Insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to cardiovascular disease biomarkers in obese adolescents

Abstract

Context Insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-1 have been linked to cardiovascular disease (CVD) risk and pathophysiology in adults, but there are limited data in youth. Objective The aim of the study was to examine the relationship between IGF and IGFBP-1 with traditional and non-traditional CVD risk factors including inflammatory markers and body composition in an obese pediatric cohort. Design A cross-sectional study. Setting The study was carried out at a university children’s hospital. Subjects Sixty-one obese non-diabetic adolescents. Outcomes Fasting IGF-I, IGFBP-1, lipoprotein profiles, high-sensitivity C-reactive protein (hsCRP), and total adiponectin as well as insulin sensitivity measures, blood pressure (BP), and anthropometrics. Results IGFBP-1 was negatively associated with insulin sensitivity measures, body mass index (BMI), and diastolic BP in males. IGF-I was negatively associated with hsCRP (r = −0.479, p < 0.0005), and IGFBP-1 was positively associated with adiponectin (r = 0.545, p < 0.0005). The IGF-I/CRP and IGFBP-1/adiponectin associations remained significant when controlling for both BMI and insulin sensitivity index (SI). Both IGF-I and IGFBP-1 were negatively associated with waist circumference (r = −0.327 and r = −0.275, respectively) and sagittal abdominal diameter (r = −0.333 and r = −0.371, respectively), while IGFBP-1 was negatively associated with fat mass (r = −0.347, p = 0.01) as well as neck circumference and fat-free mass in males. Controlling for BMI z-score and SI, IGFBP-1 remained negatively associated with diastolic blood pressure (r = 0.706, p = 0.001 and neck circumference (r = −0.548, p = 0.15) in males. Conclusions IGF-I and IGFBP-1 associate with CVD risk markers and may add to clinical assessments of cardiometabolic dysfunction in youth.

A Functional Interplay between IGF-1 and Adiponectin

“…When the relationship of cardiac parameters with IGF-1 or adiponectin was explored in patients with severe obesity, Sirbu et al reported the negative association of adiponectin and the positive association of IGF-1 with the left ventricular mass (LVM) [ 95 ]. On the other hand, in obese adolescents, it has been recently reported that IGF-1 and IGFBP-1 are negatively associated with traditional CV disease biomarkers and IGFBP-1 is positively associated with adiponectin [ 96 ].…”

Marcadores de riesgo cardiovascular en niños menores de 10 años y su relación con niveles séricos de IGF-1, IGFBP-1, IGFBP-2 e IGFBP-3

“…41 IGF-1 production in response to an increased number of adipocytes may play a role in the decreased output of GH observed in patients who suffer from obesity. 20,42,43 However, this decrease in the secretion of this hormone is not associated with an alteration in the speed of growth, since obese children usually have a normal or even increased height for their age; for example, in this study, the obese group was 7cm taller than children of similar age with adequate weight.…”

“…18 Circulating concentrations of this protein are high during fasting, malnutrition and both types of diabetes, and are low in overweight cases. 19,20 There is also evidence that suggests that IGFBP-1 is a useful predictive marker of CVD risk given its relationship with BMI, circulating proinsulin levels, MS, 21 IR 11,17,22 and even fatty liver. 9,16 On the other hand, IGFBP-2 is a biomarker that allows identifying IR and high CVD risk in adults.…”

“…Moreover, several studies have described an increase in IGF-1 and IGFBP-3 levels in overweight and obese adolescents. 15,19,20 This protein appears to have an antiproliferative action in vascular smooth muscle cells, 11 which inhibits the formation of atheromatous plaque.…”

Insulin-Like Growth Factors and Metabolic Syndrome in Obese Children

“…In childhood, IGF-I has been connected to cardiovascular risk markers in nondiabetic obese adolescents [9], and low IGF-I levels were found in obese Chinese children with low high-density lipoprotein cholesterol (HDL-c) levels [10]. …”