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J Ludvigsson

Publications and source records attributed to J Ludvigsson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Bioethical theory and practice in genetic screening for type 1 diabetes.

Due to the potential ethical and psychological implications of screening, and especially in regard 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 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 the ethical criteria of autonomy and respect, were emphasised by our respondents. We believe the issues brought up may promote further discussion, and do suggest issues for consideration by, among others, researchers, bioethicists and Institutional Review Boards.

Adult↗
PubMed2003

Parents want to know if their child is at high risk of getting diabetes.

Not least among professionals, voices have been raised against screening research projects, which have been regarded as involving a risk of being unethical as they may disturb, scare, or even harm the included people without giving enough benefit. This problem with large-scale screening should be especially pronounced if increased risk of a serious disease like type 1 diabetes is identified when no effective prevention is available, and even more problematic if children were involved. ABIS (All Babies in Southeast Sweden) is a screening project including 17,000 newborn babies in the general population, followed prospectively to identify children at risk to get diabetes, and to study the influence of environmental factors causing the disease process. Four hundred randomly selected ABIS families received a questionnaire on attitudes and ethical questions regarding the project to be answered anonymously: 293/400 (73.3%) answered; 279/293 (95.3%) stated that they regarded it their right to be informed of results in the study and 278/293 (94.9%) said they really want to know. In fact, 254/293 (86.7%) report wanting to know if their child has increased risk of getting diabetes even if there is no preventive measure available. This clear result supports the view that this type of study may well be ethically justified as long as informed consent can be given based on adequate understanding and voluntariness. The results may have implications for the design of future screening studies.

Adult↗
PubMed2003

Vaccinations may induce diabetes-related autoantibodies in one-year-old children.

Vaccinations have been discussed as one among many environmental candidates contributing to the immune process that later may lead to type 1 diabetes. ABIS (All Babies in Southeast Sweden) is a prospective cohort study following a nonselected birth cohort of general population. In a randomly selected sample collection from 4400 children, GADA and IA-2A have been determined at the age of 1 year. The information on vaccinations was collected from questionnaires answered by the parents and was related to beta cell autoantibodies. When studying the induction of autoantibodies using the autoantibody level of 90th percentile as cutoff level, hemophilus influenza B (HIB) vaccination appeared to be a risk factor for IA-2A [OR 5.9 (CI 1.4-24.4; p = 0.01)] and for GADA [OR 3.4 (CI 1.1-10.8; p = 0.04)] in logistic regression analyses. Furthermore, the titers of IA-2A were significantly higher (p < 0.01 in Mann-Whitney test) in those children who had got HIB vaccination. When 99th percentile was used as cutoff to identify the children at risk of type 1 diabetes, BCG vaccination was associated with increased prevalence of IA-2A (p < 0.01). We conclude that HIB vaccination may have an unspecific stimulatory polyclonal effect increasing the production of GADA and IA-2A. This might be of importance under circumstances when the beta cell-related immune response is activated by other mechanisms.

Autoantibodies↗
PubMed2003

Stressful life events, social support and confidence in the pregnant woman and risk of coeliac disease in the offspring.

BACKGROUND: Stressful life events just before conception or during pregnancy can affect fetal development and increase the risk of disease in the offspring. The purpose of our study was to examine stressful life events, maternal social support and confidence during pregnancy and the risk of coeliac disease in the offspring. METHODS: Prospective cohort study of 16,286 children born between 1 October 1997 and 1 October 1999 in southeast Sweden. The study was part of the ABIS study (ABIS = All Babies In Southeast Sweden). Data on independent variables were obtained through questionnaires distributed at birth. The questionnaire included questions about parental disease, socio-economic factors, smoking, alcohol intake but also infections during pregnancy. Eight paediatric departments prospectively recorded all children with coeliac disease (confirmed through biopsy). RESULTS: Exposure to stressful life events (OR = 0.48: 95% CI OR = 0.12-2.01; P = 0.318), lack of social support (OR = 3.17; 95% CI OR = 0.43-23.22; P = 0.257) and lack of confidence (OR = 0.04; 95% CI OR = 0.00-2.48 x 10(9);P = 0.794) in the pregnant woman were not linked to coeliac disease in the offspring. CONCLUSION: The study indicates that stressful life events, lack of social support and lack of confidence during pregnancy play no role in the development of coeliac disease in the offspring.

Adult↗
PubMed2002

Severity at onset of childhood type 1 diabetes in countries with high and low incidence of the condition.

Severity of Type 1 diabetes mellitus (DM) at presentation was compared between south-east Sweden and Lithuania where incidence of childhood Type 1 diabetes is three times lower than in Sweden. New cases of diabetes at age 0-15 years from August 1995 to March 1999 in south-east Sweden and from August 1996 to August 2000 in Lithuania were included. Symptoms and clinical characteristics at diagnosis were recorded. Data about the close environment were collected using questionnaires. Lithuanian children were diagnosed in a more severe condition, mean pH 7.30 and HbA(1c) 11.5% compared with mean pH 7.36 and HbA(1c) 9.7% in Swedish children (P<0.0001). More Lithuanian than Swedish children were diagnosed in ketoacidosis (pH < or = 7.2, hyperglycaemia and ketonuria), 21.3 versus 7.3% (P<0.0001). Only 4.6% of Swedish children and 1.0% of Lithuanian children had no symptoms (P=0.007). Children in families with at least one first degree relative with diabetes (12.2% in Sweden and 8.4% in Lithuania, NS) had laboratory values at diagnosis closer to normal than sporadic cases in either country. Factors predicting ketoacidosis in Sweden were an unemployed mother and absence of infections in the 6 months before diagnosis. In Lithuania it was younger age and mother with less education. Additional educational activities for doctors are needed in countries with low incidence to reduce prevalence of ketoacidosis at onset.

Adolescent↗
PubMed2002

Attitudes to bioethical issues: a case study of a screening project.

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.

Anxiety↗
PubMed2002

Prevalence of retinopathy differs with age at onset of diabetes in a population of patients with Type 1 diabetes.

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 diagnosis 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 Jönköping, Kalmar or Ostergötland. 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 chi2 for linear trend for all ages 0.017, for age at onset 0-19 years P = 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.

Adolescent↗
PubMed2002

Inflammatory bowel disease in mother or father and neonatal outcome.

UNLABELLED: 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 10399 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.

Birth Weight↗
PubMed2002

Newborn screening for high-risk human leukocyte antigen markers associated with insulin-dependent diabetes mellitus: the ABIS study.

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 (32)P-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.

Diabetes Mellitus, Type 1↗
PubMed2002

DR3 is associated with type 1 diabetes and blood group ABO incompatibility.

Type 1 diabetes is associated with autoimmunity against pancreatic beta 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, P(c) < 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.

ABO Blood-Group System↗
PubMed2001

Nerve conduction defects are retarded by tight metabolic control in type I diabetes.

This follow-up study examines whether the development of nerve dysfunction is retarded by tight metabolic control in patients with type I diabetes mellitus. Seventy-one patients and 115 age-matched healthy control subjects underwent studies of nerve conduction in peroneal and sural nerves. The presence of diabetes was associated with a reduction in peroneal motor nerve conduction velocity (MCV) by 5.9 m/s, sural sensory nerve conduction velocity (SCV) by 3.4 m/s, and sural sensory nerve action potential (SNAP) amplitude by 22%. Dysfunction in peroneal MCV, sural SCV, and sural SNAP were related to long-term poor metabolic control. Eleven of 12 patients with HbA1c <6.5% had normal nerve conduction or abnormality in only one nerve as compared to 2 of 15 patients with HbA1c >8.0%. It is concluded that tight long-term metabolic control (HbA1c <6.5%) can retard nerve dysfunction in patients with type I diabetes mellitus and a mean disease duration of 12 years.

Action Potentials↗
PubMed2001

Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic and healthy children.

AIMS/HYPOTHESIS: Cows' milk proteins have been proposed to play a part in the pathogenesis of Type I (insulin-dependent) diabetes mellitus but both epidemiological and immunological studies have given conflicting results. Thus we aimed to study the immunological response to cows' milk proteins among diabetic and healthy children, focusing on the balance of Th1- and Th2-like lymphocytes. METHODS: Peripheral blood mononuclear cells from 30 Type I diabetic children (4 to 18 years old) were examined and compared with peripheral blood mononuclear cells from 18 healthy age-matched control children (7 to 15 years old). Expression of IFN-gamma and IL-4 mRNA were detected by realtime RT-PCR and as protein by ELISA after stimulation with BSA, the ABBOS-peptide (a. a. 152-169) and beta-lactoglobulin (betaLG) from cows' milk and ovalbumin from hens' egg. Phytohaemagglutinin and keyhole limpet haemocyanin were used as positive and negative controls, respectively. RESULTS: Bovine serum albumin caused a weak Th2-like response in Type I diabetic children, whereas BSA antibodies decreased with age only among healthy children. Otherwise, cows' milk proteins (BSA, ABBOS and betaLG) caused increased expression for IFN-gamma and IL-4 mRNA in diabetic and healthy children. BetaLG caused the strongest immunological response, which decreased with age only among diabetic children. However, ovalbumin from egg caused a similar activation of the immune system and the immune response was similar in both diabetic and healthy children. CONCLUSION/INTERPRETATION: Proteins from cows' milk caused an equal Th1- and Th2-like immune response in diabetic and healthy children. Thus, our results do not support the hypothesis that cows' milk antigens are important for the immune process associated with Type I diabetes.

Adolescent↗
PubMed2001

Islet autoantibodies in the prediction of diabetes in school children.

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

Adolescent↗
PubMed2001

Screening for prediabetes in the general child population: maternal attitude to participation.

Screening to predict serious diseases in the general population has been regarded as unethical as it is supposed to make people anxious. Therefore we have evaluated whether mothers become anxious when their babies participate in a project to predict diabetes in the general child population. Out of 21 700 newborn children, 16 300 (75%) entered the ABIS project (All Babies in South-east Sweden). The parents (usually the mothers) answered a questionnaire at the child's birth and then again after 1 yr. A total of 10 868 representative birth questionnaires had been analyzed. To the question, 'How do you feel when you know that your child is participating in this study?', only 2.5% of mothers of children with type 1 diabetes in the family answered 'more anxious/much more anxious', and even fewer (1.5%) of the mothers in the general population (p < 0.01). A total of 52.5% of the general population answered 'calmer/more reassured' (29.3% 'calmer' and 23.2% 'much calmer'), while 43.3% felt unaffected. Those 1.5% of mothers who reported becoming more anxious were more likely to be in an unstable social situation (unemployed, p < 0.001; born abroad, p < 0.001; low education, p < 0.001). At the 1-yr follow-up, 4948 unselected questionnaires had been analyzed. Only 1.2% of the mothers felt 'more anxious', while the overwhelming majority felt either unaffected (58.7%) or calmer (38.6%). At this follow-up, most of those who had felt 'more anxious' at birth did not feel that way any longer, and none of those with diabetes in the family. We conclude that large-scale screening studies for the prediction of diabetes in the general population can be performed without causing increased anxiety. A few parents, most often found in the group with known social problems, might need extra information and support.

Journal Article↗
PubMed2001

Tissue transglutaminase auto-antibodies in cord blood from children to become celiacs.

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.

Autoantibodies↗
PubMed2001

Photopheresis at onset of type 1 diabetes: a randomised, double blind, placebo controlled trial.

BACKGROUND: In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. AIM: To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. METHODS: A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included; 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). RESULTS: The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group; there was no difference between the groups regarding HbA1c values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. CONCLUSION: Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.

Adolescent↗
PubMed2001

Coeliac disease in the father affects the newborn.

BACKGROUND AND AIMS: Untreated coeliac disease in the mother is associated with lower birth weight. We examined the risk of adverse neonatal outcome when the infant's mother, father, or other relative suffered from known coeliac disease. METHODS: Mothers answered a questionnaire a few days after the birth of their infant. Of a total of 10,597 single birth infants from Southeast Sweden, 53 infants had a mother with coeliac disease (father 27, sibling 70, other close relative 442). Adjusted odds ratios and adjusted differences for neonatal outcome were calculated. RESULTS: Infants whose father suffered from coeliac disease had a lower birth weight (95% adjusted confidence interval (CI) -459, -72 g), more often belonged to the low birth weight (LBW) category (LBW < or =2499 g) (95% CI adjusted odds ratio (AOR) 1.48--17.18), and had a shorter pregnancy duration (95% adjusted CI -1.53, -0.08 weeks) than non-coeliac controls. They also weighed less than infants whose father suffered from other autoimmune diseases (95% CI -549, -93 g). Infants whose mother suffered from coeliac disease had a lower birth weight (95% adjusted CI -370, -74 g) and more often belonged to the LBW category (95% CI AOR 2.60--15.08) than non-coeliac controls. These infants were more often in the LBW category than infants whose mother suffered from non-diabetic autoimmune diseases (95% CI AOR 1.24--9.65). Coeliac disease in other relatives was not associated with any adverse effect on neonatal outcome. CONCLUSIONS: This study suggests that even treated coeliac disease, in either of the parents, has a negative effect on pregnancy, resulting in lower birth weight and perhaps shorter duration of pregnancy.

Adolescent↗