Rasmus Stenlid

All Publications

• The GLP-1 Agonist Exenatide Is Associated with Improved Adherence to Health Behavior and Lifestyle Treatment in Adolescents with Obesity: A Randomized Controlled Trial. Obesity facts Stenlid, R., Cerenius, S. Y., Torbahn, G., Aydin, B. K., Ciba, I., Vilén, H., Mörwald, K., Geiersberger, S., Roomp, K., Cadamuro, J., Gomahr, J., Lischka, J., Weghuber, D., Bergsten, P., Forslund, A., Manell, H. 2026: 1-12

  Abstract

  We aimed to study the effects of the glucagon-like peptide-1 receptor agonist exenatide on behavioral outcomes in children and adolescents with obesity.This study reports pre-specified secondary outcomes of a randomized, double-blind, placebo-controlled trial in adolescents with obesity, aged 10-18 years. Participants (n = 44) were randomized to 6 months treatment with exenatide or placebo, along with a lifestyle intervention consisting of nutritional advice from a dietitian and sessions with a psychologist to optimize physical activity. Change in choices of food and drink, portion sizes, meal frequency, sleep, screen time, and physical activity were assessed by 6-min walking test, accelerometry, and questionnaires.Exenatide treatment was associated with improved adherence to choices of recommended food and drinks (score change 4.34, 95% CI: 1.05-7.63, p = 0.01, Hedges' g 0.82, 95% CI: 0.17-1.49), decreased portion size (score change -4.05, 95% CI: -6.51 to -1.58, p = 0.002, Hedges' g -1.29, 95% CI: -2.13 to -0.45), and increased self-reported physical activity (1.82 h, 95% CI: 0.68-2.96, p = 0.002 Hedges' g 0.97, 95% CI: 0.33-1.62), while no differences in meal frequency, snacking, sleep, screen time, objectively measured physical fitness or activity were found.Exenatide treatment was associated with modest improvements in selected self-reported dietary behaviors, including improved adherence to recommended food and drink choices and reduced portion sizes, as well as increased self-reported physical activity, although no changes were observed in objective measures of physical activity or other lifestyle factors.

  View details for DOI 10.1159/000552826

  View details for PubMedID 42228680

  View details for PubMedCentralID PMC13395467

• Combining GLP-1 Receptor Agonists and Health-Behaviour and Lifestyle Therapy Yields Higher Adherence and Reduces Session Needs for Successful Weight Management in Adolescence: An Observational Real-World Single-Center Study. Pediatric obesity Lischka, J., Torbahn, G., Vallis, M., Mörwald, K., Gomahr, J., Forslund, A., Stenlid, R., Manell, H., Bergsten, P., Geiersberger, S., Bergauer, M., Forer, L., Lauth, W., Jabbour, J., Döttl, L., Swittalek, M., Lanzinger, S., Weghuber, D. 2026; 21 (6): e70122

  Abstract

  Evidence for the role of health behaviour and lifestyle treatment (HBLT) on the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in paediatric obesity is limited.To assess the role of HBLT on the effectiveness of GLP-1RAs in youth with obesity.Patients aged 8-18 years with obesity (n = 51) receiving liraglutide were retrospectively divided into continuers (ongoing liraglutide treatment), discontinuers, or switches to semaglutide or metabolic-bariatric surgery. All were offered multidisciplinary HBLT and consecutively allocated to either high-frequency (HF) HBLT (≥ 26 contact hours/year) or low-frequency obesity medication (OM)-specific HBLT (9 contacts of 0.5 h/year).After 9.7 ± 6.6 months, a BMI reduction of ≥ 5% and ≥ 10% was observed in 37.3% and 13.7%, respectively. Relative change in BMI was higher in continuers compared to discontinuers (-6.7% ± 7.5% vs. -0.7% ± 5.1%, p = 0.03). Whereas 39.2% of patients continued liraglutide, 33.3% discontinued, mainly due to gastrointestinal symptoms. 27.4% of patients switched treatment to semaglutide or underwent surgery. Patients with combined HBLT and liraglutide had markedly higher odds of continuation (OR 18.5, 95% CI 2.0-929.8, p < 0.01) and greater reductions in BMI, which was by trend higher with OM-HBLT compared to HF-HBLT (BMI change -6.9% ± 7.2% vs. -4.0% ± 6.6%).GLP-1RAs were effective in the real-world treatment of paediatric obesity. HBLT appears to be essential to increase persistence and efficacy of GLP-1RAs.

  View details for DOI 10.1111/ijpo.70122

  View details for PubMedID 42222894

• Evaluation of BMI Growth Charts for Children Living with Severe Obesity. Childhood obesity (Print) Engsner, M., Ciba, I., Aydin, B., Stenlid, R., Söderhäll, J., Bergsten, P., Forslund, A. 2025; 21 (7): 629-639

  Abstract

  Introduction: Growth charts were not designed to monitor children and adolescents with severe obesity. We evaluate three commonly used international references and their implications for children with severe obesity and develop a BMI growth chart for children with severe obesity, which we call "Reference-point BMI from adjusted World Health Organization (WHO) population" (R-BMI). Method: Growth charts from the WHO, International Obesity Task Force, and CDC were reviewed regarding population, statistical method, and cut-offs. We created the R-BMI chart from the WHO population, with adapted adjustment and reference-point cut-offs, and the layout was updated for better readability. Moreover, an interactive web app was developed for this project at the following link https://child-bmi.serve.scilifelab.se/ with the purpose of visually comparing different BMI references for children with obesity. Results: Three different references for children with severe obesity, with corresponding adjustments, are presented to illustrate implications for researchers and clinicians. Furthermore, R-BMI is presented as a method attempting to address chart challenges related to the extreme BMI. The result is reference curves which share desirable features with established references, while avoiding undesirable curve behavior. Conclusions: Growth charts present challenges for children living with severe obesity, leading to varying approaches and implications of international references. The proposed R-BMI offers monitoring of children with severe obesity that can be used from birth to adulthood. It relates to adult BMI cut-offs and allows for a terminology, and it has a layout with the potential of highlighting changes which may otherwise go unnoticed.

  View details for DOI 10.1089/chi.2024.0423

  View details for PubMedID 40569712

• Asthma diagnosis is not associated with reduced beta-cell function in children and adolescents with obesity. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology Manell, H., Stenlid, R., Alving, K. 2025; 36 (9): e70198

  View details for DOI 10.1111/pai.70198

  View details for PubMedID 40898379

  View details for PubMedCentralID PMC12405603

• Cardiometabolic risk stratification in pediatric obesity: evaluating the clinical utility of fasting insulin and BMI-SDS. Cardiovascular diabetology Stenlid, R., El Amrani, S., Cerenius, S. Y., Aydin, B. K., Manell, H., Mörwald, K., Lischka, J., Gomahr, J., Pixner, T., Ciba, I., James, S. K., Forslund, A., Weghuber, D., Bergsten, P. 2025; 24 (1): 324

  Abstract

  Patients with obesity during childhood have an increased risk of fatal and non-fatal cardiovascular events during adulthood. The severity of obesity is commonly determined by BMI. However, children with relatively low BMI may have high cardiometabolic risk. Indeed, BMI-based obesity classifications might miss children at high cardiometabolic risk. Insulin has been suggested as a marker of cardiometabolic risk. In this study, we therefore estimated and compared cardiometabolic risk using either the BMI standard deviation score (BMI-SDS) or fasting insulin in an international cohort of children and adolescents with obesity and lean controls.Study participants (712 with obesity and 99 lean controls), aged 3 to 18 years, were categorized according to their BMI-SDS as lean or obesity class I, II, or III, or by their fasting insulin quartiles as quartile 1, 2, 3, or 4 with the lean subjects in a separate control group. Prevalence of cardiometabolic risk factors was assessed in each group. Sensitivity and specificity analyses for cardiometabolic risk were conducted for both BMI-SDS and fasting insulin. Multiple regression, logistic regression, and receiver operating characteristic (ROC) analyses were performed between fasting insulin, BMI-SDS and cardiometabolic risk factors.An elevated prevalence of the cardiometabolic risk factors dyslipidemia, dysglycemia and hypertension was observed in both increasing BMI-SDS classes and increasing fasting insulin quartiles. Fasting insulin demonstrated higher areas under the curve (AUC) for detecting dyslipidemia, dysglycemia, and the combination of dyslipidemia, dysglycemia, and hypertension, compared to BMI-SDS. BMI-SDS demonstrated a higher AUC for detecting hypertension compared to fasting insulin. The same patterns were seen for the logistic regression. However, fasting insulin had an overall stronger association with the cardiometabolic risk factors studied compared to BMI-SDS.In children and adolescents with obesity, fasting insulin provides complementary information to BMI-SDS in identifying those with elevated cardiometabolic risk factors. While neither marker alone offers strong predictive accuracy, incorporating fasting insulin into clinical assessment may help prioritize individuals who require more detailed evaluation. An elevated fasting insulin value may warrant further investigation among children and adolescents with obesity, independent of obesity class based on BMI-SDS.

  View details for DOI 10.1186/s12933-025-02882-7

  View details for PubMedID 40781672

  View details for PubMedCentralID PMC12335099

• Obesity-related subclinical hypothyroidism in childhood: Elevated triglycerides but not basal metabolic rate. Pediatric research Tersander, B., Olsson, R., Aydin, B. K., Stenlid, R., Ciba, I., Manell, H. 2025; 98 (1): 182-187

  Abstract

  Studies on the associations between obesity-related subclinical hypothyroidism with basal metabolic rate and risk factors of cardiovascular disease in children and adolescents are scarce.Retrospective cohort study of children with obesity (n = 294) from the Uppsala Longitudinal Study of Childhood Obesity cohort. Differences in basal metabolic rate quantified by indirect calorimetry, and the cardiovascular risk factors; body mass index, blood lipids, fasting and 2 h oral glucose tolerance test glucose, glycated haemoglobin and insulin resistance, between subjects with and without subclinical hypothyroidism were investigated. The associations of baseline thyroid stimulating hormone (TSH) and ΔTSH with change in cardiovascular risk factors over time were assessed.Subjects with subclinical hypothyroidism had elevated triacylglycerides but no alterations in basal metabolic rate or other measured cardiovascular risk factors. ΔTSH was positively associated with Δtriacylglycerides, Δtotal-cholesterol and ΔLDL-cholesterol, independently of age, sex, Δbody mass index and ΔT4. In the subclinical hypothyroidism group, 92% of individuals normalised their TSH 0.9-2.9 years later.Children with obesity and subclinical hypothyroidism did not have an altered basal metabolic rate but elevated triacylglycerides. During the follow-up period, TSH changed in parallel with several blood lipids. Elevated TSH often normalised without pharmaceutical intervention within 3 years.The present study found that subclinical hypothyroidism in paediatric obesity is related to elevated triglycerides. The present study found that subclinical hypothyroidism is not associated to basal metabolic rate in paediatric obesity. TSH change over time correlated with the change in triglycerides and LDL and total cholesterol. Among subjects with subclinical hypothyroidism at baseline 92% normalised without pharmaceutical intervention within 3 years. This research adds to the knowledge of the longitudinal, natural course of elevated TSH in paediatric obesity which is expected to help to make informed decisions regarding follow-up and evaluation of this patient group.

  View details for DOI 10.1038/s41390-024-03691-6

  View details for PubMedID 39501062

  View details for PubMedCentralID PMC12411271

• Hormonal Crossroads in Inborn Errors of the Metabolism Impact of Puberty and Dietary Interventions on Metabolic Health. Metabolites Lundqvist, T., Stenlid, R., Halldin, M. 2025; 15 (4)

  Abstract

  Background/Objectives: Inborn errors of metabolism (IEMs) represent a diverse group of genetic disorders characterized by enzymatic defects that disrupt metabolic pathways, leading to toxic metabolite accumulation, deficits, or impaired macromolecule synthesis. While strict dietary interventions are critical for managing many of these conditions, hormonal and metabolic changes during puberty introduce new challenges. Advancements in early diagnosis and treatment have significantly extended the lifespan of individuals with IEMs. However, this increased longevity is associated with heightened risks of new medical problems, including obesity, insulin resistance, and type 2 diabetes mellitus (T2DM), as these complications share mechanistic features with those seen in obesity and T2DM. Methods: This mini-review examines current knowledge of the intricate interplay between pubertal hormones and metabolic pathways in IEM patients. Results: We address critical questions, such as if puberty intensifies the risk of metabolic derangements in these individuals and if there is a metabolic intersection where these disorders converge, leading to shared complications. We highlight the impact of puberty-induced hormonal fluctuations, such as growth hormone (GH) surges and sex steroid activity, on disorders like phenylketonuria, urea cycle defects, and fatty acid oxidation disorders. Moreover, we explore the role of dietary interventions in mitigating or exacerbating these effects, emphasizing the importance of balancing nutritional needs during growth spurts. Conclusions: A multidisciplinary approach integrating endocrinology, nutrition, and emerging therapies is advocated to optimize metabolic health during puberty. Addressing these challenges is critical for improving long-term outcomes for individuals with IEMs, particularly during this pivotal developmental phase.

  View details for DOI 10.3390/metabo15040235

  View details for PubMedID 40278364

  View details for PubMedCentralID PMC12029320

• Metformin restores prohormone processing enzymes and normalizes aberrations in secretion of proinsulin and insulin in palmitate-exposed human islets. Diabetes, obesity & metabolism Wen, Q., Chowdhury, A. I., Aydin, B., Shekha, M., Stenlid, R., Forslund, A., Bergsten, P. 2023; 25 (12): 3757-3765

  Abstract

  To elucidate how proinsulin synthesis and insulin was affected by metformin under conditions of nutrient overstimulation.Isolated human pancreatic islets from seven donors were cultured at 5.5 mmol/L glucose and 0.5 mmol/L palmitate for 12, 24 or 72 h. Metformin (25 μmol/L) was introduced after initial 12 h with palmitate. Proinsulin and insulin were measured. Expression of prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE), was determined by western blot. Adolescents with obesity, treated with metformin and with normal glucose tolerance (n = 5), prediabetes (n = 14), or type 2 diabetes (T2DM; n = 7) were included. Fasting proinsulin, insulin, glucose, 2-h glucose and glycated haemoglobin were measured. Proinsulin/insulin ratio (PI/I) was calculated.In human islets, palmitate treatment for 12 and 24 h increased proinsulin and insulin proportionally. After 72 h, proinsulin but not insulin continued to increase which was coupled with reduced expression of PC1/3 and CPE. Metformin normalized expression of PC1/3 and CPE, and proinsulin and insulin secretion. In adolescents with obesity, before treatment, fasting proinsulin and insulin concentrations were higher in subjects with T2DM than with normal glucose tolerance. PI/I was reduced after metformin treatment in subjects with T2DM as well as in subjects with prediabetes, coupled with reduced 2-h glucose and glycated haemoglobin.Metformin normalized proinsulin and insulin secretion after prolonged nutrient-overstimulation, coupled with normalization of the converting enzymes, in isolated islets. In adolescents with obesity, metformin treatment was associated with improved PI/I, which was coupled with improved glycaemic control.

  View details for DOI 10.1111/dom.15270

  View details for PubMedID 37694762

• Adolescents with obesity treated with exenatide maintain endogenous GLP-1, reduce DPP-4, and improve glycemic control. Frontiers in endocrinology Stenlid, R., Cerenius, S. Y., Wen, Q., Aydin, B. K., Manell, H., Chowdhury, A., Kristinsson, H., Ciba, I., Gjessing, E. S., Mörwald, K., Gomahr, J., Heu, V., Weghuber, D., Forslund, A., Bergsten, P. 2023; 14: 1293093

  Abstract

  GLP-1 receptor agonists (GLP-1RA) are increasingly used to treat adolescent obesity. However, the effect on endogenous GLP-1 secretory patterns following treatment in adolescents is unknown. The GLP-1RA exenatide was shown to significantly lower BMI and 2-hour glucose in adolescents with obesity, in the placebo-controlled, randomized controlled trial Combat-JUDO. The aim of this study was to evaluate effects of weekly injections of 2 mg exenatide extended release on secretory patterns of endogenous hormones during OGTT.This study was a pre-planned sub-study of the Combat-JUDO trial, set at the Pediatric clinic at Uppsala University Hospital, Sweden and Paracelsus Medical University, Austria. 44 adolescents with obesity were included and randomized 1:1 to treatment:placebo. 19 patients in the treatment group and 18 in the placebo group completed the trial. Before and after treatment, GLP-1, glucose, insulin, glucagon and glicentin levels were measured during OGTT; DPP-4 and proinsulin were measured at fasting. A per-protocol approach was used in the analyses.Exenatide treatment did not affect GLP-1 levels during OGTT. Treatment significantly lowered DPP-4, proinsulin and the proinsulin-to-insulin ratio at fasting, increased glicentin levels but did not affect insulin, C-peptide or glucagon levels during OGTT.Weekly s.c. injections with 2 mg of exenatide maintains endogenous total GLP-1 levels and lowers circulating DPP-4 levels. This adds an argument in favor of using exenatide in the treatment of pediatric obesity.clinicaltrials.gov, identifier NCT02794402.

  View details for DOI 10.3389/fendo.2023.1293093

  View details for PubMedID 38027106

  View details for PubMedCentralID PMC10646558

• Screening for Inflammatory Markers Identifies IL-18Rα as a Potential Link between Exenatide and Its Anti-Inflammatory Effect: New Results from the Combat-JUDO Randomized Controlled Trial. Annals of nutrition & metabolism Stenlid, R., Cerenius, S. Y., Manell, H., Küçükemre Aydin, B., Mörwald, K., Gomahr, J., Höghammar Mitkas, M., Eriksson, I., Ciba, I., Geiersberger, S., Thivel, D., Weghuber, D., Bergsten, P., Forslund, A. 2023; 79 (6): 522-527

  Abstract

  Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, metabolic associated fatty liver disease, and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor analogs (GLP-1RA) are clinically used to treat obesity, with known anti-inflammatory properties. How the GLP-1RA exenatide effects inflammation in adolescents with obesity is not fully investigated.Forty-four patients were randomized to receive weekly subcutaneous injections with either 2 mg exenatide or placebo for 6 months. Plasma samples were collected at baseline and at the end of the study, and 92 inflammatory proteins were measured.Following treatment with exenatide, 15 out of the 92 proteins were decreased, and one was increased. However, after adjustment for multiple testing, only IL-18Rα was significantly lowered following treatment.Weekly injections with 2 mg of exenatide lowers circulating IL-18Rα in adolescents with obesity, which may be a potential link between exenatide and its anti-inflammatory effect in vivo. This contributes to exenatide's pharmaceutical potential as a treatment for obesity beyond weight control and glucose tolerance, and should be further studied mechanistically.

  View details for DOI 10.1159/000534725

  View details for PubMedID 37883939

• Metformin Can Attenuate Beta-Cell Hypersecretion-Implications for Treatment of Children with Obesity. Metabolites Wen, Q., Stenlid, R., Chowdhury, A. I., Ciba, I., Aydin, B., Cerenius, S. Y., Manell, H., Forslund, A., Bergsten, P. 2023; 13 (8)

  Abstract

  In children with obesity, insulin hypersecretion is proposed to precede insulin resistance. We investigated if metformin could be used to attenuate insulin secretion from palmitate-treated isolated islets and its implication for children with obesity. Human islets were exposed to palmitate for 0.5 or 1 day, when metformin was introduced. After culture, glucose-stimulated insulin secretion (GSIS) was measured. Children with obesity, who had received metformin for over six months (n = 21, age 13.9 ± 1.8), were retrospectively evaluated. Children were classified as either "reducing" or "increasing" based on the difference between AUC0-120 of insulin during OGTT before and after metformin treatment. In human islets, GSIS increased after culture in palmitate for up to 1 day but declined with continued palmitate exposure. Whereas adding metformin after 1 day of palmitate exposure increased GSIS, adding metformin after 0.5 days reduced GSIS. In children with "reducing" insulin AUC0-120 (n = 9), 2 h glucose and triglycerides decreased after metformin treatment, which was not observed in patients with "increasing" insulin AUC0-120 (n = 12). In isolated islets, metformin attenuated insulin hypersecretion if introduced when islet secretory capacity was maintained. In children with obesity, improved glycemic and lipid levels were accompanied by reduced insulin levels during OGTT after metformin treatment.

  View details for DOI 10.3390/metabo13080917

  View details for PubMedID 37623862

  View details for PubMedCentralID PMC10456302

• Low Fasting Concentrations of Glucagon in Patients with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency. Metabolites Stenlid, R., Manell, H., Seth, R., Cerenius, S. Y., Chowdhury, A., Roa Cortés, C., Nyqvist, I., Lundqvist, T., Halldin, M., Bergsten, P. 2023; 13 (7)

  Abstract

  (1) Background: Deficiencies of mitochondrial fatty acid oxidation (FAO) define a subgroup of inborn errors of metabolism, with medium-chain acyl-CoA dehydrogenase deficiency (MCAD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD) being two of the most common. Hypoketotic hypoglycemia is a feared clinical complication and the treatment focuses on avoiding hypoglycemia. In contrast, carnitine uptake deficiency (CUD) is treated as a mild disease without significant effects on FAO. Impaired FAO has experimentally been shown to impair glucagon secretion. Glucagon is an important glucose-mobilizing hormone. If and how glucagon is affected in patients with VLCAD or MCAD remains unknown. (2) Methods: A cross-sectional study was performed with plasma hormone concentrations quantified after four hours of fasting. Patients with VLCAD (n = 10), MCAD (n = 7) and CUD (n = 6) were included. (3) Results: The groups were similar in age, sex, weight, and height. The glucagon and insulin levels were significantly lower in the VLCAD group compared to the CUD group (p < 0.05, respectively). The patients with CUD had glucagon concentrations similar to the normative data. No significant differences were seen in GLP-1, glicentin, glucose, amino acids, or NEFAs. (4) Conclusions: Low fasting concentrations of glucagon are present in patients with VLCAD and cannot be explained by altered stimuli in plasma.

  View details for DOI 10.3390/metabo13070780

  View details for PubMedID 37512487

  View details for PubMedCentralID PMC10386500

• Adherence to Treatment Recommendations in Chronic Disease: What Is (Im)Possible? Expert Conclusions from the 30th ECOG Workshop 2021. Annals of nutrition & metabolism Vallis, M., Boyland, E., Caroli, M., Erhardt, E., Frelut, M. L., Mazur, A., Molnar, D., Torbahn, G., Ring-Dimitriou, S., Stenlid, R., Thivel, D., Vlachopapadopoulou, E., Weghuber, D. 2022; 78 (6): 352-358

  Abstract

  Obesity is a chronic disease, in which treatment outcomes are highly dependent on patient and family adherence to behavioural recommendations. The role of healthy eating, physical activity, medication adherence as well as adherence to pre- and post-bariatric surgery protocols are of utmost importance for long-term treatment outcomes. Even the best interventions are not likely to reach their maximum benefit without significant levels of adherence on the part of the individual and family. Traditionally, the annual meeting of the European Childhood Obesity Group (ECOG) includes an expert workshop addressing one specific topic within the field of childhood obesity. During the 30th annual meeting, hosted by the University of Pécs, Hungary, as a virtual meeting, "adherence to treatment recommendations in obesity as a chronic disease" was addressed. The discussions that developed during the workshop are summarized in the following article.

  View details for DOI 10.1159/000526406

  View details for PubMedID 36037804

• High levels of FSH before puberty are associated with increased risk of metabolic syndrome during pubertal transition. Pediatric obesity Aydin, B. K., Stenlid, R., Ciba, I., Cerenius, S. Y., Dahlbom, M., Bergsten, P., Nergårdh, R., Forslund, A. 2022; 17 (8): e12906

  Abstract

  During perimenopause, the rise in serum follicle-stimulating hormone (FSH) is associated with increased adiposity, insulin resistance (IR), and metabolic syndrome (MetS). However, data for the pubertal period, which is characterized by increasing FSH levels and changing body composition, are limited.To investigate the relationships between FSH and anthropometric changes, IR markers, and development of MetS in the peripubertal period.Uppsala Longitudinal Study of Childhood Obesity (ULSCO) is an ongoing study that aims to understand the factors contributing to childhood obesity and the development of obesity-related diseases. We analysed the subset of participants who were prepubertal at the first visit (n = 95, 77 with obesity). Mean follow-up time was 3.0 ± 1.4 years.Higher serum FSH levels at the first visit were associated with an increased likelihood of elevation in body mass index (BMI SDS) (p = 0.025, OR = 16.10) and having MetS (p = 0.044, OR = 4.67) at the follow-up. We observed nonlinear relationships between varying serum FSH levels and markers of adiposity and IR, especially in girls. At the first visit, when girls were prepubertal, FSH was negatively associated with BMI (β = -0.491, p = 0.005) and positively associated with sex hormone-binding globulin (SHBG) (β = 0.625, p = 0.002). With the progression of puberty, negative associations between BMI and SHBG disappeared while FSH became positively associated with HOMA-IR (β = 0.678, p = 0.025) and fasting insulin (β = 0.668, p = 0.027).Higher serum FSH levels in prepubertal children were associated with an increased risk of MetS development during pubertal transition. Along with nonlinear associations between varying serum FSH levels and IR markers, our results might imply a relationship between FSH and IR of puberty.

  View details for DOI 10.1111/ijpo.12906

  View details for PubMedID 35226970

  View details for PubMedCentralID PMC9541214

• Altered mitochondrial metabolism in peripheral blood cells from patients with inborn errors of β-oxidation. Clinical and translational science Stenlid, R., Olsson, D., Cen, J., Manell, H., Haglind, C., Chowdhury, A. I., Bergsten, P., Nordenström, A., Halldin, M. 2022; 15 (1): 182-194

  Abstract

  Inborn errors of mitochondrial fatty acid oxidation (FAO), such as medium-chain acyl-CoA dehydrogenase deficiency (MCAD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD) affects cellular function and whole-body metabolism. Carnitine uptake deficiency (CUD) disturbs the transportation of fatty acids into the mitochondria, but when treated is a mild disease without significant effects on FAO. For improved clinical care of VLCAD in particular, estimation of FAO severity could be important. We have investigated whether the oxygen consumption rate (OCR) of peripheral blood mononuclear cells (PBMCs) obtained from patients with MCAD, VLCAD, and CUD can be used to study cellular metabolism in patients with FAO defects and to determine the severity of FAO impairment. PBMCs were isolated from patients with VLCAD (n = 9), MCAD (n = 5-7), and CUD (n = 5). OCR was measured within 6-hours of venous puncture using the Seahorse XFe96. The PBMCs were exposed to glucose alone or with caprylic acid (C8:0) or palmitic acid (C16:0). OCR was significantly lower in cells from patients with β-oxidation deficiencies (MCAD and VLCAD) compared to CUD at basal conditions. When exposed to C16:0, OCR in VLCAD cells was unchanged, whereas OCR in MCAD cells increased but not to the levels observed in CUD. However, C8:0 did not increase OCR, as would be expected, in VLCAD cells. There was no clear relationship between clinical severity level and OCR. In patients with β-oxidation deficiencies, changes of mitochondrial respiration in PBMCs are detectable, which indicate that PBMCs have translational potential for studies of β-oxidation defects. However, further studies are warranted.

  View details for DOI 10.1111/cts.13133

  View details for PubMedID 34437764

  View details for PubMedCentralID PMC8742636

• High DPP-4 Concentrations in Adolescents Are Associated With Low Intact GLP-1. The Journal of clinical endocrinology and metabolism Stenlid, R., Manell, H., Halldin, M., Kullberg, J., Ahlström, H., Manukyan, L., Weghuber, D., Paulmichl, K., Zsoldos, F., Bergsten, P., Forslund, A. 2018; 103 (8): 2958-2966

  Abstract

  Dipeptidyl peptidase 4 (DPP-4) metabolizes glucagon-like peptide-1 (GLP-1), and increased DPP4 levels are associated with obesity and visceral adiposity in adults.Investigating DPP-4 levels in adolescents and their association with (1) circulating intact GLP-1 levels and glucose tolerance; (2) body mass index (BMI); and (3) visceral, subcutaneous, and liver fat compartments.Cross-sectional study, July 2012 to April 2015.Pediatric obesity clinic, Uppsala University Hospital.Children and adolescents with obesity (n = 59) and lean controls (n = 21) aged 8 to 18 years.BMI SD score, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and oral glucose tolerance test (OGTT) concentrations of glucose, and visceral adipose tissue (VAT) and subcutaneous adipose tissue volumes and liver fat fraction.Plasma DPP-4 levels decreased with age in both obese (41 ng/mL per year) and lean subjects (48 ng/mL per year). Plasma DPP-4 levels were higher in males in both the obesity and lean groups. With adjustments for age and sex, plasma DPP-4 level was negatively associated with intact GLP-1 at fasting (β = -12.3; 95% CI: -22.9, -1.8) and during OGTT (β = -12.1; 95% CI: -22.5, -1.7). No associations were found between DPP-4 and plasma glucose levels measured at fasting or after a 2-hour OGTT. Plasma DPP-4 level was 19% higher in obese subjects. Among adipose tissue compartments, the strongest association was with VAT (β = 0.05; 95% CI: -0.02, 0.12).In adolescents, high plasma DPP-4 concentrations were associated with low proportions of intact GLP-1, high BMI, young age, and male sex. The observed associations are compatible with increased metabolism of GLP-1 in childhood obesity.

  View details for DOI 10.1210/jc.2018-00194

  View details for PubMedID 29850829

• Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes. The Journal of clinical endocrinology and metabolism Manell, H., Staaf, J., Manukyan, L., Kristinsson, H., Cen, J., Stenlid, R., Ciba, I., Forslund, A., Bergsten, P. 2016; 101 (3): 1181-9

  Abstract

  Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM).Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated.This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT).This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden.Adolescents with obesity, age 10-18 years, with normal glucose tolerance (NGT, n = 23), impaired glucose tolerance (IGT, n = 19), or T2DM (n = 4) and age-matched lean adolescents (n = 19) were included.Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin.Adolescents with obesity and IGT had lower fasting GLP-1 and glicentin levels than those with NGT (0.25 vs 0.53 pM, P < .05; 18.2 vs 23.6 pM, P < .01) and adolescents with obesity and T2DM had higher fasting glucagon levels (18.1 vs 10.1 pM, P < .01) than those with NGT. During OGTT, glicentin/glucagon ratios were lower in adolescents with obesity and NGT than in lean adolescents (P < .01) and even lower in IGT (P < .05) and T2DM (P < .001).Obese adolescents with IGT have lowered fasting GLP-1 and glicentin levels. In T2DM, fasting glucagon levels are elevated, whereas GLP-1 and glicentin levels are maintained low. During OGTT, adolescents with obesity have more products of pancreatically than intestinally cleaved proglucagon (ie, more glucagon and less GLP-1) in the plasma. This shift becomes more pronounced when glucose tolerance deteriorates.

  View details for DOI 10.1210/jc.2015-3885

  View details for PubMedID 26745255