Lp(a) does not affect intima media thickness in hypercholesterolemic children -a retrospective cross sectional study.

Purpose: Combined hyperlipidaemia results in premature atherosclerosis and a high burden of cardiovascular morbidity and mortality. Early identification of highly affected subjects within this population is of utmost importance to enable informed treatment decisions. The measurement of intima media thickness (IMT) is a readily available, non-invasive method to investigate evidence of early atherosclerosis. To assess the usefulness of this method in pediatric subjects with hypercholesterolemia, we here examined a possible interaction of LDL-C and Lp(a) on IMT. Methods: Blood lipids (Lp(a), LDL-cholesterol, total cholesterol, triglycerides, high density lipoprotein (HDL) -cholesterol, apolipoprotein A1, apolipoprotein B), anthropometric parameters (age, height, weight, body mass index (BMI)) and possibly existing early evidence of atherosclerotic lesions measured by intima media thickness (IMT zscore).as a surrogate parameter was examined retrospectively in 113 children and adolescents (aged 1-18 years) with elevated Lp(a) and/or LDL-cholesterol (Lp(a) > 30 mg/dL, LDL>130 mg/dL). Furthermore, we compared hsCRP levels between groups. Results: There were no significant differences in IMT Zscore or hsCRP between groups. Regression analysis did not reveal a statistically significant interaction between Lp(a) and LDL-C. Conclusions: At the age of 6-18 years, we found no significant differences in early markers of atherosclerosis between subjects with high Lp(a)- and/or high LDL-cholesterol with no detectable synergistic effects between the two lipoproteins.

The BACE1 inhibitor LY2886721 improves diabetic phenotypes of BACE1 knock-in mice.

AIM: The ß-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) has been identified as the central initiator of amyloid ß (Aß) generation in the brain, the key hallmark of Alzheimer's disease (AD). However, recent studies provided evidence that BACE1 also plays a crucial role in metabolic regulation, and we have shown that neuronal human BACE1 knock-in mice (PLB4) display type 2 diabetes mellitus (T2DM)-like symptoms alongside AD-like impairments. Hence, we here investigated if targeted BACE1 inhibition using LY2886721, an active site BACE1 inhibitor, would improve glucose homeostasis, insulin sensitivity and motor performance in PLB4 mice. MATERIALS AND METHODS: LY2886721 was administered as a dietary supplement (0.02% wt/wt) for six consecutive weeks. Physiological, metabolic and motor assessments were performed during the last two weeks of treatment, followed by molecular tissue analyses post-mortem. RESULTS: LY2886721 treatment improved glucose homeostasis and hepatic gluconeogenesis in diabetic PLB4 mice, as determined by improvements in basal glucose and glucose/pyruvate tolerance tests. Furthermore, LY2886721 improved hepatic insulin sensitivity, as indicated by enhanced basal hyperphosphorylation of insulin receptors. In PLB4 brains, we detected altered basal conditions of APP expression and processing, with beneficial effects on APP processing achieved by LY2886721 treatment. No improvements in motor coordination were found. CONCLUSIONS: Our data provide support for a role of BACE1 as a regulator of systemic glucose homeostasis and suggest BACE1 inhibitors for the treatment of T2DM-associated pathologies, especially in cases where diabetes is comorbid to AD.

Effects of a low-fat dietary regimen enriched with soy in children affected with heterozygous familial hypercholesterolemia.

INTRODUCTION: Familial hypercholesterolemia (FH) is an inheritable, autosomal dominant disorder leading to pathologically increased levels of low-density-lipoprotein cholesterol (LDL-C). Dietary treatment remains an important tool in the management of affected children even after the decision for the initiation of pharmacotherapy is made. However, little evidence is available regarding the optimal dietary regimen for the treatment of children affected with FH. METHODS: We present results from a randomized controlled trial in paediatric patients affected with heterozygous FH, assessing the effect of a soy-enriched fat modified diet (soy group) compared to fat modified diet (Control group) alone on LDL-C over a period of 13 weeks. Furthermore, we monitored isoflavone levels in plasma and urine as markers of adherence to the dietary treatments. RESULTS: LDL-C decrease was statistically significantly greater in the soy group compared to the control group at week 7 (Control group 176.3 ± 27.8 mg/dl, soy group 154.7 ± 29.2 mg/dl, p = 0.038), and showed a trend towards significant at week 13 (Control group 179.9 ± 41.8 mg/dl, soy group 155.0 ± 30.2 mg/dl, p = 0.089). Relative LDL-C decrease correlated significantly with the following plasma isoflavone concentrations measured in week 7: daidzein (p < 0.004, r = 0.576) and genistein (p < 0.017, r = 0.490). CONCLUSIONS: We provide evidence from a small randomized-controlled trial for the effectiveness and safety of a dietary treatment with soy in paediatric patients affected with heterozygous FH. The decrease in LDL-C was highly correlated with isoflavone levels, further highlighting a direct effect of soy ingestion. This study was registered under ClinicalTrials.gov Identifier No. NCT03563547.

The Viennese EDDY Study as a Role Model for Obesity: Prevention by Means of Nutritional and Lifestyle Interventions.

OBJECTIVES: Obesity in children and adolescents is a worldwide dramatic health problem, for which treatment is mostly unsuccessful. Therefore, prevention is the most important measure to tackle this problem. The 'EDDY' study as an interventional cohort study with a 1-year lifestyle intervention aimed to affect the lifestyle and nutrition habits of adolescents by intervention with nutritional training and sports programs to prevent obesity. METHODS: Four Viennese schools were cluster-randomized into an intervention group and a control group. A total of 141 pupils aged 11-14 years were included. The intervention group received a comprehensive, age-appropriate training on nutrition and lifestyle exercise intervention for 12 months. Before and after intervention and at two follow-ups, subjects were anthropometrically measured. In addition, knowledge of nutritional issues and eating habits were measured with questionnaires. RESULTS: The data imply an improvement of nutrition knowledge, a significant reduction in the consumption of junk food (p = 0.01), sweets (p = 0.001) and salty snacks (p < 0.001) as well as a slight improvement of physical performance after intervention. Although there was a trend for a less increase of body fat in the intervention group, no significant changes could have been shown in the anthropometric data. CONCLUSIONS: An age-adjusted lifestyle intervention based on dietary training and exercise can improve the nutritional knowledge and eating habits of school children.

Homozygous familial hypercholesterolemia: Summarized case reports.

BACKGROUND AND AIMS: Homozygous familial hypercholesterolemia (hoFH) is a rare genetic disorder with potential severe atherosclerosis in the pediatric age. METHODS: We report on 9 patients with hoFH, who had been diagnosed within the last 30 years and who were consequently treated with apheresis and drugs. RESULTS: Two deaths occurred: one at age 36 years and the other at age four and a half years before effective treatment was commenced. All other patients are still in good clinical condition today, although four of them have proven aortic stenosis or arterial plaques. CONCLUSIONS: Our case report highlights that adequate treatment should start as early as possible to delay the onset of clinical manifestations of atherosclerosis. It can be assumed that the introduction of new drugs can improve the outcome and possibly lengthen the life expectancy of patients affected by hoFH.

Bariatric surgery in morbidly obese adolescents: long-term follow-up.

OBJECTIVE: Morbid obesity is an increasingly common disease in the industrialized world and poses a great challenge to the medical community. Many obese adolescents have undergone various conservative treatment methods without adequate success so that a surgical approach became necessary. We report on 18 patients who underwent bariatric surgery as well as a long-term follow-up program. METHODS: Eight patients received a laparoscopic adjustable gastric banding (LAGB). Four of these had to undergo a gastric bypass surgery (GByp) as second procedure due to insufficient weight loss. Nine patients primarily received a gastric bypass. RESULTS: LAGB: Mean weight loss after 24 months was 20 ± 6.3 kg. Four of the patients showed a regain in weight leading to a mean weight loss of 9 kg compared to initial weight after 53.3 months mean in this group. These patients had to undergo an additional gastric bypass procedure and lost 31 ± 18.3 kg after 18 months. GByp: Mean weight loss in nine patients after gastric bypass (primary procedure) was 31 ± 10.2 kg after 12 months and 36 ± 30.1 kg at the end of the observation time. Sleeve: Initial weight in this patient was 232 kg with a weight loss of 38 kg after 24 months. DISCUSSION AND CONCLUSION: It is remarkable that in four of eight patients who underwent LAGB had to undergo a second surgical procedure (GByp). No previous indicator, neither from a psychological nor from a medical point of view, could be detected. More long-term studies including psychological aspects seem to be necessary.