A double-blind randomized trial of fish oil to lower triglycerides and improve cardiometabolic risk in adolescents.

OBJECTIVES: To determine the efficacy of 4 g/day fish oil to lower triglycerides and impact lipoprotein particles, inflammation, insulin resistance, coagulation, and thrombosis. STUDY DESIGN: Participants (n = 42, age 14 ± 2 years) with hypertriglyceridemia and low-density lipoprotein (LDL) cholesterol <160 mg/dL were enrolled in a randomized, double-blind, crossover trial comparing 4 g of fish oil daily with placebo. Treatment interval was 8 weeks with a 4-week washout. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, fibrinogen, plasminogen activator inhibitor-1, and thrombin generation were measured. RESULTS: Baseline lipid profile was total cholesterol 194 (5.4) mg/dL (mean [SE]), triglycerides 272 (21) mg/dL, high-density lipoprotein cholesterol 39 (1) mg/dL, and LDL cholesterol 112 (3.7) mg/dl. LDL particle number was 1614 (60) nmol/L, LDL size was 19.9 (1.4) nm, and large very low-density lipoprotein/chylomicron particle number was 9.6 (1.4) nmol/L. Triglycerides decreased on fish oil treatment but the difference was not significant compared with placebo (-52 ± 16 mg/dL vs -16 ± 16 mg/dL). Large very low-density lipoprotein particle number was reduced (-5.83 ± 1.29 nmol/L vs -0.96 ± 1.31 nmol/L; P < .0001). There was no change in LDL particle number or size. There was a trend towards a lower prothrombotic state (lower fibrinogen and plasminogen activator inhibitor-1; .10 > P > .05); no other group differences were seen. CONCLUSIONS: In children, fish oil (4 g/day) lowers triglycerides slightly and may have an antithrombotic effect but has no effect on LDL particles.

Obesity-related increased γ' fibrinogen concentration in children and its reduction by a physical activity-based lifestyle intervention: a randomized controlled study.

OBJECTIVE: To determine if elevated plasma γ'-fibrinogen, typically involved in the formation of fibrinolysis-resistant clots, confers an increased risk for cardiovascular disease (CVD) and thrombosis in children as it does in adults. Although obesity-related hyperfibrinogenemia is frequently reported in children, the role of γ' fibrinogen and its response to physical activity-based lifestyle are less clear in this population. STUDY DESIGN: In a randomized controlled 3-month physical activity-based lifestyle intervention, γ' fibrinogen concentration was measured in 21 children (aged 14-18 years; Tanner stage > IV), including 15 in the obese group and 6 in the normal weight group, with body mass index percentiles for age and sex of >95 and <85, respectively. RESULTS: The relationships between γ' fibrinogen and other risk factors for CVD, such as markers of insulin resistance and subclinical inflammation, along with body composition (as measured by dual-energy X-ray absortiometry), were assessed before and after the intervention. γ' fibrinogen concentration was higher in the obese group compared with the normal weight group (P < .05) and was correlated with other risk factors for CVD (adjusted R(2) = 0.9; P < .05), and insulin emerged as the major predictor of γ' fibrinogen. The intervention reduced γ'-fibrinogen concentration (P < .05). CONCLUSION: Our data reveal: (1) elevated γ' fibrinogen concentrations in obese insulin-resistant children compared with normal lean controls; (2) a relationship between γ' fibrinogen and other CVD risk factors; and (3) physical activity-induced reduction in γ' fibrinogen in obese children.

Biomarkers for cardiovascular risk in children.

PURPOSE OF REVIEW: The magnitude of lifetime risk of cardiovascular disease (CVD) has radically increased along with the high prevalence of obesity in children. The spotlight is now on dysfunctional adiposity as a precursor for the development of premature CVD. As full-blown CVD is not present in childhood, there is a critical need for surrogate markers to best assess, predict, and treat the children who are vulnerable to developing CVD. RECENT FINDINGS: Accumulation of excess fat mass can be conceived as a derangement in the balance between energy intake and expenditure. This appears to provoke various structural and metabolic alterations leading to adipocyte dysfunction, with important cardiovascular health consequences. Subclinical inflammation, insulin resistance, oxidative stress, and endothelial dysfunction appear to play important roles early in the clinical course of obesity. SUMMARY: Associations between biomarkers and noninvasive measures of early atherosclerosis in children continue to emerge and several biomarkers appear to be promising. At present, there are no explicit data to recommend any of these biomarkers as a routine clinical marker of CVD in children. More work is needed to validate these biomarkers and to improve understanding of their role in CVD risk prediction in the pediatric population.

Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association.

The rapid increase in the prevalence and severity of obesity in children is likely to lower the age of onset and increase the incidence of cardiovascular disease worldwide. Understanding the pathophysiology and improving the clinical management of cardiovascular disease involve a knowledge of novel risk factors and biomarkers. The clinical and mechanistic roles of these novel biological factors during childhood are currently being investigated. The goals of this scientific statement are to present the existing knowledge and theoretical framework of nontraditional risk factors for cardiovascular disease as they relate to children and adolescents, to describe the relevance and weight of available experimental and clinical evidence and the therapeutic implications pertaining to nontraditional risk factors in the pediatric population, and to stimulate further research with a goal of developing valid and reliable approaches to identify and validate novel risk factors that will aid in the clinical evaluation and perhaps prediction of cardiovascular disease in the pediatric population. Although several biomarkers are promising, substantial research is required before nontraditional risk factors can be used to identify and reduce cardiovascular disease risk in children and adolescents.

Insulin resistance and adiposity in relation to serum ß-carotene levels.

OBJECTIVE: To determine the effects of placebo vs an encapsulated supplement of fruit and vegetable juice concentrate (FVJC) on serum ß-carotene levels, insulin resistance, adiposity, and subclinical inflammation in boys. STUDY DESIGN: Thirty age-matched prepubertal boys (9 lean and 21 overweight (OW); age range, 6-10 years) were studied. All participants received nutrition counseling and were randomized to receive FVJC or placebo capsules for 6 months. Total cholesterol, triglycerides, lipid corrected ß-carotene, serum retinol, glucose, insulin, retinol binding protein-4, leptin, adiponectin, leptin-to-adiponectin ratio, high-sensitivity C-reactive protein, and interleukin-6 were measured before and after the 6-month intervention. Homeostasis model assessment-insulin resistance (HOMA-IR), acute insulin response to intravenous glucose, along with abdominal fat mass (dual-energy x-ray absorptiometry) were also determined. RESULTS: Baseline ß-carotene concentrations correlated inversely with HOMA-IR, leptin-to-adiponectin ratio, and abdominal fat mass (P ≤ .01). FVJC intake increased ß-carotene concentrations (P ≤ .001) but did not influence retinol or retinol binding protein-4. Retinol insufficiency <1.047 µM was present in 18% of the entire cohort at baseline and in 37% at 6 months. HOMA-IR decreased after supplementation in the OW cohort, when adjusted for percent weight change (P = .014). The percent change in abdominal fat mass increased in the placebo group and decreased in the FVJC group (P = .029). CONCLUSIONS: A 6-month supplementation with FVJC in the presence of nutritional counseling was associated with an increase in serum ß-carotene concentrations and a reduction in adiposity in conjunction with an improvement in insulin resistance in OW boys.

Effects of surgically induced weight loss by Roux-en-Y gastric bypass on osteocalcin.

BACKGROUND: Osteocalcin (OC), a protein synthesized by osteoblasts, is a marker of bone turnover with undercarboxylated OC (ucOC) being involved in glucose homeostasis. Although laparoscopic Roux-en-Y gastric bypass (LRYGB)-induced weight loss likely alters bone turnover, data on markers of bone turnover remain less clear. The aim of this study was to examine the effect of surgically induced weight loss on OC and ucOC. METHODS: A total of 32 individuals with a body mass index 50.2±10.2 kg/m(2) underwent LRYGB. Osteocalcin, ucOC, other blood analytes (e.g., vitamin D, leptin, total and high-molecular-weight adiponectin), and homeostasis model assessment for insulin resistance were measured before and after weight loss. The effect of an acute nutrient load on OC parameters after a mixed meal tolerance test also was assessed. RESULTS: Six months after surgery, there was an increase in OC (17.8±7.4 [mean±SD] [baseline] versus 31.5±9.8 ng/mL [follow-up]; P<.001) and ucOC (7.3±6.2 versus 18.5±8.9 ng/mL; P<.001). Although adiponectin increased, only the magnitude of change in OC and leptin was correlated (r =-.43; P = .017). After weight loss, an acute nutrient load reduced OC (31.5±9.8 [0-hour] versus 29.6±8.2 [2-hour] ng/mL; P = .024), whereas ucOC was higher (18.8±9.3 [0-hour] versus 21.1±8.6 [2-hour] ng/mL; P< .001). CONCLUSION: Surgically induced weight loss was associated with increases in OC and ucOC. Underlying mechanisms are unclear, but change in OC may be related to change in leptin. After a nutrient load, the increase in ucOC suggests a potential role as a short-term compensatory regulator of glucose homeostasis.

Changes in circulating satiety hormones in obese children: a randomized controlled physical activity-based intervention study.

The aims of this study are to examine in children: (i) obesity-related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity-based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 +/- 0.6 for 15 obese and 56.2 +/- 1.1 for 6 lean). The obese subjects underwent a 3-month randomized controlled physical activity-based lifestyle intervention. Leptin, soluble leptin receptor (sOB-R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual-energy X-ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB-R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB-R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity-based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.