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The Stress Hypothesis: Implications for the induction of diabetes-related autoimmunity in children?
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Second to Finland, Sweden has the world’s highest incidence of type 1 diabetes. Experiences of serious life events have retrospectively been shown to constitute a risk factor for the development of this disease, probably via the biological stress response. Parenting stress and maternal attachment insecurity are other important sources of stress in early childhood.

Psychological stress increases the need for insulin and may induce insulin resistance, which might add extra pressure on the insulin-producing beta cells in the pancreas (beta-cell stress).

The aim of the current thesis was to propose and start investigating a stress hypothesis – namely that psychological stress may induce insulin resistance leading to beta-cell stress, which could trigger an autoimmune reaction towards beta-cells in genetically predisposed children. When all the beta cells have been destroyed, insulin can no longer be produced in the body and type 1 diabetes becomes manifest.

Methods: Families from the prospective population-based ABIS-project, which follows approximately 17 000 children, participated in the empirical studies of the current thesis. The mothers completed questionnaires, including various measures of psychological stress (e.g. parenting stress and experiences of serious life events) and socio-demographic background, at the birth of the child and when the child was 1 as well as 2.5 years of age. Maternal attachment insecurity was assessed with the Adult Attachment Interview. Blood samples drawn from the children at 1 and 2.5 years of age were analyzed for type 1 diabetes-related autoantibodies towards Tyrosine phosphatase (IA-2) and Glutamic Acid Decarboxylase (GAD).

Findings and Conclusions: Parenting stress and experiences of serious life events like divorce and maternal exposure to violence were associated with the induction of diabetes-related autoimmunity in early childhood, possibly via insulin resistance and beta-cell stress. The risk of developing diabetesrelated autoimmunity after parental divorce or mothers’ exposure to violence was about threefold. None of the results were explained by any of the potential confounding factors analyzed. These results support and strengthen the stress hypothesis, which warrants further investigation.

Mothers’ attachment insecurity was not associated with the induction of diabetes-related autoimmunity in their infants. However, this lack of association was perhaps due to methodological constraints.

The vast majority of the parents were calmed or unaffected concerning their participation in the ABIS-project, suggesting that large-scale medical screening-projects in the general population are not in themselves a cause for worry and can be performed without causing increased anxiety.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2004. , 77 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 838
Keyword [en]
Psychological stress, parenting stress, attachment security, serious life events, children, attitudes, Type I diabetes, beta-cell autoantibodies, prediction, etiology
National Category
Clinical Science
Identifiers
URN: urn:nbn:se:liu:diva-5177ISBN: 91-7373-810-7 (print)OAI: oai:DiVA.org:liu-5177DiVA: diva2:21084
Public defence
2004-03-05, Aulan, Hälsans hus, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Note
On the day of the public defence the working title of article III was: Psychosocial correlates of parenting stress, lack of support and lack of confidence – A study of all babies in Southeast Sweden (ABIS). The status of article IV was: Manuscript to be submitted shortly; the status of article V was: Manuscript in preparation.Available from: 2004-03-26 Created: 2004-03-26 Last updated: 2012-01-25Bibliographically approved
List of papers
1. Screening for prediabetes in the general child population: maternal attitude to participation
Open this publication in new window or tab >>Screening for prediabetes in the general child population: maternal attitude to participation
2001 (English)In: Pediatric Diabetes, ISSN 1399-543X, Vol. 2, no 4, 170-174 p.Article in journal (Refereed) Published
Abstract [en]

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.

Keyword
attitudes, children, ethics, prediction, screening, type 1 diabetes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13628 (URN)10.1034/j.1399-5448.2001.20405.x (DOI)
Available from: 2004-03-26 Created: 2004-03-26 Last updated: 2009-08-19
2. Could parenting stress and lack of support/confidence function as mediating mechanisms between certain environmental factors and the development of autoimmunity in children? – A study within ABIS
Open this publication in new window or tab >>Could parenting stress and lack of support/confidence function as mediating mechanisms between certain environmental factors and the development of autoimmunity in children? – A study within ABIS
2002 (English)In: Annals of the New York Academy of Science, ISSN 0077-8923, Vol. 958, 431-435 p.Article in journal (Refereed) Published
Abstract [en]

Despite extensive research, the etiology of type 1 diabetes is still to a large extent unknown. We would like to propose psychoimmunology as one possible pathway. Psychological mechanisms are directly linked to hormonal and nervous signals, which increase the need for insulin and affect the immune system. Disparate factors of social, environmental, and medical character have been associated with the onset of type 1 diabetes or with the autoimmune process leading to the disease—for instance, parental age, maternal infections, delivery mood, need for neonatal intensive care, and low socioeconomic status. Our results, based on the analyses of 4337 nonselected newborn children and their mothers, show that all these risk factors were also associated with psychological mechanisms (defined as lack of social support/confidence and high parenting stress). These results support the hypothesis of psychological mechanisms as mediating variables between a number of disparate risk factors and the development of type 1 diabetes.

Keyword
type 1 diabetes, children, psychological factors, etiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13629 (URN)10.1111/j.1749-6632.2002.tb03019.x (DOI)
Available from: 2004-03-26 Created: 2004-03-26 Last updated: 2009-08-21
3. Psychosocial correlates of parenting stress, lack of support and lack of confidence/security
Open this publication in new window or tab >>Psychosocial correlates of parenting stress, lack of support and lack of confidence/security
2004 (English)In: Scandinavian Journal of Psychology, ISSN 0036-5564, Vol. 45, no 2, 169-179 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of the current study was to identify important correlates of parenting stress, frequently conceptualized as a mediator of suboptimal family function, and of social support and confidence/security, often regarded as buffers. Potential correlates of these concepts were assessed in questionnaires at delivery and at one year, in a sample of 16,000 families in Sweden. Predictors (1) of parenting stress were parental dissatisfaction and poor child sleeping patterns; (2) of lack of support included lack of confidence/security, parents born abroad, single motherhood, and maternal health problems; and (3) of lack of confidence/security were lack of support and serious life events. Mothers lacking social support or confidence/security exhibited significantly higher stress. Although parenting stress is a complex phenomenon certain risk factors can be emphasized, such as sleep problems which appear more important than child health problems. These risk factors can be used both in efforts to prevent stress and in studies of stress effects.

Keyword
Parenting stress, social support, confidence
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13630 (URN)10.1111/j.1467-9450.2004.00392.x (DOI)
Available from: 2004-03-26 Created: 2004-03-26 Last updated: 2009-08-21
4. Psychological stress may induce diabetes-related autoimmunity in infancy
Open this publication in new window or tab >>Psychological stress may induce diabetes-related autoimmunity in infancy
Show others...
2005 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 2, 290-295 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE— In retrospective studies, a number of disparate environmental factors (including experiences of serious life events) have been proposed as trigger mechanisms for type 1 diabetes or the autoimmune process behind the disease. Psychosocial stress in families may affect children negatively due to a link to hormonal levels and nervous signals that in turn influence both insulin sensitivity/insulin need and the immune system. Our aim was to investigate whether psychological stress, measured as psychosocial strain in families, is associated with diabetes-related autoimmunity during infancy.

RESEARCH DESIGN AND METHODS— The first 4,400 consecutive 1-year-old children from a large prospective population-based project participated in the study. Parents completed questionnaires at birth and at 1 year, including various measures of psychosocial stress (e.g., parenting stress) and sociodemographic background. Blood samples drawn from the children at 1 year were analyzed for type 1 diabetes–associated autoantibodies toward tyrosine phosphatase and GAD. Antibodies toward tetanus toxoid were used as non–diabetes-related control antibodies.

RESULTS— Psychosocial factors, i.e., high parenting stress (odds ratio 1.8 [95% CI 1.2–2.9], P < 0.01), experiences of a serious life event (2.3 [1.3–4.0], P < 0.01), foreign origin of the mother (2.1 [1.3–3.3], P < 0.001), and low paternal education (1.6 [1.1–2.3], P < 0.01) were associated with diabetes-related autoimmunity in the child, independent of family history of diabetes.

CONCLUSIONS— Psychological stress, measured as psychosocial strain in the family, seems to be involved in the induction, or progression, of diabetes-related autoimmunity in the child during the 1st year of life.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13631 (URN)10.2337/diacare.28.2.290 (DOI)
Available from: 2004-03-26 Created: 2004-03-26 Last updated: 2012-10-01Bibliographically approved
5. Mothers’ attachment insecurity and diabetes-related autoantibodies in their infants
Open this publication in new window or tab >>Mothers’ attachment insecurity and diabetes-related autoantibodies in their infants
2004 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, Vol. 1037, 110-113 p.Article in journal (Refereed) Published
Abstract [en]

Psychological stress may, via hormonal levels, increase insulin resistance. The aim of this study was to investigate whether mothers' attachment insecurity is associated with the induction or progression of diabetes-related autoimmunity in early childhood. Adult attachment interviews were conducted with 18 mothers of infants who were positive, and 32 mothers of infants who were negative, for glutamic acid decarboxylase, selected from ABIS, a large prospective population-based project. The proportion of children with insecure mothers was larger, but not significantly so, in the autoantibody-positive group than in the negative group. If an association exists between maternal attachment insecurity and diabetes-related autoimmunity during infancy, it does not appear to be strong.

Keyword
attachment insecurity, children, psychosocial factors, type 1 diabetes, beta cell autoantibodies
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13632 (URN)10.1196/annals.1337.016 (DOI)
Available from: 2004-03-26 Created: 2004-03-26 Last updated: 2009-08-21
6. Mothers' experiences of serious life events increase the risk of diabetes-related autoimmunity in their children
Open this publication in new window or tab >>Mothers' experiences of serious life events increase the risk of diabetes-related autoimmunity in their children
2005 (English)In: Diabetes Care, ISSN 0149-5992, Vol. 28, no 10, 2394-2399 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE—Stressful life events have been shown to constitute a risk factor for type 1 diabetes during childhood. Our aim was to investigate in the general child population (i.e., irrespective of genetic risk for type 1 diabetes) whether mothers’ experiences of serious life events, such as divorce and violence, were associated with diabetes-related autoimmunity in their children at age 2.5 years.

RESEARCH DESIGN AND METHODS—The study cohort was comprised of the first 5,986 consecutive children and their families from the prospective population-based All Babies in Southeast Sweden project for whom 2.5-year study data were available. Data were drawn from parental questionnaires that included questions about experiences of serious life events and the blood samples taken from the children when the children were age 2.5 years. The blood samples were analyzed for diabetes-related autoantibodies against tyrosine phosphatase and GAD.

RESULTS—Mothers’ experiences of divorce (odds ratio 3.6, 95% CI 1.4–9.6, P < 0.05) and violence (2.9, 1.0–7.8, P < 0.05) were associated with diabetes-related autoimmunity in the children, independent of a family history of type 1 diabetes.

CONCLUSIONS—The results support the ß-cell stress hypothesis and suggest that maternal experiences of serious life events such as divorce and violence seem to be involved in the induction or progression of diabetes-related autoimmunity in children at age 2.5 years, independent of family history of type 1 diabetes.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13633 (URN)10.2337/diacare.28.10.2394 (DOI)
Available from: 2004-03-26 Created: 2004-03-26 Last updated: 2009-06-04

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