| 1. |
- Ullsten, Sara, et al.
(author)
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Islet amyloid deposits preferentially in the highly functional and most blood-perfused islets.
- 2017
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In: Endocrine Connections. - : BIOSCIENTIFICA LTD. - 2049-3614. ; 6:7, s. 458-468
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Journal article (peer-reviewed)abstract
- Islet amyloid and beta cell death in type 2 diabetes are heterogeneous events, where some islets are affected early in the disease process, whereas others remain visibly unaffected. This study investigated the possibility that inter-islet functional and vascular differences may explain the propensity for amyloid accumulation in certain islets. Highly blood-perfused islets were identified by microspheres in human islet amyloid polypeptide expressing mice fed a high-fat diet for three or 10 months. These highly blood-perfused islets had better glucose-stimulated insulin secretion capacity than other islets and developed more amyloid deposits after 10 months of high-fat diet. Similarly, human islets with a superior release capacity formed more amyloid in high glucose culture than islets with a lower release capacity. The amyloid formation in mouse islets was associated with a higher amount of prohormone convertase 1/3 and with a decreased expression of its inhibitor proSAAS when compared to islets with less amyloid. In contrast, levels of prohormone convertase 2 and expression of its inhibitor neuroendocrine protein 7B2 were unaltered. A misbalance in prohormone convertase levels may interrupt the normal processing of islet amyloid polypeptide and induce amyloid formation. Preferential amyloid load in the most blood-perfused and functional islets may accelerate the progression of type 2 diabetes.
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| 2. |
- Ullsten, Sara, 1987-
(author)
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The Impact of Pancreatic Islet Vascular Heterogeneity on Beta Cell Function and Disease
- 2017
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Doctoral thesis (other academic/artistic)abstract
- Diabetes Mellitus is a group of complex and heterogeneous metabolic disorders characterized by hyperglycemia. Even though the condition has been extensively studied, its causes and complex pathologies are still not fully understood. The occurring damage to the pancreatic islets is strikingly heterogeneous. In type 1 diabetes, the insulin producing beta cells are all destroyed within some islets, and similarly in type 2 diabetes, some islets may be severely affected by amyloid. At the same time other islets, in the near vicinity of the ones that are affected by disease, may appear fully normal in both diseases. Little is known about this heterogeneity in susceptibility to disease between pancreatic islets. This thesis examines the physiological and pathophysiological characteristics of islet subpopulations.Two subpopulations of islets were studied; one constituting highly vascularized islets with superior beta cell functionality, and one of low-oxygenated islets with low metabolic activity. The highly functional islets were found to be more susceptible to cellular stress both in vitro and in vivo, and developed more islet amyloid when metabolically challenged. Highly functional islets preferentially had a direct venous drainage, facilitating the distribution of islet hormones to the peripheral tissues. Further, these islets had an increased capacity for insulin secretion at low glucose levels, a response that was observed abolished in patients with recent onset type 1 diabetes. The second investigated islet subpopulation, low-oxygenated islets, was found to be an over time stable subpopulation of islets with low vascular density and beta cell proliferation.In summary, two subpopulations of islets can be identified in the pancreas based on dissimilarities in vascular support and blood flow. These subpopulations appear to have different physiological functions of importance for the maintenance of glucose homeostasis. However, they also seem to differ in vulnerability, and a preferential death of the highly functional islets may accelerate the progression of both type 1 and type 2 diabetes.
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| 3. |
- Alaie, Iman, et al.
(author)
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Parent-youth conflict as a predictor of depression in adulthood : a 15-year follow-up of a community-based cohort
- 2020
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In: European Child and Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 29:4, s. 527-536
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Journal article (peer-reviewed)abstract
- Experiencing conflictual relations with one's parents while growing up has been linked to onset, recurrence, and worse treatment outcome of adolescent depression. While this suggests that significant problems in the parent-youth relationship make depressive disorders more relentless, it is not clear whether this effect lasts into adulthood. Our aim was to examine if major and minor conflict with parents while growing up predicts depression in adulthood in youth with and without a history of depression. We utilized data from the Uppsala Longitudinal Adolescent Depression Study. This community-based cohort was assessed with structured diagnostic interviews both at age 16-17 and at follow-up 15 years later. The analyses included 382 individuals (227 with a history of child or adolescent depression; 155 peers without such a history). Binary logistic regression was used, adjusting for sex, disruptive behavior disorders, and additional family-related adversities. Among individuals with adolescent depression, major conflict with parents was strongly associated with adult depression (adjusted OR 2.28, 95% CI 1.07-4.87). While major conflict with parents was rare among non-depressed controls, a non-significant association of similar magnitude was still observed. Minor conflict, on the other hand, was not significantly associated with adult depression. Overall, conflict with parents did not predict adult anxiety disorders, substance use, suicidal behavior, somatoform disorders, or psychotic disorders. In conclusion, major parent-youth conflict during upbringing seems to be linked with an increased risk of depression in adulthood. These findings underscore the need to consider contextual/familial factors in the prevention and clinical management of early-life depression.
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| 4. |
- Alm, Susanne, et al.
(author)
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Poor Family Relationships in Adolescence and the Risk of Premature Death : Findings from the Stockholm Birth Cohort Study
- 2019
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 16:10
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Journal article (peer-reviewed)abstract
- Poor family relationships during childhood have been shown to have long-term negative effects on an offspring's health. However, few studies have followed the offspring to retirement age, and relatedly, knowledge about the link between poor family relationships and premature death is scarce. The aim of this study was to examine the association between poor family relationships in adolescence and the risk of premature death, even when considering other adverse childhood conditions. Prospective data from the Stockholm Birth Cohort study were used, with 2636 individuals born in 1953 who were followed up until age 65. Information on family relations was based on interviews with the participants' mothers in 1968. Information on mortality was retrieved from administrative register data from 1969-2018. Cox proportional hazards regressions showed that poor family relationships in adolescence were associated with an increased risk of premature death, even when adjusting for childhood conditions in terms of household social class, household economic poverty, contact with the child services, parental alcohol abuse, and parental mental illness (Hazard Ratio (HR), 2.08, 95% Confidence Interval (CI), 1.40-3.09). The findings show that poor family relationships in adolescence can have severe and long-lasting health consequences, highlighting the importance of early interventions.
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| 5. |
- Alm, Susanne, et al.
(author)
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Poor family relationships in adolescence as a risk factor of in-patient psychiatric care across the life course : A prospective cohort study
- 2020
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In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 48:7, s. 726-732
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Journal article (peer-reviewed)abstract
- Background: Previous research has shown that poor family relations in childhood are associated with adverse mental health in adulthood. Yet, few studies have followed the offspring until late adulthood, and very few have had access to register-based data on hospitalisation due to psychiatric illness. The aim of this study was to examine the association between poor family relations in adolescence and the likelihood of in-patient psychiatric care across the life course up until age 55. Methods: Data were derived from the Stockholm Birth Cohort study, with information on 2638 individuals born in 1953. Information on family relations was based on interviews with the participants' mothers in 1968. Information on in-patient psychiatric treatment was derived from administrative registers from 1969 to 2008. Binary logistic regression was used. Results: Poor family relations in adolescence were associated with an increased risk of later in-patient treatment for a psychiatric diagnosis, even when adjusting for other adverse conditions in childhood. Further analyses showed that poor family relations in adolescence were a statistically significant predictor of in-patient psychiatric care up until age 36-45, but that the strength of the association attenuated over time. Conclusions: Poor family relationships during upbringing can have serious negative mental-health consequences that persist into mid-adulthood. However, the effect of poor family relations seems to abate with age. The findings point to the importance of effective interventions in families experiencing poor relationships.
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| 6. |
- Alm, Susanne, et al.
(author)
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Poor family relationships in adolescence as a risk factor of in-patient psychiatric care across the life course : A prospective cohort study
- 2020
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In: Scandinavian Journal of Public Health. - Stockholm : Sage Publications. - 1403-4948 .- 1651-1905. ; 48:7, s. 726-732
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Journal article (peer-reviewed)abstract
- Background: Previous research has shown that poor family relations in childhood are associated with adverse mental health in adulthood. Yet, few studies have followed the offspring until late adulthood, and very few have had access to register-based data on hospitalisation due to psychiatric illness. The aim of this study was to examine the association between poor family relations in adolescence and the likelihood of in-patient psychiatric care across the life course up until age 55. Methods: Data were derived from the Stockholm Birth Cohort study, with information on 2638 individuals born in 1953. Information on family relations was based on interviews with the participants' mothers in 1968. Information on in-patient psychiatric treatment was derived from administrative registers from 1969 to 2008. Binary logistic regression was used. Results: Poor family relations in adolescence were associated with an increased risk of later in-patient treatment for a psychiatric diagnosis, even when adjusting for other adverse conditions in childhood. Further analyses showed that poor family relations in adolescence were a statistically significant predictor of in-patient psychiatric care up until age 36-45, but that the strength of the association attenuated over time. Conclusions: Poor family relationships during upbringing can have serious negative mental-health consequences that persist into mid-adulthood. However, the effect of poor family relations seems to abate with age. The findings point to the importance of effective interventions in families experiencing poor relationships.
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| 7. |
- Alm, Susanne, et al.
(author)
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Poor family relationships in adolescence as a risk factor of in-patient somatic care across the life course : Findings from a 1953 cohort
- 2021
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In: SSM - Population Health. - : Elsevier. - 2352-8273. ; 14
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Journal article (peer-reviewed)abstract
- Background: Prior research has shown that poor family relations during upbringing have long-term detrimental effects on mental health. Few previous studies have, however, focused on somatic health outcomes and studies rarely cover the life span until retirement age. The aims of the current study were, firstly, to examine the association between poor family relationships in adolescence and in-patient somatic care across the life course whilst adjusting for confounders at baseline and concurrent psychiatric in-patient care; and secondly, to compare the risks of somatic and psychiatric in-patient care across the life course.Methods: Prospective data from the Stockholm Birth Cohort study were used, with 2636 participants born in 1953 who were followed up until 2016. Information on family relationships was collected from the participants' mothers in 1968. Annual information on in-patient somatic and psychiatric care was retrieved from official register data from 1969 to 2016.Results: Poisson regressions showed that poor family relationships in adolescence were associated with an increased risk of in-patient somatic care in mid- and especially in late adulthood (ages 44-53 and 54-63 years), even when controlling for the co-occurrence of psychiatric illness and a range of childhood conditions. No statistically significant association was observed in early adulthood (ages 16-43 years), when controlling for confounders. These findings are in sharp contrast to the analyses of inpatient psychiatric care, according to which the association with poor family relations was strongest in early adulthood and thereafter attenuated across the life course.Conclusion: Poor family relationships in adolescence are associated with an increased risk of severe consequences for somatic health lasting to late adulthood even when controlling for confounders including in-patient psychiatric care, emphasising the potentially important role of early interventions.
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| 8. |
- Andersson, Arne, et al.
(author)
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Amyloid Deposition in Transplanted Human Pancreatic Islets : A Conceivable Cause of Their Long-Term Failure
- 2008
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In: EXPERIMENTAL DIABETES RESEARCH. - : Hindawi Limited. - 1687-5214 .- 1687-5303. ; 2008:562985
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Journal article (peer-reviewed)abstract
- Following the encouraging report of the Edmonton group, there was a rejuvenation of the islet transplantation field. After that, more pessimistic views spread when long-term results of the clinical outcome were published. A progressive loss of the beta-cell function meant that almost all patients were back on insulin therapy after 5 years. More than 10 years ago, we demonstrated that amyloid deposits rapidly formed in human islets and in mouse islets transgenic for human IAPP when grafted into nude mice. It is, therefore, conceivable to consider amyloid formation as one potential candidate for the long-term failure. The present paper reviews attempts in our laboratories to elucidate the dynamics of and mechanisms behind the formation of amyloid in transplanted islets with special emphasis on the impact of long-term hyperglycemia.
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| 9. |
- Bohman, Hannes, et al.
(author)
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Parental separation in childhood as a risk factor for depression in adulthood : a community-based study of adolescents screened for depression and followed up after 15 years
- 2017
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In: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 17
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Journal article (peer-reviewed)abstract
- BackgroundEarlier research has investigated the association between parental separation and long-term health outcomes among offspring, but few studies have assessed the potentially moderating role of mental health status in adolescence. The aim of this study was to analyze whether parental separation in childhood predicts depression in adulthood and whether the pattern differs between individuals with and without earlier depression.MethodsA community-based sample of individuals with adolescent depression in 1991–93 and matched non-depressed peers were followed up using a structured diagnostic interview after 15 years. The participation rate was 65% (depressed n = 227; non-depressed controls n = 155). Information on parental separation and conditions in childhood and adolescence was collected at baseline. The outcome was depression between the ages 19–31 years; information on depression was collected at the follow-up diagnostic interview. The statistical method used was binary logistic regression.ResultsOur analyses showed that depressed adolescents with separated parents had an excess risk of recurrence of depression in adulthood, compared with depressed adolescents with non-separated parents. In addition, among adolescents with depression, parental separation was associated with an increased risk of a switch to bipolar disorder in adulthood. Among the matched non-depressed peers, no associations between parental separation and adult depression or bipolar disorder were found.ConclusionsParental separation may have long-lasting health consequences for vulnerable individuals who suffer from mental illness already in adolescence.
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| 10. |
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