Tracking and determinants of LDL particle size in healthy children from 7 to 11 years of age: the STRIP Study.

Serum low-density lipoprotein (LDL) particle composition varies according to lifestyle and age. To analyze its long-term tracking, we studied LDL particle size consecutively in 100 children at the ages of 7, 9 and 11 years using a high-resolution 3% polyacrylamide gel tube, electrophoresis method, searching also for long-term determinants of the particle size. The mean LDL particle sizes at 7 and 9 years, and at 7 and 11 years correlated directly (r=0.72 and 0.39, respectively). The probability that children would remain in the same LDL particle size tertile between 7 and 11 years of age was 48% (p=0.008). Longitudinally, total, high-density lipoprotein (HDL) and LDL cholesterol concentrations and body mass index (BMI) associated directly with mean LDL particle size, and triglyceride concentration and triglyceride/HDL cholesterol ratio correlated inversely. A shift from pre-puberty to puberty was associated with an increase in LDL particle size. Sex, serum insulin concentration, or energy nutrient intakes did not associate with LDL particle size. In conclusion, although mean LDL particle size tracks in 7- to 11-year-old healthy children, changes in serum triglycerides, HDL, LDL, and total cholesterol concentration, BMI, and pubertal status all modify LDL particle size.

Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial.

BACKGROUND: In mouse models of diabetes, prophylactic administration of insulin reduced incidence of the disease. We investigated whether administration of nasal insulin decreased the incidence of type 1 diabetes, in children with HLA genotypes and autoantibodies increasing the risk of the disease. METHODS: At three university hospitals in Turku, Oulu, and Tampere (Finland), we analysed cord blood samples of 116 720 consecutively born infants, and 3430 of their siblings, for the HLA-DQB1 susceptibility alleles for type 1 diabetes. 17 397 infants and 1613 siblings had increased genetic risk, of whom 11 225 and 1574, respectively, consented to screening of diabetes-associated autoantibodies at every 3-12 months. In a double-blind trial, we randomly assigned 224 infants and 40 siblings positive for two or more autoantibodies, in consecutive samples, to receive short-acting human insulin (1 unit/kg; n=115 and n=22) or placebo (n=109 and n=18) once a day intranasally. We used a restricted randomisation, stratified by site, with permuted blocks of size two. Primary endpoint was diagnosis of diabetes. Analysis was by intention to treat. The study was terminated early because insulin had no beneficial effect. This study is registered with ClinicalTrials.gov, number NCT00223613. FINDINGS: Median duration of the intervention was 1.8 years (range 0-9.7). Diabetes was diagnosed in 49 index children randomised to receive insulin, and in 47 randomised to placebo (hazard ratio [HR] 1.14; 95% CI 0.73-1.77). 42 and 38 of these children, respectively, continued treatment until diagnosis, with yearly rates of diabetes onset of 16.8% (95% CI 11.7-21.9) and 15.3% (10.5-20.2). Seven siblings were diagnosed with diabetes in the insulin group, versus six in the placebo group (HR 1.93; 0.56-6.77). In all randomised children, diabetes was diagnosed in 56 in the insulin group, and 53 in the placebo group (HR 0.98; 0.67-1.43, p=0.91). INTERPRETATION: In children with HLA-conferred susceptibility to diabetes, administration of nasal insulin, started soon after detection of autoantibodies, could not be shown to prevent or delay type 1 diabetes.

Impact of repeated dietary counseling between infancy and 14 years of age on dietary intakes and serum lipids and lipoproteins: the STRIP study.

BACKGROUND: Atherosclerosis development might be delayed or prevented by dietary measures. The aims of the present study were to evaluate the effect of low-saturated-fat, low-cholesterol dietary counseling on fat intakes, growth, serum cholesterol values, and pubertal development in children and adolescents. METHODS AND RESULTS: In the randomized prospective Special Turku Coronary Risk Factor Intervention Project (STRIP), a low-saturated-fat, low-cholesterol diet was introduced to intervention infants (n=540) at 7 months of age, and control children (n=522) received an unrestricted diet. Dietary intakes, serum cholesterol values, somatic growth, and development were followed up throughout childhood and adolescence. Saturated fat intakes, serum total cholesterol, and low-density lipoprotein cholesterol values were lower (P<0.001) in the intervention than in control children during the 14 years, whereas high-density lipoprotein cholesterol values in the 2 study groups showed no difference. Boys had lower total and low-density lipoprotein cholesterol concentrations than girls throughout childhood (P<0.001), and the intervention effect on serum cholesterol concentration was larger in boys than girls. The 2 study groups showed no difference in growth, body mass index, pubertal development, or age at menarche (median, 13.0 and 12.8 years in the intervention and control girls, respectively; P=0.52). The cholesterol values decreased as puberty progressed. Mean concentrations of total and high-density lipoprotein cholesterol decreased from approximately 4.5 and approximately 1.4 mmol/L, respectively, in Tanner stage 1 (prepubertal) boys to approximately 3.9 and approximately 1.1 mmol/L in Tanner stage 4 (late pubertal) boys. CONCLUSIONS: Repeated dietary counseling remains effective in decreasing saturated fat and cholesterol intake and serum cholesterol values at least until 14 years of age. Puberty markedly influences serum cholesterol concentrations.

Tobacco smoke exposure is associated with attenuated endothelial function in 11-year-old healthy children.

BACKGROUND: Passive smoking is associated with early arterial damage in adults, but its effect on endothelial function in children is unknown. METHODS AND RESULTS: Serum cotinine concentration was measured annually in children between 8 and 11 years of age who had participated since infancy in a randomized, prospective atherosclerosis prevention trial (Special Turku Coronary Risk Factor Intervention Project for children [STRIP]). At age 11, endothelium-dependent flow-mediated vasodilatory responses of the brachial artery were examined with high-resolution ultrasound in 402 children. These children were divided into 3 groups according to serum cotinine concentrations: the noncotinine group (nondetectable cotinine, n=229), the low cotinine group (cotinine between 0.2 and 1.6 ng/mL, n=134), and the top decile cotinine group (cotinine > or = 1.7 ng/mL, n=39). Longitudinal cotinine data in children aged 8 to 11 years and ultrasound studies were available in 327 children. At age 11, the increase in cotinine concentration was associated with attenuated peak flow-mediated dilation response (mean+/-SD: the noncotinine group 9.10+/-3.88%, the low-cotinine group 8.57+/-3.78%, and the top-decile cotinine group 7.73+/-3.85%; P=0.03 for trend). Similarly, total dilation response (the area under the dilation response versus time curve between 40 and 180 seconds after hyperemia) was affected by the cotinine level (P=0.02 for trend). These trends were not explained by traditional atherosclerosis risk factors. Arterial measures and passive smoking showed even stronger associations when longitudinal cotinine data were used (peak flow-mediated dilation, P=0.01 for trend; total dilation response, P=0.008 for trend). CONCLUSIONS: Exposure to environmental tobacco smoke confirmed by serum cotinine concentrations impairs endothelial function in a dose-dependent manner in 11-year-old children.