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  • 1.
    Agrasada, Grace V.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kylberg, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Exclusive breastfeeding of low birth weight infants for the first six months: infant morbidity and maternal and infant anthropometry2011In: Asia Pacific Journal of Clinical Nutrition, ISSN 0964-7058, E-ISSN 1440-6047, Vol. 20, no 1, p. 62-68Article in journal (Refereed)
    Abstract [en]

    Background: to report anthropometry and morbidity among term low birth weight infants and anthropometry of their first time mothers during the first six months in relation to breastfeeding practice. Methods: we examined data from a randomized controlled trial in Manila, the Philippines. Of the 204 mothers randomized, 68 mothers received eight postpartum breastfeeding counseling sessions, the rest did not. Maternal and infant anthropometric data at birth, 2, 4 and 6 months were taken. During seven follow-up hospital visits, an independent interviewer recorded feeding data. Results: the 24 infants exclusively breastfed from birth to six months did not have diarrhea compared to 134 partially breastfed (mean 2.3 days) and 21 non-breastfed infants (mean 2.5 days). Partially breastfed and non-breastfed infants compared to exclusively breastfed infants had more frequent, as well as more severe episodes of respiratory infections. At six months, neither overall gain in infant weight, length and head circumferences nor mean maternal weight and body mass index differed significantly between the feeding groups. Conclusions: exclusive breastfeeding for 6 months can be recommended in term low birth weight infants, who were protected from diarrhea, had fewer respiratory infections, required no hospitalization and had catch up growth. Exclusively breastfeeding mothers did not differ from mothers who breastfed partially or those who did not breastfeed with regard to weight changes at six months.

  • 2.
    Agrasada, Grace V
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Kylberg, Elisabeth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Ewald, Uwe
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Postnatal peer counselling on exclusive breastfeeding of low-birthweight infants: a randomized, controlled trial.2005In: Acta Paediatr, ISSN 0803-5253, Vol. 94, no 8, p. 1109-15Article in journal (Refereed)
  • 3.
    Ahlgren, Kerstin M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Moretti, Silvia
    Lundgren, Brita Ardesjö
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Iulia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åhlin, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Norling, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hallgren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Perheentupa, Jaakko
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Crewther, Pauline E.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Bensing, Sophie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Scott, Hamish S.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Romani, Luigina
    Lobell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model2011In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 41, no 1, p. 235-245Article in journal (Refereed)
    Abstract [en]

    Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.

  • 4.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Diderholm, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lipolysis and Insulin Sensitivity at Birth in Infants Who Are Large for Gestational Age2007In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 120, no 5, p. 958-965Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE. In addition to neonatal hypoglycemia, infants who are born large for gestational age are at risk for developing obesity, cardiovascular disease, and diabetes later in life. The aim of this study was to investigate glucose production, lipolysis, and insulin sensitivity in infants who were born large for gestational age to mothers without diabetes. The effect of glucagon administration on production of energy substrates was also investigated.

    METHODS. Ten healthy term infants who were born large for gestational age to mothers without diabetes were studied 16 ± 8 hours postnatally after a 3-hour fast. Rates of glucose production and lipolysis were analyzed by gas chromatography–mass spectrometry following constant rate infusion of [6,6-2H2]glucose and [2-13C]glycerol. Insulin sensitivity was assessed by the Homeostasis Assessment Model. In 8 of the infants, the effect of an intravenous injection of 0.2 mg/kg glucagon was also analyzed.

    RESULTS. Plasma glucose and glycerol averaged 3.8 ± 0.5 mmol/L and 384 ± 183 µmol/L, respectively. The glycerol production rate, reflecting lipolysis, was 12.7 ± 2.9 µmol/kg per min. Mean rate of glucose production was 30.2 ± 4.6 µmol/kg per min. Homeostasis Assessment Model insulin sensitivity corresponded to 82% ± 19%, β-cell function to 221% ± 73%, and insulin resistance to 1.3 ± 0.3. After glucagon administration, rate of glucose production increased by 13.3 ± 8.3 µmol/kg per min and blood glucose by 1.4 ± 0.5 mmol/L. Glycerol production decreased from 12.8 ± 3.0 to 10.7 ± 2.9 µmol/kg per min. Mean insulin concentration increased from 10.9 ± 3.0 to 30.9 ± 10.3 mU/L. There was a strong inverse correlation between the decrease in lipolysis and increase in insulin after glucagon administration.

    CONCLUSIONS. Infants who are born large for gestational age show increased lipolysis and a propensity for decreased insulin sensitivity already at birth. The simultaneous increase in plasma insulin correlated strongly with the noted decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants.

  • 5.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Diderholm, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Forslund, Anders H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size2013In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 168, no 1, p. 26-29Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.

    STUDY DESIGN:

    Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.

    RESULTS:

    Median (range) rate of glucose production was 805 (653-1337)μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576)μmol/min. HOMA insulin resistance averaged 1.5±0.75 and estimated fetal weights ranged between 2670 and 4175g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2±2.5mg/L and median level of leptin was 47.1 (9.9-58.0)μg/L. Adiponectin concentrations (7.2±2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.

    CONCLUSION:

    The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.

  • 6.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tuvemo, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lundgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants2007In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 96, no 3, p. 358-362Article in journal (Refereed)
    Abstract [en]

    Aim: To analyse if females born large for gestational age (LGA) have an increased risk to give birth to LGA infants and to study anthropometric characteristics in macrosomic infants of females born LGA.Methods: The investigation was performed as an intergenerational retrospective study of women born between 1973 and 1983, who delivered their first infant between 1989 and 1999. Birth characteristics of 47 783 females, included in the Swedish Birth Register both as newborns and mothers were analysed. LGA was defined as >2 SD in either birth weight or length for gestational age. The infants were divided into three subgroups: born tall only, born heavy only and born both tall and heavy for gestational age. Multiple logistic and linear regression analyses were performed.Results: Females, born LGA with regard to length or weight, had a two-fold (adjusted OR 1.96, 95% Cl 1.54-2.48) increased risk to give birth to an LGA infant. Females, born LGA concerning weight only, had a 2.6 (adjusted OR 2.63, 95%, 1.85-3.75) fold increased risk of having an LGA offspring heavy only and no elevated risk of giving birth to an offspring that was tall only, compared to females born not LGA. In addition, maternal obesity was associated with a 2.5 (adjusted OR 2.56, 95%, 2.20-2.98) fold increased risk of having an LGA newborn, compared to mothers with normal weight.Conclusion: Females, born LGA, have an increased risk to give birth to LGA infants, compared to mothers born not LGA. Maternal overweight increases this risk even further.

  • 7.
    Albertsson-Wikland, Kerstin
    et al.
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Kriström, Berit
    Pediatrics Unit, Department of Clinical Sciences, Umeå University, Sweden.
    Lundberg, Elena
    Pediatrics Unit, Department of Clinical Sciences, Umeå University, Sweden.
    Aronson, A Stefan
    Department of Pediatrics, Halmstad Hospital, Sweden.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hagenäs, Lars
    Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Ivarsson, Sten-A
    Department of Pediatrics, Lund University, Malmö, Sweden.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ritzén, Martin
    Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Tuvemo, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Westgren, Ulf
    Department of Pediatrics, Lund University, Malmö, Sweden.
    Westphal, Otto
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Aman, Jan
    School of Health and Medical Sciences, Örebro University, Sweden.
    Growth hormone dose-dependent pubertal growth: a randomized trial in short children with low growth hormone secretion2014In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, no 3, p. 158-170Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e. idiopathic isolated GH deficiency.

    METHODS: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH 33 µg/kg/day for ≥1 year. They were randomized to receive 67 µg/kg/day (GH(67)) given as one (GH(67×1); n = 35) or two daily injections (GH(33×2); n = 36), or to remain on a single 33 µg/kg/day dose (GH(33×1); n = 40). Growth was assessed as heightSDSgain for prepubertal, pubertal and total periods, as well as AHSDS versus the population and the midparental height.

    RESULTS: Pubertal heightSDSgain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33×1), 0.41, p < 0.05). AHSDS was greater on GH(67) (GH(67×1), -0.84; GH(33×2), -0.83) than GH(33) (-1.25, p < 0.05), and heightSDSgain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target heightSDS.

    CONCLUSION: Pubertal heightSDSgain and AHSDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once- and twice-daily GH(67) regimens.

  • 8.
    Albertsson-Wikland, Kerstin
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Medicinargatan 11, SE-40530 Gothenburg, Sweden..
    Martensson, Anton
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Medicinargatan 11, SE-40530 Gothenburg, Sweden.;Stat Konsultgrp, SE-41319 Gothenburg, Sweden..
    Savendahl, Lars
    Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Karolinska Inst, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, SE-17176 Stockholm, Sweden..
    Niklasson, Aimon
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg Pediat Growth Res Ctr,Dept Pediat, SE-41685 Gothenburg, Sweden..
    Bang, Peter
    Linkoping Univ, Dept Clin & Expt Med, Div Pediat, SE-58185 Linkoping, Sweden..
    Dahlgren, Jovanna
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg Pediat Growth Res Ctr,Dept Pediat, SE-41685 Gothenburg, Sweden..
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kristrom, Berit
    Umea Univ, Dept Clin Sci, Pediat, SE-90185 Umea, Sweden..
    Norgren, Svante
    Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Karolinska Inst, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, SE-17176 Stockholm, Sweden..
    Pehrsson, Nils-Gunnar
    Stat Konsultgrp, SE-41319 Gothenburg, Sweden..
    Oden, Anders
    Stat Konsultgrp, SE-41319 Gothenburg, Sweden.;Chalmers, Dept Math Sci, SE-41296 Gothenburg, Sweden..
    Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics2016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 5, p. 2149-2159Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P < .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P < .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P < .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

  • 9.
    Albertsson-Wikland, Kerstin
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Gothenburg, Sweden..
    Mårtensson, Anton
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, Gothenburg, Sweden.;Stat Konsultgrp, Gothenburg, Sweden..
    Sävendahl, Lars
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, Stockholm, Sweden..
    Niklasson, Aimon
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, GP GRC,Dept Pediat, Gothenburg, Sweden..
    Bang, Peter
    Linkoping Univ, Div Pediat, Dept Clin & Expt Med, Linkoping, Sweden..
    Dahlgren, Jovanna
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, GP GRC,Dept Pediat, Gothenburg, Sweden..
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kriström, Berit
    Umea Univ, Pediat, Dept Clin Sci, Umea, Sweden..
    Norgren, Svante
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pediat Endocrinol Unit, Stockholm, Sweden..
    Pehrsson, Nils-Gunnar
    Stat Konsultgrp, Gothenburg, Sweden..
    Odén, Anders
    Stat Konsultgrp, Gothenburg, Sweden.;Chalmers, Dept Math Sci, Gothenburg, Sweden..
    Birth Characteristics Explain One Third of Expected Deaths in rhGH-treated Patients Diagnosed with IGHD, ISS & SGA2016In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 86, no Suppl. 1, p. 49-49, article id Abstr. FC8.6Article in journal (Refereed)
  • 10.
    Aldrimer, Mattias
    et al.
    Department of Clinical Chemistry, County Hospital of Falun.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rodoo, Peo
    Department of Pediatrics, County Hospital of Falun.
    Niklasson, Frank
    Department of Clinical Chemistry, County Hospital of Falun.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Population-based pediatric reference intervals for hematology, iron and transferrin2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 3, p. 253-261Article in journal (Refereed)
    Abstract [en]

    Reference intervals are crucial decision-making tools aiding clinicians in differentiating between healthy and diseased populations. However, for children such values often are lacking or incomplete. Blood samples were obtained from 689 healthy children, aged 6 months to 18 years, recruited in day care centers and schools. Hematology and anemia analytes were measured on the Siemens Advia 2120 and Abbott Architect ci8200 platforms (hemoglobin, erythrocyte volume fraction [EVF], erythrocytes, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], reticulocytes, leukocytes, lymphocytes, monocytes, neutrophils, eosinophils, basophils, platelets, iron, transferrin, transferrin saturation). Age-and gender-specific pediatric reference intervals were defined by calculating 2.5th and 97.5th percentiles. The data generated is primarily applicable to a Caucasian population, but could be used by any laboratory if verified for the local patient population.

  • 11. Aldrimer, Mattias
    et al.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rodoo, Peo
    Niklasson, Frank
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Reference intervals on the Abbot Architect for serum thyroid hormones, lipids and prolactin in healthy children in a population-based study2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 4, p. 326-332Article in journal (Refereed)
    Abstract [en]

    Pediatric reference intervals for thyroid hormones, prolactin and lipids are of high clinical importance as deviations might indicate diseases with serious consequences. In general, previous reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. The study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy and a questionnaire on diseases and medications was filled out by parents and by the older children. TSH, free T4, free T3, total cholesterol, LDL, HDL, triglycerides and prolactin were analyzed on Abbott Architect ci8200. Age- and gender-related 2.5 and 97.5 percentiles were estimated. The thyroid hormone levels were similar to previous data for the Abbott Architect platform, but exhibited differences from studies performed with other methods. Prolactin displayed wide reference ranges, but relatively small age-related changes, and a marginal difference between sexes during adolescence. Reference intervals for lipids in the different age groups are known to vary geographically. Levels of LDL and total cholesterol were higher than those reported for children in Canada, but lower than those reported for children in China. The study gives age-and gender-specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results presented here differ from previously recommended reference intervals. In many earlier studies, retrospective hospital-based reference intervals, which may include various sub-groups have been presented. By non-hospital studies it is possible to avoid some of these biases.

  • 12. Anneren, G
    et al.
    Myrelid, Åsa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Growth retardation in down syndrome: thyroid disorders, coeliac desease and the effect of GH therapy2004In: The adult with down syndrome- a new challenge for society. Eds. JA Rondal A Rasore-Quartino and S. Soresi, Whurr Publishers Ltd. London , 2004, p. 61-65Chapter in book (Refereed)
  • 13.
    Bensing, Sophie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fetissov, Serguei
    Mulder, Jan
    Perheentupa, Jaakko
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Husebye, Eystein S.
    Oscarson, Mikael
    Ekwall, Olov
    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.
    Crock, Patricia A.
    Hökfelt, Tomas
    Hulting, Anna-Lena
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pituitary autoantibodies in autoimmune polyendocrine syndrome type 12007In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 104, no 3, p. 949-954Article in journal (Refereed)
    Abstract [en]

    Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40-50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland.

  • 14.
    Clausen, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cerebral glucose metabolism after traumatic brain injury in the rat studied by C-13-glucose and microdialysis2011In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 153, no 3, p. 653-658Article in journal (Refereed)
    Abstract [en]

    Following traumatic brain injury (TBI), a disturbed cerebral glucose metabolism contributes to secondary brain damage. To study local cerebral glucose metabolism after TBI, we delivered C-13-labeled glucose into brain tissue by microdialysis (MD). MD probes were inserted bilaterally into the parietal cortex of rat brain, one probe in the shear stress zone of the injury and the other at the corresponding contralateral coordinates. A moderately severe controlled cortical contusion was used to model TBI. Dialysate concentrations of glucose, pyruvate, lactate, and glycerol were measured, and following derivatization, C-13 enrichments of the compounds were determined by gas chromatography-mass spectrometry. We found that C-13-labeled glucose was rapidly converted into C-13-lactate and C-13-glycerol. In the hours following TBI, concentrations and C-13 enrichments of lactate and glycerol increased. The findings confirm the occurrence of anaerobic local glucose metabolism early after TBI. Only a small fraction of the glycerol was newly synthesized, suggesting that the hypothesis that most of the released glycerol after TBI comes from degradation of membrane phospholipids still holds. We conclude that the combination of microdialysis and stable isotope technique is a useful tool for investigating local glucose metabolism following brain injury.

  • 15.
    Dahl, Margareta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ahlsten, G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Proos, LA
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tuvemo, T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Oral presentation: Early puberty in boys with myelomeningocele. Risk factors for early puberty2007In: Cerebrospinal Fluid Research, 2007, 4 (Suppl I ): From 51st Annual Meeting of the Society for Research into Hydrocephalus and Spina Bifida, Heidelberg, Germany 27-30 June, 2007, p. 37-Conference paper (Other (popular science, discussion, etc.))
  • 16.
    Dalin, Frida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Ctr Mol Med, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Nordling Eriksson, Gabriel
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.
    Dahlqvist, Per
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90736 Umea, Sweden.
    Hallgren, Åsa
    Karolinska Inst, Ctr Mol Med, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Wahlberg, Jeanette
    Linkoping Univ, Div Endocrinol, Dept Med & Hlth Sci, Fac Hlth Sci, SE-58183 Linkoping, Sweden.
    Ekwall, Olov
    Linkoping Univ, Div Pediat, Dept Clin & Expt Med, SE-58183 Linkoping, Sweden.
    Söderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90736 Umea, Sweden.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Olcén, Per
    Univ Orebro, Dept Lab Med, SE-70281 Orebro, Sweden.
    Winqvist, Ola
    Karolinska Inst, Karolinska Univ Hosp, Translat Immunol, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Inst, Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, SE-17176 Stockholm, Sweden.
    Kriström, Berit
    Umea Univ, Inst Clin Sci, Pediat, SE-90736 Umea, Sweden.
    Laudius, Maria
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90736 Umea, Sweden.
    Isaksson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Halldin Stenlid, 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.
    Gustafsson, Jan
    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.
    Gebre-Medhin, Gennet
    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.
    Björnsdottir, Sigridur
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden; Karolinska Inst, Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, SE-17176 Stockholm, Sweden.
    Janson, Annika
    Karolinska Inst, Dept Womens & Childrens Hlth, SE-17176 Stockholm, Sweden.
    Åkerman, Anna-Karin
    Univ Orebro, Dept Lab Med, SE-70281 Orebro, Sweden.
    Åman, Jan
    Univ Orebro, Dept Pediat, Fac Med & Hlth, SE-70281 Orebro, Sweden.
    Duchen, Karel
    Linkoping Univ, Div Pediat, Dept Clin & Expt Med, SE-58183 Linkoping, Sweden.
    Bergthorsdottir, Ragnhildur
    Univ Gothenburg, Inst Med, SE-40530 Gothenburg, Sweden; Univ Gothenburg, Dept Endocrinol, Sahlgrenska Univ Hosp, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.
    Johannsson, Gudmundur
    Univ Gothenburg, Inst Med, SE-40530 Gothenburg, Sweden; Univ Gothenburg, Dept Endocrinol, Sahlgrenska Univ Hosp, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.
    Lindskog, Emma
    Univ Gothenburg, Dept Pediat, Inst Clin Sci, SE-40530 Gothenburg, Sweden.
    Landin-Olsson, Mona
    Skane Univ Hosp, Dept Endocrinol, SE-22362 Lund, Sweden.
    Elfving, Maria
    Lund Univ, Dept Pediat, Pediat Endocrinol, Clin Sci, SE-22362 Lund, Sweden.
    Waldenström, Erik
    Skane Univ Hosp, Dept Endocrinol, SE-22362 Lund, Sweden.
    Hulting, Anna-Lena
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden.
    Kämpe, Olle
    Karolinska Inst, Ctr Mol Med, Dept Med Solna, SE-17176 Stockholm, Sweden; Karolinska Inst, Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, SE-17176 Stockholm, Sweden.
    Bensing, Sophie
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden; Karolinska Inst, Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, SE-17176 Stockholm, Sweden.
    Clinical and immunological characteristics of Autoimmune Addison's disease: a nationwide Swedish multicenter study2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 2, p. 379-389Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.

    OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.

    DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.

    MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.

    RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).

    CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.

  • 17. Decker, Ralph
    et al.
    Albertsson-Wikland, Kerstin
    Kriström, Berit
    Nierop, Andreas F. M.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bosaeus, Ingvar
    Fors, Hans
    Hochberg, Ze'ev
    Dahlgren, Jovanna
    Metabolic outcome of GH treatment in prepubertal short children with and without classical GH deficiency2010In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 73, no 3, p. 346-354Article in journal (Refereed)
    Abstract [en]

    P>Context Few studies have evaluated the metabolic outcomes of growth hormone (GH) treatment in idiopathic short stature (ISS). Moreover, children with ISS appear to need higher GH doses than children with GH deficiency (GHD) to achieve the same amount of growth and may therefore be at increased risk of adverse events during treatment. The individualized approach using prediction models for estimation of GH responsiveness, on the other hand, has the advantage of narrowing the range of growth response, avoiding too low or high GH doses. Design Short prepubertal children with either isolated GHD (39) or ISS (89) participated in a 2-year randomized trial of either individualized GH treatment with six different GH doses (range, 17-100 mu g/kg/day) or a standard dose (43 mu g/kg/day). Objective To evaluate if individualized GH treatment reduced the variance of the metabolic measures as shown for growth response and to compare changes in metabolic variables in children with ISS and GHD. Hypothesis Individualized GH dose reduces the range of metabolic outcomes, and metabolic outcomes are similar in children with ISS and GHD. Results We observed a narrower variation for fasting insulin (-34 center dot 2%) and for homoeostasis model assessment (HOMA) (-38 center dot 9%) after 2 years of individualized GH treatment in comparison with standard GH dose treatment. Similar metabolic changes were seen in ISS and GHD. Delta (delta) height SDS correlated with delta insulin-like growth factor I (IGF-I), delta leptin and delta body composition. Principal component analysis identified an anabolic and a lipolytic component. Anabolic variables [delta lean body mass (LBM) SDS and delta IGF-I SDS] clustered together and correlated strongly with delta height SDS and GH dose, whereas lipolytic variables [delta fat mass (FM) SDS and delta leptin] were clustered separately from anabolic variables. Regression analysis showed GH dose dependency in ISS, and to a lesser degree in GHD, for delta LBM SDS and delta height SDS, but not for changes in FM. Conclusions Individualized GH dosing during catch-up growth reduces the variance in insulin and HOMA and results in equal metabolic responses irrespective of the diagnosis of GHD or ISS.

  • 18.
    Decker, Ralph
    et al.
    Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Nygren, Anders
    Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Kriström, Berit
    Institute of Clinical Sciences, Department of Pediatrics, Umeå University, Sweden.
    Nierop, Andreas F
    Muvara bv, Multivariate Analysis of Research Data, Leiderdorp, Netherlands.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Albertsson-Wikland, Kerstin
    Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Dahlgren, Jovanna
    Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children2012In: BMC Endocrine Disorders, ISSN 1472-6823, E-ISSN 1472-6823, Vol. 12, no 1, p. 26-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In addition to stimulating linear growth in children, growth hormone (GH) influences metabolism and body composition. These effects should be considered when individualizing GH treatment as dose-dependent changes in metabolic markers have been reported. Hypothesis: There are different dose-dependent thresholds for metabolic effects in response to GH treatment. METHOD: A randomized, prospective, multicentre trial TRN 98-0198-003 was performed for a 2-year catch-up growth period, with two treatment regimens (a) individualized GH dose including six different dose groups ranging from 17--100 mug/kg/day (n=87) and (b) fixed GH dose of 43 mug/kg/day (n=41). The individualized GH dose group was used for finding dose--response effects, where the effective GH dose (ED 50%) required to achieve 50% Delta effect was calculated with piecewise linear regressions. RESULTS: Different thresholds for the GH dose were found for the metabolic effects. The GH dose to achieve half of a given effect (ED 50%, with 90% confidence interval) was calculated as 33(+/-24.4) mug/kg/day for [increment] left ventricular diastolic diameter (cm), 39(+/-24.5) mug/kg/day for [increment] alkaline phosphatase (mukat/L), 47(+/-43.5) mug/kg/day for [increment] lean soft tissue (SDS), 48(+/-35.7) mug/kg/day for [increment] insulin (mU/L), 51(+/-47.6) mug/kg/day for [increment] height (SDS), and 57(+/-52.7) mug/kg/day for [increment] insulin-like growth factor I (IGF-I) SDS. Even though lipolysis was seen in all subjects, there was no dose--response effect for Delta fat mass (SDS) or Delta leptin ng/ml in the dose range studied. None of the metabolic effects presented here were related to the dose selection procedure in the trial. CONCLUSIONS: Dose-dependent thresholds were observed for different GH effects, with cardiac tissue being the most responsive and level of IGF-I the least responsive. The level of insulin was more responsive than that of IGF-I, with the threshold effect for height in the interval between.

  • 19.
    Diderholm, B
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Stridsberg, M
    Department of Medical Sciences.
    Norden-Lindeberg, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, J
    Decreased maternal lipolysis in intrauterine growth restriction in the third trimester.2006In: BJOG, ISSN 1470-0328, Vol. 113, no 2, p. 159-64Article in journal (Refereed)
  • 20.
    Diderholm, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Cambridge, Addenbrookes Hosp NHS Fdn Trust, Dept Paediat, Cambridge, England..
    Beardsall, Kathryn
    Univ Cambridge, Addenbrookes Hosp NHS Fdn Trust, Dept Paediat, Cambridge, England..
    Murgatroyd, Peter
    Addenbrookes Hosp, Wellcome Trust Clin Res Facil, Cambridge, England..
    Lees, Christoph
    Rosie Matern Hosp, Dept Obstet & Gynaecol, Cambridge, England..
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dunger, David
    Univ Cambridge, Addenbrookes Hosp NHS Fdn Trust, Dept Paediat, Cambridge, England..
    Maternal rates of lipolysis and glucose production in late pregnancy are independently related to foetal weight2017In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 87, no 3, p. 272-278Article in journal (Refereed)
    Abstract [en]

    Objective: Associations between maternal glucose levels and increased foetal growth are well established, and independent relationships with maternal weight, weight gain and insulin resistance are also observed. The relative roles of lipolysis and glucose production in the determination of these observations remain unclear. Design: We examined, through detailed physiological studies, the relationship between maternal late gestational energy substrate production (glucose and glycerol), maternal weight and weight gain, and estimated foetal size in the third trimester. Patients: Twenty-one nulliparous pregnant women, without gestational diabetes (GDM) assessed at 28 weeks with oral glucose tolerance test, were recruited. Measurements: Rates of hepatic glucose production (GPR) and rates of glycerol production (reflecting lipolysis) using [C-13(6)]-glucose and [H-2(5)]-glycerol were measured at 34-36 weeks of gestation. Respiratory quotient was assessed by indirect calorimetry and body composition by measurements of total body water (TBW; (H2O)-O-18) and body density (BODPOD). Foetal weight was estimated from ultrasound measures of biparietal diameter, femoral length and abdominal circumference. Results: At 34-36 weeks, bivariate analyses showed that GPR and lipolysis correlated with estimated foetal weight (r=.71 and .72, respectively) as well as with maternal weight, fat mass and fat-free mass, but not maternal weight gain. In multivariate analyses, rates of both glucose production (r=.42) and lipolysis (r=.47) were independently associated with foetal size explaining 63% of the variance. Conclusions: Both maternal rates of lipolysis and hepatic glucose production in late gestation are strongly related to estimated foetal weight.

  • 21.
    Diderholm, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ewald, Uwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ahlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Energy substrate production in infants born small for gestational age2007In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 96, no 1, p. 29-34Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate energy substrate production and its hormonal regulation in infants born small for gestational age.

    Methods: Eleven infants, aged 24.4 ± 5.3 hour, were studied following a fast of 4.0 ± 0.6 hour. Gestational age was 35.4 ± 2.8 weeks and birth weight 1804 ± 472 g (<−2 SD). Rates of glucose production and lipolysis were analyzed using [6,6-2H2]-glucose and [2-13C]-glycerol.

    Results: Plasma levels of glucose and glycerol were 4.1 ± 1.1 mmol . L−1 and 224 ± 79 μmol . L−1, respectively. Glucose appearance averaged 30.3 ± 8.2 and glucose production rate 21.1 ± 6.1 μmol . kg−1 . minutes−1. Glycerol production rate was 5.6 ± 1.6 μmol . kg−1 . minutes−1, correlating strongly to birth weight (r = 0.904, p < 0.001). Of the glycerol produced, 55 ± 22% was converted to glucose, corresponding to 8 ± 3% of the glucose production.

    Conclusions: Even though the infants could produce energy substrates, lipolysis was reduced and the glucose production was in the low end of the normal range compared with infants born appropriate for gestational age. The correlation between glycerol production and birth weight indicates that lipolysis depends on the amount of stored fat. Data on insulin and insulin-like growth factor binding protein 1 support the view that insulin sensitivity in these infants is reduced in the liver but increased peripherally.

  • 22.
    Diderholm, Barbro
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Stridsberg, Mats
    Department of Medical Sciences. Clinical Chemstry.
    Ewald, Uwe
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Lindeberg-Norden, Solveig
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Increased lipolysis in non-obese pregnant women studied in the third trimester.2005In: BJOG, ISSN 1470-0328, Vol. 112, no 6, p. 713-8Article in journal (Refereed)
  • 23.
    Englund, Annika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jonsson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Zander, Cecilia Soussi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Annerén, Göran
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Genetics.
    Changes in mortality and causes of death in the Swedish Down syndrome population2013In: American Journal of Medical Genetics. Part A, ISSN 1552-4825, E-ISSN 1552-4833, Vol. 161A, no 4, p. 642-649Article in journal (Refereed)
    Abstract [en]

    During the past few decades age at death for individuals with Down syndrome (DS) has increased dramatically. The birth frequency of infants with DS has long been constant in Sweden. Thus, the prevalence of DS in the population is increasing. The aim of the present study was to analyze mortality and causes of death in individuals with DS during the period 19692003. All individuals with DS that died between 1969 and 2003 in Sweden, and all individuals born with DS in Sweden between 1974 and 2003 were included. Data were obtained from the Swedish Medical Birth Register, the Swedish Birth Defects Register, and the National Cause of Death Register. Median age at death has increased by 1.8 years per year. The main cause of death was pneumonia. Death from congenital heart defects decreased. Death from atherosclerosis was rare but more frequent than reported previously. Dementia was not reported in any subjects with DS before 40 years of age, but was a main or contributing cause of death in 30% of the older subjects. Except for childhood leukemia, cancer as a cause of death was rare in all age groups. Mortality in DS, particularly infant mortality, has decreased markedly during the past decades. Median age at death is increasing and is now almost 60 years. Death from cancer is rare in DS, but death from dementia is common.

  • 24.
    Englund, Hillevi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Annerén, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wester, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wiltfang, Jens
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Blennow, Kaj
    Höglund, Kina
    Increase in beta-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome2007In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 24, no 5, p. 369-374Article in journal (Refereed)
    Abstract [en]

    Background: Individuals with Down syndrome (DS) invariably develop Alzheimer's disease (AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis. Aim: To investigate how levels of different amyloid- (A) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change over time. The first CSF sample was taken at 8 months and the following two samples at 20-40 and 54 months of age. Results: Individual levels of the A peptides, as well as total A levels in CSF increased over time when measured with Western blot. Tau in CSF decreased whereas there was no change in levels of phosphorylated tau over time. Conclusion: The increasing levels of A in CSF during early childhood of DS patients observed in this study are probably due to the trisomy of the A precursor APP, which leads to an overproduction of A. Despite the increased CSF concentrations of A, there were no signs of an AD-indicating tau pattern in CSF, since the levels of total tau decreased and phosphorylated tau remained unchanged. This observation further strengthens the theory of A pathology preceding tau pathology in AD.

  • 25.
    Frisk, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Arvidson, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Lönnerholm, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Growth post transplant. Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia2004In: Bone Marrow Transplantation, Vol. 33, p. 205-210Article in journal (Refereed)
  • 26.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lönnerholm, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia2004In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 33, no 2, p. 205-210Article in journal (Refereed)
    Abstract [en]

    We describe pubertal development and growth in 17 children who underwent bone marrow transplantation (BMT), including total body irradiation (TBI) for ALL. Seven children also received cranial irradiation (CI) and five boys testicular irradiation. All underwent transplantation before (n=15) or at the beginning of (n=2) puberty and reached a final height (FH). Puberty started spontaneously in all boys not given testicular irradiation. All boys who received testicular irradiation developed hypergonadotrophic hypogonadism. Puberty started spontaneously in two girls and was induced with increasing doses of ethinylestradiol in two girls. In two girls, a low dose of ethinylestradiol was given until menarche. In one girl with early onset of puberty and short stature, puberty was blocked with a GnRH analogue. The standard deviation score for height decreased significantly from BMT to FH, both in the children who received TBI only (-1.1, P=0.005) as well as in those given additional CI (-1.7, P=0.027). Most of the loss occurred during puberty. In all, 10 children received growth hormone (GH) treatment. CI, young age at BMT, and short duration of GH treatment were predictors of height loss after BMT. Although limited by the small and heterogeneous sample, our study supports the use of early GH treatment in children with decelerating growth rate and low GH levels.

  • 27.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D2012In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 47, no 5, p. 657-662Article in journal (Refereed)
    Abstract [en]

    We measured bone mineral density (BMD) with dual-energy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age- and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score <−1) at one or more measurement sites, as opposed to two of the controls (11%, P=0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P=0.044) and were significantly correlated with total body BMD in the patient group (r=0.55, P=0.021). All six patients with low bone mass had hypovitaminosis D (37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P=0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.

  • 28.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Normal long-term parathyroid function after autologous bone marrow transplantation in children2007In: Pediatric Transplantation, ISSN 1397-3142, E-ISSN 1399-3046, Vol. 11, no 2, p. 205-208Article in journal (Refereed)
    Abstract [en]

    Parathyroid function was recently reported to be affected in more than one-third of pediatric BMT patients conditioned without irradiation. Our aim was to describe parathyroid function in children with malignant hematological disease after autologous BMT with and without TBI. PTH, albumin-corrected serum calcium, and serum phosphate were analyzed in 35 children followed for six months to nine yr after BMT. Twelve patients were conditioned with chemotherapy alone, and 23 patients received TBI as well. In the TBI group, 11 patients had previously received additional CRT. We found normal levels of PTH in children post-BMT, with the exception of four patients (11%) who showed transient PTH elevation during the first year of follow-up, There was no difference between those who had received irradiation and those who had not. Serum calcium was unchanged after BMT. An age-corrected quotient of serum phosphate decreased slightly. Renal function which was normal before BMT decreased slightly in both groups after BMT, but was within the normal range. Parathyroid function was found to be normal during the time frame of this study, irrespective of whether irradiation had been given.

  • 29.
    Frisk, Per
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Arvidson, Johan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Normal spontaneous cortisol secretion in children after autologous bone marrow transplantation.2005In: Acta Paediatr, ISSN 0803-5253, Vol. 94, no 10, p. 1411-5Article in journal (Refereed)
  • 30.
    Frisk, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rössner, S M
    Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Norgren, S
    Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Glucose metabolism and body composition in young adults treated with TBI during childhood2011In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 46, no 10, p. 1303-1308Article in journal (Refereed)
    Abstract [en]

    After SCT in childhood, survivors may develop disorders of glucose metabolism. The role of obesity is controversial. We measured insulin sensitivity using the homeostasis model assessment (HOMA) and the frequently sampled i.v. glucose tolerance test (FSIVGTT), as well as body composition using dual-energy X-ray absorptiometry in 18 young adults median 18.2 years after SCT and compared them with matched controls. We also measured growth hormone (GH) secretion, and levels of leptin and adiponectin. HOMA showed insulin resistance in eight patients (44%), as opposed to none of the controls (P=0.008) and FSIVGTT showed a decreased sensitivity index in the patients (2.98 vs 4.54 mU/L/min, P=0.042). Dual energy X-ray absorptiometry showed a higher percentage fat mass in the patients (34.9 vs 24.3%, P=0.011), which correlated inversely with the sensitivity index (r=-0.52, P=0.032). The patients had a lower peak value of GH (GH(max) 9 vs 20.7 mU/L, P=0.002). Time post SCT correlated with percentage fat mass and inversely with GH(max). The patients had higher levels of leptin and lower levels of adiponectin, even after adjustment for fat mass. We propose that the decreased insulin sensitivity may primarily be explained by the adverse body composition, which may owe to long-standing GH deficiency.

  • 31.
    Groth, Torgny
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Ewald, Uwe
    Department of Women's and Children's Health.
    Gustafsson, Jan
    Department of Women's and Children's Health.
    Errors in estimating neonatal production of glucose with stable isotopes during2001In: Scand J Clin Lab Invest, Vol. 61, p. 663-680Article in journal (Refereed)
  • 32.
    Gustafsson, J
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Alimohammadi, M
    Ekvall, O
    Halldin-Stenlid, M
    Landgren, E
    Nilsson, T
    Rorsman, F
    Sköldberg, F
    Winqvist, O
    Kämpe, O
    APS I - svår autoimmun sjukdom med endokrina och icke-endokrina symtom2004In: Läkartidningen, Vol. 101, no 24, p. 2096-2103Article in journal (Refereed)
  • 33.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hur klarar det nyfödda barnet sin energiförsörjning?2006In: Pediatrisk Endokrinologi, ISSN 0801-5732, no 20, p. 6-13Article in journal (Refereed)
  • 34.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Neonatal endokrinologi2010In: Akut Pediatrik / [ed] Svante Norgren, Jonas F. Ludvigsson, Mikael Norman, Tomas Widlund, Stockholm: Lieber AB , 2010Chapter in book (Other academic)
  • 35.
    Gustafsson, Jan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Neonatal endokrinologi.2005In: Akut Pediatrik., Liber AB Stockholm , 2005, p. 68-77Chapter in book (Other scientific)
  • 36.
    Gustafsson, Jan
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Alvelius, Gunvor
    Björkhem, Ingemar
    Nemeth, Antal
    Bile acid metabolism in extrahepatic biliary atresia: lithocholic acid in stored dried blood collected at neonatal screening.2006In: Ups J Med Sci, ISSN 0300-9734, Vol. 111, no 1, p. 131-6Article in journal (Refereed)
  • 37.
    Gustafsson, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Eriksson, J.
    Marcus, C.
    Glucose metabolism in human adipose tissue studied by 13C-glucose and microdialysis2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 2, p. 155-164Article in journal (Refereed)
    Abstract [en]

    Objective. Microdialysis can be used to monitor carbohydrate metabolism and lipolysis in adipose tissue. This method, however, does not discriminate between local metabolite production and delivery from other tissues. Our aim was to study glucose metabolism by direct delivery of 13C-labelled glucose into adipose tissue by microdialysis. Material and methods. Seven healthy adults were studied after an overnight fast. In three of them the effect of physical activity on glucose metabolism was tested. Microdialysis catheters were introduced into abdominal adipose tissue and 25 mM 13C-labelled glucose was added to the perfusion fluid. An extraction procedure for separating lactic acid from glucose and glycerol in the microdialysate samples was developed. After derivatization, the 13C enrichment of the compounds was analysed by gas chromatography-mass spectrometry. Results. 13C-labelled lactate was detected in the first 15-min eluate fraction following that in which 13C-glucose had reached the microdialysis probe. In the different subjects, 22-35 % of adipose tissue lactate was produced locally. During exercise there was an increase in the lactate concentration and a decrease in 13C enrichment of lactate. Although lactate production in the adipose tissue increased during exercise, most adipose tissue lactate resulted from inflow. The administered 13C-labelled glucose also rapidly converted to 13C-glycerol. The 13C enrichment of glycerol was lower than that of lactate. During exercise the 13C enrichment of glycerol increased, indicating that newly synthesized depot fat was preferentially hydrolysed during physical activity. Conclusions. Metabolism of glucose to lactate and glycerol in subcutaneous adipose tissue is a rapid process that can be monitored in vivo by administration of stable isotope labelled glucose into the microdialysis probe. In adults at rest about one-fourth of adipose tissue lactate is produced locally.

  • 38.
    Gustafsson, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hagenäs, L
    Barnendokrinologi2011In: Pediatrik / [ed] Christian Moëll & Jan Gustafsson, Stockholm: Liber, 2011, p. 266-287Chapter in book (Refereed)
  • 39.
    Gustafsson, Jan
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Hagenäs, Lars
    Pediatrisk endokrinologi: Barnets tillväxt speglar hälsa och socioekonomiska förhållanden2004In: Endokrinologi, 2004, p. 321-61Chapter in book (Refereed)
  • 40.
    Gustavson, KH
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Anneren, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Axelsson, O
    Department of Women's and Children's Health.
    Eriksson, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
    Gustafsson, J
    Department of Women's and Children's Health.
    Lonnerholm, T
    Rehnberg, L
    Skeletal dysplasia. Medical interdisciplinary care is necessary for optimal treatment.1995In: Läkartidningen, Vol. 92, p. 3425-Article in journal (Refereed)
  • 41. Gyllenhammar, Irina
    et al.
    Diderholm, Barbro
    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.
    Gustafsson, Jan
    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.
    Berger, Urs
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Benskin, Jonathan P
    Lignell, Sanna
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Glynn, Anders
    Perfluoroalkyl acid levels in first-time mothers in relation to offspring weight gain and growth2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 111, p. 191-199Article in journal (Refereed)
    Abstract [en]

    We investigated if maternal body burdens of perfluoroalkyl acids (PFAAs) at the time of delivery are associated with birth outcome and if early life exposure (in utero/nursing) is associated with early childhood growth and weight gain. Maternal PFAA body burdens were estimated by analysis of serum samples from mothers living in Uppsala County, Sweden (POPUP), sampled three weeks after delivery between 1996 and 2011. Data on child length and weight were collected from medical records and converted into standard deviation scores (SDS). Multiple linear regression models with appropriate covariates were used to analyze associations between maternal PFAA levels and birth outcomes (n=381). After birth Generalized Least Squares models were used to analyze associations between maternal PFAA and child growth (n=200). Inverse associations were found between maternal levels of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), and birth weight SDS with a change of -0.10 to -0.18 weight SDS for an inter-quartile range (IQR) increase in ng/g PFAA. After birth, weight and length SDS were not significantly associated with maternal PFAA. However, BMI SDS was significantly associated with PFOA, PFNA, and PFHxS at 3 and 4years of age, and with PFOS at 4 and 5years of age. If causal, these associations suggest that PFAA affects fetal and childhood body development in different directions.

  • 42.
    Haglind, C Bieneck
    et al.
    Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Nordenström, A
    Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Ask, S
    Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    von Döbeln, U
    Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Stenlid, Maria Halldin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Increased and early lipolysis in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency during fast2015In: Journal of Inherited Metabolic Disease, ISSN 0141-8955, E-ISSN 1573-2665, Vol. 38, no 2, p. 315-322Article in journal (Refereed)
    Abstract [en]

    Children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. Knowledge on substrate metabolism in children with LCHAD deficiency during fasting is limited. Treatment guidelines differ between centers, both as far as length of fasting periods and need for night feeds are concerned. To increase the understanding of fasting intolerance and improve treatment recommendations, children with LCHAD deficiency were investigated with stable isotope technique, microdialysis, and indirect calometry, in order to assess lipolysis and glucose production during 6 h of fasting. We found an early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia. The rate of glycerol production, reflecting lipolysis, averaged 7.7 ± 1.6 µmol/kg/min, which is higher compared to that of peers. The rate of glucose production was normal for age; 19.6 ± 3.4 µmol/kg/min (3.5 ± 0.6 mg/kg/min). Resting energy expenditure was also normal, even though the respiratory quotient was increased indicating mainly glucose oxidation. The results show that lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested.

  • 43.
    Halldin Stenlid, Maria U.
    et al.
    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.
    von Döbeln, U
    Eklund, C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Increased lipolysis in LCHAD deficiency2007In: Journal of Inherited Metabolic Disease, ISSN 0141-8955, E-ISSN 1573-2665, Vol. 30, no 1, p. 39-46Article in journal (Refereed)
    Abstract [en]

    An increasing number of fatty acid oxidation defects are being detected owing to diagnostic improvements and a greater awareness among clinicians. The metabolic block leads to energy disruption, fatty infiltration, and toxic effects on organ functions exerted by β-oxidation metabolites. This investigation was undertaken to assess the influence of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency on lipolysis and energy turnover. We addressed the question whether the lipolysis and glucose production rates would be altered in the fasting state in a child with this disease. Lipolysis, glucose production and resting energy expenditure (REE) were studied in a 17-month-old girl with LCHAD deficiency and her healthy twin sister. Lipolysis and glucose production were determined after a 4–6 h fast by constant-rate infusion of [1,1,2,3,3-2H5]glycerol and [6,6-2H2]glucose and analysis by gas chromatography–mass spectrometry. REE was estimated by indirect calorimetry. The affected girl showed 50% higher lipolysis than did her sister, whereas the glucose production rates were similar. Plasma levels of dicarboxylic acids of 6–12 carbon atoms chain length, 3-hydroxy fatty acids of 6–18 carbon atoms chain length, total free fatty acids, and acylcarnitines were increased in the patient, as was REE. Since glucose production rates and plasma glucose levels were similar in the two girls, the increased lipolysis observed in the patient probably represents a compensatory mechanism for energy generation. This is achieved at the price of an augmented risk for fatty acid infiltration and toxic effects of β-oxidation intermediates. This highlights the importance of avoiding fasting in these patients.

  • 44.
    Holmbäck, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Fridman, Jennifer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Proos, Lemm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundelin, Claes
    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.
    Overweight more prevalent among children than among adolescents2007In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 96, no 4, p. 577-581Article in journal (Refereed)
    Abstract [en]

    Aims

    To study if there is a change in paediatric overweight/obesity prevalence from 1982 to 2002 in a population with a high proportion of post-graduate education.

    Design

    Two samples of children in Uppsala County, Sweden, were compared: children who were 4, 10 and 16 year old in 1982; or 4, 10 and 16 year old in 2002. Mean BMI (in the lowest 10%, middle 50% and highest 10%) and ISO-BMI ('age adjusted BMI') cut-off values were calculated in each age and gender group.

    Results

    Using the mean BMI or ISO-BMI cut-off values, the BMI-distribution shifted from 1982 to 2002. More 4- and 10-year-old girls and boys were overweight/obese, although this shift was larger in girls. No shift was seen in the 16-year-olds, only the middle 50% group in the 16-year-old girls had a slight increase of their mean BMI. In the 2002 4-year-old, and both 10-year-old samples, a higher proportion of the girls were overweight/obese compared to the boys, but no difference was seen in the 16-year-old sample.

    Conclusion

    Young children, especially girls, have become much more overweight/obese during the past 20 years, despite a high proportion of post-graduate education in the population. The lack of major change in 16-year-olds may suggest a rather recent change in the children's environment/lifestyle.

  • 45.
    Johnsson, Inger W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Haglund, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Ahlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    A high birth weight is associated with increased risk of type 2 diabetes and obesity2015In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 10, no 2, p. 77-83Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The association between low birth weight and adult disease is well known. Less is known on long-term effects of high birth weight.

    OBJECTIVE: This study aims to investigate whether a high birth weight increases risk for adult metabolic disease.

    METHODS: Swedish term single births, 1973-1982 (n = 759 999), were studied to age 27.5-37.5 years using Swedish national registers. Hazard ratios (HRs) were calculated in relation to birth weight for type 2 diabetes, obesity, hypertension and dyslipidaemia.

    RESULTS: Men with birth weights between 2 and 3 standard deviation score (SDS) had a 1.9-fold increased risk (HR 1.91, 95% confidence interval [CI] 1.25-2.90) of type 2 diabetes, whereas those with birth weights above 3 SDS had a 5.4-fold increased risk (HR 5.44, 95% CI 2.70-10.96) compared to men with birth weights between -2 and 2 SDS. The corresponding HRs for women were 0.60 (95% CI 0.40-0.91) and 1.71 (95% CI 0.85-3.43) for birth weights 2-3 SDS and >3 SDS, respectively. Men with birth weights between 2 and 3 SDS had a 1.5-fold increased risk (HR 1.47, 95% CI 1.22-1.77) of obesity. The corresponding risk for women was 1.3-fold increased (HR 1.32, 95% CI 1.19-1.46). For men and women with birth weights above 3 SDS, the risks of adult obesity were higher, HR 2.46 (95% CI 1.63-3.71) and HR 1.85 (95% CI 1.44-2.37), respectively.

    CONCLUSIONS: A high birth weight, particularly very high, increases the risk of type 2 diabetes in male young adults. The risk of obesity increases with increasing birth weight in both genders.

  • 46.
    Johnsson, Inger W
    et al.
    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.
    Naessén, Tord
    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), Gynecological endocrinology.
    Ahlsson, Fredrik
    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), Perinatal, Neonatal and Pediatric Cardiology Research.
    Gustafsson, Jan
    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.
    High birth weight was associated with increased radial artery intima thickness but not with other investigated cardiovascular risk factors in adulthood.2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227Article in journal (Refereed)
    Abstract [en]

    AIM: This study investigated whether a high birth weight was associated with increased risk factors for cardiovascular disease when Swedish adults reached 34-40.

    METHODS: We studied 27 subjects born at Uppsala University Hospital in 1975-1979, weighing at least 4500 g, and compared them with 27 controls selected by the Swedish National Board of Welfare with birth weights within ±1 standard deviations scores and similar ages and gender. The study included body mass index (BMI), blood pressure, lipid profile, haemoglobin A1c (HbA1c), C-reactive protein (CRP) and high-frequency ultrasound measurements of intima-media thickness, intima thickness (IT) and intima:media ratio of the carotid and radial arteries.

    RESULTS: Subjects with a high birth weight did not differ from controls with regard to BMI, blood pressure, lipid profile, high-sensitivity CRP, HbA1c or carotid artery wall dimensions. However, their radial artery intima thickness was 37% greater than the control group and their intima:media ratio was 44% higher.

    CONCLUSION: Our findings indicate that a high birth weight was associated with increased radial artery intima thickness, but not with other investigated cardiovascular risk factors, at 34-40 years of age. The clinical implications of these findings should be investigated further, especially in subjects born with a very high birth weight.

  • 47.
    Landegren, Nils
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sharon, Donald
    Freyhult, Eva
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Hallgren, Åsa
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eriksson, Daniel
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Edqvist, Per-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bensing, Sophie
    Wahlberg, Jeanette
    Nelson, Lawrence M
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Husebye, Eystein S
    Anderson, Mark S
    Snyder, Michael
    Kämpe, Olle
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 12016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20104Article in journal (Refereed)
    Abstract [en]

    Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.

  • 48.
    Landegren, Nils
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Sharon, Donald
    Shum, Anthony K.
    Khan, Imran S.
    Fasano, Kayla J.
    Hallgren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kampf, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ardesjo-Lundgren, Brita
    Alimohammadi, Mohammad
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Rathsman, Sandra
    Ludvigsson, Jonas F.
    Lundh, Dan
    Motrich, Ruben
    Rivero, Virginia
    Fong, Lawrence
    Giwercman, Aleksander
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Perheentupa, Jaakko
    Husebye, Eystein S.
    Anderson, Mark S.
    Snyder, Michael
    Kämpe, Olle
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity.
    Transglutaminase 4 as a prostate autoantigen in male subfertility2015In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, no 292, article id 292ra101Article in journal (Refereed)
    Abstract [en]

    Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.

  • 49.
    Lindblad, Frank
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Eickhoff, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Forslund, Anders H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Isaksson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Fasting blood glucose and HbA1c in children with ADHD2015In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 226, no 2-3, p. 515-516Article in journal (Refereed)
    Abstract [en]

    Reports of hypocortisolism and overweight in pediatric ADHD motivate an investigation of blood glucose regulation in this group. Fasting blood glucose and HbA1c were investigated in 10 children (10-15 years) with ADHD and 22 comparisons. Fasting blood glucose was similar in both groups. HbA1c values were higher in the ADHD-group. BMI-SDS was also higher in the ADHD-group but did not predict HbA1c. The results suggest an association between ADHD and an altered blood glucose homeostasis.

  • 50.
    Lundgren, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Morgården, E.
    Gustafsson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Is obesity a risk factor for impaired cognition in young adults with low birth weight?2014In: Pediatric Obesity, ISSN 2047-6302, E-ISSN 2047-6310, Vol. 9, no 5, p. 319-326Article in journal (Refereed)
    Abstract [en]

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Obesity is associated with metabolic disease and impaired cognitive function in adults. Low birth weight is known to be associated with adult metabolic disease and low intellectual performance.

    WHAT THIS STUDY ADDS: Adolescent overweight and obesity are associated with increased risk of low intellectual performance. Overweight/obese adolescents, born with a low weight, have a further increased risk of low intellectual performance. A high birth weight increases the risk of adolescent obesity. Overweight/obese adolescents, born with a high weight, do not have a further increased risk of low intellectual performance.

    BACKGROUND: Overweight and obesity are risk factors for cardiovascular disease. There is also an association between body mass index (BMI) and cognitive ability. Since low birth weight is associated with adult metabolic disease, particularly in obese subjects, the question emerges whether obesity has an additional negative effect on cognitive function in subjects with low birth weight.

    OBJECTIVES: The aim was to analyse whether overweight or obesity influence intellectual performance in young adults with particular focus on those with a low birth weight.

    METHODS: Data were collected from the Swedish Medical Birth Register on 620 834 males born between 1973 and 1988 and matched to results on intellectual performance and BMI at conscription.

    RESULTS: The risk for low intellectual performance was higher for those with high BMI compared to those with normal. The highest risk was found among subjects with low birth weight and overweight or obesity in young adulthood (odds ratios, 1.98 [1.73-2.22] and 2.59 [2.00-3.34], respectively). However, subjects with further high birth weight and a high BMI at conscription had no further increased risk.

    CONCLUSIONS: Overweight and obesity are associated with an increased risk of subnormal intellectual performance in young adult males. Subjects with low birth weight and adolescent overweight/obesity are at particular risk of subnormal performance. A high birth weight increases the risk for obesity, but a high adult BMI does not further increase the risk for subnormal performance.

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