The prevalence of child and adolescent obesity has plateaued at high levels in most high-income c... more The prevalence of child and adolescent obesity has plateaued at high levels in most high-income countries and is increasing in many low-income and middle-income countries. Obesity arises when a mix of genetic and epigenetic factors, behavioural risk patterns and broader environmental and sociocultural influences affect the two body weight regulation systems: energy homeostasis, including leptin and gastrointestinal tract signals, operating predominantly at an unconscious level, and cognitive-emotional control that is regulated by higher brain centres, operating at a conscious level. Health-related quality of life is reduced in those with obesity. Comorbidities of obesity, including type 2 diabetes mellitus, fatty liver disease and depression, are more likely in adolescents and in those with severe obesity. Treatment incorporates a respectful, stigma-free and family-based approach involving multiple components, and addresses dietary, physical activity, sedentary and sleep behaviours. In adolescents in particular, adjunctive therapies can be valuable, such as more intensive dietary therapies, pharmacotherapy and bariatric surgery. Prevention of obesity requires a whole-system approach and joinedup policy initiatives across government departments. Development and implementation of interventions to prevent paediatric obesity in children should focus on interventions that are feasible, effective and likely to reduce gaps in health inequalities.
TO, CM and EG were involved in study conception, design, data collection and analysis, and writin... more TO, CM and EG were involved in study conception, design, data collection and analysis, and writing the manuscript. AB, GB and MN were involved in study design, data collection and analysis, and writing the manuscript. CEF, JD, KE, PF, GG, KJ, JK and SM were involved in study design, data collection and writing the manuscript. MP was involved in study design, data analysis and writing the manuscript. All authors had full access to all data and approved the final manuscript. Trial registration number-NCT00289705-ClinicalTrials.gov Conflicts of interest: TO reports receiving consulting fees for serving as a participant in the global advisory board and lecturing for Ethicon Endo surgery. TO has also received fees for lecturing for AstraZeneca and Sanofi. AJB reports receiving funding from the Royal College of Surgeons of England in the form of a clinical research fellowship. KJ reports receiving a lecturing fee from Nestlé. MN reports receiving consulting fees for participation in the scientific advisory committee of Itrim. Further, MN has received research grants from Pfizer, Cambridge Weight Plan, Novo Nordisk and Astra Zeneca; and lecture and consulting fees from Pfizer, Sanofi-Aventis, Roche and Strategic Health Resources. CM reports receiving consulting fees for participation in the scientific advisory committee of Itrim, Oriflame Wellnes and Sigrid Therapeutics AB. Further, CM has received research grants from Novo Nordisk. EG,
BACKGROUND: Pediatric obesity lifestyle treatment is not always successful. Frequent clinical vis... more BACKGROUND: Pediatric obesity lifestyle treatment is not always successful. Frequent clinical visits are of major importance to certify sufficient effect but are difficult due to the associated costs and the great demands on families. We hypothesized that an interactive digital support may reduce the need for frequent physical visits. The aim of the study was to assess 1-year weight outcome for patients using a digital support system compared with standard care. METHODS: An obesity lifestyle treatment with a digital support system was implemented in one clinic in Stockholm, Sweden. Measurements from a custom-made body scale without digits for daily home measurement of weights were transferred via Bluetooth to a mobile application, where BMI Z-score was calculated and presented graphically with an individualized weight loss target curve. An automatic transfer of data to the web-based clinic interface enables a close monitoring of treatment progress, and frequent written communication between the clinical staff and families via the application. One-year outcome was compared with a randomly retrieved, age and sex matched control group from the Swedish childhood obesity treatment register (BORIS), which received standard treatment at other clinics. Main outcome was change in BMI Z-score and missing data was imputed. RESULTS: 107 children were consecutively included to digi-physical treatment and 321 children to standard care. Age range 4.1-17.4 years (67% males). The attrition rate was 36% and 46% respectively, p = 0.08. After 1 year, the mean ± SD change in BMI Zscore in the treatment group was −0.30 ± 0.39 BMI Z-score units and in the standard care group −0.15 ± 0.28, p = 0.0002. The outcome was better for both sexes and all age groups in the digi-physical treated group. CONCLUSION: A digital support system with a personalized weight-loss target curve and daily weight measurements shared by the family and the clinic is more effective than a standard care childhood obesity treatment. CLINICALTRIAL.GOV ID: NCT04323215
Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, clos... more Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33), to be associated with body mass. STK33, a relatively understudied protein, has been linked to KRAS mutation-driven cancers and explored as a potential antineoplastic drug target. The strongest association with body mass observed at this loci in GWAS was rs4929949, a single nucleotide polymorphism located within intron 1 of the gene encoding STK33. The functional implications of rs4929949 or related variants have not been explored as of yet. We have genotyped rs4929949 in two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross-sectional cohort of 2308 Greek school children. We found that the minor allele of rs4929949 was associated with obesity in the cohort of Swedish children and adolescents (OR = 1.199 (95%CI: 1.002-1.434), p = 0.047), and with body mass in the cross-sectional cohort of Greek children (b = 0.08147 (95% CI: 0.1345-0.1618), p = 0.021). We observe the effects of rs4929949 on body mass to be detectable already at adolescence. Subsequent analysis did not detect any association of rs4929949 to phenotypic measurements describing body adiposity or to metabolic factors such as insulin levels, triglycerides and insulin resistance (HOMA).
Objective-Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothe... more Objective-Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes HLA-DQ risk genotypes may be associated with an increased body mass index (BMI). Design-The type 1 diabetes high risk HLA-DQ A1*05:01-B1*02:01/A1*03:01-B1*03:02 genotype along with lower risk DQ genotypes were determined at the time of clinical onset by Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
overexpression of the one located closely to the olfactory receptor 1322 gene exerted in a mouse ... more overexpression of the one located closely to the olfactory receptor 1322 gene exerted in a mouse hepatoma cell line the robust transcriptional regulatory activity on ~100 proteincoding genes that were accumulated in several distinct biological pathways. Our results indicate that mouse serum contains biologically active intergenic sncRNAs in addition to other known forms. The results also suggest their potential biological importance and/or usefulness in disease diagnosis and treatment in humans.
Objective: Preventive measures to contain the epidemic of obesity have become a major focus of at... more Objective: Preventive measures to contain the epidemic of obesity have become a major focus of attention. This report reviews the scientific evidence for medical interventions aimed at preventing obesity during childhood and adolescence. Design: A systematic literature review involving selection of primary research and other systematic reviews. Articles published until 2004 were added to an earlier (2002) review by the Swedish Council on Technology Assessment in Health Care. Methods: Inclusion criteria required controlled studies with follow-up of at least 12 months and results measured as body mass index, skinfold thickness or the percentage of overweight/obesity. Children could be recruited from normal or high-risk populations. Results: Combining the new data with the previous review resulted in an evaluation of 24 studies involving 25 896 children. Of these, eight reported that prevention had a statistically significant positive effect on obesity, 16 reported neutral results and none reported a negative result (sign test; P ¼ 0.0078). Adding the studies included in five other systematic reviews yielded, in total, 15 studies with positive, 24 with neutral and none with negative results. Thus, 41% of the studies, including 40% of the 33 852 children studied, showed a positive effect from prevention. These results are unlikely to be a random chance phenomenon (P ¼ 0.000061). Conclusion: Evidence shows that it is possible to prevent obesity in children and adolescents through limited, school-based programs that combine the promotion of healthy dietary habits and physical activity.
Background: To increase the knowledge about physical activity (PA) patterns and correlates among ... more 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.
IMPORTANCE There is a lack of studies evaluating sleeve gastrectomy compared with intensive lifes... more IMPORTANCE There is a lack of studies evaluating sleeve gastrectomy compared with intensive lifestyle treatment in patients with class 1 obesity (body mass index [BMI] 30 to <35 [calculated as weight in kilograms divided by height in meters squared]). OBJECTIVE To compare outcomes and safety of sleeve gastrectomy compared with intensive nonoperative obesity treatment in patients with class 1 obesity. DESIGN, SETTING, AND PARTICIPANTS This matched, nationwide cohort study included patients with class 1 obesity who underwent a sleeve gastrectomy or intensive lifestyle treatment between January 1, 2012, and December 31, 2017, and who were registered in the Scandinavian Obesity Surgery Registry or the Itrim health database. Participants with class 1 obesity were matched 1:2 using a propensity score including age, sex, BMI, treatment year, education level, income, cardiovascular disease, and use of antibiotic drugs, antidepressants, and anxiolytics. INTERVENTIONS Sleeve gastrectomy or intensive lifestyle treatment. MAIN OUTCOMES AND MEASURES Outcomes included weight loss after intervention, changes in metabolic comorbidities, substance use disorders, self-harm, and major cardiovascular events
Introduction: The obesity epidemic has become one of the most important public health issues of m... more Introduction: The obesity epidemic has become one of the most important public health issues of modern times. Impaired insulin sensitivity seems to be the cornerstone of multiple obesity related comorbidities. However, there is no accepted definition of impaired insulin sensitivity. Objective: We hypothesize that assessment of insulin resistance differs between centers. Methods: The ESPE Obesity Working Group (ESPE ObWG) Scientific Committee developed a questionnaire with a focus on the routine practices of assessment of hyperinsulinemia and insulin resistance, which was distributed through Google Docs platform to the clinicians and researchers from the current ESPE ObWG database (n = 73). Sixty-one complete responses (84% response rate) from clinicians and researchers were analyzed: 32 from European Union (EU) centers (representatives of 14 countries) and 29 from Non-EU centers (representatives from 10 countries). Standard statistics were used for the data analysis. Results: The ma...
BACKGROUND Obesity is a chronic disease with limited treatment options in pediatric patients. Lir... more BACKGROUND Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity. METHODS In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56. RESULTS A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, -4.64 percentage points) and for body weight (estimated difference, -4.50 kg [for absolute change] and -5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment. CONCLUSIONS In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).
The prevalence of obesity among adolescents has increased and we lack effective treatments. OBJEC... more The prevalence of obesity among adolescents has increased and we lack effective treatments. OBJECTIVE: To determine if gastric bypass is safe and effective for an unselected cohort of adolescents with morbid obesity in specialized health care. DESIGN, SETTING AND PATIENTS: Intervention study for 81 adolescents (13-18 years) with a body mass index (BMI) range 36-69 kg m À 2 undergoing laparoscopic gastric bypass surgery in a university hospital setting in Sweden between April 2006 and May 2009. For weight change comparisons, we identified an adult group undergoing gastric bypass surgery (n ¼ 81) and an adolescent group (n ¼ 81) receiving conventional care. MAIN OUTCOME MEASUREMENTS: Two-year outcome regarding BMI in all groups, and metabolic risk factors and quality of life in the adolescent surgery group. RESULTS: Two-year follow-up rate was 100% in both surgery groups and 73% in the adolescent comparison group. In adolescents undergoing surgery, BMI was 45.5 ± 6.1 (mean ± s.d.) at baseline and 30.2 (confidence interval 29.1-31.3) after 2 years (Po0.001) corresponding to a 32% weight loss and a 76% loss of excess BMI. The 2-year weight loss was 31% in adult surgery patients, whereas 3% weight gain was seen in conventionally treated adolescents. At baseline, hyperinsulinemia (420 mU l À 1) was present in 70% of the adolescent surgery patients, which was reduced to 0% at 1 year and 3% at 2 years. Other cardiovascular risk factors were also improved. Two-thirds of adolescents undergoing surgery had a history of psychopathology. Nevertheless, the treatment was generally well tolerated and, overall, quality of life increased significantly. Adverse events were seen in 33% of patients. CONCLUSIONS: Adolescents with severe obesity demonstrated similar weight loss as adults following gastric bypass surgery yet demonstrating high prevalence of psychopathology at baseline. There were associated benefits for health and quality of life. Surgical and psychological challenges during follow-up require careful attention.
Five novel loci recently found to be associated with body mass in two GWAS of East Asian populati... more Five novel loci recently found to be associated with body mass in two GWAS of East Asian populations were evaluated in two cohorts of Swedish and Greek children and adolescents. These loci are located within, or in the proximity of: CDKAL1, PCSK1, GP2, PAX6 and KLF9. No association with body mass has previously been reported for these loci in GWAS performed on European populations. The single nucleotide polymorphisms (SNPs) with the strongest association at each loci in the East Asian GWAS were genotyped in two cohorts, one obesity case control cohort of Swedish children and adolescents consisting of 496 cases and 520 controls and one cross-sectional cohort of 2293 nine-to-thirteen year old Greek children and adolescents. SNPs were surveyed for association with body mass and other phenotypic traits commonly associated with obesity, including adipose tissue distribution, insulin resistance and daily caloric intake. No association with body mass was found in either cohort. However, among the Greek children, association with insulin resistance could be observed for the two CDKAL1-related SNPs: rs9356744 (b = 0.018, p = 0.014) and rs2206734 (b = 0.024, p = 0.001). CDKAL1-related variants have previously been associated with type 2 diabetes and insulin response. This study reports association of CDKAL1-related SNPs with insulin resistance, a clinical marker related to type 2 diabetes in a cross-sectional cohort of Greek children and adolescents of European descent.
The Swedish study Better Diabetes Diagnosis (BDD) has now been ongoing for ten years and detailed... more The Swedish study Better Diabetes Diagnosis (BDD) has now been ongoing for ten years and detailed information and blood samples have been collected from more than 8000 children and adolescents with newly diagnosed diabetes. We have been able to demonstrate that by means of HLA diabetes antibodies and C-peptide the discrimination between type one and type 2 diabetes is improved. These analyses are therefore included in the clinical check-up for all children and adolescents in Sweden who are diagnosed with diabetes. Type 1 diabetes is by far the most prevalent type of diabetes among Swedish children and adolescents. Type 2 diabetes is still relatively rare in Sweden but it is urgent to obtain a correct diagnosis as the long-term prognosis depends on a prompt pharmacological treatment. Monogenic diabetes (MODY) is also important to identify early. We therefore recommend that sequencing of MODY genes should be performed if an individual with newly-diagnosed diabetes is auto-antibody neg...
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2020
Purpose Metabolic and bariatric surgery (MBS) is increasingly used in adolescents. The aim was to... more Purpose Metabolic and bariatric surgery (MBS) is increasingly used in adolescents. The aim was to explore symptoms of depression and anxiety in young adults over 5 years’ follow-up after undergoing MBS. Methods Beck Depression Inventory-2 and the Beck Anxiety Inventory were used to assess symptoms of depression and anxiety in 62 patients 1, 2, and 5 years after having Roux-en-Y gastric bypass at 13–18 years of age. Mental health, eating-related problems, and weight outcomes were tested for association with suicidal ideation at the 5-year follow-up. Results At the 5-year follow-up, the mean score for depression was 11.4 (± 12.4), indicating minimal symptoms of depression. The mean score for anxiety was 12.82 (± 11.50), indicating mild anxiety symptoms. Still, several participants reported moderate or severe symptoms of depression (26%) and anxiety (32%). Women reported more symptoms than men (P = 0.03 and 0.04). No significant changes were found in self-reported symptoms of depressio...
HLA-DQA1 and -DQB1 are strongly associated with type 1 diabetes (T1D), and DQ8.1 and DQ2.5 are ma... more HLA-DQA1 and -DQB1 are strongly associated with type 1 diabetes (T1D), and DQ8.1 and DQ2.5 are major risk haplotypes. Next-generation targeted sequencing of HLA-DQA1 and -DQB1 in Swedish newly diagnosed 1- to 18 year-old patients (n = 962) and control subjects (n = 636) was used to construct abbreviated DQ haplotypes, converted into amino acid (AA) residues, and assessed for their associations with T1D. A hierarchically organized haplotype (HOH) association analysis allowed 45 unique DQ haplotypes to be categorized into seven clusters. The DQ8/9 cluster included two DQ8.1 risk and the DQ9 resistant haplotypes, and the DQ2 cluster included the DQ2.5 risk and DQ2.2 resistant haplotypes. Within each cluster, HOH found residues α44Q (odds ratio [OR] 3.29, P = 2.38 * 10−85) and β57A (OR 3.44, P = 3.80 * 10−84) to be associated with T1D in the DQ8/9 cluster representing all ten residues (α22, α23, α44, α49, α51, α53, α54, α73, α184, β57) due to complete linkage disequilibrium (LD) of α44 ...
Background and aims: Roux-en-Y gastric bypass is an effective obesity treatment in adults and is ... more Background and aims: Roux-en-Y gastric bypass is an effective obesity treatment in adults and is becoming established in adolescents. Information is scarce on long-term changes in dietary intake, nutritional status and energy metabolism in adolescents undergoing gastric bypass. The overall aim of this thesis is to study these phenomena, to help improve treatment protocols (which currently are based on adult patients). The aim is also to evaluate the accuracy of the dietary assessment method, diet history interview, against the gold standard method, doubly labeled water, in this population. Methods: Eighty-five adolescents (67% girls, mean age 16.5 years, mean BMI 45.5 kg/m 2) were followed in a longitudinal cohort study and assessed pre-surgically and at one, two and five years after gastric bypass surgery (paper I, II, and III). They completed diet history interviews (paper I, II, and III), including a form on adherence to prescribed supplementation (paper II), in addition, assessments on body composition (paper I and III), biochemistry (paper II), and energy expenditure (paper III). Eighty-one matched adolescents receiving conventional medical nutrition therapy for obesity, served as a nonsurgical control group, and were assessed at five years (paper I, II and III). The accuracy of the diet history interviews is evaluated in comparison to doubly labeled water (paper III). Results: Weight was decreased by 28% at five years following surgery while controls had gained 13%. Energy intake decreased (from preoperative 2558 kcal/day) by 34, 22 and 10% after one, two and five years. Dietary energy density decreased initially (at one year) but was no longer different at two years. Adherence to prescribed supplementation ranged between 44-61% through five years. Adhering to supplements was associated with more favorable biochemistry. By five years biochemistry showed a decrease in ferritin and hemoglobin and 61% had iron deficiency. Among females with iron deficiency, most did not adhere to supplementation, and 59% of these had anemia. A high prevalence of vitamin D insufficiency at baseline lasted through five years, and 80% of adolescents' nonadherent to supplementation had insufficiency at five years. Assessment of muscle mass showed better preservation in males and a protein intake ≥60 g/day was associated with preserved muscle mass. At five years adolescents who had undergone surgery and non-surgical controls had similar fat-free mass, total energy expenditure and resting energy expenditure. There was no vii association between reported energy intake from the diet history interviews and total energy expenditure measured with doubly labeled water in all adolescents. There was, however, a positive correlation in the surgically treated adolescents. Conclusion: Energy intake and dietary energy density might be important factors, in weight loss following gastric bypass surgery in adolescents. Adequate protein intake could possibly facilitate preservation of muscle mass following surgery. Results support current recommendations; on monitoring of micronutrient intake and biochemistry in all patients following gastric bypass surgery; higher (>800 IU/20 µg) preventive supplementation of vitamin D; and iron in both sexes. Despite large difference in weight and similar fat-free mass, five years after gastric bypass surgery or conventional medical nutrition therapy, total energy expenditure and resting energy expenditure was similar between the groups. The diet history interview did not capture total energy expenditure in young adults with obesity or severe obesity.
Aims/hypothesis By genome-wide association meta-analysis, 17 genetic loci associated with fasting... more Aims/hypothesis By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs). Methods Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women. Basal lipolytic activity was measured as glycerol release from adipose tissue explants. Adipocytes were isolated and insulin-stimulated incorporation of radiolabelled glucose into lipids was used to quantify adipocyte insulin sensitivity. Small interfering RNA-mediated knockout in human mesenchymal stem cells was used for functional evaluation of genes. Results Adipose expression of 48 of the studied candidate genes associated significantly with FSI, whereas expression of 24, 17 and 2 genes, respectively, associated with adipocyte insulin sensitivity, lipolysis and/or WAT morphology (i.e. fat cell size relative to total body fat mass). Four genetic loci contained eQTLs. In one chromosome 4 locus (rs3822072), the FSI-increasing allele associated with lower FAM13A expression and FAM13A expression associated with a beneficial metabolic profile including decreased WAT lipolysis (regression coefficient, R = −0.50, p = 5.6 × 10 −7). Knockdown of FAM13A increased lipolysis by~1.5fold and the expression of LIPE (encoding hormone-sensitive lipase, a rate-limiting enzyme in lipolysis). At the chromosome 7 locus (rs1167800), the FSI-increasing allele associated with lower POM121C expression. Consistent with an insulin-sensitising function, POM121C expression associated with systemic insulin sensitivity (R = −0.22, p = 2.0 × 10 −2), adipocyte insulin sensitivity (R = 0.28, p = 3.4 × 10 −3) and adipose hyperplasia (R = −0.29, p = 2.6 × 10 −2). POM121C knockdown decreased expression of all adipocyte-specific markers by 25-50%, suggesting that POM121C is necessary for adipogenesis. Conclusions/interpretation Gene expression and adipocyte functional studies support the notion that FAM13A and POM121C control adipocyte lipolysis and adipogenesis, respectively, and might thereby be involved in genetic control of systemic insulin sensitivity.
Objectives: This study explored the association between tissue transglutaminase autoantibody (tTG... more Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D). Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA). Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p ¼ .00001) and those with DQX/X (p .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p ¼ .018). Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.
Five-year changes in dietary intake and body composition in adolescents with severe obesity under... more Five-year changes in dietary intake and body composition in adolescents with severe obesity undergoing Laparoscopic Roux-en-Y Gastric Bypass surgery, Surgery for Obesity and Related Diseases (2018),
The prevalence of child and adolescent obesity has plateaued at high levels in most high-income c... more The prevalence of child and adolescent obesity has plateaued at high levels in most high-income countries and is increasing in many low-income and middle-income countries. Obesity arises when a mix of genetic and epigenetic factors, behavioural risk patterns and broader environmental and sociocultural influences affect the two body weight regulation systems: energy homeostasis, including leptin and gastrointestinal tract signals, operating predominantly at an unconscious level, and cognitive-emotional control that is regulated by higher brain centres, operating at a conscious level. Health-related quality of life is reduced in those with obesity. Comorbidities of obesity, including type 2 diabetes mellitus, fatty liver disease and depression, are more likely in adolescents and in those with severe obesity. Treatment incorporates a respectful, stigma-free and family-based approach involving multiple components, and addresses dietary, physical activity, sedentary and sleep behaviours. In adolescents in particular, adjunctive therapies can be valuable, such as more intensive dietary therapies, pharmacotherapy and bariatric surgery. Prevention of obesity requires a whole-system approach and joinedup policy initiatives across government departments. Development and implementation of interventions to prevent paediatric obesity in children should focus on interventions that are feasible, effective and likely to reduce gaps in health inequalities.
TO, CM and EG were involved in study conception, design, data collection and analysis, and writin... more TO, CM and EG were involved in study conception, design, data collection and analysis, and writing the manuscript. AB, GB and MN were involved in study design, data collection and analysis, and writing the manuscript. CEF, JD, KE, PF, GG, KJ, JK and SM were involved in study design, data collection and writing the manuscript. MP was involved in study design, data analysis and writing the manuscript. All authors had full access to all data and approved the final manuscript. Trial registration number-NCT00289705-ClinicalTrials.gov Conflicts of interest: TO reports receiving consulting fees for serving as a participant in the global advisory board and lecturing for Ethicon Endo surgery. TO has also received fees for lecturing for AstraZeneca and Sanofi. AJB reports receiving funding from the Royal College of Surgeons of England in the form of a clinical research fellowship. KJ reports receiving a lecturing fee from Nestlé. MN reports receiving consulting fees for participation in the scientific advisory committee of Itrim. Further, MN has received research grants from Pfizer, Cambridge Weight Plan, Novo Nordisk and Astra Zeneca; and lecture and consulting fees from Pfizer, Sanofi-Aventis, Roche and Strategic Health Resources. CM reports receiving consulting fees for participation in the scientific advisory committee of Itrim, Oriflame Wellnes and Sigrid Therapeutics AB. Further, CM has received research grants from Novo Nordisk. EG,
BACKGROUND: Pediatric obesity lifestyle treatment is not always successful. Frequent clinical vis... more BACKGROUND: Pediatric obesity lifestyle treatment is not always successful. Frequent clinical visits are of major importance to certify sufficient effect but are difficult due to the associated costs and the great demands on families. We hypothesized that an interactive digital support may reduce the need for frequent physical visits. The aim of the study was to assess 1-year weight outcome for patients using a digital support system compared with standard care. METHODS: An obesity lifestyle treatment with a digital support system was implemented in one clinic in Stockholm, Sweden. Measurements from a custom-made body scale without digits for daily home measurement of weights were transferred via Bluetooth to a mobile application, where BMI Z-score was calculated and presented graphically with an individualized weight loss target curve. An automatic transfer of data to the web-based clinic interface enables a close monitoring of treatment progress, and frequent written communication between the clinical staff and families via the application. One-year outcome was compared with a randomly retrieved, age and sex matched control group from the Swedish childhood obesity treatment register (BORIS), which received standard treatment at other clinics. Main outcome was change in BMI Z-score and missing data was imputed. RESULTS: 107 children were consecutively included to digi-physical treatment and 321 children to standard care. Age range 4.1-17.4 years (67% males). The attrition rate was 36% and 46% respectively, p = 0.08. After 1 year, the mean ± SD change in BMI Zscore in the treatment group was −0.30 ± 0.39 BMI Z-score units and in the standard care group −0.15 ± 0.28, p = 0.0002. The outcome was better for both sexes and all age groups in the digi-physical treated group. CONCLUSION: A digital support system with a personalized weight-loss target curve and daily weight measurements shared by the family and the clinic is more effective than a standard care childhood obesity treatment. CLINICALTRIAL.GOV ID: NCT04323215
Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, clos... more Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33), to be associated with body mass. STK33, a relatively understudied protein, has been linked to KRAS mutation-driven cancers and explored as a potential antineoplastic drug target. The strongest association with body mass observed at this loci in GWAS was rs4929949, a single nucleotide polymorphism located within intron 1 of the gene encoding STK33. The functional implications of rs4929949 or related variants have not been explored as of yet. We have genotyped rs4929949 in two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross-sectional cohort of 2308 Greek school children. We found that the minor allele of rs4929949 was associated with obesity in the cohort of Swedish children and adolescents (OR = 1.199 (95%CI: 1.002-1.434), p = 0.047), and with body mass in the cross-sectional cohort of Greek children (b = 0.08147 (95% CI: 0.1345-0.1618), p = 0.021). We observe the effects of rs4929949 on body mass to be detectable already at adolescence. Subsequent analysis did not detect any association of rs4929949 to phenotypic measurements describing body adiposity or to metabolic factors such as insulin levels, triglycerides and insulin resistance (HOMA).
Objective-Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothe... more Objective-Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes HLA-DQ risk genotypes may be associated with an increased body mass index (BMI). Design-The type 1 diabetes high risk HLA-DQ A1*05:01-B1*02:01/A1*03:01-B1*03:02 genotype along with lower risk DQ genotypes were determined at the time of clinical onset by Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
overexpression of the one located closely to the olfactory receptor 1322 gene exerted in a mouse ... more overexpression of the one located closely to the olfactory receptor 1322 gene exerted in a mouse hepatoma cell line the robust transcriptional regulatory activity on ~100 proteincoding genes that were accumulated in several distinct biological pathways. Our results indicate that mouse serum contains biologically active intergenic sncRNAs in addition to other known forms. The results also suggest their potential biological importance and/or usefulness in disease diagnosis and treatment in humans.
Objective: Preventive measures to contain the epidemic of obesity have become a major focus of at... more Objective: Preventive measures to contain the epidemic of obesity have become a major focus of attention. This report reviews the scientific evidence for medical interventions aimed at preventing obesity during childhood and adolescence. Design: A systematic literature review involving selection of primary research and other systematic reviews. Articles published until 2004 were added to an earlier (2002) review by the Swedish Council on Technology Assessment in Health Care. Methods: Inclusion criteria required controlled studies with follow-up of at least 12 months and results measured as body mass index, skinfold thickness or the percentage of overweight/obesity. Children could be recruited from normal or high-risk populations. Results: Combining the new data with the previous review resulted in an evaluation of 24 studies involving 25 896 children. Of these, eight reported that prevention had a statistically significant positive effect on obesity, 16 reported neutral results and none reported a negative result (sign test; P ¼ 0.0078). Adding the studies included in five other systematic reviews yielded, in total, 15 studies with positive, 24 with neutral and none with negative results. Thus, 41% of the studies, including 40% of the 33 852 children studied, showed a positive effect from prevention. These results are unlikely to be a random chance phenomenon (P ¼ 0.000061). Conclusion: Evidence shows that it is possible to prevent obesity in children and adolescents through limited, school-based programs that combine the promotion of healthy dietary habits and physical activity.
Background: To increase the knowledge about physical activity (PA) patterns and correlates among ... more 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.
IMPORTANCE There is a lack of studies evaluating sleeve gastrectomy compared with intensive lifes... more IMPORTANCE There is a lack of studies evaluating sleeve gastrectomy compared with intensive lifestyle treatment in patients with class 1 obesity (body mass index [BMI] 30 to <35 [calculated as weight in kilograms divided by height in meters squared]). OBJECTIVE To compare outcomes and safety of sleeve gastrectomy compared with intensive nonoperative obesity treatment in patients with class 1 obesity. DESIGN, SETTING, AND PARTICIPANTS This matched, nationwide cohort study included patients with class 1 obesity who underwent a sleeve gastrectomy or intensive lifestyle treatment between January 1, 2012, and December 31, 2017, and who were registered in the Scandinavian Obesity Surgery Registry or the Itrim health database. Participants with class 1 obesity were matched 1:2 using a propensity score including age, sex, BMI, treatment year, education level, income, cardiovascular disease, and use of antibiotic drugs, antidepressants, and anxiolytics. INTERVENTIONS Sleeve gastrectomy or intensive lifestyle treatment. MAIN OUTCOMES AND MEASURES Outcomes included weight loss after intervention, changes in metabolic comorbidities, substance use disorders, self-harm, and major cardiovascular events
Introduction: The obesity epidemic has become one of the most important public health issues of m... more Introduction: The obesity epidemic has become one of the most important public health issues of modern times. Impaired insulin sensitivity seems to be the cornerstone of multiple obesity related comorbidities. However, there is no accepted definition of impaired insulin sensitivity. Objective: We hypothesize that assessment of insulin resistance differs between centers. Methods: The ESPE Obesity Working Group (ESPE ObWG) Scientific Committee developed a questionnaire with a focus on the routine practices of assessment of hyperinsulinemia and insulin resistance, which was distributed through Google Docs platform to the clinicians and researchers from the current ESPE ObWG database (n = 73). Sixty-one complete responses (84% response rate) from clinicians and researchers were analyzed: 32 from European Union (EU) centers (representatives of 14 countries) and 29 from Non-EU centers (representatives from 10 countries). Standard statistics were used for the data analysis. Results: The ma...
BACKGROUND Obesity is a chronic disease with limited treatment options in pediatric patients. Lir... more BACKGROUND Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity. METHODS In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56. RESULTS A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, -4.64 percentage points) and for body weight (estimated difference, -4.50 kg [for absolute change] and -5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment. CONCLUSIONS In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).
The prevalence of obesity among adolescents has increased and we lack effective treatments. OBJEC... more The prevalence of obesity among adolescents has increased and we lack effective treatments. OBJECTIVE: To determine if gastric bypass is safe and effective for an unselected cohort of adolescents with morbid obesity in specialized health care. DESIGN, SETTING AND PATIENTS: Intervention study for 81 adolescents (13-18 years) with a body mass index (BMI) range 36-69 kg m À 2 undergoing laparoscopic gastric bypass surgery in a university hospital setting in Sweden between April 2006 and May 2009. For weight change comparisons, we identified an adult group undergoing gastric bypass surgery (n ¼ 81) and an adolescent group (n ¼ 81) receiving conventional care. MAIN OUTCOME MEASUREMENTS: Two-year outcome regarding BMI in all groups, and metabolic risk factors and quality of life in the adolescent surgery group. RESULTS: Two-year follow-up rate was 100% in both surgery groups and 73% in the adolescent comparison group. In adolescents undergoing surgery, BMI was 45.5 ± 6.1 (mean ± s.d.) at baseline and 30.2 (confidence interval 29.1-31.3) after 2 years (Po0.001) corresponding to a 32% weight loss and a 76% loss of excess BMI. The 2-year weight loss was 31% in adult surgery patients, whereas 3% weight gain was seen in conventionally treated adolescents. At baseline, hyperinsulinemia (420 mU l À 1) was present in 70% of the adolescent surgery patients, which was reduced to 0% at 1 year and 3% at 2 years. Other cardiovascular risk factors were also improved. Two-thirds of adolescents undergoing surgery had a history of psychopathology. Nevertheless, the treatment was generally well tolerated and, overall, quality of life increased significantly. Adverse events were seen in 33% of patients. CONCLUSIONS: Adolescents with severe obesity demonstrated similar weight loss as adults following gastric bypass surgery yet demonstrating high prevalence of psychopathology at baseline. There were associated benefits for health and quality of life. Surgical and psychological challenges during follow-up require careful attention.
Five novel loci recently found to be associated with body mass in two GWAS of East Asian populati... more Five novel loci recently found to be associated with body mass in two GWAS of East Asian populations were evaluated in two cohorts of Swedish and Greek children and adolescents. These loci are located within, or in the proximity of: CDKAL1, PCSK1, GP2, PAX6 and KLF9. No association with body mass has previously been reported for these loci in GWAS performed on European populations. The single nucleotide polymorphisms (SNPs) with the strongest association at each loci in the East Asian GWAS were genotyped in two cohorts, one obesity case control cohort of Swedish children and adolescents consisting of 496 cases and 520 controls and one cross-sectional cohort of 2293 nine-to-thirteen year old Greek children and adolescents. SNPs were surveyed for association with body mass and other phenotypic traits commonly associated with obesity, including adipose tissue distribution, insulin resistance and daily caloric intake. No association with body mass was found in either cohort. However, among the Greek children, association with insulin resistance could be observed for the two CDKAL1-related SNPs: rs9356744 (b = 0.018, p = 0.014) and rs2206734 (b = 0.024, p = 0.001). CDKAL1-related variants have previously been associated with type 2 diabetes and insulin response. This study reports association of CDKAL1-related SNPs with insulin resistance, a clinical marker related to type 2 diabetes in a cross-sectional cohort of Greek children and adolescents of European descent.
The Swedish study Better Diabetes Diagnosis (BDD) has now been ongoing for ten years and detailed... more The Swedish study Better Diabetes Diagnosis (BDD) has now been ongoing for ten years and detailed information and blood samples have been collected from more than 8000 children and adolescents with newly diagnosed diabetes. We have been able to demonstrate that by means of HLA diabetes antibodies and C-peptide the discrimination between type one and type 2 diabetes is improved. These analyses are therefore included in the clinical check-up for all children and adolescents in Sweden who are diagnosed with diabetes. Type 1 diabetes is by far the most prevalent type of diabetes among Swedish children and adolescents. Type 2 diabetes is still relatively rare in Sweden but it is urgent to obtain a correct diagnosis as the long-term prognosis depends on a prompt pharmacological treatment. Monogenic diabetes (MODY) is also important to identify early. We therefore recommend that sequencing of MODY genes should be performed if an individual with newly-diagnosed diabetes is auto-antibody neg...
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2020
Purpose Metabolic and bariatric surgery (MBS) is increasingly used in adolescents. The aim was to... more Purpose Metabolic and bariatric surgery (MBS) is increasingly used in adolescents. The aim was to explore symptoms of depression and anxiety in young adults over 5 years’ follow-up after undergoing MBS. Methods Beck Depression Inventory-2 and the Beck Anxiety Inventory were used to assess symptoms of depression and anxiety in 62 patients 1, 2, and 5 years after having Roux-en-Y gastric bypass at 13–18 years of age. Mental health, eating-related problems, and weight outcomes were tested for association with suicidal ideation at the 5-year follow-up. Results At the 5-year follow-up, the mean score for depression was 11.4 (± 12.4), indicating minimal symptoms of depression. The mean score for anxiety was 12.82 (± 11.50), indicating mild anxiety symptoms. Still, several participants reported moderate or severe symptoms of depression (26%) and anxiety (32%). Women reported more symptoms than men (P = 0.03 and 0.04). No significant changes were found in self-reported symptoms of depressio...
HLA-DQA1 and -DQB1 are strongly associated with type 1 diabetes (T1D), and DQ8.1 and DQ2.5 are ma... more HLA-DQA1 and -DQB1 are strongly associated with type 1 diabetes (T1D), and DQ8.1 and DQ2.5 are major risk haplotypes. Next-generation targeted sequencing of HLA-DQA1 and -DQB1 in Swedish newly diagnosed 1- to 18 year-old patients (n = 962) and control subjects (n = 636) was used to construct abbreviated DQ haplotypes, converted into amino acid (AA) residues, and assessed for their associations with T1D. A hierarchically organized haplotype (HOH) association analysis allowed 45 unique DQ haplotypes to be categorized into seven clusters. The DQ8/9 cluster included two DQ8.1 risk and the DQ9 resistant haplotypes, and the DQ2 cluster included the DQ2.5 risk and DQ2.2 resistant haplotypes. Within each cluster, HOH found residues α44Q (odds ratio [OR] 3.29, P = 2.38 * 10−85) and β57A (OR 3.44, P = 3.80 * 10−84) to be associated with T1D in the DQ8/9 cluster representing all ten residues (α22, α23, α44, α49, α51, α53, α54, α73, α184, β57) due to complete linkage disequilibrium (LD) of α44 ...
Background and aims: Roux-en-Y gastric bypass is an effective obesity treatment in adults and is ... more Background and aims: Roux-en-Y gastric bypass is an effective obesity treatment in adults and is becoming established in adolescents. Information is scarce on long-term changes in dietary intake, nutritional status and energy metabolism in adolescents undergoing gastric bypass. The overall aim of this thesis is to study these phenomena, to help improve treatment protocols (which currently are based on adult patients). The aim is also to evaluate the accuracy of the dietary assessment method, diet history interview, against the gold standard method, doubly labeled water, in this population. Methods: Eighty-five adolescents (67% girls, mean age 16.5 years, mean BMI 45.5 kg/m 2) were followed in a longitudinal cohort study and assessed pre-surgically and at one, two and five years after gastric bypass surgery (paper I, II, and III). They completed diet history interviews (paper I, II, and III), including a form on adherence to prescribed supplementation (paper II), in addition, assessments on body composition (paper I and III), biochemistry (paper II), and energy expenditure (paper III). Eighty-one matched adolescents receiving conventional medical nutrition therapy for obesity, served as a nonsurgical control group, and were assessed at five years (paper I, II and III). The accuracy of the diet history interviews is evaluated in comparison to doubly labeled water (paper III). Results: Weight was decreased by 28% at five years following surgery while controls had gained 13%. Energy intake decreased (from preoperative 2558 kcal/day) by 34, 22 and 10% after one, two and five years. Dietary energy density decreased initially (at one year) but was no longer different at two years. Adherence to prescribed supplementation ranged between 44-61% through five years. Adhering to supplements was associated with more favorable biochemistry. By five years biochemistry showed a decrease in ferritin and hemoglobin and 61% had iron deficiency. Among females with iron deficiency, most did not adhere to supplementation, and 59% of these had anemia. A high prevalence of vitamin D insufficiency at baseline lasted through five years, and 80% of adolescents' nonadherent to supplementation had insufficiency at five years. Assessment of muscle mass showed better preservation in males and a protein intake ≥60 g/day was associated with preserved muscle mass. At five years adolescents who had undergone surgery and non-surgical controls had similar fat-free mass, total energy expenditure and resting energy expenditure. There was no vii association between reported energy intake from the diet history interviews and total energy expenditure measured with doubly labeled water in all adolescents. There was, however, a positive correlation in the surgically treated adolescents. Conclusion: Energy intake and dietary energy density might be important factors, in weight loss following gastric bypass surgery in adolescents. Adequate protein intake could possibly facilitate preservation of muscle mass following surgery. Results support current recommendations; on monitoring of micronutrient intake and biochemistry in all patients following gastric bypass surgery; higher (>800 IU/20 µg) preventive supplementation of vitamin D; and iron in both sexes. Despite large difference in weight and similar fat-free mass, five years after gastric bypass surgery or conventional medical nutrition therapy, total energy expenditure and resting energy expenditure was similar between the groups. The diet history interview did not capture total energy expenditure in young adults with obesity or severe obesity.
Aims/hypothesis By genome-wide association meta-analysis, 17 genetic loci associated with fasting... more Aims/hypothesis By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs). Methods Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women. Basal lipolytic activity was measured as glycerol release from adipose tissue explants. Adipocytes were isolated and insulin-stimulated incorporation of radiolabelled glucose into lipids was used to quantify adipocyte insulin sensitivity. Small interfering RNA-mediated knockout in human mesenchymal stem cells was used for functional evaluation of genes. Results Adipose expression of 48 of the studied candidate genes associated significantly with FSI, whereas expression of 24, 17 and 2 genes, respectively, associated with adipocyte insulin sensitivity, lipolysis and/or WAT morphology (i.e. fat cell size relative to total body fat mass). Four genetic loci contained eQTLs. In one chromosome 4 locus (rs3822072), the FSI-increasing allele associated with lower FAM13A expression and FAM13A expression associated with a beneficial metabolic profile including decreased WAT lipolysis (regression coefficient, R = −0.50, p = 5.6 × 10 −7). Knockdown of FAM13A increased lipolysis by~1.5fold and the expression of LIPE (encoding hormone-sensitive lipase, a rate-limiting enzyme in lipolysis). At the chromosome 7 locus (rs1167800), the FSI-increasing allele associated with lower POM121C expression. Consistent with an insulin-sensitising function, POM121C expression associated with systemic insulin sensitivity (R = −0.22, p = 2.0 × 10 −2), adipocyte insulin sensitivity (R = 0.28, p = 3.4 × 10 −3) and adipose hyperplasia (R = −0.29, p = 2.6 × 10 −2). POM121C knockdown decreased expression of all adipocyte-specific markers by 25-50%, suggesting that POM121C is necessary for adipogenesis. Conclusions/interpretation Gene expression and adipocyte functional studies support the notion that FAM13A and POM121C control adipocyte lipolysis and adipogenesis, respectively, and might thereby be involved in genetic control of systemic insulin sensitivity.
Objectives: This study explored the association between tissue transglutaminase autoantibody (tTG... more Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D). Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18 years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA). Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p ¼ .00001) and those with DQX/X (p .00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p ¼ .018). Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.
Five-year changes in dietary intake and body composition in adolescents with severe obesity under... more Five-year changes in dietary intake and body composition in adolescents with severe obesity undergoing Laparoscopic Roux-en-Y Gastric Bypass surgery, Surgery for Obesity and Related Diseases (2018),
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Papers by Claude Marcus