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Sökning: WFRF:(Ludvigsson Johnny 1943 )

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1.
  • Bojestig, M, et al. (författare)
  • The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes
  • 2000
  • Ingår i: jraas. Journal of the renin-angiotensin-aldosterone system. - 1470-3203 .- 1752-8976. ; 1:4, s. 353-356
  • Tidskriftsartikel (refereegranskat)abstract
    • Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA1c during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA1c. >8.4% compared with those with mean HbA1c 7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.
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2.
  • Brekke, Hilde Kristin, 1972, et al. (författare)
  • Breastfeeding and introduction of solid foods in Swedish infants: the All Babies in Southeast Sweden study.
  • 2005
  • Ingår i: The British journal of nutrition. - 0007-1145 .- 1475-2662. ; 94:3, s. 377-82
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this report is to describe breastfeeding duration and introduction of foods in Swedish infants born 1997-9, in relation to current recommendations. A secondary aim is to examine breastfeeding duration and introduction of certain allergenic foods in allergy-risk families (for whom allergy-preventive advice has been issued). Out of 21,700 invited infants, screening questionnaires were completed for 16,070 infants after delivery. Parents to 11,081 infants completed a follow-up questionnaire regarding breastfeeding and introduction of foods and 9849 handed in detailed food diaries at 1 year of age. The percentages of infants who were exclusively breast-fed at 3, 6 and >or=9 months of age were 78.4, 10.1 and 3.9, respectively. The corresponding percentages for partial breastfeeding were 87.8, 68.9 and 43.6. Gluten-containing foods were introduced to 66% of infants between 4 and 6 months, as recommended at the time of the study, and one-quarter had stopped breastfeeding when gluten was introduced. More than 90% of parents introduced the first sample of solid food during months 4-6, as recommended. Fish and eggs had been introduced during the first year in 43% and 29%, respectively, of infants with atopic heredity. Exclusive breastfeeding duration and time of introduction of solid foods, including gluten, seemed to have been in line with Swedish recommendations at the time, although gluten was often introduced late, and not during ongoing breastfeeding as recommended. The adherence to allergy-preventive advice was less than optimal in infants with atopic heredity.
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3.
  • Kullberg, C, et al. (författare)
  • Prevalence of retinopathy differs with age at onset of diabetes in a population of patients with Type 1 diabetes
  • 2002
  • Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 19:11, s. 924-931
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim. The VISS study (Vascular complications in South-east Sweden) investigates prevalence and incidence of vascular complications in a population with Type 1 diabetes, from a well-defined geographical area and followed from diag-nosis with HbA1c measurement. Method. The study population comprised all 440 patients with Type 1 diabetes onset before the age of 36 years, onset during 1983-1987, and at the time of onset living within the counties of J÷nk÷ping, Kalmar or ╓sterg÷tland. Retinopathy was examined with fundus photography 1994-1995, and classified according to a modified Airlie House protocol. Results. Fundus photographs from 390 patients were evaluated. In 277 (71%) patients no retinopathy was seen. The prevalence of retinopathy increased from 11% among patients < 5 years old at diabetes onset, to 48% among those 15-19 years old at diabetes onset, and then decreased to 30% for patients 30-35 years old at diabetes onset (P for ?2 for linear trend for all ages 0.017, for age at onset 0-19 yearsP = 0.0003), without corresponding differences in duration or HbA1c between patients with different onset age. Patients with HbA1c in the highest quartile (> 8.3% HbA1c) had a relative risk of 2.4 (95% confidence) interval (CI) 1.7-3.2) of having any retinopathy compared with patients with lower HbA1c, and a relative risk of 7.1 (95% CI 3.0-16.7) of having other forms of retinopathy than microaneurysms. Conclusion. In patients with diabetes duration of 6-13 years, the prevalence of retinopathy is clearly related to glycaemic control. Furthermore, the risk of retinopathy varies with different age at onset, independently of differences in duration or glycaemic control.
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4.
  • Ludvigsson, Jonas, et al. (författare)
  • Exclusive breastfeeding and risk of atopic dermatitis in some 8300 infants
  • 2005
  • Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 16:3, s. 201-208
  • Tidskriftsartikel (refereegranskat)abstract
    • Earlier studies on breastfeeding and atopy in infants have yielded contradictory results. We examined the relationship between exclusive breastfeeding and atopic dermatitis (AD) in a cohort of infants born between 1 October 1997 and 1 October 1999 in south-east Sweden. We evaluated the risk of AD 'at least once' or 'at least three times' during the first year of life in relation to duration of exclusive breastfeeding: < 4 months (short exclusive breastfeeding, SEBF) vs. ≥4 months. All data were obtained through questionnaires. Of 8346 infants with breastfeeding data, 1943 (23.3%) had suffered from AD during the first year of life. Duration of exclusive breastfeeding was not associated with lower risk of AD (p = 0.868). SEBF did not influence the risk of any AD (OR = 1.03, 95% CI OR = 0.91-1.17, p = 0.614) or AD at least three times (OR = 0.97, 95% CI OR = 0.81-1.16, p = 0.755) during the first year of life. Adjustment for confounders did not change these point estimates. Neither was there any link between SEBF and risk of AD among infants with a family history of atopy [adjusted odds ratio (AOR) = 1.16, 95% CI AOR = 0.90-1.48, p = 0.254]. Furred pets at home were linked to a lower risk of AD both among infants with a family history of atopy (AOR = 0.76, 95% CI AOR = 0.60-0.96, p = 0.021) and among infants with no such history (AOR = 0.79, 95% CI AOR = 0.69-0.90, p < 0.001). Infants with no family history of atopy were less prone to develop AD if parents smoked (AOR = 0.76, 95% CI AOR = 0.61-0.95, p = 0.016). This study indicates that exclusive breastfeeding does not influence the risk of AD during the first year of life, while presence of furred pets at home seems to be negatively associated with AD. Copyright © 2005 Blackwell Munksgaard.
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5.
  • Ludvigsson, Jonas F., et al. (författare)
  • Celiac disease and risk of subsequent type 1 diabetes : a general population cohort study of children and adolescents
  • 2006
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 29:11, s. 2483-2488
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:Earlier studies suggest that children with type 1 diabetes are more likely to have a subsequent diagnosis of celiac disease. However, research is sparse on the risk of subsequent type 1 diabetes in individuals with celiac disease. We sought to determine the risk of subsequent type 1 diabetes diagnosed before the age of 20 years in children and adolescents with celiac disease in a national, general population-based cohort.RESEARCH DESIGN AND METHODS:We identified 9,243 children with a diagnosis of celiac disease in the Swedish national inpatient register between 1964 and 2003. We then identified five reference individuals matched at time of diagnosis for age, calendar year, sex, and county (n = 45,680). Only individuals with >1 year of follow-up after study entry (diagnosis of celiac disease) were included in the analyses.RESULTS:Celiac disease was associated with a statistically significantly increased risk of subsequent type 1 diabetes before age 20 years (hazard ratio 2.4 [95% CI 1.9-3.0], P < 0.001). This risk increase was seen regardless of whether celiac disease was first diagnosed between 0 and 2 (2.2 [1.7-2.9], P < 0.001) or 3 and 20 (3.4 [1.9-6.1], P < 0.001) years of age. Individuals with prior celiac disease were also at increased risk of ketoacidosis or diabetic coma before the age of 20 years (2.3 [1.4-3.9], P = 0.001).CONCLUSIONS:Children with celiac disease are at increased risk of subsequent type 1 diabetes. This risk increase is low considering that 95% of individuals with celiac disease are HLA-DQ2 positive.
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6.
  • Ludvigsson, Jonas F., et al. (författare)
  • Coeliac disease and risk of renal disease : a general population cohort study
  • 2006
  • Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 21:7, s. 1809-1815
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Coeliac disease (CD) may be a risk factor for renal disease.METHODS:We investigated the risk of any form of glomerulonephritis (GN) (acute, chronic and non-specified), chronic glomerulonephritis (CGN) and renal replacement therapy including dialysis treatment and kidney transplantation (KT) in patients with CD in a general population-based cohort study. We used Cox regression to assess the risk of renal disease in 14,336 patients who had received a diagnosis of CD (1964-2003) and 69,875 reference individuals matched for age, calendar year, sex and county. Patients were identified using the Swedish Hospital Discharge Registry. Follow-up began 1 year after study entry.RESULTS:CD was associated with an increased risk of any form of GN (hazard ratio (HR) = 1.64; 95% confidence intervals (CI) = 1.01-2.66; P = 0.046; 89 events), CGN (HR = 2.65; 95% CI = 1.34-5.24; P = 0.005; 39 events), dialysis (HR = 3.48; 95% CI = 2.26-5.37; P < 0.001; 102 positive events) and KT (HR = 3.15; 95% CI = 1.29-7.71; P = 0.012; 22 events).CONCLUSION:We suggest that immune characteristics associated with CD increase the risk of chronic renal disease. Individuals with CD may also be at a moderately increased risk of any form of GN.
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7.
  • Ludvigsson, Jonas F., et al. (författare)
  • Effect of HLA DQ2, dietary exposure and coeliac disease on the development of antibody response to gliadin in children
  • 2006
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 919-928
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To study the effect of HLA DQ2, dietary history and development of coeliac disease (CD) on the induction of antibody response to wheat gliadin and cow's milk, beta-lactoglobulin between 1 and 2.5 years of age in children who developed CD and in healthy children. MATERIAL AND METHODS: Infants participating in a birth cohort study (the ABIS study) in Sweden were studied. Thirty-nine children developed CD (=cases), confirmed through biopsy, during follow-up until 2.5-5 years of age. A total of 181 healthy control children were matched for duration of exclusive breast-feeding, birth-weight, gender, maternal smoking and season of birth. IgG and IgA antigliadin and anti-beta-lactoglobulin antibodies were measured using enzyme immunoassay (EIA). The effects of HLA-risk genotypes, DQ2 and DQ8, on CD were also considered. RESULTS: Children who developed CD had higher IgG and IgA antigliadin and anti-beta-lactoglobulin antibody levels at 1 year of age than controls (all comparisons: p<0.001). Similar differences were seen between cases with as yet undiagnosed CD by 1 year of age and controls, and also when cases were compared with HLA-matched controls. Higher levels of IgG and IgA antibodies to beta-lactoglobulin (p=0.003; p=0.001), but not to gliadin, were found in treated cases versus controls at 2.5 years of age. HLA-DQ2-positive healthy children had lower levels of IgG and IgA antigliadin antibodies than HLA-DQ2 negative controls at 1 year of age (p=0.004; p=0.012). CONCLUSIONS: Enhanced humoral response emerging not only to gliadin, but also to other food antigens seems to be primarily associated with CD. Poor induction of antibody response to wheat gliadin in healthy children with the HLA-DQ2 risk molecule could at least partly explain the genetic predisposition to gluten intolerance and CD.
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8.
  • Ludvigsson, Jonas F., 1943-, et al. (författare)
  • Milk consumption during pregnancy and infant birthweight
  • 2004
  • Ingår i: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 93:11, s. 1474-1478
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To examine the risk of low birthweight (>2500 g, LBW), intrauterine growth retardation (IUGR) and preterm birth (gestational age >37wk) in relation to milk intake.Methods: Observational study in southeast Sweden. Questionnaires were used to collect data on milk consumption during pregnancy and infant birthweight from mother-infant pairs during a 2-y period as part of the ABIS (All Babies in Southeast Sweden) study. Data on IUGR were obtained through the Swedish medical birth registry.Results: Adjusting for confounders, low milk intake during pregnancy was associated with an increased risk of IUGR (p= 0.019; n= 12880). LBW (p= 0.191) and preterm birth (p= 0.921) were not associated with milk intake during pregnancy.Conclusion: This study indicates that low milk intake in the pregnant mother may be associated with IUGR of the newborn. We cannot exclude the possibility that the correlation found between milk consumption and intrauterine growth may be due to undetected confounders. Hence, further research is needed to evaluate the relationship between low milk intake, birthweight and risk of IUGR.
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9.
  • Ludvigsson, Jonas F, et al. (författare)
  • Tissue Transglutaminase Auto-antibodies in Cord Blood from Children to Become Celiacs
  • 2001
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 36:12, s. 1279-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Determination of tissue transglutaminase auto-antibodies (tTGAA) has been shown to be a sensitive and specific diagnostic tool for large-scale screening for celiac disease. The purpose of this study was to measure tissue tTGAA in cord blood in infants that later developed celiac disease to evaluate if this assay could serve as a predictive tool for later development of celiac disease.Methods: IgG tTGAA were analyzed in cord blood through immunoprecipitation from 51 future celiac patients and 102 age-matched controls. Cut-off level was set at 0.040.Results: No difference in tTGAA levels was found between cord blood from infants who later developed celiac disease and controls ( P = 0.746). 2/51 future celiac patients (3.9%) had levels above cut-off-value in cord blood, while 3/102 controls were positive (2.9%) ( P = 1.000). tTGAA levels were higher in the 1980s and at the beginning of the 1990s than they have been in recent years ( P = 0.003).Conclusions: Determination of tissue tTGAA in cord blood does not predict future celiac disease in children. tTGAA levels vary with time, which should be considered in retrospective studies analyzing tTGAA.
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10.
  • Ludvigsson, Jonas, et al. (författare)
  • Inflammatory bowel disease in mother or father and neonatal outcome
  • 2002
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 91:2, s. 145-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Even a minor decrease in birthweight predisposes to adult disease. Inflammatory bowel disease (IBD) in the mother is a risk factor for low birthweight and preterm infants. This study investigated the effect of IBD in the mother or father, adjusting for confounders, on the newborn infant, with the focus on birthweight and pregnancy duration. A total of 10 399 single-birth mother-infant pairs was prospectively enrolled within the ABIS project (All Babies In Southeast Sweden). Outcome measures included birth week, preterm birth (<37 wk), birthweight, low birthweight (<2500 g), birth length, caesarean section and neonatal hospital care. Ulcerative colitis (UC) in the mother was associated with lower birthweight in the infant (adjusted difference:—330 g, adjusted 95% confidence interval:—509 to—150 g, p < 0.001), and with even lower birthweight when the mother was treated with Mesalazine or steroids. No decrease in birthweight was seen in infants whose mother suffered from Crohn's disease (CD) (adjusted difference:—65 g, adjusted 95% confidence interval:—354 to 224 g, p > 0.05). Maternal UC or CD did not affect the pregnancy duration. The neonatal outcome of infants whose father suffered from UC and CD did not differ from the control group.Conclusion: UC in the mother affects the birthweight of the infant, which may predispose to future disease in the infant. Most women and men with UC and CD can, however, expect a healthy child with neither preterm birth nor low birthweight.
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11.
  • Ludvigsson, Johnny, 1943-, et al. (författare)
  • Parental smoking and risk of coeliac disease in offspring
  • 2005
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 40:3, s. 336-342
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. In adults, smoking seems to give protection against coeliac disease (CD). But, only one study has thus far investigated the association between maternal smoking during pregnancy and risk of CD in offspring. However, that study did not adjust for duration of exclusive breastfeeding, or look at passive smoking after birth. Material and methods. The current study was part of a prospective cohort study of infants born between 1 October 1997 and 1 October 1999 (the ABIS study, All Babies in Southeast Sweden). Data on smoking and exclusive breastfeeding were obtained through questionnaires distributed at infant birth and at 1 year of age. Coeliac disease was confirmed through small-bowel biopsy. Subgroup analyses were carried out according to maternal body mass index. Results. Nine out of 53 (17%) children with CD as opposed to 1699 out of 15,344 (11.1%) non-coeliac children had mothers who had smoked during pregnancy (p = 0.172). Mothers who had smoked during pregnancy were hence not at increased risk of having a child with CD (OR = 1.64, 95% CI OR = 0.80-3.37). Adjusting for duration of exclusive breastfeeding and the sex of infants in some 9585 children with data on exclusive breastfeeding lowered the OR for CD in mothers who smoked (adjusted OR (AOR) = 0.89, 95% CI AOR = 0.27-2.93, p = 0.843). Parents who smoked during the child's first year of life were not at increased risk of having an offspring with CD (OR = 1.94, 95% CI AOR = 0.69-5.47, p = 0. 203). Conclusions. No association was found between CD and parental smoking habits during pregnancy or during the child's first year of life. However, further studies with larger numbers of coeliac children are needed.
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12.
  • Ludvigsson, Jonas, 1969-, et al. (författare)
  • Socio-economic determinants, maternal smoking and coffee consumption, and exclusive breastfeeding in 10 205 children
  • 2005
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 94:9, s. 1310-1319
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To examine socio-economic factors, smoking, coffee consumption and exclusive breastfeeding duration. Methods: This study was part of a prospective cohort study of children born between 1 October 1997 and 1 October 1999 (the All Babies in Southeast Sweden (ABIS) study). Eleven socio-economic characteristics (parental employment, civil status, whether parents were born in Sweden, parental education, residence at birth and during child's first year, crowded living), maternal smoking, coffee consumption, infant sex, siblings, parental age, and maternal alcohol consumption during pregnancy were analysed using logistic regression and Cox's proportional hazards method. All data were obtained through questionnaires distributed at infant birth and at 1 y of age. Exclusive breastfeeding duration <4 mo and actual breastfeeding duration were our main outcome measures. Results: Out of 10205 infants, 2206 (21.6%) were exclusively breastfed for less than 4 mo ("short exclusive breastfeeding", SEBF). Backward stepwise regression analysis identified the following risk factors for SEBF: maternal smoking (95% confidence interval for adjusted odds ratio, 95% CI AOR 2.00-2.82), low maternal education (95% CI AOR 1.45-2.19), maternal employment less than 3 mo during pregnancy (95% CI AOR 1.17-1.54), paternal age ≤29 y (95% CI AOR 1.14-1.47), maternal age ≤29 y (95% CI AOR 1.08-1.39) and low paternal education (95% CI AOR 1.08-1.48). The odds ratio for SEBF increased with the number of cigarettes smoked. Coffee consumption was not associated with duration of exclusive breastfeeding. Conclusion: This study indicates that socio-economic factors and smoking may be of importance to the risk of breastfeeding exclusively for less than 4 mo, while coffee consumption is not. © 2005 Taylor & Francis Group Ltd.
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13.
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14.
  • Saduaskaite-Kühne, Vaiva, 1970-, et al. (författare)
  • Inheritance of MHC class II genes in lithuanian families with type 1 diabetes
  • 2003
  • Ingår i: IMMUNOLOGY OF DIABETES II: PATHOGENESIS FROM MOUSE TO MAN. - : New York Academy of Sciences. - 1573314609 ; 1005, s. 295-300
  • Konferensbidrag (refereegranskat)abstract
    • Type 1 diabetes mellitus (DM) is caused by genetic and environmental factors. Twice as many fathers as mothers of children with type 1 DM have the disease. The reason for the differences remains unclear. We looked at the transmission rates of diabetes-related alleles from parents to children with diabetes. All children with newly diagnosed type 1 DM from August 1, 1996 to August 1, 2000, aged 0 to 15 years, in Lithuania were invited to participate. Blood samples for full genetic analysis were available from 125 families. HLA DQA1, DQB1, and DRB1 typing was done on DNA extracted from peripheral blood, by polymerase chain reaction amplification, manual dot-blotting onto nylon membranes, synthetic sequence-specific oligonucleotide probe 3′-end labeling with 32P-dCTP, and hybridization, followed by stringency washes, autoradiography, and allele calling. Frequency of diabetes risk-related alleles DQB1*0302, DQA1*0201, DR4, and DR3 was less prevalent among Lithuanian than among Swedish children with type 1 DM. Transmission rates of DR4-DQB1*0302-DQA1*0301 and DR3-DQB1*0201-DQA1*0501 haplotypes from parents were higher than expected: χ2 (TDT) 30.56, p < 0.0001, and χ2 (TDT) 11.26, p= 0.0008, respectively. DQB1*0302 and DR4 were significantly more frequently transmitted from both parents, but DR3 was transmitted more frequently only from mothers. Any of these alleles had similar frequencies among female and male offspring. We conclude that, besides DR4-DQB1*0302-DQA1*0301 and DR3-DQB1*0201-DQA1*0501, there are other inherited alleles that determine risk for type 1 DM among children in Lithuania. Fathers might transfer other alleles of disease susceptibility in higher frequency or mothers might provide a protective environment during pregnancy, which results in higher risk to offspring of fathers than mothers to develop diabetes.
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15.
  • Ahmadi, Shilan Seyed, et al. (författare)
  • Risk factors for nephropathy in persons with type 1 diabetes: a population-based study
  • 2022
  • Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 59, s. 761-772
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Albuminuria is strongly associated with risk of renal dysfunction, cardiovascular disease and mortality. However, clinical guidelines diverge, and evidence is sparse on what risk factor levels regarding blood pressure, blood lipids and BMI are needed to prevent albuminuria in adolescents and young adults with type 1 diabetes. Methods A total of 9347 children and adults with type 1 diabetes [mean age 15.3 years and mean diabetes duration 1.4 years at start of follow-up] from The Swedish National Diabetes Registry were followed from first registration until end of 2017. Levels for risk factors for a risk increase in nephropathy were evaluated, and the gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. Results During the follow-up period, 8610 (92.1%) remained normoalbuminuric, 737 (7.9%) individuals developed micro- or macroalbuminuria at any time period of whom 132 (17.9% of 737) individuals developed macroalbuminuria. Blood pressure >= 140/80 mmHg was associated with increased risk of albuminuria (p <= 0.0001), as were triglycerides >= 1.0 mmol/L (p = 0.039), total cholesterol >= 5.0 mmol/L (p = 0.0003), HDL < 1.0 mmol/L (p = 0.013), LDL 3.5- < 4.0 mmol/L (p = 0.020), and BMI >= 30 kg/m(2) (p = 0.033). HbA1c was the strongest risk factor for any albuminuria estimated by the measure gradient of risk per 1 SD, followed by diastolic blood pressure, triglycerides, systolic blood pressure, cholesterol and LDL. In patients with HbA1c > 65 mmol/mol (> 8.1%), blood pressure > 140/70 mmHg was associated with increased risk of albuminuria. Conclusions Preventing renal complications in adolescents and young adults with type 1 diabetes need avoidance at relatively high levels of blood pressure, blood lipids and BMI, whereas very tight control is not associated with further risk reduction. For patients with long-term poor glycaemic control, stricter blood pressure control is advocated.
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16.
  • Andersson White, Pär, et al. (författare)
  • Household income and maternal education in early childhood and risk of overweight and obesity in late childhood : Findings from seven birth cohort studies in six high-income countries
  • 2022
  • Ingår i: International Journal of Obesity. - : Springer Nature. - 0307-0565 .- 1476-5497. ; 46, s. 1703-1711
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/objectives This study analysed the relationship between early childhood socioeconomic status (SES) measured by maternal education and household income and the subsequent development of childhood overweight and obesity. Subjects/methods Data from seven population-representative prospective child cohorts in six high-income countries: United Kingdom, Australia, the Netherlands, Canada (one national cohort and one from the province of Quebec), USA, Sweden. Children were included at birth or within the first 2 years of life. Pooled estimates relate to a total of N = 26,565 included children. Overweight and obesity were defined using International Obesity Task Force (IOTF) cut-offs and measured in late childhood (8-11 years). Risk ratios (RRs) and pooled risk estimates were adjusted for potential confounders (maternal age, ethnicity, child sex). Slope Indexes of Inequality (SII) were estimated to quantify absolute inequality for maternal education and household income. Results Prevalence ranged from 15.0% overweight and 2.4% obese in the Swedish cohort to 37.6% overweight and 15.8% obese in the US cohort. Overall, across cohorts, social gradients were observed for risk of obesity for both low maternal education (pooled RR: 2.99, 95% CI: 2.07, 4.31) and low household income (pooled RR: 2.69, 95% CI: 1.68, 4.30); between-cohort heterogeneity ranged from negligible to moderate (p: 0.300 to < 0.001). The association between RRs of obesity by income was lowest in Sweden than in other cohorts. Conclusions There was a social gradient by maternal education on the risk of childhood obesity in all included cohorts. The SES associations measured by income were more heterogeneous and differed between Sweden versus the other national cohorts; these findings may be attributable to policy differences, including preschool policies, maternity leave, a ban on advertising to children, and universal free school meals.
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17.
  • Andersson White, Pär, 1983- (författare)
  • Social Inequalities in Child Health : Type 1 Diabetes, Obesity, Cardiovascular Risk Factors and the Role of Self-control
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The Swedish Commission on Health Inequality defined health inequality as systematic differences in health between groups in society with different social positions. All avoidable socioeconomic health inequalities are unfair, and as stated by WHO's Commission on the Social Determinants of Health, we have a moral obligation to try to reduce them. "Putting these inequities right is a matter of social justice. Reducing health inequities is, for the Commission on Social Determinants of Health, an ethical imperative." This ethical imperative is especially apparent regarding the health of children and adolescents. Children’s right to the highest attainable standard of health is also enshrined in Article 24 of the Convention on the Rights of the Child. To reach the goal of a reduction of health inequalities, research is necessary to describe the social gradients of health. Research is also needed to better understand why these gradients occur. A better understanding and knowledge about health inequalities can lead to policies that reduce these inequalities and ensure children’s right to health.This thesis investigates social inequality in child health using data from a Swedish population-based prospective birth cohort, the All Babies in Southeast Sweden (ABIS) cohort. Social inequality in obesity in the ABIS cohort is also compared with other birth cohorts participating in the Elucidating Pathways to Child Health Inequality (EPOCH) collaboration which includes cohorts from six high-income countries; Sweden, the Netherlands, Canada (one national and one cohort from Quebec), UK, Australia, and USA.In Paper 1 we show that health inequalities in overweight and obesity are detectable already at two years of age and that these inequalities increase during childhood. In adolescents, low socioeconomic status increases the risk of becoming overweight and the risk of components of the metabolic syndrome, including high blood pressure and dyslipidemia (low high-density cholesterol).The level of inequality in obesity in the Swedish ABIS cohort was lower than in the other participating countries in the EPOCH collaboration (Paper 2). Inequality was lower in absolute and relative terms when SES was measured by household income. Inequality was also lower in absolute, but not relative, terms when SES was measured by maternal education. This finding indicates that some of the policies implemented in Sweden may attenuate social inequalities in obesity in children. Examples of such policies with evidence for reducing social inequality in obesity implemented in Sweden include universal preschools and free school meals.This thesis also investigates health inequalities in autoimmune disease (Paper 3). In this study, we found that low socioeconomic status increased the risk of Type 1 Diabetes but not the other autoimmune diseases investigated. Path analysis indicated that part of the increased risk in children with low SES of Type 1 Diabetes might be mediated by a higher body mass index and an elevated risk of serious life events.In the final paper, this thesis tests the hypothesis that differences in maternal and child self-control mediate social inequalities in obesity. Two measures of self-control were used; for mothers, the self-control variable was based on behaviors related to self-control (smoking during pregnancy, smoking during the child’s first year of life, breastfeeding duration, and participating in the ABIS study with biological samples). For the children, the self-control variable was based on questionnaire data on the impulsivity subscale of the Strengths and Difficulties Questionnaire (SDQ). The results showed that the two measures of self-control mediated 87.5 % of the increased risk of obesity at age 19 years in children with low maternal education and 93 % of the risk if maternal BMI was also included in the selfcontrol variable.In the discussion part of this thesis, the conclusions that can be deduced from understanding the mechanisms of social inequality in child health are discussed. A theory with a central role of self-control for health inequality predicts that social inequality will increase without interventions. In an environment with rising numbers of stimuli of the human reward system, stimuli that also have negative long-term consequences (socalled Limbic traps), child and adolescent health, in general, will decrease. Because of the mechanisms related to SES and self-control, children with low SES will be disproportionally affected. The result of this development will be increasing levels of social inequalities in child health.The discussion also includes implications for policies that may improve health and reduce inequalities. These policies should reduce the exposure of children and adolescents to harmful behaviors/limbic traps. Examples of policies that have this effect include universal preschools for all children, free healthy meals in preschools and schools, increased after-school activities for all children, and longer school days for adolescents with increased hours for physical activity, music, and art. Mobile phones and social media restrictions in schools and policies to reduce use at home should also be implemented. Finally, policies should be implemented to reduce residential and school segregation in the community.
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18.
  • Antepohl, Wolfram, 1968-, et al. (författare)
  • A follow-up of medical graduates of a problem-based learning curriculum
  • 2003
  • Ingår i: Medical Education. - : Wiley. - 0308-0110 .- 1365-2923. ; 37:2, s. 155-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: There is little information available on the effects of problem-based undergraduate curricula on doctors and their performances after graduation. Therefore, we conducted a questionnaire study of all graduates of the new medical programme at the Faculty of Health Sciences, Link÷ping University. Methods: All 446 medical students who had graduated from the new programme were asked to fill in a questionnaire about selected activities during their studies and their careers after graduation. They were also asked to evaluate the quality of their undergraduate education retrospectively. Statistical analysis was performed using descriptive, multivariate and bivariate approaches. Results: A total of 77% of the graduates responded. They showed a high degree of overall contentment with their undergraduate education and felt well prepared for professional life during their preregistration period and specialist education (mean = 4.0 on a 6-point Likert scale ranging from 0 to 5). They felt especially well prepared in terms of skills for communication with patients, collaboration with other health professionals and development of critical thinking/scientific attitudes. The students' age at the beginning of their studies correlated positively with their contentment as graduates, especially in terms of preparation for patient communication and collaboration with other health professionals. No differences between students originally admitted via a local admission procedure and those admitted via a national procedure were detected concerning retrospective evaluation of undergraduate medical education. Conclusion: Graduates of the new curriculum showed a high degree of satisfaction with their undergraduate education and its preparation of them for medical practice. Specifically, they were very content with the particular emphases of the new curriculum.
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19.
  • Beam, Craig A., et al. (författare)
  • GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis
  • 2017
  • Ingår i: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 60:1, s. 43-49
  • Tidskriftsartikel (refereegranskat)abstract
    • GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.
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20.
  • Bélteky, Malin, et al. (författare)
  • Infant gut microbiome composition correlated with type 1 diabetes acquisition in the general population: the ABIS study
  • 2023
  • Ingår i: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 66:6, s. 1116-1128
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis While autoantibodies are traditional markers for type 1 diabetes development, we identified gut microbial biomarkers in 1-year-old infants associated with future type 1 diabetes up to 20 years before diagnosis. Methods Infants enrolled in the longitudinal general population cohort All Babies In Southeast Sweden (ABIS) provided a stool sample at a mean age of 12.5 months. Samples (future type 1 diabetes, n=16; healthy controls, n=268) were subjected to 16S ribosomal RNA (rRNA) sequencing and quantitative PCR. Microbial differences at the taxonomic and core microbiome levels were assessed. PICRUSt was used to predict functional content from the 16S rRNA amplicons. Sixteen infants, with a future diagnosis of type 1 diabetes at a mean age of 13.3 +/- 5.4 years, and one hundred iterations of 32 matched control infants, who remained healthy up to 20 years of age, were analysed. Results Parasutterella and Eubacterium were more abundant in healthy control infants, while Porphyromonas was differentially more abundant in infants with future type 1 diabetes diagnosis. Ruminococcus was a strong determinant in differentiating both control infants and those with future type 1 diabetes using random forest analysis and had differing trends of abundance when comparing control infants and those with future type 1 diabetes. Flavonifractor and UBA1819 were the strongest factors for differentiating control infants, showing higher abundance in control infants compared with those with future type 1 diabetes. Alternatively, Alistipes (more abundant in control infants) and Fusicatenibacter (mixed abundance patterns when comparing case and control infants) were the strongest factors for differentiating future type 1 diabetes. Predicted gene content regarding butyrate production and pyruvate fermentation was differentially observed to be higher in healthy control infants. Conclusions/interpretation This investigation suggests that microbial biomarkers for type 1 diabetes may be present as early as 1 year of age, as reflected in the taxonomic and functional differences of the microbial communities. The possibility of preventing disease onset by altering or promoting a healthy gut microbiome is appealing. Data availability The forward and reverse 16S raw sequencing data generated in this study are available through the NCBI Sequence Read Archive under BioProject PRJNA875929. Associated sample metadata used for statistical comparison are available in the source data file. R codes used for statistical comparisons and figure generation are available at: https://github.com/PMilletich/T1D_Pipeline.
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21.
  • Berryman, Meghan A., et al. (författare)
  • Autoimmune-associated genetics impact probiotic colonization of the infant gut
  • 2022
  • Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 133
  • Tidskriftsartikel (refereegranskat)abstract
    • To exemplify autoimmune-associated genetic influence on the colonization of bacteria frequently used in probiotics, microbial composition of stool from 1326 one-year-old infants was analyzed in a prospective general-population cohort, All Babies In Southeast Sweden (ABIS). We show that an individual's HLA haplotype composition has a significant impact on which common Bifidobacterium strains thrive in colonizing the gut. The effect HLA has on the gut microbiome can be more clearly observed when considered in terms of allelic dosage. HLA DR1-DQ5 showed the most significant and most prominent effect on increased Bifidobacterium relative abundance. Therefore, HLA DR1-DQ5 is proposed to act as a protective haplotype in many individuals. Protection-associated HLA haplotypes are more likely to influence the promotion of specific bifidobacteria. In addition, strain-level differences are correlated with colonization proficiency in the gut depending on HLA haplotype makeup. These results demonstrate that HLA genetics should be considered when designing effective probiotics, particularly for those at high genetic risk for autoimmune diseases.
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22.
  • Berzina, L., et al. (författare)
  • DR3 is associated with type 1 diabetes and blood group ABO incompatibility
  • 2002
  • Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 345-348
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes is associated with autoimmunity against pancreatic β cells. ABO incompatibility is associated with ABO immunization during pregnancy. Type 1 diabetes is associated with certain HLA DR and DQ haplotypes. The mechanism by which blood group incompatibility is associated with the risk of type 1 diabetes is not known. We propose that certain HLA alleles contribute to the development of both type 1 diabetes and ABO blood group incompatibility. We studied 57 children with ABO blood group incompatibility, 118 children with type 1 diabetes, and 98 age- and sex-matched unrelated healthy controls from Linköping. Typing of HLA DQA1, DQB1, and DRB1 was done on DNA extracted from peripheral blood, by PCR amplification, manual dot-blotting onto nylon membranes, synthetic sequence-specific oligonucleotide (SSO) probe 3′ end-labeling with 32P-dCTP, and hybridization followed by stringency washes and autoradiography. We observed that DR3 allele was more frequent in patients with ABO incompatibility when compared to healthy controls (OR = 2.7, Pc < 0.05). Patients with type 1 diabetes had significantly higher frequency of DR3, DQ2, DR4, and DQ8 alleles when compared to healthy controls. No significant difference was observed in frequency of DR3 between ABO blood group incompatibility and type 1 diabetes patients. We conclude that DR3 is associated with both the development of type 1 diabetes and ABO incompatibility.
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23.
  • Berzina, L, et al. (författare)
  • Newborn screening for high-risk human leukocyte antigen markers associated with insulin-dependent diabetes mellitus : The ABIS study
  • 2002
  • Ingår i: Annals of the New York Academy of Sciences. - 0077-8923 .- 1749-6632. ; 958, s. 312-316
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 (insulin-dependent) diabetes mellitus is associated with specific high-risk HLA DQ and DR haplotypes and islet cell antibodies. IDDM susceptibility in Caucasians is more strongly associated with DQ2/DQ8 (DQA1*0501-DQB1*0201/DQA1*0301-DQB1*0302) and DQ6 (B1*0604) than with DRB1*03/DRB1*04, while a single copy of DQ6 (B1*0602) gives sufficient protection against type 1 diabetes. As a part of the ABIS (All Babies in Southeast Sweden) study we have done typing of DQA1, DQB1, and DRB1 by polymerase chain reaction (PCR) amplification of the second exon of the genes, manually dot-blotting onto nylon membranes synthetic sequence-specific oligonucleotide (SSO) probes, 3' end-labeling with 32P-dCTP, and hybridization followed by stringency washes and autoradiography using the SSO probe. Among 3756 newborns born in southeast Sweden we have found the high-risk genotype DQ2/DR3-DO8/DR4 to be present in 1%, haplotype DQ8/DR4 in 7.8%, and haplotype DQ2/DR3 in 9.6%. DQ2/DR3 or DQ8/DR4 was carried by 16.4% of newborns, the low-risk DQ6 molecule was carried by newborns as follows: DQ2/DR3-DQ6/DR15, 1.3%, DQ8/DR4-DQ6/DR15, 1.3%, and DQ6/DR15, 9.4%. We conclude from our results that the high incidence of IDDM in Sweden is at least in part due to increased prevalence of high-risk HLA haplotypes compared to protective haplotypes (20% vs. 13%) in the general population.
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24.
  • Björklund, Anneli, et al. (författare)
  • Latent Autoimmune Diabetes in Adults : Background, Safety and Feasibility of an Ongoing Pilot Study With Intra-Lymphatic Injections of GAD-Alum and Oral Vitamin D
  • 2022
  • Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundLatent Autoimmune Diabetes in Adults (LADA) constitutes around 10% of all diabetes. Many LADA patients gradually lose their insulin secretion and progress to insulin dependency. In a recent trial BALAD (Behandling Av LADa) early insulin treatment compared with sitagliptin failed to preserve insulin secretion, which deteriorated in individuals displaying high levels of antibodies to GAD (GADA). These findings prompted us to evaluate a treatment that directly affects autoimmunity. Intra-lymphatic GAD-alum treatment has shown encouraging results in Type 1 diabetes patients. We therefore tested the feasibility of such therapy in LADA-patients (the GADinLADA pilot study). Material and MethodsFourteen GADA-positive (>190 RU/ml), insulin-independent patients 30-70 years old, with LADA diagnosed within < 36 months were included in an open-label feasibility trial. They received an intra-nodal injection of 4 mu g GAD-alum at Day 1, 30 and 60 plus oral Vitamin D 2000 U/d from screening 30 days before (Day -30) for 4 months if the vitamin D serum levels were below 100 nmol/L (40 ng/ml). Primary objective is to evaluate safety and feasibility. Mixed Meal Tolerance Test and i.v. Glucagon Stimulation Test at baseline and after 5 and 12 months are used for estimation of beta cell function. Results will be compared with those of the recent BALAD study with comparable patient population. Immunological response is followed. ResultsPreliminary results show feasibility and safety, with almost stable beta cell function and metabolic control during follow-up so far (5 months). ConclusionsIntra-lymphatic GAD-alum treatment is an option to preserve beta cell function in LADA-patients. An ongoing trial in 14 LADA-patients show feasibility and safety. Clinical and immunological responses will determine how to proceed with future trials.
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25.
  • Brekke, Hilde Kristin, 1972, et al. (författare)
  • Predictors and dietary consequences of frequent intake of high-sugar, low-nutrient foods in 1-year-old children participating in the ABIS study.
  • 2007
  • Ingår i: The British journal of nutrition. - 0007-1145 .- 1475-2662. ; 97:1, s. 176-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Foods rich in sugar have been suggested to contribute to the increasing prevalence of obesity in children. The aim of this report is to investigate the dietary pattern in 1-year-old children who frequently receive foods rich in sugar but low in nutrients and to study associated demographic and parental factors. During 1977-9, 21,700 infants were invited to participate in this prospective, population-based, longitudinal cohort study. Screening questionnaires were completed for 16,070 infants after delivery. Follow-up questionnaires from 10,762 children at 1 year of age are included in the analysis. It was found that 24% of the children received sweets/pastries more often than one or two times per week. They had a higher intake of French fries, potato crisps and cream as well as a lower intake of fruit and vegetables. A frequent intake of sugar-rich, low-nutrient foods was significantly associated with several maternal factors (high intake of sweets/pastries during pregnancy, young age, mother living alone) as well as presence of older siblings. Maternal smoking during pregnancy and maternal overweight were of borderline significance. Parental education level was inversely associated with the frequency of intake of sweets/pastries in the child. Children who frequently receive sweets/pastries also have an otherwise unfavourable dietary pattern. Several parental and demographic factors were associated with this feeding pattern, especially high intake of sweets/pastries during pregnancy. Screening of pregnant women for risk predictors like consumption of sweets/pastries, young age and smoking could be possible ways of identifying children at future risk for low dietary quality.
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26.
  • Brekke, Hilde, et al. (författare)
  • Vitamin D supplementation and diabetes-related autoimmunity in the ABIS study
  • 2007
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 8:1, s. 11-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Supplementation with vitamin D during infancy, as well as intake of vitamin D during pregnancy, has been associated with decreased risk of type 1 diabetes or diabetes-related autoantibodies in children. The primary aim of this report was to investigate whether vitamin D supplementation during infancy is associated with diabetes-related autoimmunity at 1 and 2.5 yr in the children. Second, we examined whether consumption of vitamin-D-containing supplements during pregnancy is related to risk of autoimmunity in the offspring. Screening questionnaires were completed for 16 070 infants after delivery, including a food-frequency questionnaire regarding the mother's use of dietary supplements during pregnancy. Parents of 11 081 and 8805 infants completed a follow-up questionnaire regarding the use of vitamin supplementation at 1 and 2.5 yr, respectively. Autoantibodies against glutamic acid decarboxylase and islet antigen-2 (IA-2) were analyzed in whole blood from 8694 children at 1 yr and 7766 children at 2.5 yr. Supplementation with AD-drops was not associated with autoantibodies at 1 or 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced diabetes-related autoimmunity at 1 yr (adjusted odds ratio: 0.707, confidence interval: 0.520-0.962, p = 0.028) but not at 2.5 yr. In conclusion, no association was found between an intermediate dose of vitamin D supplementation during infancy and development of diabetes-related autoantibodies at 1 and 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced development.
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27.
  • Bruzzaniti, Sara, et al. (författare)
  • High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease
  • 2022
  • Ingår i: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 65, s. 1390-1397
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time. Methods Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5 years after diabetes onset. Differences in soluble ICM levels between the groups were assessed, and a Cox regression analysis was used to evaluate their association with the risk of development of an additional autoimmune disease over time. To validate the data, circulating ICMs were measured in an independent cohort of 60 children with new-onset type 1 diabetes stratified into two groups. Results We found that the levels of circulating ICMs were significantly higher in children with new-onset diabetes compared with healthy children. Further, we observed that children with type 1 diabetes who developed a second autoimmune disease over time (T1D-AAD(+) children) had higher levels of soluble ICMs than children with type 1 diabetes who did not (T1D-AAD(-) children). Cox regression models revealed that high circulating levels of CD137/4-1BB and PD-1 molecules at diabetes diagnosis were associated with the risk of developing an additional autoimmune disease in both type 1 diabetes cohorts. Conclusions/interpretation Our findings suggest that soluble CD137/4-1BB and PD-1 molecules may be used as prognostic biomarkers in children with type 1 diabetes, and may pave the way for novel immunological screening at diabetes onset, allowing early identification of children at higher risk of developing other autoimmune conditions over time.
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28.
  • Bybrant, M. C., et al. (författare)
  • Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes
  • 2021
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.
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29.
  • Carlsson, Annelie, et al. (författare)
  • Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY : Lessons From a 5-Year Pediatric Swedish National Cohort Study
  • 2020
  • Ingår i: Diabetes Care. - Arlington, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:1, s. 82-89
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population.RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK, HNF1A, and HNF4A, through either routine clinical or research testing.RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c <7.5% (58 mmol/mol) at diagnosis identified 36 out of 46 (78%) patients with MODY (detection rate 49%). On follow-up, the 46 patients with MODY had excellent glycemic control, with an HbA1c of 6.4% (47 mmol/mol), with 42 out of 46 (91%) patients not on insulin treatment.CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY. Testing all 12% patients negative for four islet autoantibodies is an effective strategy for not missing MODY but will result in a lower detection rate. Identifying MODY results in excellent long-term glycemic control without insulin.
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30.
  • Casas, Rosaura, 1954-, et al. (författare)
  • Intra-lymphatic administration of GAD-alum in type 1 diabetes : long-term follow-up and effect of a late booster dose (the DIAGNODE Extension trial)
  • 2022
  • Ingår i: Acta Diabetologica. - : Springer. - 0940-5429 .- 1432-5233. ; 59:5, s. 687-696
  • Tidskriftsartikel (refereegranskat)abstract
    •  Aim: To evaluate the long-term effect of intra-lymphatic administration of GAD-alum and a booster dose 2.5 years after the first intervention (DIAGNODE Extension study) in patients with recent-onset type 1 diabetes.Methods: DIAGNODE-1: Samples were collected from 12 patients after 30 months who had received 3 injections of 4 μg GAD-alum into a lymph node with one-month interval. DIAGNODE Extension study: First in human, a fourth booster dose of autoantigen (GAD-alum) was given to 3 patients at 31.5 months, who were followed for another 12 months. C-peptide was measured during mixed meal tolerance tests (MMTTs). GADA, IA-2A, GADA subclasses, GAD65-induced cytokines, PBMCs proliferation and T cells markers were analyzed.Results: After 30-month treatment, efficacy was still seen in 8/12 patients (good responders, GR). Partial remission (IDAA1c < 9) had decreased compared to 15 months, but did not differ from baseline, and HbA1c remained stable. GAD65-specific immune responses induced by the treatment started to wane after 30 months, and most changes observed at 15 months were undetectable. GADA subclasses IgG2, IgG3 and IgG4 were predominant in the GR along with IgG1. A fourth intra-lymphatic GAD-alum dose to three patients after 31.5 months gave no adverse events. In all three patients, C-peptide seemed to increase the first 6 months, and thereafter, C-peptide, HbA1c, insulin requirement and IDAA1c remained stable.Conclusion: The effect of intra-lymphatic injections of GAD-alum had decreased after 30 months. Good responders showed a specific immune response. Administration of a fourth booster dose after 31.5 months was safe, and there was no decline in C-peptide observed during the 12-month follow-up.
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31.
  • Dahlgren, Lars-Ove, 1946-, et al. (författare)
  • Varför PBI?
  • 1993
  • Ingår i: Problembaserad inlärning. - Lund : Studentlitteratur. - 9144372612 ; , s. 13-27
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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32.
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33.
  • Danne, Thomas, et al. (författare)
  • A cross-sectional international survey of continuous subcutaneous insulin infusion in 377 children and adolescents with type 1 diabetes mellitus from 10 countries
  • 2005
  • Ingår i: Pediatric Diabetes. - 1399-543X .- 1399-5448. ; 6:4, s. 193-198
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To document current practices using continuous subcutaneous insulin infusion (CSII) by downloading electronically the 90-d pump data held within the pump memory and relating that to clinical data from children and adolescents in different pediatric diabetes centers from Europe and Israel. Methods: Data of patients (1-18 yr) treated with CSII in 23 centers from nine European countries and Israel were recorded with the ENCAPTURE software (PEC International, Frankfurt, Germany). The number of patients who participated was 377 (48% female, mean diabetes duration ± SD: 6.8 ± 3.7 yr, age: 12.9 ± 3.8 yr, preschool n = 33, prepubertal n = 95, adolescent n = 249, CSII duration: 1.6 ± 1.2 yr, local HbA1c: 8.1 ± 1.2%). Results: The total insulin dose was lower than previously reported for injection therapy (0.79 ± 0.20 U/kg/d). Covariance coefficient of daily total insulin was high in all age groups (adolescents 19 ± 9%, prepubertal 18 ± 8 and preschool 17 ± 8). The distribution of basal insulin infusion rates over 24 hr (48 ± 12% of total dose) varied significantly between centers and age groups. The number of boluses per day (7 ± 3) was not significantly different between the age groups (average daily bolus amount: 0.42 ± 0.16 U /kg). The rate of severe hypoglycemia (coma/convulsions) was 12.4 episodes per 100 patient-years and the number of diabetes-related hospital days was 124 per 100 patient-years. Discussion: Pediatric CSII patients show a high variability in their insulin therapy. This relates both to age-dependent differences in the distribution of basal insulin as to the age-independent day-to-day variation in prandial insulin. © Blackwell Munksgaard, 2005.
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34.
  • Danne, Thomas, et al. (författare)
  • Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes : Experience of the PedPump Study in 17 countries
  • 2008
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:9, s. 1594-1601
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. Methods: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA 1c was measured centrally. Results: A total of 1,041 patients (age: 11.8±4.2 years, diabetes duration: 6.0±3.6 years, average CSII duration: 2.0±1.3 years, HbA1c: 8.0±1.3% [means±SD]) participated. Glycaemic control was better in preschool (n=142, 7.5±0.9%) and pre-adolescent (6-11 years, n=321, 7.7±1.0%) children than in adolescent patients (12-18 years, n=578, 8.3±1.4%). There was a significant negative correlation between HbA1c and daily bolus number, but not between HbA1c and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA1c level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. Conclusions/ interpretation: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA1c. © 2008 Springer-Verlag.
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35.
  • Dietrich, Fabricia, et al. (författare)
  • Immune response differs between intralymphatic or subcutaneous administration of GAD-alum in individuals with recent onset Type 1 diabetes
  • 2022
  • Ingår i: Diabetes/Metabolism Research Reviews. - : John Wiley & Sons. - 1520-7552 .- 1520-7560. ; 38:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Immunomodulation with autoantigens potentially constitutes a specific and safe treatment for Type 1 diabetes (T1D). Studies with GAD-alum administrated subcutaneously have shown to be safe, but its efficacy has been inconclusive. Administration of GAD-alum into the lymph nodes, aimed to optimize antigen presentation, has shown promising results in an open-label clinical trial. Here we compared the immune response of the individuals included in the trial with a group who received GAD-alum subcutaneously in a previous study.Materials and methods: Samples from T1D individuals collected 15 months after administration of either three doses 1 month apart of 4 μg GAD-alum into lymph nodes (LN, n=12) or two doses one month apart of 20 μg subcutaneously (SC, n=12) were studied. GADA, GADA subclasses, GAD65 -induced cytokines, PBMCs proliferation and T cells markers were analyzed.Results: Low doses of GAD-alum into the lymph nodes induced higher GADA levels than higher doses administrated subcutaneously. Immune response in the LN group was characterized by changes in GADA subclasses, with a relative reduction of IgG1 and enhanced IgG2, IgG3 and IgG4 proportion, higher GAD65 -induced secretion of IL-5, IL-10 and TNF-α and reduction of cell proliferation and CD8+ T cells. These changes were not observed after subcutaneous injections of GAD-alum.Conclusions: GAD-specific immune responses 15 months after lymph node injections of GAD-alum differed from the ones induced by subcutaneous administration of the same autoantigen.
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36.
  • Duchén, Karel, 1961-, et al. (författare)
  • Fatty fish intake in mothers during pregnancy and in their children in relation to the development of obesity and overweight in childhood: The prospective ABIS study
  • 2020
  • Ingår i: Obesity Science and Practice. - : Wiley. - 2055-2238. ; 6:1, s. 57-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although controversial, lower maternal intake of n-3 polyunsaturated fatty acid (PUFA) during pregnancy and lower levels of omega-3 PUFA in serum phospholipids during childhood have been related to obesity. The main source of omega-3 PUFA is fatty fish in the diet. Objectives: To assess the relationship between overweight/obesity and the intake of fatty fish in maternal diet during pregnancy and in children up to 8 years of age. Methods: The prospective cohort All Children in South-East Sweden (ABIS) followed babies from birth to 8 years of age. A total of 6749 children at 5 years of age (boys 52.6%) and 3017 children at 8 years (boys 52.3%) participated. A “fatty-fish index” was constructed on the basis of self-reports of nutritional habits. Results: The prevalence of overweight and obesity in children at 5 years were 12.9% and 4.2%, respectively. At 8 years, 12.2% of the children presented overweight and 2.3% obesity. Girls were more affected than boys by overweight/obesity. A higher fish index during pregnancy was not related to overweight/obesity in the children, whereas a higher fish index in the children during the first years of life was related to obesity at 5 and 8 years of age. This relationship disappeared in a multivariable analysis. Maternal body mass index (BMI), maternal education, maternal smoking during pregnancy, birth weight, and physical activity all remained related to overweight/obesity at both 5 and 8 years of age. Conclusion: No relationships were found between a lower intake of fatty fish in the diet, neither in mothers during pregnancy nor in early childhood, and increased risk of overweight/obesity. © 2019 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd
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37.
  • Duchén, Karel, 1961-, et al. (författare)
  • Predicting the development of overweight and obesity in children between 2.5 and 8 years of age : The prospective ABIS study
  • 2020
  • Ingår i: Obesity Science & Practice. - : WILEY. - 2055-2238. ; 6:4, s. 401-408
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A relationship between overweight and obesity early in life and adolescence has been reported. The aim of this study was to track changes in overweight/obesity in children and to assess risk factors related to the persistence of overweight/obesity between 2.5 and 8 years. Study design: Children who participated in all three follow-ups at 2.5, 5 and 8 years in the prospective cohort All Children in Southeast Sweden (ABIS) (N = 2245, 52.1% boys and 47.9% girls) were classified as underweight, normal, overweight or with obesity, and changes within categories with age were related to risk factors for development of obesity in a multivariate analysis. Results: The prevalence of overweight and obesity between 2.5 and 8 years was 11%-12% and 2%-3%, respectively. Children with normal weight remained in the same category over the years, 86% between 2.5 to 5 years and 87% between 5 and 8 years. Overweight and obesity at 5 and 8 years were positively related to each other (p < 0.0001 for both). High level of TV watching at 8 years and high maternal body mass index (BMI) when the child was 5 years were related to lower probability to a normalized ISO-BMI between 5 and 8 years of age (p < 0.05 for both). Conclusion: Children with ISO-BMI 18.5 to 24.9 remain in that range during the first 8 years of life. Children with overweight early in life gain weight and develop obesity, and children with obesity tend to remain with obesity up to 8 years of age. TV watching and high maternal BMI were related to lower probability to weight normalization between 5 and 8 years of age. A multidisciplinary approach to promote dietary and physical activity changes in the entire family should be used for the treatment and prevention of overweight and obesity in early childhood.
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38.
  • Ernerudh, Jan, 1952-, et al. (författare)
  • Effect of photopheresis on lymphocyte population in children with newly diagnosed type 1 diabetes
  • 2004
  • Ingår i: Clinical and Diagnostic Laboratory Immunology. - 1071-412X. ; 11:5, s. 856-861
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3+) and T-helper cells (CD4+) and a higher proportion of naïve CD4 +CD45RA+ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4 (CD29 +) and the CD8 (CD11a+) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.
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39.
  • Faresjö, Maria, 1971-, et al. (författare)
  • Cytokine profile in children during the first 3 months after the diagnosis of type 1 diabetes
  • 2004
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 59:5, s. 517-526
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 1 diabetes is an autoimmune disease with an inflammatory process directed against the β cells in pancreas. This investigation aimed at studying the immune response during the first 3 months after the diagnosis of type 1 diabetes, with focus on the balance of T-helper 1 (Th1)- and Th2-like cytokines, produced spontaneously and in response to relevant autoantigens. Peripheral blood mononuclear cells (PBMCs) were collected from type 1 diabetic children (10-17 years) at 5, 20, 35 and 90 days after diagnosis. Expression of interferon-γ (IFN-γ) and interleukin-4 (IL-4) mRNA were detected by real-time reverse transcriptase polymerase chain reaction and IFN-γ, IL-10 and IL-13 by enzyme-linked immunosorbent assay in cell supernatant after stimulation with a glutamic acid decarboxylase 65 (GAD65)-peptide [amino acid (a.a.) 247-279], insulin, the ABBOS-peptide (a.a. 152-169), phytohaemagglutinin and keyhole limpet haemocyanin. Spontaneous and antigen-induced expression and secretion of cytokines were low at the diagnosis of type 1 diabetes. During the first month, after diagnosis, the GAD 65-peptide caused an increased ratio of IFN-γ/IL-4 mRNA expression (P < 0.05) and increased secretion of IFN-γ (P = 0.07). Expression of IFN-γ mRNA did also increase from stimulation with insulin (P < 0.05), even though cytokine secretion remained low. Thus, duration after diagnosis as well as metabolic state should be carefully considered both in studies of the pathogenesis of type 1 diabetes and in immune intervention studies at onset.
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40.
  • Faresjö, Maria, 1971-, et al. (författare)
  • Diminished Th1-like response to autoantigens in children with a high risk of developing type 1 diabetes
  • 2005
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:2, s. 173-179
  • Tidskriftsartikel (refereegranskat)abstract
    • The exact role of T-helper (Th) cells that precede the clinical manifestation of type 1 diabetes remains unclear. The aim of this investigation was to study the Th1- and Th2-like profile in children and adults with high risk of developing the disease. Peripheral blood mononuclear cells were collected from high-risk children and adults and from healthy individuals matched for age and gender. Using the sensitive enzyme-linked immunospot (ELISPOT) technique to divide Th1- from Th2-like lymphocytes, secretion of interferon-γ (IFN-γ) and interleukin-4 was analysed from lymphocytes spontaneously and after in vitro stimulation with different antigens, based on present paradigms regarding the pathogenesis of type 1 diabetes. Compared to the response observed in healthy individuals, we found that individuals with a high risk of developing type 1 diabetes, especially children, responded with less IFN-γ secretion to the three autoantigens glutamic acid decarboxylase 65 (GAD 65), insulin and tyrosinphosphatase (IA-2). Thus, a diminished Th1-like response by in vitro autoantigen stimulation was observed in especially children with a high risk of developing type 1 diabetes. Reduced Th1/Th2 response was related to signs of β cell exhaustion.
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41.
  • Faresjö, Maria, 1971-, et al. (författare)
  • The immunological effect of photopheresis in children with newly diagnosed type 1 diabetes
  • 2005
  • Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 58:3, s. 459-466
  • Tidskriftsartikel (refereegranskat)abstract
    • Photopheresis has been claimed to have immune-modulating effects, but the mechanisms of action are unknown. This study investigated the immune effect of photopheresis in children with type 1 diabetes, with a focus on the balance of Th1- and Th2-like cytokines. Ten children with newly diagnosed type 1 diabetes (10-17 y) were treated with five double treatments of photopheresis and 10 children matched for disease, age, and gender were given placebo tablets and sham pheresis. Expression of IFN-γ and IL-4 mRNA was determined by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and secretion of IFN-γ, IL-10, and IL-13 in cell-culture supernatants by ELISA after stimulation with glutamic acid decarboxylase (GAD65) (a.a. 247-279), the ABBOS peptide (a.a. 152-169), insulin, phytohemagglutinin (PHA), and keyhole limpet hemocyanin (KLH). Photopheresis changed antigen-stimulated immune balance in line with a Th2-like shift. Thus, the ratio of IFN-γ/IL-4 mRNA expression after in vitro stimulation with a peptide of the autoantigen GAD 65 was reduced after treatment in the photopheresis group. The IFN-γ/IL-4 mRNA expression ratio after in vitro stimulation with insulin was also lower in children treated with photopheresis compared with the placebo group. Photopheresis has an immune-modulating effect in children with type 1 diabetes, causing a Th2-like deviation. Copyright © 2005 International Pediatric Research Foundation, Inc.
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42.
  • Faresjö, Tomas, 1954-, et al. (författare)
  • Folkhälsoskillnaderna består mellan Norrköping och Linköping [Public health differences between »the twin cities« persist].
  • 2019
  • Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 116
  • Tidskriftsartikel (refereegranskat)abstract
    • A decade ago, major public health differences between two neighboring, equal sized large Swedish cities, Norrköping and Linköping (»the Twin cities«) were revealed. These differences were considerable for cardiovascular mortality and life expectancy. An important finding was that cardiovascular mortality rates for men and women in the city of Norrköping were highest compared to other major Swedish cities. In this follow-up, a decade later, cardiovascular mortality rates are still highest for the Norrköping population in comparison to the largest Swedish cities. There are also still profound and major public health differences between these twin cities. The differences seem to persist over time. These differences could not be explained by differences in health care, but are rather reflecting different social history and socioeconomic and life style differences in these two cities.
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43.
  • Faresjö, Tomas, 1954-, et al. (författare)
  • Tvillingstäder med stora sociala skillnader i folkhälsa - ett samhällsmedicinskt experiment inleds i Norrköping och Linköping : [Twin cities with big social differences when it comes to public health. A sociomedical "experiment" introduced in Norrkoping and Linkoping]
  • 2007
  • Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 104:23, s. 1788-1790
  • Tidskriftsartikel (refereegranskat)abstract
    • An interdisciplinary research group entitled ”Twincities Research Group” has been initiated at Linköping University. The term twin cities refer to the Swedish cities Linköping and Norrköping, neighbours that are nearly equal in size. These two cities, located within a distance of only 40 km, are governed by the same county council and consequently have the same health care structure. However, health is remarkably different in these twin cities. The comparison of public health in these two cities during the development from the industrial to the post-industrial era has a design similar to classical experiments with a control and an experiment group, since the social history and the socio-economic structures of the cities are radically different. Through an interdisciplinary research design including historical, epidemiological and clinical competence we have a unique opportunity to increase our understanding of how social environment may affect public health.
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44.
  •  
45.
  • Gjessing, Kristian, 1967-, et al. (författare)
  • Using early childhood infections to predict late childhood antibiotic consumption: a prospective cohort study
  • 2020
  • Ingår i: BJGP open. - : Royal College of General Practitioners. - 2398-3795. ; 4:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the Swedish welfare system, the prescription and price of antibiotics is regulated. Even so, socioeconomic circumstances might affect the consumption of antibiotics for children.Aim: This study aimed to investigate if socioeconomic differences in antibiotic prescriptions could be found for children aged 2–14 years, and to find predictors of antibiotic consumption in children, especially if morbidity or socioeconomic status in childhood may function as predictors.Design & setting: Participants were from All Babies In Southeast Sweden (ABIS), a prospectively followed birth cohort (N = 17 055), born 1997-1999. Pharmaceutical data for a 10-year period, from 2005–2014 were used (the cohort were aged from 5–7, up to 14–16 years). Participation at the 5-year follow-up was 7443 children. All prescriptions from inpatient, outpatient, and primary care were included. National registries and parent reports were used to define socioeconomic data for all participants. Most children’s infections were treated in primary healthcare centres.Method: Parents of included children completed questionnaires about child morbidity at birth and at intervals up to 12 years. Their answers, combined with public records and national registries, were entered into the ABIS database and analysed. The primary outcome measure was the number of antibiotic prescriptions for each participant during a follow-up period between 2005–2014.Results: The most important predictor for antibiotic prescription in later childhood was parent-reported number of antibiotic-treated infections at age 2–5 years (odds ratio (OR) range 1.21 to 2.23, depending on income quintile; P<0.001). In the multivariate analysis, lower income and lower paternal education level were also significantly related to higher antibiotic prescription.Conclusion: Parent-reported antibiotic-treated infection at age 2–5 years predicted antibiotic consumption in later childhood. Swedish doctors are supposed to treat all patients individually and to follow official guidelines regarding antibiotics, to avoid antibiotics resistance. As socioeconomic factors are found to play a role, awareness is important to get unbiased treatment of all children.
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46.
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47.
  • Greenbaum, Carla, et al. (författare)
  • Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes
  • 2008
  • Ingår i: Diabetes Care. - 0149-5992 .- 1935-5548. ; 31:10, s. 1966-1971
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS: In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS: Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS: The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.
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48.
  • Gullstrand, Camilla, 1977-, et al. (författare)
  • Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study
  • 2008
  • Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 9:3 PART 1, s. 182-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.
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49.
  • Gustafsson Stolt, Ulrica, 1965-, et al. (författare)
  • Attitudes to bioethical issues : a case study of a screening project
  • 2002
  • Ingår i: Social Science and Medicine. - 0277-9536 .- 1873-5347. ; 54:9, s. 1333-1344
  • Tidskriftsartikel (refereegranskat)abstract
    • Commonly expressed in theoretical discussions about ethical problems in the context of epidemiology and screening is the need for more data. A study was carried out involving 21 explorative interviews with participant and nonparticipant mothers in a neonatal research screening project in progress in Sweden, ABIS (All Babies in Southeast Sweden). The respondents were asked, by way of open-ended questions, to give their opinions about certain ethical issues: informed consent; reasons for joining/declining; surrogate decision; the collection, analysis and storage of written and “live” material (biobanks); intervention etc.The ethical implications mentioned in the literature mostly concern the risk of creating distress and anxiety (anxiety and possible stigmatisation in respect of positive or false-positive results, worry about material collected and stored, distress caused by blood sampling procedures, etc.). Our results do not support the idea that the risks are substantial. The respondents rather indicate an attitude of benevolence—they are positive both to the current research on children, to the material they contribute (both written material and “biomaterial”), to possible results and intervention plans. On the other hand the participants expressed concern about the storage of material and the right to be informed of any screening/project results. Further studies in this field are needed and would be of help in theoretical discussion, the work of ethical committees and the designing of, for example, screening and research projects.
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50.
  • Gustafsson Stolt, Ulrica, 1965-, et al. (författare)
  • Bioethical theory and practice in genetic screening for type 1 diabetes
  • 2003
  • Ingår i: Medicine, Health care and Philosophy. - 1386-7423 .- 1572-8633. ; 6:1, s. 45-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to the potential ethical and psychological implications of screening, and especially inregard of screening on children without available and acceptable therapeutic measures, there is a common view that such procedures are not advisable. As part of an independent research- and bioethical case study, our aim was therefore to explore and describe bioethical issues among a representative sample of participant families (n = 17,055 children) in the ABIS (All Babies In South-east Sweden) research screening for Type 1 diabetes (IDDM).The primary aim is the identification of risk factors important for the development of diabetes and other multifactorial immune-mediated diseases. Four hundred, randomly chosen, participant mothers were asked to complete a questionnaire exploring issues of information, informed consent, bio-material, confidentiality and autonomy, and of prevention/intervention. 293 completed the questionnaire, resulting in a response rate of 73.3%. The majority of questions had the form of 6-point Likert-type response scales (1–6).We found that the majority of respondents felt calm in regard of samples and written material, and also concerning the possibility of their child in the future being identified as having high risk of developing Type 1 diabetes. An important finding concerning access and control of mainly biological data was indicated, with the respondents expressing concern for potential future use. We believe our findings indicate that this kind of empirical studies can substantially contribute to our understanding of bioethical issues of medical research involving genetics. Issues, such as safeguards ensuring theethical criteria of autonomy and respect, were emphasised by our respondents. We believe theissues brought up may promote further discussion, and do suggest issues for consideration by, among others, researchers, bioethicists and Institutional Review Boards.
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