Circulating IGF-1 Independently Predicts Blood Pressure in Children With Higher Calcium-Phosphorus Product Levels.

OBJECTIVE: To study the association between insulin-like growth factor 1 (IGF-1) and blood pressure in children, in particular, the potential interaction with the serum calcium-phosphorus product (Ca*P). METHODS: A longitudinal study included 521 children (age 8.8 ± 0.1) from northeastern Spain, of whom 158 were followed-up after 5 years. IGF-1, insulin-like growth factor-binding protein 3 (IGFBP-3), and serum calcium and phosphorus were measured at baseline. Anthropometric (body-mass index [BMI] and waist) and cardiometabolic variables (systolic [SBP] and diastolic blood pressure), pulse pressure, insulin, homeostatic model assessment of insulin resistance [HOMA-IR], high-density lipoprotein [HDL]-cholesterol, and triglycerides) were assessed at baseline and at the end of follow-up. Statistical analysis included Pearson correlations followed by multivariable linear regression analyses. RESULTS: Baseline IGF-1 and IGF-1/IGFBP-3 molar ratio positively correlated with baseline and follow-up BMI, waist, SBP, pulse pressure, insulin, HOMA-IR and triglycerides (r 0.138-0.603; all P < 0.05). The associations with SBP were stronger with increasing Ca*P (r 0.261-0.625 for IGF-1; and r 0.174-0.583 for IGF-1/IGFBP-3). After adjusting for confounding variables, baseline IGF-1 and IGF-1/IGFBP-3 remained independently associated with both baseline and follow-up SBP in children in the highest Ca*P tertile (ß = 0.245-0.381; P < 0.01; model R2 = 0.246-0.566). CONCLUSIONS: Our results suggest that IGF-1 in childhood is an independent predictor of SBP in apparently healthy children, especially in those with high Ca*P levels.

Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study.

BACKGROUND: Metformin treatment (1000-2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR). We aimed to ascertain if long-term treatment (24 months) with lower doses of metformin (850 mg/day) normalizes the endocrine-metabolic abnormalities, improves body composition, and reduces the carotid intima-media thickness (cIMT) in pre-puberal and early pubertal children with obesity. METHODS: A pilot double-blind, placebo-controlled trial was conducted on 18 pre-puberal and early pubertal (Tanner stage I-II) children with obesity and risk markers for metabolic syndrome. Patients were randomly assigned (1:1) to receive metformin (850 mg/day) or placebo for 24 months. Clinical, biochemical (insulin, lipids, leptin, and high-sensitivity C-reactive protein [hsCRP]), and imaging (body composition [dual-energy X-ray absorptiometry and magnetic resonance imaging]) parameters as well as cIMT (ultrasonography) were assessed at baseline and at 6, 12, and 24 months. RESULTS: The 12-month treatment tend to cause a reduction in weight standard deviation scores (SDS), BMI-SDS, leptin, leptin-to-high-molecular-weight (HMW) adiponectin ratio, hsCRP, cIMT, fat mass, and liver fat in metformin-treated children compared with placebo. The effect of metformin on the reduction of BMI-SDS, leptin, leptin-to-HMW adiponectin ratio, hsCRP, and liver fat seemed to be maintained after completing the 24 months of treatment. No changes in insulin sensitivity (HOMA-IR) or adverse effects were detected. CONCLUSION: In this pilot study, metformin treatment in pre-puberal and early pubertal children with obesity seemed to improve body composition and inflammation markers. Our data encourage the development of future fully powered trials using 850 mg/day metformin in young children, highlighting its excellent tolerance and potential long-term benefits.