From plasma triglycerides to triglyceride metabolism: effects on mortality in the Copenhagen General Population Study.

AIMS: It is unclear whether higher triglyceride metabolism per se contributes to mortality separate from elevated triglyceride-rich lipoproteins and body mass index. This study tested the hypotheses that higher triglyceride metabolism, measured as higher plasma glycerol and ß-hydroxybutyrate, is associated with increased all-cause, cardiovascular, cancer, and other mortality. METHODS AND RESULTS: This study included 30 000 individuals nested within 109 751 individuals from the Copenhagen General Population Study. During a median follow-up of 10.7 years, 9897 individuals died (2204 from cardiovascular, 3366 from cancer, and 2745 from other causes), while none were lost to follow-up. In individuals with glycerol >80 µmol/L (highest fourth) vs. individuals with glycerol <52 µmol/L (lowest fourth), the multivariable adjusted hazard ratio for all-cause mortality was 1.31 (95% confidence interval 1.22-1.40). In individuals with ß-hydroxybutyrate >154 µmol/L (highest fourth) vs. individuals with ß-hydroxybutyrate <91 µmol/L (lowest fourth), the multivariable adjusted hazard ratio for all-cause mortality was 1.18 (1.11-1.26). Corresponding values for higher plasma glycerol and ß-hydroxybutyrate were 1.37 (1.18-1.59) and 1.18 (1.03-1.35) for cardiovascular mortality, 1.24 (1.11-1.39) and 1.16 (1.05-1.29) for cancer mortality, and 1.45 (1.28-1.66) and 1.23 (1.09-1.39) for other mortality, respectively. Results were robust to exclusion of first years of follow-up, to stratification for covariates including plasma triglycerides and body mass index, and to further adjustments. CONCLUSION: This study observed an increased risk of all-cause, cardiovascular, cancer, and other mortality with higher triglyceride metabolism. This was not explained by higher plasma triglycerides and body mass index. The hypothesis studied in the present paper should be further validated by isotope flux studies.

Experiences with regular testing of students for SARS-CoV-2 in primary and secondary schools: results from a cross-sectional study in two Norwegian counties, autumn 2021.

BACKGROUND: To allow for normal school attendance during the COVID-19 pandemic, regular testing of students was introduced in the autumn 2021 in Norway to manage COVID-19 transmission. We mapped the experiences of five stakeholders (parents, students, school staff and administration, contact tracing teams) regarding the implementation of regular testing in primary and secondary schools in Oslo and Viken counties, to assess the acceptability through different indicators and improve future guidelines. METHODS: A cross-sectional survey was conducted between October and November 2021 to explore experiences of implementation, compliance, satisfaction, difficulties, concerns, confidence in regular testing, quality of teaching and school attendance. Five stakeholder groups were invited to participate: contact tracing teams; school administrators and employees in primary, lower secondary, and upper-secondary school; students in upper-secondary school and parents of primary and lower secondary students. Bivariate analyses were performed for students, parents, and school employees groups. Descriptive analyses were done for contact tracing teams and school administrators. RESULTS: Four thousand five hundred sixty-five participants were included in our study. School attendance increased for most of the students in primary and lower secondary schools in Oslo and Viken after the implementation of regular testing. Students across all school levels reported high testing compliance and satisfaction with the implementation. Compliance was significantly associated with an increasing number of weekly tests across all school levels up to two weekly tests. Contact tracing teams were less satisfied with the cooperation with the educational authorities compared to the school employees. Higher educational level of parents was significantly associated with decreased concern of their children getting infected at school after regular testing implementation. Concerned parents were more likely to keep children at home from school, to protect all household members from becoming infected. Lack of time and communication were reported as challenging factors to implementation. CONCLUSION: Compliance, satisfaction, and confidence in regular testing of COVID-19 were high among stakeholders. An acceptable testing regime for a future regular testing implementation would be a home-based, bi-weekly test. Increased awareness of the importance of school attendance, safety of regular testing along with good communication and role clarification should be prioritized for stakeholders involved in regular testing.

Per-Particle Triglyceride-Rich Lipoproteins Imply Higher Myocardial Infarction Risk Than Low-Density Lipoproteins: Copenhagen General Population Study.

[Figure: see text].

Very Low-Density Lipoprotein Cholesterol May Mediate a Substantial Component of the Effect of Obesity on Myocardial Infarction Risk: The Copenhagen General Population Study.

BACKGROUND: Individuals with obesity have higher concentrations of very low-density lipoprotein (VLDL) cholesterol and increased risk of myocardial infarction. We hypothesized that VLDL cholesterol explains a fraction of the excess myocardial infarction risk in individuals with obesity. METHODS: We included 29 010 individuals free of myocardial infarction at baseline, nested within 109 751 individuals from the Copenhagen General Population Study. During 10 years of follow-up, 2306 individuals developed myocardial infarction. Cholesterol content in large and small VLDLs, in intermediate-density lipoprotein (IDL), and in LDL was measured directly with nuclear magnetic resonance spectroscopy. RESULTS: Median concentrations of cholesterol in large and small VLDLs were 0.12 mmol/L (interquartile range [IQR], 0.07-0.20 mmol/L; 4.5 mg/dL [IQR, 2.6-6.9 mg/dL]) and 0.6 mmol/L (IQR, 0.5-0.8 mmol/L; 25 mg/dL [IQR, 20-30 mg/dL]) in individuals with obesity vs 0.06 mmol/L (IQR, 0.03-0.1 mmol/L; 2.2 mg/dL [IQR, 1.1-3.8 mg/dL]), and 0.5 mmol/L (IQR, 0.4-0.6 mmol/L; 20 mg/dL (IQR, 16-25 mg/dL]) in individuals with normal weight; in contrast, concentrations of IDL and LDL cholesterol were similar across body mass index (BMI) categories. Cholesterol in large and small VLDLs combined explained 40% (95% CI, 27%-53%) of the excess risk of myocardial infarction associated with higher BMI. In contrast, IDL and LDL cholesterol did not explain excess risk of myocardial infarction, whereas systolic blood pressure explained 17% (11%-23%) and diabetes mellitus explained 8.6% (3.2%-14%). CONCLUSIONS: VLDL cholesterol explains a large fraction of excess myocardial infarction risk in individuals with obesity. These novel findings support a focus on cholesterol in VLDL for prevention of myocardial infarction and atherosclerotic cardiovascular disease in individuals with obesity.

Outbreak caused by the SARS-CoV-2 Omicron variant in Norway, November to December 2021.

In late November 2021, an outbreak of Omicron SARS-CoV-2 following a Christmas party with 117 attendees was detected in Oslo, Norway. We observed an attack rate of 74% and most cases developed symptoms. As at 13 December, none have been hospitalised. Most participants were 30-50 years old. Ninety-six percent of them were fully vaccinated. These findings corroborate reports that the Omicron variant may be more transmissible, and that vaccination may be less effective in preventing infection compared with Delta.

Disturbed eating behaviours do not impact treatment response in a paediatric obesity chronic care treatment programme.

AIM: This study investigates the prevalence of disturbed eating behaviours in children and adolescents initiating obesity treatment, and how the prevalence varies with age, sex and body mass index (BMI) standard deviation score (SDS). Secondly, it examines whether the presence of disturbed eating behaviours at enrolment is associated with the degree of weight loss after 12 months of treatment. METHODS: A total of 3621 patients aged 3-18 years enrolled in a multidisciplinary obesity treatment programme were studied. Follow-up data after a median of 12.4 months were available for 2055 patients. Upon entry, patients were assessed for the following disturbed eating behaviours: meal skipping, emotional eating, overeating and rapid eating. Height and weight were measured at baseline and follow-up. RESULTS: At enrolment, median age was 11.4 years, median BMI SDS was 2.87, and 82.2% of patients exhibited one or more disturbed eating behaviours. The prevalence of meal skipping, emotional eating and rapid eating increased with age (P < 0.01). Patients who reported overeating or rapid eating exhibited a 0.06-0.11 higher BMI SDS at enrolment than patients without these disturbed eating behaviours (P < 0.02). After 1 year of treatment, BMI SDS was reduced in 75.7% of patients, and the median reduction was 0.24 (95% confidence interval: 0.22-0.27). Overeating was associated with a higher degree of weight loss, while meal skipping, emotional eating and rapid eating did not associate with the degree of weight loss at follow-up. CONCLUSIONS: Disturbed eating behaviours were highly prevalent in children and adolescents with overweight or obesity, and varied with age and sex. After 1 year of treatment, the degree of obesity improved, regardless of the presence of disturbed eating behaviours at treatment initiation.

An adult-based insulin resistance genetic risk score associates with insulin resistance, metabolic traits and altered fat distribution in Danish children and adolescents who are overweight or obese.

AIMS/HYPOTHESIS: A genetic risk score (GRS) consisting of 53 insulin resistance variants (GRS53) was recently demonstrated to associate with insulin resistance in adults. We speculated that the GRS53 might already associate with insulin resistance during childhood, and we therefore aimed to investigate this in populations of Danish children and adolescents. Furthermore, we aimed to address whether the GRS associates with components of the metabolic syndrome and altered body composition in children and adolescents. METHODS: We examined a total of 689 children and adolescents who were overweight or obese and 675 children and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS53 was examined for association with metabolic traits in children by linear regressions using an additive genetic model. RESULTS: In overweight/obese children and adolescents, the GRS53 associated with higher HOMA-IR (ß = 0.109 ± 0.050 (SE); p = 2.73 × 10-2), fasting plasma glucose (ß = 0.010 ± 0.005 mmol/l; p = 2.51 × 10-2) and systolic BP SD score (ß = 0.026 ± 0.012; p = 3.32 × 10-2) as well as lower HDL-cholesterol (ß = -0.008 ± 0.003 mmol/l; p = 1.23 × 10-3), total fat-mass percentage (ß = -0.143 ± 0.054%; p = 9.15 × 10-3) and fat-mass percentage in the legs (ß = -0.197 ± 0.055%; p = 4.09 × 10-4). In the population-based sample of children, the GRS53 only associated with lower HDL-cholesterol concentrations (ß = -0.007 ± 0.003 mmol/l; p = 1.79 × 10-2). CONCLUSIONS/INTERPRETATION: An adult-based GRS comprising 53 insulin resistance susceptibility SNPs associates with insulin resistance, markers of the metabolic syndrome and altered fat distribution in a sample of Danish children and adolescents who were overweight or obese.

Subjective evaluation of psychosocial well-being in children and youths with overweight or obesity: the impact of multidisciplinary obesity treatment.

PURPOSE: To investigate the effects of a multidisciplinary childhood obesity treatment programme on subjective evaluations of psychosocial well-being and quality of life. METHODS: This longitudinal observational study included 1291 children, adolescents and young adults, 6-22 years of age, with overweight or obesity. At entry and after 2-82 months of obesity treatment, the patients evaluated the following domains of psychosocial well-being on a visual analogue scale: quality of life, mood, appetite, bullying, motivation for weight loss and body image satisfaction. The degree of overweight was calculated using a body mass index (BMI) standard deviation score (SDS) at each visit. RESULTS: At entry, the mean BMI SDS was 2.81 (range: 1.35-6.65, 95% confidence interval (95% CI): 2.44-3.18). After a median of 14 months of treatment, the median reduction in BMI SDS was 0.29 (95% CI: 0.26-0.31, p < 0.0001). Improvements were observed in the domains of quality of life, mood, appetite, bullying and body image satisfaction (p < 0.0001). Larger reductions in BMI SDS were associated with greater improvements in the domains of quality of life (p = 0.001), mood (p = 0.04) and body image satisfaction (p < 0.0001), independent of BMI SDS at entry. However, improvements in psychosocial well-being were also observed in those increasing their BMI SDS (n = 315). CONCLUSIONS: In a large group of children and youths, psychosocial well-being improved during a multidisciplinary childhood obesity treatment programme, irrespective of the degree of obesity at treatment entry. Greater reductions in BMI SDS were associated with greater improvements in psychosocial well-being, but even in the group increasing their BMI SDS improvements were observed.

Triglyceride content increases while cholesterol content decreases in HDL and LDL+IDL fractions following normal meals: The Copenhagen General Population Study of 25,656 individuals.

BACKGROUND AND AIMS: During fat tolerance tests, plasma triglycerides increase while high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and intermediate-density lipoprotein (IDL) cholesterol decrease. However, it is unknown whether triglyceride content increases and cholesterol content decreases in HDL and LDL + IDL fractions following normal meals in the general population. Therefore, we tested the hypothesis that triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions following normal meals. METHODS: In this cross-sectional study, we included 25,656 individuals aged 20-100 years, all without lipid-lowering therapy at examination and selected for metabolomic profiling from the Copenhagen General Population Study. Triglyceride and cholesterol content of 14 lipoprotein fractions weas measured using nuclear magnetic resonance (NMR) spectroscopy. Time since last meal was recorded by the examiner immediately before blood sampling. RESULTS: Following normal meals in age and sex-adjusted analyses and when compared with fasting levels, plasma triglycerides were higher for up to 5-6 h, and triglyceride content was higher for up to 6-7 h in HDL fractions, for up to 6-7 h in LDL + IDL fractions, and for up to 5-6 h in very-low-density lipoprotein (VLDL) fractions. Further, plasma cholesterol was lower for up to 2-3 h, and cholesterol content was lower for up to 0-1 h in HDL fractions and for up to 4-5 h in LDL + IDL fractions, while cholesterol content was higher for up to 4-5 h in VLDL fractions. CONCLUSIONS: Following normal meals, triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions.

The First GAEN-Based COVID-19 Contact Tracing App in Norway Identifies 80% of Close Contacts in "Real Life" Scenarios.

The coronavirus disease 2019 (COVID-19) response in most countries has relied on testing, isolation, contact tracing, and quarantine (TITQ), which is labor- and time-consuming. Therefore, several countries worldwide launched Bluetooth-based apps as supplementary tools. The aim of using contact tracing apps is to rapidly notify people about their possible exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thus make the process of TITQ more efficient, especially upon exposure in public places. We evaluated the Norwegian Google Apple exposure notification (GAEN)-based contact tracing app Smittestopp v2 under relevant "real-life" test scenarios. We used a total of 40 devices, representing six different brands, and compared two different exposure configurations, experimented with different time thresholds and weights of the Bluetooth attenuation levels (buckets), and calculated the true notification rates among close contacts (≤2 m and ≥15 min) and false notification of sporadic contacts. In addition, we assessed the impact of using different operating systems and locations of the phone (hand/pocket). The best configuration tested to trigger exposure notification resulted in the correct notification of 80% of the true close contacts and incorrect notification of 34% of the sporadic contacts. Among those who incorrectly received notifications, most (67%) were within 2 m but the duration of contact was <15 min and thus they were not, per se, considered as "close contacts." Lower sensitivity was observed when using the iOS operating systems or carrying the phone in the pocket instead of in the hand. The results of this study were used to improve and evaluate the performance of the Norwegian contact-tracing app Smittestopp.

Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents.

BACKGROUND: Midazolam is a first-line drug for the treatment of status epilepticus, both by buccal and intravenous administration. In children and adolescents with obesity, midazolam pharmacokinetics may be altered, and the current dosing guidelines may therefore be insufficient. OBJECTIVE: The objective of this study was to investigate the pharmacokinetics of midazolam, after intravenous administration, in obese and non-obese adolescents aged 11-18 years. METHODS: All trial participants received a 1-µg midazolam microdose as an intravenous bolus. 13 blood samples were collected per participant at pre-specified timepoints. Plasma concentration-time data were fitted to pharmacokinetic models using non-linear mixed-effects modeling. Covariates such as weight, age, and body mass index standard deviation score were tested to explain the inter-individual variability associated with the pharmacokinetic parameters. RESULTS: Sixty-seven adolescents were included in the analysis. The pharmacokinetics of midazolam was best described with a two-compartment model. The rate of distribution was faster, and the peripheral volume of distribution was larger in adolescents with a high body mass index standard deviation score compared with adolescents with a lower standard deviation score. Simulations revealed that long-term infusions based on total body weight could lead to high plasma concentrations in adolescents with obesity. Furthermore, simulated plasma concentrations after a fixed buccal dose indicated that adolescents with obesity may be at risk of sub-therapeutic midazolam plasma concentrations. CONCLUSIONS: The body mass index standard deviation score was shown to have a significant influence on the peripheral volume of distribution and the inter-compartmental clearance of midazolam. The current dosing guidelines for status epilepticus, where the midazolam dose is adjusted to total body weight or age, may lead to supra- and sub-therapeutic plasma concentrations, respectively, in adolescents with obesity. TRIAL REGISTRATION: EudraCT: 2014-004554-34.

Genetic Susceptibility for Childhood BMI has no Impact on Weight Loss Following Lifestyle Intervention in Danish Children.

OBJECTIVE: This study aimed to investigate the effect of a genetic risk score (GRS) comprising 15 single-nucleotide polymorphisms, previously shown to associate with childhood BMI, on the baseline cardiometabolic traits and the response to a lifestyle intervention in Danish children and adolescents. METHODS: Children and adolescents with overweight or obesity (n = 920) and a population-based control sample (n = 698) were recruited. Anthropometric and biochemical measures were obtained at baseline and in a subgroup of children and adolescents with overweight or obesity again after 6 to 24 months of lifestyle intervention (n = 754). The effects of the GRS were examined by multiple linear regressions using additive genetic models. RESULTS: At baseline, the GRS associated with BMI standard deviation score (SDS) both in children and adolescents with overweight or obesity (ß = 0.033 [SE = 0.01]; P = 0.001) and in the population-based sample (ß = 0.065 [SE = 0.02]; P = 0.001). No associations were observed for cardiometabolic traits. The GRS did not influence changes in BMI SDS or cardiometabolic traits following lifestyle intervention. CONCLUSIONS: A GRS for childhood BMI was associated with BMI SDS but not with other cardiometabolic traits in Danish children and adolescents. The GRS did not influence treatment response following lifestyle intervention.

A large frontal QRS-T angle is a strong predictor of the long-term risk of myocardial infarction and all-cause mortality in the diabetic population.

BACKGROUND: A large angle between the QRS vector and the T-wave vector (QRS-T angle) in electrocardiograms (ECGs) has recently been introduced as a marker of poor prognosis. The prognostic value in diabetes is unknown. We assessed the long-term predictive power of the frontal plane QRS-T angle in the diabetic population. METHODS: In 1992-93, the diabetic population of the municipality of Horsens, Denmark, was delineated by the prescription method, and an age- and gender-stratified sample of 240 diabetic persons was randomly selected. In 2015, 12-lead ECGs taken in 1993-94 were analyzed. Vital statistics were obtained from the Danish Civil Registration System and data regarding hospitalizations taken from The National Patient Registry in July 2015. RESULTS: In total, 178 people agreed to participate (74%) in the study, with the mean (sd) age being 58.9 (10.2) years and 56% being male. The total observation time was 21.5 (0.18) years, during which time 122 (69%) persons died, 32 (18%) suffered a myocardial infarction (MI) and 126 (71%) reached the composite endpoint of non-fatal MI or all-cause death. In Cox regression multivariate analysis a QRS-T angle above 90° was found to be an independent predictor of all-cause death (HR=2.2 (95% CI: 1.3-3.8)), MI (HR=2.95 (95% CI: 1.1-7.7)) and MI or all-cause death (HR=2.0 (95% CI: 1.2-3.5)) (all p<0.05), when adjusting for the effects of co-variates (gender, age, length of diabetes, BMI, total cholesterol, diabetes type, hemoglobin A1c, smoking, hypertension and previous MI). CONCLUSION: A large QRS-T angle is a strong, independent long-term predictor of all-cause mortality, MI and MI or all-cause death in the diabetic population.