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  • 51.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Gustafsson, Britt
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Increased prevalence of malignant diseases in the close neighborhood of children with cancer2001In: Journal of environmental health, ISSN 0022-0892, Vol. 64, no 7, p. 18-22Article in journal (Refereed)
    Abstract [en]

    Clustering of cancer in families may be due to chance, inherited genetic mutations, common exposure to environmental agents, or a combination of these factors. The authors, to address a clinical impression that cancer occurs more often in the environment of a child with cancer, investigated whether the prevalence of cancer among children and adults in the neighborhood of children with cancer was higher than the prevalence in the neighborhood of healthy children. One hundred thirty-seven children diagnosed with a malignant disease between 1981 and 1992 at the Department of Pediatrics, University Hospital of Link÷ping, Sweden, were investigated and compared with 232 healthy control children. The control children were traced from the official Swedish population registry. It was found that 13 percent of the children with cancer and six percent of the control children were dose neighbors of other children diagnosed with cancer (p < .05). Cancer also was more common in the circles of acquaintances around the children with cancer than in circles of acquaintances around control children (p < .03). The frequency of cancer in the neighborhood or in the circle of acquaintances was significantly greater in older children than in younger children. These results support the hypothesis that environmental factors can initiate or precipitate cancer in children as well as in adults.

  • 52.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hanås, Ragnar
    Barnkliniken NÄL, Uddevalla.
    Whiss, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Do high blood glucose peaks contribute to higher HbA1c? Results from repeated continuous glucose measurements in children2008In: World Journal of Pediatrics, ISSN 1708-8569, Vol. 4, no 3, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Background: HbA1c levels are infl uenced by the glycemic control of previous 2-3 months. Sometimes patients have surprisingly low HbA1c in spite of many correctly measured high blood glucose values, which is diffi cult to explain. As glucose sensors give an objective picture based on glucose readings several times per minute over 24 hours, we used the area under the curve (AUC) of such subcutaneous glucose profi les to evaluate their relationship with HbA1c. Methods: Thirty-two patients were randomized into two study arms, one open and the other blinded. Both arms had 8 pump users and 8 patients with multiple daily injections (MDI). After three months the two arms crossed over. Both study arms wore a continuous glucose monitoring system (CGMS) for 3 days every 2 weeks. HbA1c was determined before and after each 3-month study period. Results: There was no relationship between HbA1c and s.c. glucose AUC or between HbA1c and the number of peaks >15.0 mmol/L when all CGMS profi les during the 6 months were taken together. Children on MDI showed a positive relationship between HbA1c and AUC (P<0.01) as well as the number of peaks (P<0.01). Children with a negative relationship between HbA1c and AUC generally had fewer fluctuations in blood glucose values, whereas children with a positive relationship had wide fluctuations. Conclusions: Although there was no relationship between s.c. glucose AUC and HbA1c, the results indicate that wide blood glucose fluctuations may be related to high HbA1c values. Therefore, complications and therapeutic interventions should aim at reducing such fluctuations. © Springer 2008.

  • 53.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Johansson, C
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Month of birth and risk of developing insulin dependent diabetes in south east Sweden.  1999In: Archives of Disease in Childhood, ISSN 0003-9888, E-ISSN 1468-2044, Vol. 81, p. 143-146Article in journal (Refereed)
  • 54.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindblad, B
    Queen Silvia Children's Hospital, Sweden.
    Carlsson, A
    Lund University Hospital, Sweden.
    Forsander, G
    Queen Silvia Children's Hospital, Sweden.
    Ivarsson, S
    University Hospital MAS, Sweden.
    Kockum, I
    Karolinska Institute, Sweden.
    Lernmark, A
    Lund University, Sweden.
    Marcus, C
    Karolinska University Hospital, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Residual beta cell function at diagnosis of type 1 diabetes in children and adolescents varies with gender and season2013In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 29, no 1, p. 85-89Article in journal (Refereed)
    Abstract [en]

    Background

    There are seasonal variations and gender differences in incidence of type 1 diabetes (T1D), metabolic control and responses to immune interventions at onset of the disease.

    We hypothesized that there are seasonal and gender differences in residual insulin secretion already at diagnosis of T1D.

    Methods

    In 2005, a national study, the Better Diabetes Diagnosis, was started to classify all newly diagnosed children and adolescents with diabetes. About 95% (3824/4017) of the patients were classified as T1D, and our analyses are based on the patients with T1D.

    Results

    C-peptide was lower in younger children, 0–10 years of age (0.23 ± 0.20 nmol/L) than in older children, 11–18 years of age (0.34 ± 0.28 nmol/L) (p  < 0.000 ). There was a seasonal variation in non-fasting serum C-peptide, significantly correlated to the seasonal variation of diagnosis (p < 0.01). Most children were diagnosed in January, February and March as well as in October when C-peptide was highest, whereas fewer patients were diagnosed in April and May when serum C-peptide was significantly lower (p < 0.01). The seasonal variation of C-peptide was more pronounced in boys than in girls (p < 0.000 and p < 0.01, respectively). Girls had higher C-peptide than boys (p < 0.05), especially in early puberty.

    Conclusions

    Both seasonal and gender differences in residual beta cell function exist already at diagnosis of T1D. These observations have consequences for treatment and for randomizing patients in immune intervention clinical trials.

  • 55.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindell, Nina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Akesson, Karin
    Ryhov County Hospital, Sweden; Futurum Academic Health and Care, Sweden; Jonköping University, Sweden.
    Carlsson, Annelie
    Lund University, Sweden.
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Caesarean section per se does not increase the risk of offspring developing type 1 diabetes: a Swedish population-based study2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no 11, p. 2517-2524Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Some studies have revealed a relationship between Caesarean section (CS) and type 1 diabetes, while other studies have not. By using the Swedish paediatric quality register we investigated whether birth by CS is related to the risk of developing type 1 diabetes during childhood. Methods All children diagnosed with type 1 diabetes from 2000 to 2012 and included in the register (n= 9,376) were matched with four controls by year, day of birth, sex and county of birth from the Swedish Medical Birth Register. Results Overall, 13.5% of deliveries were by CS. By group, 14.7% of children who developed type 1 diabetes were delivered by CS compared with 13.3% of control children (p less than 0.001). Mothers with diabetes more often gave birth by CS than mothers without diabetes (78.8% vs 12.7%, p less than 0.001). In a logistic regression model adjusting for maternal age, maternal diabetes and BMI in early pregnancy, the OR for CS was 1.0. A child who developed type 1 diabetes and had a mother with type 1 diabetes at the time of delivery had the highest OR to have been born by CS. Children of mothers without diabetes, delivered by CS, had no increased risk of developing type 1 diabetes. Maternal diabetes was the strongest predictor of childhood diabetes (OR 3.4), especially if the mother had type 1 diabetes (OR 7.54). Conclusions/interpretation CS had no influence on the risk of type 1 diabetes during childhood or adolescence. However, maternal diabetes itself strongly increased the risk of offspring developing type 1 diabetes.

  • 56.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Seasonal variation of birth month and breastfeeding in children with diabetes mellitus2001In: Journal of Pediatric Endocrinology & Metabolism (JPEM), ISSN 0334-018X, E-ISSN 2191-0251, Vol. 14, no 1, p. 43-46Article in journal (Refereed)
    Abstract [en]

    Objective: As breastfeeding is suggested to protect against diabetes mellitus we decided to investigate whether the seasonal variation of month of birth of diabetic children, with more diabetes in children born in summer, can be explained to some extent by a seasonal variation of exclusive breastfeeding. Patients: A population-based group of 297 children who had been diagnosed with diabetes mellitus before the age of 15 years was compared with 792 matched healthy subjects. Results: There was no difference in duration of breast-feeding between children who later got diabetes and the controls. Children (both diabetics and controls) born during the summer were exclusively breastfed for a mean period of 2.2 months. Corresponding figures for children born during winter were 2.8 months (p<0.04), spring 2.5 months (n.s.) and autumn 2.7 months (p<0.05). Seasonality was most pronounced in children who developed diabetes between the ages of 10 and 15 years. Conclusion: These results indicate that children born during the summer, who have increased risk of developing diabetes mellitus, have also been exclusively breastfed for a shorter time.

  • 57.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    The concentrations of short-chain fatty acids and other microflora-associated characteristics in faeces from children with newly diagnosed Type 1 diabetes and control children and their family members2004In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 21, no 1, p. 64-67Article in journal (Refereed)
    Abstract [en]

    Aims: The gut flora is quantitatively the most important source of microbial stimulation and may provide a primary signal in the maturation of the immune system. We compared the microflora-associated characteristics (MACs) in 22 children with newly diagnosed diabetes, 27 healthy controls, and their family members to see if there were differences between the children and if there was a familial pattern. Methods: The MACs were assessed by determining the concentrations of eight short-chain fatty acids (SCFA), mucin, urobilin, b-aspartylglycine, coprastanol and faecal tryptic activity (FTA). Results: There were no statistically significant differences between the concentrations of SCFA in the diabetes and control children. Members of families with a diabetic child had a higher concentration of acetic acid (P < 0.02) and lower concentrations of several other SCFAs than control families (P < 0.05-0.02). The other MACs showed no differences between the children or between the two family groups. Conclusion: In this pilot study we saw no differences in the MACs between children with diabetes and their controls. There were, however, some differences between the family members of diabetic children and controls that may indicate a familial pattern regarding the production of SCFAs by the gut flora. The role of the gut flora in relation to the risk of developing Type 1 diabetes needs to be analysed in larger and/or prospective studies.

  • 58.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    When should determination of ketonemia be recommended?2002In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 4, no 5, p. 645-650Article in journal (Refereed)
    Abstract [en]

    Diabetic ketoacidosis is a serious complication of type diabetes. β-Hydroxybutyrate (β-OHB) accounts for about 75% of ketones, and blood concentration can be determined with a sensor. The aim of this study was to investigate the frequency and degree of ketonemia in daily life of children with diabetes and to make a base for recommendations for determination of ketonemia in clinical practice. During 3 months 45 patients with type 1 diabetes since 1-10 years old (mean 4.4 ± 3.3 years old) at the pediatric clinic in Linköping, Sweden, performed 24-h profiles (eight determinations) in 2 weeks with blood glucose and β-OHB. The children performed 11,189 blood glucose and 7,057 β-OHB measurements. Only 0.3% (n = 21) of β-OHB measurements were ≥ 1.0 mmol/L. An β-OHB concentration > 0.2 mmol/L was more common in the morning than during the rest of the day (p < 0.001). Young children (4-7 years old) had values ≥ 0.2 mmol/L more often than adolescents (p < 0.001). Blood glucose values > 15 mmol/L were more often accompanied by β-OHB > 0.2 mmol/L (p < 0.001). High β-OHB concentrations are rare in diabetic children with reasonably good metabolic control. Already a value > 0.4 mmol/L seems abnormal, and we recommend that patients retest glucose and ketones with β-OHB > 0.4 mmol/L. Furthermore, we recommend that diabetic children and adolescents measure β-OHB when symptoms like nausea or vomiting occur to differentiate ketoacidosis from gastroenteritis, and during infections, during periods with high blood glucose (> 15 mmol/L), and if they notice ketonuria. Monitoring β-OHB should be routine for patients on pump therapy.

  • 59.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Löfman, Owe
    Norwegian University of Life Science, Norway.
    Geochemical Correlates to Type 1 Diabetes Incidence in Southeast Sweden: An Environmental Impact?2014In: Journal of environmental health, ISSN 0022-0892, Vol. 76, no 6, p. 146-154Article in journal (Refereed)
    Abstract [en]

    The authors aim was to explore whether geological factors contribute to geographical variation in the incidence of type 1 diabetes. All children diagnosed with type 1 diabetes in southeastern Sweden during 1977-2006 were defined geographically by their place of residence and were allocated x and y coordinates in the national grid. The population at risk, all children 0-16 years of age, was geocoded in a similar manner. Three of the analyzed minerals in moraine and one of the analyzed minerals in brook water plants were significantly associated with type 1 diabetes at the time of diagnosis. Additionally, the birthplace of the children who subsequently developed diabetes differed in relation to some of the minerals. In communities with high incidence and in communities with low incidence, children were diagnosed with type 1 diabetes in areas with the same high or low level of elements. The authors findings in their pilot study indicate a possible geographical covariation of incidence and some geological factors.

  • 60.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Löfman, Owe
    Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences. Linköping University, Faculty of Health Sciences.
    Geographical mapping of type 1 diabetes in children and adolescents in south east Sweden2004In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 58, no 5, p. 388-392Article in journal (Refereed)
    Abstract [en]

    Study objective: As earlier studies have shown space-time clusters at onset of type 1 diabetes in the south east region of Sweden we investigated if there also has been any geographical clusters of diabetes in this region.

    Design: The place of residence (coordinates) at the time of diagnosis were geocoded in a geographical information system (GIS). All children diagnosed with type 1 diabetes up to 16 years of age at diagnosis between 1977–1995 were included. The population at risk was obtained directly from the population registry for the respective years and geographical area levels.

    Setting: South east region of Sweden containing 5 counties, 49 municipalities, and 525 parishes.

    Main results: A significant geographical variation in incidence rate were found between the municipalities (p<0.001) but not between the counties. The variation became somewhat weaker when excluding the six largest municipalities (p<0.02). In municipalities with increased risk (>35.1/100 000) the major contribution comes from children in age group 6–10 years of age at diagnosis. There were no obvious differences between the age groups in municipalities with decreased risk (<20.1/100 000). Boys and girls had about the same degree of geographical variation.

    Conclusions: Apart from chance, the most probable explanation for the geographical variation in the risk for children and adolescents to develop type 1 diabetes between the municipalities in the region is that local environmental factors play a part in the process leading to the disease.

  • 61.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Oikarinen, Sami
    University of Tampere.
    Hyoty, Heikki
    University of Tampere.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Low zinc in drinking water is associated with the risk of type 1 diabetes in children2011In: PEDIATRIC DIABETES, ISSN 1399-543X, Vol. 12, no 3, p. 156-164Article in journal (Refereed)
    Abstract [en]

    Aim: To explore if drinking water may influence the development of type 1 diabetes in children, either via enterovirus spread via drinking water or quality of drinking water related to acidity or concentration of certain minerals. Methods: One hundred and forty-two families with a child with diabetes and who lived either in seven municipalities with a high annual diabetes incidence during 1977-2001 and in six municipalities with the lowest incidence during those 25 yr were asked to participate. Three hundred and seventy-three families in these communities were used as controls. The families filled a 200-mL plastic bottle with their tap drinking water and returned it by mail. The water samples were analyzed for pH, zinc, iron, nitrate, nitrite, nitrate-nitrogen and nitrite-nitrogen, and occurrence of enterovirus RNA. Results: Enterovirus RNA was not found in the tap water samples. The concentration of zinc, nitrate, and nitrate-nitrogen was lower in the municipalities with high incidence of type 1 diabetes. The water samples from families with a child with diabetes had lower concentration of zinc than water samples from control families. Conclusion: Low zinc in drinking water is associated with the risk of developing type 1 diabetes during childhood. Enterovirus does not seem to be spread via drinking water in a country with modern water works.

  • 62.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Saduaskaite-Kühne, Vaiva
    Laboratory of Paediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Padaiga, Zilvinas
    Laboratory of Paediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    A fourfold difference in the incidence of type 1 diabetes between Sweden and Lithuania but similar prevalence of autoimmunity2004In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 66, no 2, p. 173-181Article in journal (Refereed)
    Abstract [en]

    We investigated whether other autoimmune disorders in addition to type 1 diabetes are more common in Sweden than Lithuania, and if there are any differences in inheritance patterns of both type 1 diabetes and other autoimmune disorders.

    Data from 517 children in southeast Sweden and 286 children in Lithuania aged 0–15 years were included in the study. Age- and sex-matched control children were randomly selected. Information was collected by questionnaire.

    Of the children with diabetes in Sweden, 13.2% had a family member with type 1 diabetes compared to 7% of children with diabetes in Lithuania (P<0.01) (OR=2.01). No such difference was seen for other autoimmune diseases in family members of children with diabetes (Sweden 12%, Lithuania 14%, n.s.). Control children in Lithuania had family members with autoimmunity more frequently (15.3%) than control children in Sweden (7.4%, P<0.001) (OR=2.26). This difference was most pronounced in mothers. The Lithuanian control children had an autoimmune disease more frequently than the controls in Sweden (4.7% versus 1.5%, respectively, P<0.001) (OR=3.21).

    There seem to be environmental factors that specifically contribute to the development of type 1 diabetes, factors which are less related to the development of autoimmunity in general.

  • 63.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Steineck, Isabelle
    Herning Hospital, Denmark .
    Gubbjornsdottir, Soffia
    University of Gothenburg, Sweden .
    A high mean-HbA1c value 3-15 months after diagnosis of type 1 diabetes in childhood is related to metabolic control, macroalbuminuria, and retinopathy in early adulthood - a pilot study using two nation-wide population based quality registries2014In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 15, no 3, p. 229-235Article in journal (Refereed)
    Abstract [en]

    BackgroundIntensive treatment of patients with type 1 diabetes delays the onset of long-term complications. ObjectivesOn the basis of the information from two nation-wide quality registers, we investigated to which extent HbA1c values 3-15months after diagnosis in childhood are related to metabolic control, albuminuria, and retinopathy in early adulthood. MethodsIn Sweden, physicians register all children and adolescents with type 1 diabetes mellitus in the Swedish Pediatric Quality Registry. After 18yr of age, people with diabetes are followed by the Swedish National Diabetes Register. We identified 1543 children and adolescents with a mean age of 13.9yr at diagnosis and a mean duration of type 1 diabetes mellitus of 7.1yr. ResultsChildren and adolescents with poor metabolic control (mean HbA1c 70mmol/mol (8.6 %)) adjacent to diagnosis had a significantly higher mean HbA1c value years later as adults than did patients with a good metabolic control [less than50mmol/mol (6.7%) (pless than0.001)]. The patients in the high group were also less physically active and smoked more as adults. The proportion of females was higher in the poor metabolic group. Patients with a high mean HbA1c 3-15months after diagnosis had significantly more often macroalbuminuria and retinopathy in early adulthood. ConclusionsMetabolic control adjacent to the diagnosis of type 1 diabetes in childhood or adolescence can predict metabolic control in early adulthood. It is therefore very important that pediatric diabetes teams identify key factors for successful early metabolic control. Actively using quality registries may be one such factor.

  • 64.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Clinical characteristics at onset of Type 1 diabetes in children diagnosed between 1977 and 2001 in the south-east region of Sweden2005In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 68, no 1, p. 49-55Article in journal (Refereed)
    Abstract [en]

    To survey clinical characteristics at diagnosis for children diagnosed with Type 1 diabetes during 25 years in the south-east part of Sweden we included all 1903 children <16 years of age and who had been diagnosed between 1977 and 2001 in the south-east region of Sweden. A nurse or doctor in the diabetes team obtained information from medical records. Over the 25 years the mean duration of symptoms prior to diagnosis was 17.8 ± 26.4 days and the mean glucose level at diagnosis was 23.6 ± 9.7 mmol/l. Three percent of the children (n = 50) had a pH value ≤ 7.1. The youngest children (0-5 years) had shorter duration of symptoms, lower blood-glucose levels and less often had ketonuria than the oldest children (11-15 years) but more often suffered from infections prior to diagnosis. The proportion of children diagnosed in the group 0-5 years of age increased over the study-period, apart from the last 5 years, while children with pH value ≤ 7.3 decreased significantly as did the proportion of children with ketonuria or infection. The clinical characteristics at diagnosis of diabetes are heterogeneous, especially in the oldest age group. Some characteristics varied with time. © 2004 Elsevier Ireland Ltd. All rights reserved.

  • 65.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Sundkvist, G
    Borg, H
    Fernlund, P
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Islet autoantibodies in the prediction of diabetes in school children2001In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 51, no 1, p. 51-57Article in journal (Refereed)
    Abstract [en]

    In 1987 serum was collected from 1031 non-diabetic schoolchildren in the Southeast area of Sweden with the aim of evaluating islet autoantibody status (ICA, GADA and IA2-ab) in the prediction of diabetes in schoolchildren. The clinical development of Type 1 diabetes in the children was assessed in 1994 and 1997. The combination of ICA, GADA and IA2-ab were found in four subjects whereas six had two and 35 children one of these antibodies. After 10 years, six of the 1031 children had developed clinical diabetes and five of these six children were positive for islet antibodies. Two were positive for all three antibodies, two were positive for ICA and GADA, and one was positive for GADA. Among the individual autoantibodies, ICA showed the highest positive predictive value (29%) whereas the predictive value for the combination of two autoantibodies was highest for GADA and ICA (40%). Thus, GADA and ICA measurements may be a rational approach to detect schoolchildren at risk for developing diabetes. ⌐ 2001 Elsevier Science Ireland Ltd.

  • 66.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Åkesson, Karin
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Peterson, Anette
    Jonkoping Univ, Sweden; Jonkoping Univ, Sweden.
    Hanas, Ragnar
    Uddevalla Cent Hosp, Sweden; Univ Gothenburg, Sweden.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Continued improvement of metabolic control in Swedish pediatric diabetes care2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 1, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Background: To prospectively investigate if the grand mean HbA1c and the differences in mean HbA1c between centers in Sweden could be reduced, thereby improving care delivered by pediatric diabetes teams. Methods: We used an 18-month quality improvement collaborative (QIC) together with the Swedish pediatric diabetes quality registry (SWEDIABKIDS). The first program (IQ-1), started in April 2011 and the second (IQ-2) in April 2012; together they encompassed 70% of Swedish children and adolescents with diabetes. Results: The proportion of patients in IQ-1 with a mean HbA1c amp;lt;7.4% (57 mmol/mol) increased from 26.4% before start to 35.9% at 36 months (P amp;lt; .001), and from 30.2% to 37.2% (P amp;lt; .001) for IQ-2. Mean HbA1c decreased in both participating and non-participating (NP) centers in Sweden, thereby indicating an improvement by a spatial spill over effect in NP centers. The grand mean HbA1c decreased by 0.45% (4.9 mmol/mol) during 36 months; at the end of 2014 it was 7.43% (57.7 mmol/mol) (P amp;lt; .001). A linear regression model with the difference in HbA1c before start and second follow-up as dependent variable showed that QIC participation significantly decreased mean HbA1c both for IQ-1 and IQ-2. The proportion of patients with high HbA1c values (amp;gt;8.7%, 72 mmol/mol) decreased significantly in both QICs, while it increased in the NP group. Conclusions: The grand mean HbA1c has decreased significantly in Sweden from 2010 to 2014, and QICs have contributed significantly to this decrease. There seems to be a spatial spill-over effect in NP centers.

  • 67.
    Soderstrom, U.
    et al.
    University of Örebro, Sweden; Uppsala University, Sweden; Malarsjukhuset Hospital, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Sahlqvist, L.
    Uppsala University, Sweden.
    Aman, J.
    University of Örebro, Sweden; Örebro University Hospital, Sweden.
    Impaired metabolic control and socio-demographic status in immigrant children at onset of Type 1 diabetes2014In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 31, no 11, p. 1418-1423Article in journal (Refereed)
    Abstract [en]

    AimThe aim of the present study was to compare clinical and socio-demographic conditions at the onset of Type1 diabetes in children born to immigrant families and children born to Swedish families, and to assess whether those conditions had an impact on metabolic status. Methods and designThis was an observational nationwide population-based matched cohort study on prospectively recorded registry data of all children with diabetes in Sweden and their families during 2000-2010. Out of a total of 13415 children from the Swedish Childhood Diabetes Registry (SWEDIABKIDS), 879 children born to immigrant parents were collected. To these we added 2627 children with Swedish-born parents, matched for gender, age and year of onset of Type1 diabetes. ResultsThe proportion of low capillary pH (less than7.30) at onset was higher in the immigrant cohort [25.8% vs. 16.4% in the Swedish cohort (Pless than0.001)]. HbA(1c) was also higher [95mmol/mol (10.8%) vs. 88mmol/mol (10.2%), respectively (Pless than0.001)]. In a logistic regression model with low pH as the dependent variable, we were unable to reveal any significant association to socio-demographic factors, but the odds ratio for HbA(1c) was 0.983 (95%CI 0.976-0.991) and for plasma glucose was 0.953 (95%CI 0.933-0.973). ConclusionChildren born to immigrant parents have lower capillary pH and higher HbA(1c) at diabetes onset. Immigrant families harbour lower socio-demographic living conditions, but this fact does not seem to influence the inferior metabolic condition at diabetes onset.

  • 68.
    Svensson, M.
    et al.
    Lund University, Sweden .
    Ramelius, A.
    Lund University, Sweden .
    Nilsson, A.-L.
    Ostersund Hospital, Sweden .
    Delli, A.J.
    Lund University, Sweden .
    Elding Larsson, H.
    Lund University, Sweden .
    Carlsson, A.
    Lund University, Sweden .
    Forsander, G.
    Sahlgrens University Hospital, Sweden .
    Ivarsson, S.A.
    Lund University, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Kockum, I.
    Karolinska Institute, Sweden .
    Marcus, C.
    Karolinska Institute, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ortqvist, E.
    Karolinska Institute, Sweden .
    Lernmark, A.
    Lund University, Sweden .
    Antibodies to Influenza Virus A/H1N1 Hemagglutinin in Type 1 Diabetes Children Diagnosed Before, During and After the SWEDISH A(H1N1)pdm09 Vaccination Campaign 2009-20102014In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, no 2, p. 137-148Article in journal (Refereed)
    Abstract [en]

    We determined A/H1N1-hemagglutinin (HA) antibodies in relation to HLAD-Q genotypes and islet autoantibodies at clinical diagnosis in 1141 incident 0.7 to 18-year-old type 1 diabetes patients diagnosed April 2009-December 2010. Antibodies to S-35-methionine-labelled A/H1N1 hemagglutinin were determined in a radio-binding assay in patients diagnosed before (n = 325), during (n = 355) and after (n = 461) the October 2009-March 2010 Swedish A(H1N1) pdm09 vaccination campaign, along with HLA-DQ genotypes and autoantibodies against GAD, insulin, IA-2 and ZnT8 transporter. Before vaccination, 0.6% patients had A/H1N1-HA antibodies compared with 40% during and 27% after vaccination (P less than 0.0001). In children less than3 years of age, A/H1N1-HA antibodies were found only during vaccination. The frequency of A/H1N1-HA antibodies during vaccination decreased after vaccination among the 3 less than 6 (P = 0.006) and 13 less than 18 (P = 0.001), but not among the 6 less than 13-year-olds. HLA-DQ2/8 positive children less than3 years decreased from 54% (15/28) before and 68% (19/28) during, to 30% (9/30) after vaccination (P = 0.014). Regardless of age, DQ2/2; 2/X (n = 177) patients had lower frequency (P = 0.020) and levels (P = 0.042) of A/H1N1-HA antibodies compared with non-DQ2/2; 2/X (n = 964) patients. GADA frequency was 50% before, 60% during and 51% after vaccination (P = 0.009). ZnT8QA frequency increased from 30% before to 34% during and 41% after vaccination (P = 0.002). Our findings suggest that young (less than3 years) along with DQ2/2; 2/X patients were low responders to Pandemrix (R). As the proportion of DQ2/8 patients less than3 years of age decreased after vaccination and the frequencies of GADA and ZnT8QA were enhanced, it cannot be excluded that the vaccine affected clinical onset of type 1 diabetes.

  • 69.
    Söderström, Ulf
    et al.
    University of Örebro, Sweden; Uppsala University, Sweden; Malarsjukhuset Hospital, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Åman, Jan
    University of Örebro, Sweden; Örebro University Hospital, Sweden.
    National Swedish study of immigrant children with type 1 diabetes showed impaired metabolic control after three years of treatment2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 8, p. 935-939Article in journal (Refereed)
    Abstract [en]

    Aim: This study examined the clinical status and socio-demographic conditions of children with type 1 diabetes at baseline and after three years of treatment, comparing those born to immigrant parents and Swedish parents. Methods: This observational nationwide population-based cohort study used prospectively collected registry data from Swediabkids, the National Quality Registry for Paediatric Diabetes in Sweden from 2000 to 2010. Of the 13 415 children with type 1 diabetes, there were 879 born to immigrant parents. We selected three children born to Swedish parents from the same registry for each immigrant child matching them by gender, age and year of diabetes onset (n = 2627; with 10 control children missing probably due to the matching procedure). Results: Immigrant children had a higher median glycated haemoglobin level (HbA1c) than their Swedish peers, but there was no difference in the frequency of hypoglycaemia or ketoacidosis between the two cohorts. A linear regression model with HbA1c as a dependent variable showed that insulin units per kilogram of body weight were the main reason for inferior metabolic control. Conclusion: Children with type 1 diabetes born to immigrant parents had inferior metabolic control three years after disease onset compared to children with Swedish born parents. Social family support and educational coping programmes are needed to improve treatment outcomes in immigrants with diabetes.

  • 70.
    Zhao, Lue Ping
    et al.
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Papadopoulos, George K.
    Technol Educ Inst Epirus, Greece; Univ Ioannina, Greece.
    Kwok, William W.
    Benaroya Res Inst Virginia Mason, WA USA.
    Xu, Bryan
    Univ Calif Berkeley, CA 94720 USA.
    Kong, Matthew
    Carnegie Mellon Univ, PA 15213 USA.
    Moustakas, Antonis K.
    Ionian Univ, Greece.
    Bondinas, George P.
    Technol Educ Inst Epirus, Greece; Univ Ioannina, Greece.
    Carlsson, Annelie
    Lund Univ, Sweden.
    Elding-Larsson, Helena
    Lund Univ, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Marcus, Claude
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Persson, Martina
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Wang, Ruihan
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Pyo, Chul-Woo
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Nelson, Wyatt C.
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Geraghty, Daniel E.
    Fred Hutchinson Canc Res Ctr, WA 98104 USA.
    Lernmark, Ake
    Lund Univ, Sweden.
    Eleven Amino Acids of HLA-DRB1 and Fifteen Amino Acids of HLA-DRB3, 4, and 5 Include Potentially Causal Residues Responsible for the Risk of Childhood Type 1 Diabetes2019In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 68, no 8, p. 1692-1704Article in journal (Refereed)
    Abstract [en]

    Next-generation targeted sequencing of HLA-DRB1 and HLA-DRB3, -DRB4, and -DRB5 (abbreviated as DRB345) provides high resolution of functional variant positions to investigate their associations with type 1 diabetes risk and with autoantibodies against insulin (IAA), GAD65 (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A). To overcome exceptional DR sequence complexity as a result of high polymorphisms and extended linkage disequilibrium among the DR loci, we applied a novel recursive organizer (ROR) to discover disease-associated amino acid residues. ROR distills disease-associated DR sequences and identifies 11 residues of DRB1, sequences of which retain all significant associations observed by DR genes. Furthermore, all 11 residues locate under/adjoining the peptide-binding groove of DRB1, suggesting a plausible functional mechanism through peptide binding. The 15 residues of DRB345, located respectively in the beta 49-55 homodimerization patch and on the face of the molecule shown to interact with and bind to the accessory molecule CD4, retain their significant disease associations. Further ROR analysis of DR associations with autoantibodies finds that DRB1 residues significantly associated with ZnT8A and DRB345 residues with GADA. The strongest association is between four residues (beta 14, beta 25, beta 71, and beta 73) and IA-2A, in which the sequence ERKA confers a risk association (odds ratio 2.15, P = 10(-18)), and another sequence, ERKG, confers a protective association (odds ratio 0.59, P = 10(-11)), despite a difference of only one amino acid. Because motifs of identified residues capture potentially causal DR associations with type 1 diabetes, this list of residuals is expected to include corresponding causal residues in this study population.

  • 71. Zwaan, Christian M
    et al.
    Reinhardt, Dirk
    Corbacioglu, Selim
    van Wering, Elisabeth R
    Bökkerink, Jos PM
    Tissing, Wím JE
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Feingold, Jay
    Creutzig, Ursula
    Kaspers, Gertjan
    Gemtuzumab ozomagicin: first clinical experiences in children with relapsed/refractory acute myeloid leukemia treated onc ompassionate use basis.2003In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 101, p. 3868-3871Article in journal (Refereed)
  • 72. Zwaan, CM
    et al.
    Reinhardt, D
    Corbacioglu, S
    Jurgens, H
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Biondi, A
    Smith, OP
    Bokkerink, JPM
    Tissing, WJE
    Creutzig, U
    Kaspers, GJL
    First clinical experiences with Gemtuzumab ozogamicin (GO, Mylotarg (c)) in CD33 positive relapsed/refractory leukemia in children2003In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 17, no 3, p. P51a-Conference paper (Other academic)
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