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  • 1.
    Allbrand, Marianne
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Åman, Jan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Lodefalk, Maria
    Örebro University, School of Medical Sciences.
    Adipocytokines in placenta and cord blood in relation to maternal obesity, and foetal and postnatal growth of the child2015In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, no Suppl. 1, p. 47-48Article in journal (Other academic)
    Abstract [en]

    Background: The nutritional and hormonal state in utero may be a link between maternal obesity and obesity in the offspring. The gene expression in placentae in pregnancies complicated by diabetes is reduced for leptin, but increased for ghrelin. It is not known whether these genes’ expressions in placentae are altered in maternal obesity.

    Objectives and hypotheses: To compare obese and normal-weight women and their children concerning gene expressions of leptin and ghrelin in placentae; leptin, ghrelin, adiponectin, and C-peptide levels in cord blood, birth size and postnatal growth. Changes in the expression of these adipocytokines may lead to an altered hypothalamic sensitivity to leptin and ghrelin resulting in an increased risk of obesity in the offspring.

    Method: 32 women with pre-pregnancy obesity, but otherwise healthy, were compared to 32 matched, normal-weight controls. Full-term placenta biopsies were analysed with qPCR for leptin mRNA and ghrelin mRNA. Cord blood samples were examined with ELISA for leptin, ghrelin, adiponectin, and C-peptide concentrations. Birth size and postnatal growth of the children were collected from clinical registers at the Child Health Care Units.

    Results: The leptin and ghrelin gene expressions in placentae did not differ between obese and normal-weight women. The leptin concentration in cord blood was higher in children of obese mothers (P=0.021). It correlated with birth weight Z-score (r=0.467, P<0.001) and C-peptide level in cord blood (r=0.446, P<0.001). Children of obese women were slightly heavier at birth, but postnatal growth did not differ between groups. Children with birth weight  ≤−0.67 Z-score had higher ghrelin levels in cord blood than heavier children (P=0.042). The leptin level in cord blood correlated negatively with weight gain at 6 months (r=−0.332, P=0.009). The ghrelin level in cord blood correlated with weight gain at 3 months in girls (r=0.611, P=0.001), but not in boys. The adiponectin level in cord blood correlated negatively with length gain at 3 years in the obese group (r=−0.571, P=0.033), but not in the normal-weight group.

    Conclusion: Leptin and ghrelin placental gene expressions are not altered in obese women, but foetal adipocytokine production may influence early postnatal growth, possibly by influencing hunger signalling or insulin levels

  • 2.
    Allbrand, Marianne
    et al.
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynecology.
    Åman, Jan
    Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Lodefalk, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital. Health Care Research Center, Region Örebro County, Örebro, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Placental ghrelin and leptin expression and cord blood ghrelin, adiponectin, leptin, and C-peptide levels in severe maternal obesity2017In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 31, no 21, p. 2839-2846Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study is to investigate placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels in maternal obesity and associations between placental ghrelin expression, cord blood ghrelin levels and maternal and infant variables.

    MATERIALS AND METHODS: Placental ghrelin and leptin expression were analyzed by RT-PCR in 32 severely obese and 32 matched normal-weight women. Cord blood ghrelin, adiponectin, leptin, and C-peptide concentrations were analyzed by ELISA.

    RESULTS: Neither ghrelin nor leptin expression and neither cord blood ghrelin nor adiponectin levels differed between the groups. Placental ghrelin expression was associated with BMI at delivery in the obese women (r = 0.424, p = .016) and in the infants born to normal-weight women with their weight z-scores at six (r = -0.642, p = .010), nine (r = -0.441, p = .015), and 12 months of age (r = -0.402, p = .028).

    CONCLUSIONS: Placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels do not seem to be altered in severe maternal obesity. Placenta-derived ghrelin may influence the infants' postnatal weight gain, but possibly only when the mother has normal weight.

  • 3.
    Allbrand, Marianne
    et al.
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynecology.
    Åman, Jan
    Department of Pediatrics, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsson, Kerstin
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynecology.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lodefalk, Maria
    Örebro University, School of Medical Sciences. Department of Pediatrics, School of Medical Sciences, Örebro University, Örebro, Sweden; University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Expression of genes involved in inflammation and growth: does sampling site in human full-term placenta matter?2019In: Journal of Perinatal Medicine, ISSN 0300-5577, E-ISSN 1619-3997, Vol. 47, no 5, p. 539-546Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the placental gene expression of substances in the inflammatory cascade and growth factors at nine different well-defined sampling sites in full-term placentas from 12 normal weight healthy non-smoking women with an uncomplicated singleton pregnancy.

    Methods: All placentas (six girls and six boys) were delivered vaginally. Quantitative real-time polymerase chain reaction was used to analyze toll receptor-2 and -4, interleukin-6 and -8, tumor necrosis factor-α, leptin, ghrelin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor (IR).

    Results: The leptin gene and the IR gene showed higher expression in lateral regions near the chorionic plate compared to central regions near the basal plate (P = 0.028 and P = 0.041, respectively).

    Conclusion: Our results suggest that the sampling site may influence the gene expression for leptin and IR in placental tissue obtained from full-term normal pregnancies. We speculate that this may be due to differences in placental structure and perfusion and may be important when future studies are designed.

  • 4. Hoermann, Henrike
    et al.
    El-Rifai, Omar
    Schebek, Martin
    Lodefalk, Maria
    Örebro University, School of Medical Sciences.
    Brusgaard, Klaus
    Bachmann, Nadine
    Bergmann, Carsten
    Mayatepek, Ertan
    Christesen, Henrik
    Meissner, Thomas
    Kummer, Sebastian
    Characteristics of children with Kabuki syndrome and hyperinsulinemic hypoglycemia2019Conference paper (Other academic)
  • 5.
    Lodefalk, Maria
    Karolinska institutet, Stockholm, Sweden.
    Adolescent type 1 diabetes: Eating and gastrointestinal function2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Adolescents with type 1 diabetes (T1DM) are given nutritional education, but the knowledge about their adherence to the food recommendations and associations between dietary intake and metabolic control is poor. Gastrointestinal symptoms are more prevalent in adults with T1DM than in healthy controls, which may be due to disturbed gastrointestinal motility. The meal content affects the gastric emptying rate and the postprandial glycaemia in healthy adults and adults with type 2 diabetes. Meal ingestion also elicits several postprandial hormonal changes of importance for gastrointestinal motility and glycaemia. Eating disorders are more prevalent in young females with T1DM than in healthy females, and are associated with poor metabolic control. The prevalence of eating disorders in adolescent boys with T1DM is not known.

     This thesis focuses on eating and gastrointestinal function in adolescents with T1DM. Three population-based, cross-sectional studies demonstrated that adolescents with T1DM consume healthy foods more often and have a more regular meal pattern than age- and sex-matched controls. Yet both boys and girls are heavier than controls. The intake of saturated fat is higher and the intake of fibre is lower than recommended in adolescents with T1DM. Patients with poor metabolic control consume more fat and less carbohydrates than patients with better metabolic control. Gastrointestinal symptoms are common in adolescents with T1DM, but the prevalence is not increased compared with controls. Gastrointestinal symptoms in patients are associated with female gender, daily cigarette smoking, long duration of diabetes, poor metabolic control during the past year, and an irregular meal pattern. Adolescent boys with T1DM are heavier and have higher drive for thinness than healthy boys, but do not differ from them in scales measuring psychopathology associated with eating disorders. 

     In a randomized, cross-over study, we found that a meal with a high fat and energy content reduces the initial (0–2 hours) postprandial glycaemic response and delays gastric emptying in adolescents with T1DM given a fixed prandial insulin dose compared with a low-fat meal. The glycaemic response is significantly associated with the gastric emptying rate. Both a high- and a low-fat meal increase the postprandial concentrations of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) and suppress the postprandial ghrelin levels in adolescents with T1DM. The postprandial changes of these hormones are more pronounced after the high-fat meal. Insulin-like growth factor binding-protein (IGFBP) –1 concentrations decrease after insulin administration irrespective of meal ingestion. The GLP-1 response is negatively associated with the gastric emptying rate. The fasting ghrelin levels are negatively associated with the postprandial glycaemic response, and the fasting IGFBP-1 levels are positively associated with the fasting glucose levels.

     We conclude that nutritional education to adolescents with T1DM should focus more on energy intake and expenditure to prevent and treat weight gain. It should also focus on fat quality and fibre intake to reduce the risk of macrovascular complications and improve glycaemia. Gastrointestinal symptoms in adolescents with T1DM should be investigated and treated as in other people irrespective of having diabetes. However, adolescents with long duration of diabetes, poor metabolic control, and symptoms from the upper gut should have their gastric emptying rate examined during euglycaemia. There may be an increased risk for development of eating disorders in adolescent males with T1DM since they are heavier than healthy boys and have higher drive for thinness. This should be investigated in future, larger studies.

     For the first time, we showed that a fat-rich meal delays gastric emptying and reduces the initial glycaemic response in patients with T1DM. The action profile of the prandial insulin dose to a fat-rich meal may need to be postponed and prolonged compared with the profile to a low-fat meal to reach postprandial normoglycaemia. Circulating insulin levels affect postprandial GIP, GLP-1, and ghrelin, but not IGFBP-1, responses less than the meal content. The pronounced GIP-response to a fat- and energy-rich meal may promote adiposity, since GIP stimulates lipogenesis. Such an effect would be disadvantageous for adolescents with T1DM since they already have increased body fat mass and higher weights compared with healthy adolescents. Adolescents with T1DM may have subnormal postprandial ghrelin suppression, which may be due to their increased insulin resistance or elevated growth hormone levels. This needs to be investigated in future, controlled studies.

     

     

    List of papers
    1. Food habits, energy and nutrient intake in adolescents with Type 1 diabetes mellitus
    Open this publication in new window or tab >>Food habits, energy and nutrient intake in adolescents with Type 1 diabetes mellitus
    2006 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 23, no 11, p. 1225-1232Article in journal (Refereed) Published
    Abstract [en]

    AIMS: The aims were to describe the food habits of adolescents with Type 1 diabetes (Type 1 DM) and to compare them with healthy control subjects; to describe the distribution of energy-providing nutrients in patients and compare it with current recommendations and previous reports; and finally, to investigate associations between dietary intake and glycaemic control. METHODS: One hundred and seventy-four adolescents with Type 1 DM and 160 age- and sex-matched healthy control subjects completed a validated food frequency questionnaire, and 38 randomly chosen patients completed a prospective 4-day food record. RESULTS: Patients ate more regularly, and more often ate fruit and fruit juice, potatoes and root vegetables, meat, fish, egg, offal and sugar-free sweets than control subjects. Control subjects more often ate ordinary sweets and snacks. Patients chose coarse rye bread and dairy products with less fat to a greater extent than control subjects. Patients were heavier than control subjects. The intake of saturated fat was higher in patients compared with recommendations and, for boys with diabetes, the intake of protein was higher than recommended. Patients with poorer glycaemic control ate vegetables, fruit and fish less often than patients with better control. CONCLUSIONS: The food habits of adolescents with Type 1 DM were healthier than those of control subjects. The intake of energy-providing nutrients was in line with current recommendations and showed improvements compared with previous reports, with the exception of fibre intake. The association between dietary intake and glycaemic control needs further investigation in prospective studies.

    Place, publisher, year, edition, pages
    Oxon, United Kingdom: Wiley-Blackwell, 2006
    Keywords
    Adolescence, diet, glycaemic control, Type 1 diabetes
    National Category
    Medical and Health Sciences Pediatrics Endocrinology and Diabetes
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-12064 (URN)10.1111/j.1464-5491.2006.01971.x (DOI)000241367000012 ()17054600 (PubMedID)2-s2.0-33750175427 (Scopus ID)
    Available from: 2010-10-05 Created: 2010-10-05 Last updated: 2017-12-12Bibliographically approved
    2. Effects of fat supplementation on postprandial GIP, GLP-1, ghrelin and IGFBP-1 levels: a pilot study on adolescents with type 1 diabetes
    Open this publication in new window or tab >>Effects of fat supplementation on postprandial GIP, GLP-1, ghrelin and IGFBP-1 levels: a pilot study on adolescents with type 1 diabetes
    Show others...
    2010 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 73, no 5, p. 355-62Article in journal (Refereed) Published
    Abstract [en]

    Aims: To compare the responses of GIP, GLP-1, ghrelin and IGFBP-1 between meals with different fat and energy content in adolescents with type 1 diabetes (T1DM) and to relate them to gastric emptying and glycaemia.

    Methods: On different days and in a random order, 7 adolescents with T1DM ingested a high- and low-fat meal (fat content: 38 and 2 g, energy content: 640 and 320 kcal, respectively). At normoglycaemia, the same prandial insulin dose was given at both meals and to all subjects. Postprandial blood samples were taken repeatedly over 4 hours. Gastric emptying was estimated by the paracetamol absorption method.

    Results: The area under the curve (AUC) for GIP(0-240 min) and for GLP-1(0-120 min) was larger, but smaller for relative ghrelin(0-240 min), after the high-fat meal (p = 0.002, 0.030 and 0.043, respectively). IGFBP-1 decreased significantly, but not differently, after the meals. Larger GLP-1 secretion correlated with slower gastric emptying (p = 0.029) and higher fasting ghrelin levels correlated with lower postprandial glycaemia (p = 0.007).

    Conclusion: In adolescents with T1DM, the postprandial responses of GIP, GLP-1 and ghrelin, but not that of IGFBP-1, depend more on meal size than on insulin.

    Place, publisher, year, edition, pages
    Basel, Switzerland: S. Karger, 2010
    Keywords
    Adolescence, gastric emptying, ghrelin, IGFBP-1, incretin hormones, type 1 diabetes
    National Category
    Medical and Health Sciences Nutrition and Dietetics
    Identifiers
    urn:nbn:se:oru:diva-44976 (URN)10.1159/000308168 (DOI)000277570100008 ()20389106 (PubMedID)2-s2.0-77954040563 (Scopus ID)
    Available from: 2015-06-23 Created: 2015-06-23 Last updated: 2018-04-25Bibliographically approved
    3. Gastrointestinal symptoms in adolescents with type 1 diabetes
    Open this publication in new window or tab >>Gastrointestinal symptoms in adolescents with type 1 diabetes
    2010 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 11, no 4, p. 265-70Article in journal (Refereed) Published
    Abstract [en]

    Objective: To compare the prevalence of gastrointestinal (GI) symptoms in adolescents with and without type 1 diabetes (T1DM) and to relate the symptoms in patients to demographic, socioeconomic, diabetes-specific variables, and food habits.

    Method: In a population-based, cross-sectional setting, 173 adolescents with T1DM and 160 matched controls completed a questionnaire. Moreover, 13 patients and 1 control were excluded due to having a GI disorder.

    Results: Moreover, 75% of patients and 77% of controls reported at least one GI symptom (ns). More girls than boys reported symptoms. Reflux episodes were more prevalent in patients with poorer socioeconomic status. Poor appetite, loss of weight, an uncomfortable feeling of fullness, swallowing difficulties, and nausea were more prevalent in patients smoking daily compared with patients not smoking daily. Vomiting was more prevalent in patients with duration of diabetes >7 yr, and patients with reflux episodes had higher glycated hemoglobin (HbA1c). Belching and early satiety were more prevalent in patients with an irregular meal pattern.

    Conclusions: GI symptoms in adolescents are common, but the prevalence is not increased in those with T1DM. GI symptoms in adolescents with T1DM are associated with female sex, poorer socioeconomic status, daily cigarette smoking, longer duration of diabetes, poorer metabolic control, and an irregular meal pattern.

    Place, publisher, year, edition, pages
    Hoboken, USA: John Wiley & Sons, 2010
    Keywords
    Adolescent, diabetes mellitus, food habits, GI, type 1
    National Category
    Medical and Health Sciences Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-44974 (URN)10.1111/j.1399-5448.2010.00664.x (DOI)000278196700010 ()20618744 (PubMedID)2-s2.0-77954485881 (Scopus ID)
    Available from: 2015-06-23 Created: 2015-06-23 Last updated: 2018-04-25Bibliographically approved
    4. Effects of fat supplementation on glycaemic response and gastric emptying in adolescents with Type 1 diabetes
    Open this publication in new window or tab >>Effects of fat supplementation on glycaemic response and gastric emptying in adolescents with Type 1 diabetes
    2008 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 25, no 9, p. 1030-1035Article in journal (Refereed) Published
    Abstract [en]

    AIMS: To compare the glycaemic response to meals with different fat content in adolescents with Type 1 diabetes mellitus (T1DM) and to investigate associations with gastric emptying.

    METHODS: In this randomized, cross-over study, paired results were obtained from seven adolescents with T1DM who ingested on different days two meals with the same carbohydrate and protein content, but different fat and energy content (2 and 38 g fat, 320 and 640 kcal, respectively). Paracetamol was mixed into the meals and gastric emptying was estimated by the paracetamol absorption method. All subjects were normoglycaemic and given 7 IU insulin aspart at commencement of ingestion. Postprandial blood samples were taken during 4 h.

    RESULTS: The areas under the curves for plasma glucose and serum paracetamol concentrations were larger after the low-fat than after the high-fat meal during the first 2 h (P = 0.047 and P = 0.041, respectively). The difference between meals in time-to-peak in glucose and paracetamol concentrations did not reach statistical significance (high-fat vs. low-fat meal: 210 min (120-240) vs. 120 min (50-240), P = 0.080 and 120 min (75-180) vs. 60 min (60-120), P = 0.051, respectively). Changes in glucose concentrations correlated with simultaneous changes in paracetamol concentrations (P < 0.001).

    CONCLUSIONS: For the first time, we have shown that the initial glycaemic response is reduced after a meal with higher compared with a meal with lower fat content in adolescents with T1DM given a rapid-acting insulin analogue preprandially. The type and dose of preprandial insulin may need adjustment to the fat content of the meal to reach postprandial normoglycaemia.

    Place, publisher, year, edition, pages
    Oxford: Blackwell, 2008
    Keywords
    adolescents, dietary fat, gastric emptying, postprandial glycaemic response, Type 1 diabetes
    National Category
    Medical and Health Sciences Endocrinology and Diabetes Clinical Medicine
    Research subject
    Internal Medicine
    Identifiers
    urn:nbn:se:oru:diva-6949 (URN)10.1111/j.1464-5491.2008.02530.x (DOI)19183308 (PubMedID)
    Available from: 2009-05-27 Created: 2009-05-27 Last updated: 2017-12-13Bibliographically approved
    5. Higher drive for thinness in adolescent males with insulin-dependent diabetes mellitus compared with healthy controls
    Open this publication in new window or tab >>Higher drive for thinness in adolescent males with insulin-dependent diabetes mellitus compared with healthy controls
    2003 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 92, p. 114-117Article in journal (Refereed) Published
    Place, publisher, year, edition, pages
    Oslo, Norway: Taylor & Francis, 2003
    Keywords
    diabetes mellitus, ätstörning, ungdomar, pojkar
    National Category
    Medical and Health Sciences Pediatrics
    Research subject
    Pediatrics
    Identifiers
    urn:nbn:se:oru:diva-46125 (URN)000181612300021 ()12650311 (PubMedID)2-s2.0-0347927478 (Scopus ID)
    Available from: 2015-10-15 Created: 2015-10-15 Last updated: 2017-12-01Bibliographically approved
  • 6.
    Lodefalk, Maria
    et al.
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Carlsson-Skwirut, C.
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Holst, J. J.
    Department of Medical Physiology, Panum Institute, Copenhagen, Denmark .
    Aman, J.
    Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Bang, P
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Effects of fat supplementation on postprandial GIP, GLP-1, ghrelin and IGFBP-1 levels: a pilot study on adolescents with type 1 diabetes2010In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 73, no 5, p. 355-62Article in journal (Refereed)
    Abstract [en]

    Aims: To compare the responses of GIP, GLP-1, ghrelin and IGFBP-1 between meals with different fat and energy content in adolescents with type 1 diabetes (T1DM) and to relate them to gastric emptying and glycaemia.

    Methods: On different days and in a random order, 7 adolescents with T1DM ingested a high- and low-fat meal (fat content: 38 and 2 g, energy content: 640 and 320 kcal, respectively). At normoglycaemia, the same prandial insulin dose was given at both meals and to all subjects. Postprandial blood samples were taken repeatedly over 4 hours. Gastric emptying was estimated by the paracetamol absorption method.

    Results: The area under the curve (AUC) for GIP(0-240 min) and for GLP-1(0-120 min) was larger, but smaller for relative ghrelin(0-240 min), after the high-fat meal (p = 0.002, 0.030 and 0.043, respectively). IGFBP-1 decreased significantly, but not differently, after the meals. Larger GLP-1 secretion correlated with slower gastric emptying (p = 0.029) and higher fasting ghrelin levels correlated with lower postprandial glycaemia (p = 0.007).

    Conclusion: In adolescents with T1DM, the postprandial responses of GIP, GLP-1 and ghrelin, but not that of IGFBP-1, depend more on meal size than on insulin.

  • 7.
    Lodefalk, Maria
    et al.
    Örebro University, School of Medical Sciences. Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Frykholm, Carina
    Immunology, Genetics, and Pathology, University of Uppsala, Uppsala, Sweden.
    Esbjörner, Elisabeth
    Department of Paediatrics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ljunggren, Östen
    Medical Sciences, University of Uppsala, Uppsala, Sweden.
    Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication2016In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 85, no 3, p. 213-218Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Partial duplication of 2p is a rare condition that causes facial anomalies, psychomotor delay, and growth failure. Hypercalcaemia is rare in children. So far, duplication of 2p has never been associated with hypercalcaemia.

    METHODS: Here, we report a girl with a partial duplication of 2p presenting with moderate to severe hypercalcaemia at the age of 2 years. She also had hypercalciuria, nephrocalcinosis, decreased renal function, and secondary hyperparathyroidism at presentation. She was thoroughly investigated, including genetic testing of the CYP24A1, CASR, ALPL, and NOD2 genes, to determine the cause of hypercalcaemia.

    RESULTS: 1,25-dihydroxyvitamin D levels were increased. Hypercalcaemia and hypercalciuria responded well to glucocorticoids but not to cinacalcet. Hyperparathyroidism resolved with improving renal function. Apart from the known duplication of 2p, no pathogenic variants were detected in the studied genes. The duplication of 2p contains the PPP3R1 gene, which encodes for the calcineurin B subunit.

    CONCLUSION: We conclude that partial duplication of 2p can be associated with hypercalcaemia and hypercalciuria and hypothesise that the underlying mechanism is an increased extra-renal, parathyroid hormone-independent 25-hydroxyvitamin D 1α-hydroxylase activity, leading to raised amounts of 1,25-dihydroxyvitamin D. The increased enzymatic activity could possibly be caused by calcineurin B subunit-related macrophage stimulation.

  • 8.
    Lodefalk, Maria
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; University Health Care Research Center, Region Örebro County, Örebro, Sweden.
    Nilsson, Ola
    Örebro University, School of Medical Sciences. Department of Paediatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Division of Paediatric Endocrinology, Department of Women’s and Children’s Health, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    To Prime or Not to Prime - Is That Still a Question?: A Comment on the US Guidelines on Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents2017In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, no 2, p. 179-180Article in journal (Refereed)
  • 9.
    Lodefalk, Maria
    et al.
    Department of Paediatric Diabetology and Endocrinology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm; Department of Paediatrics, Örebro University Hospital, Örebro.
    Åman, Jan
    Department of Paediatric Diabetology and Endocrinology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm; Department of Paediatrics, Örebro University Hospital, Örebro.
    Food habits, energy and nutrient intake in adolescents with Type 1 diabetes mellitus2006In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 23, no 11, p. 1225-1232Article in journal (Refereed)
    Abstract [en]

    AIMS: The aims were to describe the food habits of adolescents with Type 1 diabetes (Type 1 DM) and to compare them with healthy control subjects; to describe the distribution of energy-providing nutrients in patients and compare it with current recommendations and previous reports; and finally, to investigate associations between dietary intake and glycaemic control. METHODS: One hundred and seventy-four adolescents with Type 1 DM and 160 age- and sex-matched healthy control subjects completed a validated food frequency questionnaire, and 38 randomly chosen patients completed a prospective 4-day food record. RESULTS: Patients ate more regularly, and more often ate fruit and fruit juice, potatoes and root vegetables, meat, fish, egg, offal and sugar-free sweets than control subjects. Control subjects more often ate ordinary sweets and snacks. Patients chose coarse rye bread and dairy products with less fat to a greater extent than control subjects. Patients were heavier than control subjects. The intake of saturated fat was higher in patients compared with recommendations and, for boys with diabetes, the intake of protein was higher than recommended. Patients with poorer glycaemic control ate vegetables, fruit and fish less often than patients with better control. CONCLUSIONS: The food habits of adolescents with Type 1 DM were healthier than those of control subjects. The intake of energy-providing nutrients was in line with current recommendations and showed improvements compared with previous reports, with the exception of fibre intake. The association between dietary intake and glycaemic control needs further investigation in prospective studies.

  • 10.
    Lodefalk, Maria
    et al.
    Pediatric Endocrinology and Diabetes Unit, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Åman, Jan
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Gastrointestinal symptoms in adolescents with type 1 diabetes2010In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 11, no 4, p. 265-70Article in journal (Refereed)
    Abstract [en]

    Objective: To compare the prevalence of gastrointestinal (GI) symptoms in adolescents with and without type 1 diabetes (T1DM) and to relate the symptoms in patients to demographic, socioeconomic, diabetes-specific variables, and food habits.

    Method: In a population-based, cross-sectional setting, 173 adolescents with T1DM and 160 matched controls completed a questionnaire. Moreover, 13 patients and 1 control were excluded due to having a GI disorder.

    Results: Moreover, 75% of patients and 77% of controls reported at least one GI symptom (ns). More girls than boys reported symptoms. Reflux episodes were more prevalent in patients with poorer socioeconomic status. Poor appetite, loss of weight, an uncomfortable feeling of fullness, swallowing difficulties, and nausea were more prevalent in patients smoking daily compared with patients not smoking daily. Vomiting was more prevalent in patients with duration of diabetes >7 yr, and patients with reflux episodes had higher glycated hemoglobin (HbA1c). Belching and early satiety were more prevalent in patients with an irregular meal pattern.

    Conclusions: GI symptoms in adolescents are common, but the prevalence is not increased in those with T1DM. GI symptoms in adolescents with T1DM are associated with female sex, poorer socioeconomic status, daily cigarette smoking, longer duration of diabetes, poorer metabolic control, and an irregular meal pattern.

  • 11.
    Lodefalk, Maria
    et al.
    Örebro University, School of Health and Medical Sciences. Paediatric Endocrinology and Diabetes Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Åman, Jan
    Örebro University, School of Health and Medical Sciences. Departm ent of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Bang, P.
    Paediatric Endocrinology and Diabetes Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm.
    Effects of fat supplementation on glycaemic response and gastric emptying in adolescents with Type 1 diabetes2008In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 25, no 9, p. 1030-1035Article in journal (Refereed)
    Abstract [en]

    AIMS: To compare the glycaemic response to meals with different fat content in adolescents with Type 1 diabetes mellitus (T1DM) and to investigate associations with gastric emptying.

    METHODS: In this randomized, cross-over study, paired results were obtained from seven adolescents with T1DM who ingested on different days two meals with the same carbohydrate and protein content, but different fat and energy content (2 and 38 g fat, 320 and 640 kcal, respectively). Paracetamol was mixed into the meals and gastric emptying was estimated by the paracetamol absorption method. All subjects were normoglycaemic and given 7 IU insulin aspart at commencement of ingestion. Postprandial blood samples were taken during 4 h.

    RESULTS: The areas under the curves for plasma glucose and serum paracetamol concentrations were larger after the low-fat than after the high-fat meal during the first 2 h (P = 0.047 and P = 0.041, respectively). The difference between meals in time-to-peak in glucose and paracetamol concentrations did not reach statistical significance (high-fat vs. low-fat meal: 210 min (120-240) vs. 120 min (50-240), P = 0.080 and 120 min (75-180) vs. 60 min (60-120), P = 0.051, respectively). Changes in glucose concentrations correlated with simultaneous changes in paracetamol concentrations (P < 0.001).

    CONCLUSIONS: For the first time, we have shown that the initial glycaemic response is reduced after a meal with higher compared with a meal with lower fat content in adolescents with T1DM given a rapid-acting insulin analogue preprandially. The type and dose of preprandial insulin may need adjustment to the fat content of the meal to reach postprandial normoglycaemia.

  • 12.
    Rodanaki, Maria
    et al.
    Örebro University, School of Medical Sciences. Department of Paediatrics.
    Lodefalk, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Paediatrics, School of Medical Sciences, Örebro University, Örebro, Sweden; University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Forssell, Katharina
    Department of Paediatrics, Central Hospital, Karlstad, Sweden.
    Arvidsson, Carl-Göran
    Department of Paediatrics, Västerås Hospital, Västerås, Sweden.
    Forssberg, Maria
    Department of Paediatrics, Central Hospital, Karlstad, Sweden.
    Åman, Jan
    Department of Paediatrics, School of Medical Sciences, Örebro University, Örebro, Sweden.
    The Incidence of Childhood Thyrotoxicosis Is Increasing in Both Girls and Boys in Sweden2019In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 91, no 3, p. 195-202Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We found an increase in the incidence rate (IR) of childhood thyrotoxicosis (CT) during the 1990s in central Sweden. The optimal treatment method for CT is a subject that is still debated upon.

    OBJECTIVES: To investigate whether the increase in IR of CT in Sweden persists and to study the treatment outcome.

    METHOD: Children <16 years of age diagnosed with CT during 2000-2009 and living in 1 of 5 counties in central Sweden were identified retrospectively using hospital registers. Data on clinical and biochemical characteristics and outcomes of treatment were collected from medical records. The corresponding data from 1990 to 1999 were pooled with the new data.

    RESULTS: In total, 113 children were diagnosed with CT during 1990-2009 in the study area. The overall IR was 2.2/100,000 person-years (95% CI 1.2-2.5/100,000 person-years). The IR was significantly higher during 2000-2009 than during 1990-1999 (2.8/100,000 [2.2-3.6] vs. 1.6/100,000 person-years [1.2-2.2], p = 0.006). The increase was significant for both sexes. Seventy percent of the patients who completed the planned initial treatment with antithyroid drugs (ATDs) and were not lost to follow-up relapsed within 3 years. Boys tended to relapse earlier than girls (6.0 months after drug withdrawal [95% CI 1.9-10.0] vs. 12.0 months [95% CI 6.8-17.3], p = 0.074).

    CONCLUSIONS: The IR of CT is increasing in both girls and boys. Relapse rate after withdrawal of ATD treatment is 70%. Boys tend to relapse earlier than girls, and this needs to be further investigated.

  • 13.
    Rodanaki, Maria
    et al.
    Örebro University, School of Medical Sciences. Department of Pediatrics.
    Lodefalk, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pediatrics, Örebro University, Örebro, Sweden; Faculty of Medicine and Health, University Health Care Research Center, Örebro University, Örebro, Sweden.
    Åman, Jan
    Department of Pediatrics, Örebro University, Örebro, Sweden.
    Incidence and Treatment Outcome of Childhood Thyrotoxicosis2018In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 90, no Suppl.1, p. 90-91, article id RFC5.3Article in journal (Refereed)
    Abstract [en]

    Aim: To study the incidence of childhood thyrotoxicosis in five counties in central Sweden during 1990–2009 and to study the treatment outcome.

    Methods: Children below the age of 16 years diagnosed with thyrotoxicosis during the 20-years period and living in the study area were identified retrospectively. Data on the total number of children below 16 years of age living in the area during the study period was collected from the National Board of Statistics, Sweden. Data regarding clinical and biochemical characteristics and the outcome of the treatment were collected from medical records.

    Results: 113 patients were identified. The annual incidence was 2.2/100,000 children during the whole study period. The incidence was higher during the last ten studied years as compared to the first ten studied years (2.8 vs. 1.6/100,000, p = 0.006). The increase in incidence was seen in both girls and boys (p = 0.041 and p = 0.038, respectively). Treatment with antithyroid drugs (ATD) was the first hand choice, but 69% of the patients relapsed within three years after the planned discontinuation of the ATD treatment. Boys relapsed more often than girls (p = 0.013), but we could not identify any other significant predictor for relapse.

    Conclusion: Thyrotoxicosis is uncommon in pediatric patients but the incidence seems to be increasing. The outcome of the initial treatment with ATD is poor with high relapse rates. Boys seems to have an increased risk for relapse compared to girls. More studies are needed to identify an optimal treatment protocol for each individual.

  • 14.
    Rodanaki, Maria
    et al.
    Örebro University, School of Medical Sciences. Department of Pediatrics, Örebro University Hospital, Örebro,.
    Rask, Eva
    Örebro University, School of Medical Sciences. Department of Endocrinology, Örebro University, Örebro, Sweden.
    Lodefalk, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pediatrics.
    Incidence of Delayed Puberty in Adolescents: A Population-Based Study in a County in Central Sweden2018In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 90, no Suppl.1, p. 510-510, article id P2-P311Article in journal (Refereed)
    Abstract [en]

    Introduction: Delayed puberty is defined as the absence of physical signs of puberty by the age of 14 years in boys and 13 years in girls. According to this definition, the prevalence of delayed puberty would be 2%, if the ages of pubertal onset were normally distributed in the population. However, the prevalence or incidence of delayed puberty has not been described before, as far as we know. Our aim was to study the incidence of delayed puberty in central Sweden.

    Methods: In this population-based retrospective study all adolescents given the ICD-10 diagnosis “delayed puberty” in Örebro county during the period 2013-2015 were identified. Adolescents with other diagnoses potentially related to delayed puberty (e.g. short stature) were also identified to ensure that there were no additional cases. The medical records of these patients, except those not willing to participate, were systematically reviewed to ensure that the diagnosis was correct. The cases were then categorized into four groups depending on how accurate we found the diagnosis (certain, possible, wrong diagnosis, or unclear cases). Data on the total numbers of adolescents in Örebro county were obtained from the authority of statistics in Sweden.

    Results: One hundred and twenty-eight of 180 eligible medical records were reviewed (response rate: 71 %). Nine boys and one girl were diagnosed with delayed puberty during the study time period and fulfilled our strict criteria for a certain diagnosis and 4 boys were classified as possible new cases. The total population in Örebro county for boys aged 14-18 years was on average 6,546 each year during the time period. The minimal annual incidence for boys was 46 per 100,000 (95% confidence interval (CI) 15-142 per 100,000). When possible cases were included, the annual incidence for boys increased to 66 (CI 26-170) per 100,000. Due to the low number of girls with delayed puberty no incidence for girls was calculated.

    Discussion: This is, to our knowledge, the first study describing the incidence of delayed puberty in boys. We evaluated the accuracy of the diagnosis using strict criteria. The presented incidence should be regarded as the minimum incidence since some adolescents with delayed puberty may not seek medical advice or may be unrecognized by the health services in schools. Because of our small study population, larger studies are needed to confirm our findings and for calculation of the incidence in girls, where our data implies a much lower incidence.

  • 15. Samuelson, Gösta
    et al.
    Åman, Jan
    Örebro University, School of Health and Medical Sciences.
    Lodefalk, Maria
    Detlofsson, Ingalill
    Cederholm, Ulla
    Vall, Helene
    Mat vid diabetes2008In: Barn- och ungdomsdiabetes / [ed] Sture Sjöblad, Lund: Studentlitteratur , 2008, 2, p. 93-101Chapter in book (Other academic)
  • 16.
    [Svensson] Lodefalk, Maria
    et al.
    Department of Paediatrics, Örebro University Hospital.
    Engström, Ingemar
    Department of Paediatrics, Örebro University Hospital; Psychiatric Research Centre, Örebro.
    Åman, Jan
    Department of Paediatrics, Örebro University Hospital.
    Higher drive for thinness in adolescent males with insulin-dependent diabetes mellitus compared with healthy controls2003In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 92, p. 114-117Article in journal (Refereed)
  • 17.
    Östling, Hanna
    et al.
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Lodefalk, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Infants born small-for-gestational age have different placental expression of microRNAs2017In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, no Suppl. 1, p. 100-101, article id P1-508Article in journal (Other academic)
  • 18.
    Östling, Hanna
    et al.
    Örebro University, School of Medical Sciences. Department of Obstetrics and Gynecology.
    Kruse, Robert
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Lodefalk, Maria
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pediatrics.
    Placental expression of microRNAs in infants born small for gestational age2019In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 81, p. 46-53Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The molecular mechanisms behind poor foetal growth are not fully known. The aim of this study was to explore global microRNA expression in placentas of infants born small for gestational age (SGA) compared to infants with a normal birth weight (NBW).

    METHODS: Placental biopsies from term infants were identified in a biobank and divided into four groups: infants born SGA with (n = 13) or without (n = 9) exposure to low maternal gestational weight gain (GWG) and infants born with NBWs with (n = 20) or without (n = 26) exposure to low GWG. All women and infants were healthy, and no woman smoked during pregnancy. Only vaginal deliveries were included. Next-generation sequencing was performed with single read sequencing of >9 million reads per sample. Differential microRNA expression was analysed using ANOVA for unequal variances (Welch) with multiple testing corrections through the Benjamini-Hochberg method. A fold change >2 and a corrected p value < 0.05 were considered significant. Adjustments for possible confounding factors were made using a linear regression model.

    RESULTS: A total of 1870 known, mature human microRNAs were detected in the sample. MiR-3679-5p and miR-193b-3p were significantly upregulated, and miR-379-3p, miR-335-3p, miR-4532, miR-519e-3p, miR-3065-5p, and miR-105-5p were significantly downregulated after adjustment for potential confounding factors in SGA infants with normal GWG compared to infants with NBWs and normal GWG.

    DISCUSSION: Infants born unexplained SGA show differential microRNA expression in their placenta. Important pathways for the differentially expressed microRNAs include inflammation and the insulin-IGF system.

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