| 1. |
- Almgren, Malin, et al.
(författare)
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Adenovirus-36 Is Associated with Obesity in Children and Adults in Sweden as Determined by Rapid ELISA
- 2012
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals. Principal Findings: Using a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 nondiabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from similar to 7% in 1992-1998 to 15-20% in 2002-2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08). Conclusion: Using a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals.
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| 2. |
- Bergqvist-Norén, Linnea, et al.
(författare)
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Patterns and correlates of objectively measured physical activity in 3-year-old children
- 2020
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To increase the knowledge about physical activity (PA) patterns and correlates among children under the age of 4, there is a need for study's using objective measurements. The aim of this study was therefore to investigate if objectively measured PA among 3-year-old children differed between day of week and time of day and whether it correlated to child weight status and sex as well as parental weight status and education.METHODS: Totally 61 children (51% girls) aged 3, participating in Early Stockholm Obesity Prevention Project were included. PA was measured with a tri-axial accelerometer (ActiGraph GT3X+) worn on the non-dominant wrist for one week. The main outcome was average PA expressed as counts per minute from the vector magnitude. PA and demographics/family-related factors were collected at baseline and at age 3. To analyze the results simple linear regression, ANOVA and paired t-tests were performed.RESULTS: The mean number of valid days was 6.7 per child. The children were more active on weekdays than weekends (p < 0.01) and the hourly pattern differed over the day with children being most active midmorning and midafternoon (p = 0.0001). Children to parents with low education were more active (p = 0.01) than those with highly educated parents. No differences in PA by child weight status, sex nor parental weight status were found.CONCLUSIONS: PA in 3-year-old children was lower during weekends than weekdays and varied over the day. Boys and girls had similar PA patterns, these patterns were independent of child or parental weight status. Children to parents with low education were more active than their counterparts. The fact that PA differed between weekdays and weekends indicates that PA might be affectable in 3-year-old children.
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| 3. |
- Hagman, Emilia
(författare)
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Elevated fasting glucose levels in obese children and adolescents : prevalence and long-term consequences
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Obesity in childhood and adolescents is a major concern in Sweden, as in many parts of the world. Already during the pediatric years is obesity associated with several metabolic complications, which often persists into adulthood. An important metabolic concern is the disturbance of the glucose-insulin homeostasis. One early sign is impaired fasting glycaemia (IFG) which is considered a prediabetic stage as IFG is associated with markedly increased risk for development of type 2 diabetes mellitus (T2DM) in adults. IFG refers to elevated, but not yet diabetic, glucose levels in the fasting state. At present, two different cut-off values for IFG are used in parallel; the American Diabetes Association (ADA) suggest 5.6 mmol/L and the World Health Organization (WHO) promotes 6.1 mmol/L as the cut-off for IFG. In adults, IFG has been associated with increased risk for cardiovascular disease, cancer, and premature also in the absence of the development of T2DM. The prevalence of IFG in the obese pediatric population has been reported with vast differences across different countries and populations. Further, the long-term consequences of IFG in the obese pediatric population are not clear. However, obesity as well as obesity-induced dysglycemia, may affect several brain functions important for schooling. The aim of this thesis is to investigate the prevalence, risk groups, and consequences of IFG in obese children and adolescents. Method: All studies included in this thesis contains data from the Swedish Childhood Obesity Register – BORIS (Barn Obesitas Register I Sverige). BORIS is a national quality register for obesity treatment in childhood and adolescence and was initiated in 2005. In addition, data from Germany and Poland regarding children and adolescents who have been undergoing obesity treatment are included. Study I and II are cross-sectional observational studies and Study III and IV are prospective cohort studies, which in addition to BORIS data using data from several national registries. Results: The total prevalence of IFG among obese children in the German cohort according to the ADA was 5.7% and according to the WHO it was 1.1%. In Sweden, the corresponding prevalence was 17.1% and 3.9%, respectively. IFG risk was associated with increasing age, male sex and degree of obesity. Further, Swedish obese young children had higher glucose levels than Polish obese young children. The use of T2DM medication retrieved from the national prescribed drug registry was used as a proxy for the diagnosis of T2DM. The pediatric obese population in Sweden, based on the BORIS cohort, had a 24 times increased use of T2DM medications in early adulthood in relation to a population-based comparison group, regardless of gender and ethnicity. While the WHO-defined IFG predicted future use of T2DM medication in early adulthood with an adjusted hazard ratio of 3.84 compared with those who had fasting glucose levels <5.6mmol/L. A fasting glucose level of 5.6-6.0 mmol/L, i.e. the IFG glucose interval added by ADA, did not increase the use of T2DM medication in young adults more than pediatric obesity itself. Female gender and more severe degree of obesity increased the risk for future T2DM medication. In the obese cohort, 55.4% completed ≥12 years in school, compared with 76.2% in the comparison group. IFG did not correlate significantly with school completion; 50.8% for those with IFG according to ADA and 48.4% for those with IFG according to WHO completed school compared with 55.8% for non-IFG. When analyzing glucose as a continuous variable, a non-significant tendency on school completion could be seen (adjusted p=0.06). Conclusion: IFG is highly prevalent among obese children in Sweden compared with Poland and Germany. There are no known explanations for the large regional differences in both IFG prevalence and fasting glucose levels. IFG according to WHO, but not the additional interval added by ADA (5.6-6.0 mmol/L) can be considered as a prediabetic stage in the obese pediatric population. Thus, these studies indicate that risk markers identified in adults can not directly be transferred to children. Obesity in childhood and adolescence was associated with low educational level in early adulthood but IFG did not statistically significantly increase the risk for low education in obese individuals.
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| 4. |
- Hagman, Emilia, et al.
(författare)
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Oral intake of mesoporous silica is safe and well tolerated in male humans
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- Background Precisely engineered mesoporous silica has been shown to induce weight loss in mice, but whether it is safe to use in humans have not investigated.Objective The aim was to determine whether oral dosing, up to 9 grams/day, of precisely engineered mesoporous silica as a food additive can be used safely in male humans.Design This single blinded safety study consisted of two study arms including 10 males each (18-35 years). One arm consisted of participants with normal weight and one with obesity. After a placebo run-in period, all subjects were given porous silica three times daily, with increasing dose up to 9 grams/day (Phase 1). Subjects with obesity continued the study with highest dose for additional 10 weeks (Phase 2).Results All participants completed Phase 1 and 90% completed Phase 2, with approximately 1% missed doses. Participants reported no abdominal discomfort, and changes in bowel habits were minor and inconsistent. The side effects observed were mild and tolerable, biomarkers did not give any safety concern, and no severe adverse events occurred.Conclusion Mesoporous silica intake of up to 9 grams/day can be consumed by males without any major adverse events or safety concerns.
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| 5. |
- Hagman, Emilia, et al.
(författare)
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Predictors of responses to clinic-based childhood obesity care
- 2018
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 19:8, s. 1351-1356
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objective: Lifestyle modification is the therapy of choice for childhood obesity, yet the response rate is variable and may be affected by genetic factors. We aimed to investigate predictors of poor response to lifestyle modification obesity treatment in children. Methods: A prospective cohort study of 434 youths (64.5% females) between 4 and 20 years of age undergoing a standard care of lifestyle modification obesity management for 35.9 ± 20.8 months at Yale Childhood Obesity Clinic, USA. The primary outcome was a “poor response,” defined as the quintile with the largest increase in BMI Z-score over time. The secondary outcome was the endpoint BMI Z-score. Covariates investigated were sex, baseline pubertal status and degree of obesity, race, biochemical profile, and family history of overweight. A subsample (n = 214) had FTO genotyping (SNP rs8050136) tested. Results: Males (hazard ratio [HR] = 5.35, 95% confidence interval [CI] [3.32-8.61], P < 0.0001) and pubertal adolescents (HR = 2.78, [1.40-5.50], P = 0.003) compared to prepubertal children were more prone to respond poorly. Baseline degree of obesity was associated with relative protection from responding poorly (HR per BMI Z-score unit = 0.32, [0.17-0.61], P = 0.0006). Carriers of the FTO obesity-predisposing allele (AA genotype) were protected from responding poorly compared to non-carriers (CC genotype) (HR = 0.33, [0.12-0.88], P = 0.028). Conclusions: Boys and pubertal adolescents are more prone to respond poorly to standard obesity care while those with greater baseline degree of obesity and carriers of the FTO obesity-predisposing allele are not.
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| 6. |
- Waara, Erik R., et al.
(författare)
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Entrapping Digestive Enzymes with Engineered Mesoporous Silica Particles Reduces Metabolic Risk Factors in Humans
- 2020
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Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Engineered mesoporous silica particles (MSP) are thermally and chemically stable porous materials composed of pure silica and have attracted attention for their potential biomedical applications. Oral intake of engineered MSP is shown to reduce body weight and adipose tissue in mice. Here, clinical data from a first-in-humans study in ten healthy individuals with obesity are reported, demonstrating a reduction in glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol, which are well-established metabolic and cardiovascular risk factors. In vitro investigations demonstrate sequestration of pancreatic alpha-amylase and lipase in an MSP pore-size dependent manner. Subsequent ex vivo experiments in conditions mimicking intestinal conditions and in vivo experiments in mice show a decrease in enzyme activity upon exposure to the engineered MSP, presumably by the same mechanism. Therefore, it is suggested that tailored MSP act by lowering the digestive enzyme availability in the small intestine, resulting in decreased digestion of macronutrient and leading to reduced caloric uptake. This novel MSP based mechanism-of-action, combined with its excellent safety in man, makes it a promising future agent for prevention and treatment of metabolic diseases.
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