (adj. R2=0.46, p<0.0001). In girls, BMI explained a great magnitude of the variation in leptin (adj. R2=0.60, p<0.0001). These findings indicate that in the state of childhood and adolescent obesity, total adiposity but not insulin or insulin resistance index is the main determinant for leptin. In contrast to obese girls, the fat free mass and triglycerides contribute significantly to the variation in leptin in obese boys. The biological significance for these findings should be elucidated in longitudinal studies.

Leptin responses to insulin administration in children with short stature

“…Our observation of a positive correlation between plasma leptin levels and IGF-1 in children with short stature complements previous studies in prepubertal [31] and peripubertal [32] children and in children with severe malnutrition [33]. As it has been demonstrated that body fat mass is a main determinant for plasma leptin levels [4,5,19,28,34] and IGF-1 is positively correlated with nutritional status [23,35], the close relationship between plasma leptin levels and IGF-1 can be explained. This finding is supported by our data demonstrating higher IGF-1 levels in patients with higher BMI.…”

“…Since the discovery of leptin, the understanding of its physiological role has evolved from a satiety signal to that of an integrative hormone that responds to and regulates different endocrine pathways with direct metabolic effects on peripheral tissues [2][3][4][5].…”

Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

“…However, conflicting results are published about the dependent versus independent associations between body fatness, leptin levels, and insulin resistance in obese children. [51–53] A clearer understanding of the leptin-obesity–insulin resistance relationship is still required during childhood and adolescence relative to the development of risk factors and type 2 diabetes.…”

Leptin is not associated independently with hypertension in Japanese-Brazilian women

“…The association of hypertension with hyperinsulinemia was documented in some (18) but not all studies (19). Controversies also exist regarding an association between hypertension and leptin levels (20)(21)(22)(23)(24)(25)(26)(27)). …”

“…An association between hyperleptinemia and hypertension has been found in obese subjects at risk for metabolic syndrome (2,8,(27)(28)(29). Most studies regarding the involvement of hormonal factors in the genesis of hypertension include obese subjects.…”