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  • 1.
    Ciba, Iris
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Weghuber, D.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria.;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria..
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Staaf, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Dahlbom, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Paulmichl, K.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria.;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria..
    Zsoldos, F.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria.;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria..
    Widhalm, K.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria.;Acad Inst Clin Nutr, Vienna, Austria..
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Development of Glucose Intolerance in Obese Children Studied in the Beta-Judo Cohort2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no S466, p. 12-12Article in journal (Other academic)
  • 2.
    Forslund, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Weghuber, D.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Paulmichl, K.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Zsoldos, F.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Widhalm, K.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Vheu, M. D.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Lagler, F.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Cadamuro, J.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Brunner, S.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Hofmann, J.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Lidström, M.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Vilen, H.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Alderborn, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Exenatide Once Weekly Reduces Weight, Liver Fat And 2-Hour Postprandial Glucose In Obese Adolescents2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 470, p. 14-15Article in journal (Other academic)
  • 3.
    Heu, Verena
    et al.
    PMU, Univ Klin Kinder & Jugendheilkunde, Salzburg, Austria..
    Aigner, Elmar
    PMU, Univ Klin Innere Med 1, Salzburg, Austria..
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Cadamuro, Janne
    PMU, Univ Inst Med Chem Lab Diagnost, Salzburg, Austria..
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Endocrinology.
    Dahlbom, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Endocrinology.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Endocrinology.
    Kedenko, Ludmilla
    PMU, Univ Klin Innere Med 1, Salzburg, Austria..
    Lang, Josef
    PMU, Univ Klin Innere Med 1, Salzburg, Austria..
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Katharina, Paulmichl
    PMU, Univ Klin Kinder & Jugendheilkunde, Salzburg, Austria..
    Bernhard, Paulweber
    PMU, Univ Klin Innere Med 1, Salzburg, Austria..
    Kirsten, Roomp
    Univ Luxemburg, LCSB, Luxembourg, Luxembourg..
    Kurt, Widhalm
    PMU, Univ Klin Kinder & Jugendheilkunde, Salzburg, Austria..
    Fanni, Zsoldos
    PMU, Univ Klin Kinder & Jugendheilkunde, Salzburg, Austria..
    Daniel, Weghuber
    PMU, Univ Klin Kinder & Jugendheilkunde, Salzburg, Austria..
    Effect of Glucose Load on the Incretin Response (GLP-1) in obese Adolescents compared to the normal-weight Adolescents2017In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 129, no 19-20, p. 736-736Article in journal (Other academic)
  • 4.
    Hogmark, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Klingberg-Allvin, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gemzell-Danielsson, Kristina
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Ohlsson, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Essén, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Medical students' knowledge, attitudes and perceptions towards contraceptive use and counselling: a cross-sectional survey in Maharashtra, India.2013In: BMJ open, ISSN 2044-6055, Vol. 3, no 12, p. e003739-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study aimed to investigate the knowledge, attitudes and perceptions towards contraceptive use and counselling among medical students in Maharashtra, India.

    SETTING: Considerable global maternal mortality and morbidity could be avoided through the use of effective contraception. In India, contraception services are frequently unavailable or there are obstacles to obtaining modern, reversible contraceptives.

    PARTICIPANTS: A cross-sectional descriptive study using a self-administered questionnaire was conducted among 1996 medical students in their fifth year of study at 27 medical colleges in the state of Maharashtra, India. Descriptive and analytical statistics interpreted the survey instrument and significant results were presented with 95% CI.

    RESULTS: Respondents expressed a desire to provide contraceptive services. A few students had experienced training in abortion care. There were misconceptions about modern contraceptive methods and the impact of sex education. Attitudes towards contraception were mainly positive, premarital counselling was supported and the influence of traditional values and negative provider attitudes on services was recognised. Gender, area of upbringing and type of medical college did not change the results.

    CONCLUSIONS: Despite mostly positive attitudes towards modern contraceptives, sex education and family planning counselling, medical students in Maharashtra have misconceptions about modern methods of contraception. Preservice and in-service training in contraceptive counselling should be implemented in order to increase women's access to evidence-based maternal healthcare services.

  • 5.
    Kristinsson, Hjalti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dahlbom, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Presto, J.
    Mercodia, Uppsala, Sweden.
    Garedal, C.
    Mercodia, Uppsala, Sweden.
    Ritzen, H.
    Mercodia, Uppsala, Sweden.
    Vilhelmsson, M.
    Mercodia, Uppsala, Sweden.
    Kilstedt, E.
    Mercodia, Uppsala, Sweden.
    Johnson, F.
    Mercodia, Uppsala, Sweden.
    Stenberg, H.
    Mercodia, Uppsala, Sweden.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bergsten, P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The initial rise in GIP secretion during OGTT correlates with the initial suppression of glucagon secretion in adolescents with obesity and type 2 diabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S247-S247Article in journal (Other academic)
  • 6.
    Kristinsson, Hjalti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sargsyan, Ernest
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Smith, D. M.
    AstraZeneca, Discovery Sci Innovat Med & Early Dev Biotech Uni, Cambridge, England..
    Gopel, S. O.
    AstraZeneca R&D Gothenburg, CVMD Biosci, Gothenburg, Sweden..
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Basal hypersecretion of glucagon and insulin from palmitate-exposed human islets depends on FFAR1 but not decreased somatostatin secretion2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 4657Article in journal (Refereed)
    Abstract [en]

    In obesity fasting levels of both glucagon and insulin are elevated. In these subjects fasting levels of the free fatty acid palmitate are raised. We have demonstrated that palmitate enhances glucose-stimulated insulin secretion from isolated human islets via free fatty acid receptor 1 (FFAR1/GPR40). Since FFAR1 is also present on glucagon- secreting alpha-cells, we hypothesized that palmitate simultaneously stimulates secretion of glucagon and insulin at fasting glucose concentrations. In addition, we hypothesized that concomitant hypersecretion of glucagon and insulin was also contributed by reduced somatostatin secretion. We found basal glucagon, insulin and somatostatin secretion and respiration from human islets, to be enhanced during palmitate treatment at normoglycemia. Secretion of all hormones and mitochondrial respiration were lowered when FFAR1 or fatty acid beta-oxidation was inhibited. The findings were confirmed in the human beta-cell line EndoC-beta H1. We conclude that fatty acids enhance both glucagon and insulin secretion at fasting glucose concentrations and that FFAR1 and enhanced mitochondrial metabolism but not lowered somatostatin secretion are crucial in this effect. The ability of chronically elevated palmitate levels to simultaneously increase basal secretion of glucagon and insulin positions elevated levels of fatty acids as potential triggering factors for the development of obesity and impaired glucose control.

  • 7.
    Lundström, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ljungberg, Joy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Andersson, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation, Metabolism and Child Health Research.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation, Metabolism and Child Health Research.
    Weghuber, Daniel
    Mörwald, Katharina
    Zsoldos, Fanni
    Widhalm, Kurt
    Meissnitzer, Matthias
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical.
    Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents2019In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 14, no 9, article id e12531Article in journal (Refereed)
    Abstract [en]

    Background

    Despite therapeutic potential against obesity and diabetes, the associations of brown adipose tissue (BAT) with glucose metabolism in young humans are relatively unexplored.

    Objectives

    To investigate possible associations between magnetic resonance imaging (MRI) estimates of BAT and glucose metabolism, whilst considering sex, age, and adiposity, in adolescents with normal and overweight/obese phenotypes.

    Methods

    In 143 subjects (10‐20 years), MRI estimates of BAT were assessed as cervical‐supraclavicular adipose tissue (sBAT) fat fraction (FF) and T*2 from water‐fat MRI. FF and T*2 of neighbouring subcutaneous adipose tissue (SAT) were also assessed. Adiposity was estimated with a standardized body mass index, the waist‐to‐height ratio, and abdominal visceral and subcutaneous adipose tissue volumes. Glucose metabolism was represented by the 2h plasma glucose concentration, the Matsuda index, the homeostatic model assessment of insulin resistance, and the oral disposition index; obtained from oral glucose tolerance tests.

    Results

    sBAT FF and T*2 correlated positively with adiposity before and after adjustment for sex and age. sBAT FF, but not T*2, correlated with 2h glucose and Matsuda index, also after adjustment for sex, age, and adiposity. The association with 2h glucose persisted after additional adjustment for SAT FF.

    Conclusions

    The association between sBAT FF and 2h glucose, observed independently of sex, age, adiposity, and SAT FF, indicates a role for BAT in glucose metabolism, which potentially could influence the risk of developing diabetes. The lacking association with sBAT T*2 might be due to FF being a superior biomarker for BAT and/or to methodological limitations in the T*2 quantification.

  • 8.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Impaired Glucose Tolerance in Childhood Obesity: Contribution of Glucagon, GLP-1 and Inflammation2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the wake of increased obesity prevalence, impaired glucose tolerance (IGT) and type 2 diabetes (T2D) in childhood and adolescence is increasingly common. Given the negative impacts these conditions have on health over time, understanding the pathophysiology in those affected early in life is important. Both the proglucagon-derived peptides and low-grade inflammation have been implicated in the development of obesity-related complications. The aim of this thesis was to study across the glucose tolerance spectrum in children and adolescents with obesity 1) proglucagon-derived peptides glucagon, GLP-1 and glicentin, 2) dipeptidyl peptidase-4 (DPP-4) and its degradation of GLP-1 and 3) novel inflammatory markers. To this end, children and adolescents of the Uppsala Longitudinal Study of Childhood Obesity were studied.   

    Children and adolescents with obesity had higher fasting plasma glucagon concentrations than lean controls. In particular visceral adiposity, hyperinsulinemia, triglycerides and free fatty acids (FFAs) were associated with high plasma glucagon concentrations. In isolated islets elevated FFAs caused hypersecretion of glucagon. In children and adolescents with IGT or T2D, fasting plasma glucagon was further elevated and the GLP-1 and glicentin response to an oral glucose tolerance test (OGTT) was decreased. In T2D plasma glucagon increased during the first 15 minutes of OGTT. Plasma DPP-4 concentrations were elevated in obesity and associated with lower proportion of intact GLP-1 but not with IGT. Several pro-inflammatory markers were elevated in children and adolescents with obesity but not further elevated in IGT or T2D with the exception of low plasma Tumor necrosis factor-related weak inducer of apoptosis (TWEAK) levels, which were associated with IGT, hyperinsulinemia and hyperglucagonemia. High plasma hepatocyte growth factor (HGF) concentration was associated with increased risk of further weight gain in children and adolescents with obesity.

    In conclusion, elevated glucagon concentration at fasting, a hyperglucagonemic response to OGTT and reduced GLP-1 and glicentin are characteristics of IGT and T2D development in childhood obesity reflecting altered usage of the proglucagon gene. DPP-4 concentrations are elevated in childhood obesity but not associated with IGT. Reduced circulating TWEAK was identified as a novel marker of IGT early in life. Children with obesity and high HGF are less likely to respond well to lifestyle intervention.

    List of papers
    1. Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes
    Open this publication in new window or tab >>Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes
    Show others...
    2016 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 3, p. 1181-1189Article in journal (Refereed) Published
    Abstract [en]

    CONTEXT: Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM).

    OBJECTIVE: Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated.

    DESIGN: This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT).

    SETTING: This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden.

    PATIENTS AND PARTICIPANTS: 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.

    MAIN OUTCOME MEASURES: Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin.

    RESULTS: 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).

    CONCLUSIONS: 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.

    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-292749 (URN)10.1210/jc.2015-3885 (DOI)000378811300051 ()26745255 (PubMedID)
    Funder
    VINNOVAEU, FP7, Seventh Framework Programme, 279153Swedish Diabetes Association, DIA 2013-043
    Available from: 2016-05-09 Created: 2016-05-09 Last updated: 2019-03-28Bibliographically approved
    2. High DPP-4 concentrations in adolescents are associated with low intact GLP-1
    Open this publication in new window or tab >>High DPP-4 concentrations in adolescents are associated with low intact GLP-1
    Show others...
    2018 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 8, p. 2958-2966Article in journal (Refereed) Published
    Abstract [en]

    Context: 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.

    Objective: Investigating DPP-4 levels in adolescents and association with, firstly, circulating intact GLP-1 levels and glucose tolerance, secondly, BMI, and, thirdly visceral, subcutaneous and liver fat compartments.

    Design: Cross-sectional study, July 2012 to April 2015.

    Setting: Pediatric obesity clinic, Uppsala University Hospital.

    Patients and participants: Children and adolescents with obesity (n=59) and lean controls (n=21), age 8-18.

    Main outcome measures: BMI SDS, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and OGTT concentrations of glucose and visceral (VAT) and subcutaneous (SAT) adipose tissue volumes and liver fat fraction.

    Results: Plasma DPP-4 decreased with age both in obese (41 ng/ml per year) and lean subjects (48 ng/ml per year). Plasma DPP-4 was higher in males both in the obesity and lean group. When adjusting for age and sex, plasma DPP-4 was negatively associated with intact GLP-1 at fasting, B=-12.3, 95% CI [-22.9, -1.8] and during OGTT, B=-12.1, 95% CI [-22.5, -1.7]. No associations were found between DPP-4 and plasma glucose measured at fasting or after a 2-hour OGTT. Plasma DPP-4 was 19% higher in the obese subjects. Among adipose tissue compartments the strongest association was with VAT, B=0.05, 95% CI [-0.02, 0.12].

    Conclusions: In adolescents, high plasma DPP-4 concentrations are associated with low proportion of intact GLP-1, high BMI, young age and male sex. The observed associations are compatible with an increased metabolism of GLP-1 in childhood obesity.

    Place, publisher, year, edition, pages
    Endocrine Society, 2018
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-354234 (URN)10.1210/jc.2018-00194 (DOI)000442236900022 ()29850829 (PubMedID)
    Funder
    EU, FP7, Seventh Framework Programme, 279153Swedish Diabetes Association, DIA 2016-146Ernfors Foundation, 160504Swedish Research Council, 2016-01040EXODIAB - Excellence of Diabetes Research in SwedenErik, Karin och Gösta Selanders Foundation
    Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2019-03-28Bibliographically approved
    3. Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance
    Open this publication in new window or tab >>Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance
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    2019 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, no 7, p. 880-891Article in journal (Refereed) Published
    Abstract [en]

    Objective: To delineate mechanisms for fasting hyperglucagonemia in childhood obesity bystudying the associations between fasting plasma glucagon concentrations and plasmalipid parameters and fat compartments.

    Methods: Cross-sectional study of children and adolescents with obesity (n=147) and leancontrols (n=43). Differences in free fatty acids (FFA), triglycerides, insulin and fatcompartments (quantified by magnetic resonance imaging) across quartiles of fastingplasma glucagon concentration were analysed. Differences in OGTT glucagonresponse was tested in high vs low FFAs, triglycerides and insulin. Human islets ofLangerhans were cultured at 5.5 mmol/l glucose and in the absence or presence of aFFA mixture with total FFA concentration of 0.5 mmol/l and glucagon secretionquantified.

    Results: In children with obesity, the quartile with the highest fasting glucagon had higherinsulin (201±174 vs 83±39 pmol/l, p<0.01), FFAs (383±52 vs 338±109 μmol/l,p=0.02), triglycerides (1.5±0.9 vs 1.0±0.7 mmol/l, p<0.01), visceral adipose tissuevolume (1.9±0.8 vs 1.2±0.3 dm3, p<0.001) and a higher prevalence of impairedglucose tolerance (41% vs 8%, p=0.01) than the lowest quartile. During OGTT,children with obesity and high insulin had a worse suppression of glucagon during thefirst 10 minutes after glucose intake. Glucagon secretion was 2.6-fold higher in isletstreated with FFAs than in those not treated with FFAs.4

    Conclusion: Hyperglucagonemia in childhood obesity is associated with hyperinsulinemia, highplasma FFAs, high plasma triglycerides, visceral adiposity and impaired glucosetolerance. The glucagonotropic effect of FFAs on isolated human islets provides apotential mechanism linking high fasting plasma FFAs and glucagon levels.

    Keywords
    Childhood obesity, glucagon, free fatty acids, insulin, visceral adiposity, impaired glucose tolerance, type 2 diabetes
    National Category
    Pediatrics Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-380313 (URN)10.1111/pedi.12890 (DOI)000476081000001 ()31271247 (PubMedID)
    Funder
    EU, FP7, Seventh Framework Programme, 279153EXODIAB - Excellence of Diabetes Research in SwedenErnfors FoundationErik, Karin och Gösta Selanders FoundationSwedish Research Council, 2015-4870Swedish Diabetes Association
    Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-12-06Bibliographically approved
    4. Screening of inflammatory markers finds hepatocyte growth factor to be associated with weight gain in children and adolescents with obesity
    Open this publication in new window or tab >>Screening of inflammatory markers finds hepatocyte growth factor to be associated with weight gain in children and adolescents with obesity
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-380315 (URN)
    Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-03-28
  • 9.
    Manell, Hannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Paulmichl, K.
    Paracelsus Med Univ, Pediat, Salzburg, Austria.;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria..
    Cadamuro, J.
    Paracelsus Med Univ, Lab Med, Salzburg, Austria..
    Zsoldos, F.
    Paracelsus Med Univ, Pediat, Salzburg, Austria.;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria..
    Staaf, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sargsyan, Ernest
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Weghuber, D.
    Paracelsus Med Univ, Pediat, Salzburg, Austria.;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria..
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Hyperglucagonaemia is associated with elevated plasma triglycerides and increased visceral fat in children and adolescents2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S267-S268Article in journal (Refereed)
  • 10.
    Manell, Hannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Paulmichl, Katharina
    Paracelsus Med Privatuniv, Abt Kinder & Jugendheilkunde, Salzburg, Austria.;Paracelsus Med Privatuniv, Obes Res Unit, Salzburg, Austria..
    Staaf, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Cadamuro, Janne
    Paracelsus Med Privatuniv, Abt Med Chem Labordiagnost, Salzburg, Austria..
    Zsoldos, Fanni
    Paracelsus Med Privatuniv, Abt Kinder & Jugendheilkunde, Salzburg, Austria.;Paracelsus Med Privatuniv, Obes Res Unit, Salzburg, Austria..
    Gopel, Sven
    AstraZeneca R&D, Molndal, Sweden..
    Sargsyan, Ernest
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Weghuber, Daniel
    Paracelsus Med Privatuniv, Abt Kinder & Jugendheilkunde, Salzburg, Austria.;Paracelsus Med Privatuniv, Obes Res Unit, Salzburg, Austria..
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Hyperglucagonemia is associated with a Increase of Plasma Triglycerides as well as visceral Fat Tissue in a pediatric Cohort2016In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 128, no 19-20, p. 747-747Article in journal (Other academic)
  • 11.
    Manell, Hannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ubhayasekera, Sarojini Jayantha Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Mörwald, Katharina
    Paracelsus Medical University.
    Staaf, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cadamuro, Janne
    Paracelsus Medical University.
    Zsoldos, Fanni
    Paracelsus Medical University.
    Göpel, Sven
    AstraZeneca.
    Sargsyan, Ernest
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Weghuber, Daniel
    Paracelsus Medical University.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance2019In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, no 7, p. 880-891Article in journal (Refereed)
    Abstract [en]

    Objective: To delineate mechanisms for fasting hyperglucagonemia in childhood obesity bystudying the associations between fasting plasma glucagon concentrations and plasmalipid parameters and fat compartments.

    Methods: Cross-sectional study of children and adolescents with obesity (n=147) and leancontrols (n=43). Differences in free fatty acids (FFA), triglycerides, insulin and fatcompartments (quantified by magnetic resonance imaging) across quartiles of fastingplasma glucagon concentration were analysed. Differences in OGTT glucagonresponse was tested in high vs low FFAs, triglycerides and insulin. Human islets ofLangerhans were cultured at 5.5 mmol/l glucose and in the absence or presence of aFFA mixture with total FFA concentration of 0.5 mmol/l and glucagon secretionquantified.

    Results: In children with obesity, the quartile with the highest fasting glucagon had higherinsulin (201±174 vs 83±39 pmol/l, p<0.01), FFAs (383±52 vs 338±109 μmol/l,p=0.02), triglycerides (1.5±0.9 vs 1.0±0.7 mmol/l, p<0.01), visceral adipose tissuevolume (1.9±0.8 vs 1.2±0.3 dm3, p<0.001) and a higher prevalence of impairedglucose tolerance (41% vs 8%, p=0.01) than the lowest quartile. During OGTT,children with obesity and high insulin had a worse suppression of glucagon during thefirst 10 minutes after glucose intake. Glucagon secretion was 2.6-fold higher in isletstreated with FFAs than in those not treated with FFAs.4

    Conclusion: Hyperglucagonemia in childhood obesity is associated with hyperinsulinemia, highplasma FFAs, high plasma triglycerides, visceral adiposity and impaired glucosetolerance. The glucagonotropic effect of FFAs on isolated human islets provides apotential mechanism linking high fasting plasma FFAs and glucagon levels.

  • 12.
    Manell, Hannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Shen, Qiujin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Endocrinology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Endocrinology.
    TNFSF14: a potential contributor to hyperinsulinaemia in childhood obesity2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S168-S168Article in journal (Other academic)
  • 13.
    Manell, Hannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Shen, Qiujin
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Roomp, Kirsten
    University of Luxembourg.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dahlbom, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Weghuber, Daniel
    Paracelsus Medical University.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Screening of inflammatory markers finds hepatocyte growth factor to be associated with weight gain in children and adolescents with obesityManuscript (preprint) (Other academic)
  • 14.
    Manell, Hannes
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Staaf, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Manukyan, Levon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Cen, Jing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Stenlid, Rasmus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Altered Plasma Levels of Glucagon, GLP-1 and Glicentin During OGTT in Adolescents With Obesity and Type 2 Diabetes2016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 3, p. 1181-1189Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Proglucagon-derived hormones are important for glucose metabolism, but little is known about them in pediatric obesity and type 2 diabetes mellitus (T2DM).

    OBJECTIVE: Fasting and postprandial levels of proglucagon-derived peptides glucagon, GLP-1, and glicentin in adolescents with obesity across the glucose tolerance spectrum were investigated.

    DESIGN: This was a cross-sectional study with plasma hormone levels quantified at fasting and during an oral glucose tolerance test (OGTT).

    SETTING: This study took place in a pediatric obesity clinic at Uppsala University Hospital, Sweden.

    PATIENTS AND PARTICIPANTS: 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.

    MAIN OUTCOME MEASURES: Outcome measures were fasting and OGTT plasma levels of insulin, glucagon, active GLP-1, and glicentin.

    RESULTS: 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).

    CONCLUSIONS: 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.

  • 15.
    Norgren, A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Stenlid, R.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dahlbom, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Early Adiposity Rebound and its Association with Obesity and Neuropsychiatric Disorders2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no S466, p. 16-16Article in journal (Other academic)
  • 16.
    Paulmichl, K.
    et al.
    PMU, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria;PMU, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Brunner, S.
    PMU, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria;PMU, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria;PMU, Univ Hosp Salzburg, Ctr Expertise THERAPEP, Salzburg, Austria.
    Cadamuro, J.
    PMU, Univ Hosp Salzburg, Dept Med Chem Lab Diagnost, Salzburg, Austria.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Nasemann, J.
    Roomp, K.
    Univ Luxembourg, Luxembourg Ctr Syst Biomed, Luxembourg, Luxembourg.
    Widhalm, K.
    Zsoldos, F.
    PMU, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria;PMU, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.
    Weghuber, D.
    PMU, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria;PMU, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.
    Association Between Non-Alcoholic Fatty Liver Disease (NAFLD) and Iron Metabolism in Obese Children and Adolescents: Results of the Beta-JUDO Study2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no S470, p. 13-13Article in journal (Other academic)
  • 17.
    Roomp, Kirsten
    et al.
    Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Belval, Luxembourg..
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Schvartz, Domitille
    Univ Geneva, Human Prot Sci Dept, Ctr Med Univ, Geneva, Switzerland..
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sargsyan, Ernest
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Manukyan, Levon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Chowdhury, Azazul Islam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Satagopam, Venkata
    Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Belval, Luxembourg..
    Groebe, Karlfried
    Pivot Biomed Sci GmbH, Trier, Germany..
    Schneider, Reinhard
    Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Belval, Luxembourg..
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sanchez, Jean-Charles
    Univ Geneva, Human Prot Sci Dept, Ctr Med Univ, Geneva, Switzerland..
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Combined lipidomic and proteomic analysis of isolated human islets exposed to palmitate reveals time-dependent changes in insulin secretion and lipid metabolism2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0176391Article in journal (Refereed)
    Abstract [en]

    Studies on the pathophysiology of type 2 diabetes mellitus (T2DM) have linked the accumulation of lipid metabolites to the development of beta-cell dysfunction and impaired insulin secretion. In most in vitro models of T2DM, rodent islets or beta-cell lines are used and typically focus is on specific cellular pathways or organs. Our aim was to, firstly, develop a combined lipidomics and proteomics approach for lipotoxicity in isolated human islets and, secondly, investigate if the approach could delineate novel and/or confirm reported mechanisms of lipotoxicity. To this end isolated human pancreatic islets, exposed to chronically elevated palmitate concentrations for 0, 2 and 7 days, were functionally characterized and their levels of multiple targeted lipid and untargeted protein species determined. Glucosestimulated insulin secretion from the islets increased on day 2 and decreased on day 7. At day 7 islet insulin content decreased and the proinsulin to insulin content ratio doubled. Amounts of cholesterol, stearic acid, C16 dihydroceramide and C24: 1 sphingomyelin, obtained from the lipidomic screen, increased time-dependently in the palmitate-exposed islets. The proteomic screen identified matching changes in proteins involved in lipid biosynthesis indicating up-regulated cholesterol and lipid biosynthesis in the islets. Furthermore, proteins associated with immature secretory granules were decreased when palmitate exposure time was increased despite their high affinity for cholesterol. Proteins associated with mature secretory granules remained unchanged. Pathway analysis based on the protein and lipid expression profiles implicated autocrine effects of insulin in lipotoxicity. Taken together the study demonstrates that combining different omics approaches has potential in mapping of multiple simultaneous cellular events. However, it also shows that challenges exist for effectively combining lipidomics and proteomics in primary cells. Our findings provide insight into how saturated fatty acids contribute to islet cell dysfunction by affecting the granule maturation process and confirmation in human islets of some previous findings from rodent islet and cell-line studies.

  • 18.
    Staaf, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Labmayr, Viktor
    Paulmichl, Katharina
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cen, Jing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dahlbom, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Roomp, Kirsten
    Anderwald, Christian-Heinz
    Meissnitzer, Matthias
    Schneider, Reinhard
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Widhalm, Kurt
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Weghuber, Daniel
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 3, p. 358-365Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Adolescents with obesity have increased risk of type 2 diabetes and metabolic syndrome (MetS). Pancreatic fat has been related to these conditions; however, little is known about associations in pediatric obesity. The present study was designed to explore these associations further.

    METHODS: We examined 116 subjects, 90 with obesity. Anthropometry, MetS, blood samples, and oral glucose tolerance tests were assessed using standard techniques. Pancreatic fat fraction (PFF) and other fat depots were quantified using magnetic resonance imaging.

    RESULTS: The PFF was elevated in subjects with obesity. No association between PFF and body mass index-standard deviation score (BMI-SDS) was found in the obesity subcohort. Pancreatic fat fraction correlated to Insulin Secretion Sensitivity Index-2 and Homeostatic Model Assessment of Insulin Resistance in simple regression; however, when using adjusted regression and correcting for BMI-SDS and other fat compartments, PFF correlated only to visceral adipose tissue and fasting glucose. Highest levels of PFF were found in subjects with obesity and MetS.

    CONCLUSIONS: In adolescents with obesity, PFF is elevated and associatedto MetS, fasting glucose, and visceral adipose tissue but not to beta-cellfunction, glucose tolerance, or BMI-SDS. This study demonstrates thatconclusions regarding PFF and its associations depend on the body massfeatures of the cohort.

  • 19.
    Stenlid, R.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dipeptidyl Peptidase-4 is Associated with Elevated Liver Enzymes, Impaired Glucose Tolerance and Lowered Glucagon-Like Peptide-1 in Obese Children2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no S466, p. 15-15Article in journal (Other academic)
  • 20.
    Stenlid, Rasmus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Halldin, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, SE-43183 Molndal, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Med, SE-43183 Molndal, Sweden.
    Manukyan, Levon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Weghuber, D
    Paulmichl, K
    Zsoldos, F
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    High DPP-4 concentrations in adolescents are associated with low intact GLP-12018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 8, p. 2958-2966Article in journal (Refereed)
    Abstract [en]

    Context: 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.

    Objective: Investigating DPP-4 levels in adolescents and association with, firstly, circulating intact GLP-1 levels and glucose tolerance, secondly, BMI, and, thirdly visceral, subcutaneous and liver fat compartments.

    Design: Cross-sectional study, July 2012 to April 2015.

    Setting: Pediatric obesity clinic, Uppsala University Hospital.

    Patients and participants: Children and adolescents with obesity (n=59) and lean controls (n=21), age 8-18.

    Main outcome measures: BMI SDS, fasting plasma concentrations of DPP-4, total and intact GLP-1, fasting and OGTT concentrations of glucose and visceral (VAT) and subcutaneous (SAT) adipose tissue volumes and liver fat fraction.

    Results: Plasma DPP-4 decreased with age both in obese (41 ng/ml per year) and lean subjects (48 ng/ml per year). Plasma DPP-4 was higher in males both in the obesity and lean group. When adjusting for age and sex, plasma DPP-4 was negatively associated with intact GLP-1 at fasting, B=-12.3, 95% CI [-22.9, -1.8] and during OGTT, B=-12.1, 95% CI [-22.5, -1.7]. No associations were found between DPP-4 and plasma glucose measured at fasting or after a 2-hour OGTT. Plasma DPP-4 was 19% higher in the obese subjects. Among adipose tissue compartments the strongest association was with VAT, B=0.05, 95% CI [-0.02, 0.12].

    Conclusions: In adolescents, high plasma DPP-4 concentrations are associated with low proportion of intact GLP-1, high BMI, young age and male sex. The observed associations are compatible with an increased metabolism of GLP-1 in childhood obesity.

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