Modernization’s Doppelgänger

This is the author accepted manuscript. The final version is available from Cambridge University Press via http://dx.doi.org/10.1017/S147924431500041

Increasing plasma glucose before the development of type 1 diabetes-the TRIGR study

Objective: The beta-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. Research Design and Methods: A cohort of children (N = 2159) with an affected first-degree relative and increased HLA risk were recruited 2002-2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan-Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately. Results: A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp < 0.001) and the development of diabetes (p < 0.002 resp < 0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003). Conclusions: A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes.Peer reviewe

Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals : the TRIGR cohort

Aims/hypothesis Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not. Methods A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the first year of life and the development of autoantibodies or clinical type 1 diabetes was analysed using univariable and multivariable Cox regression models. As this study was exploratory, no adjustment was made for multiple comparisons. Results Adjusting for HLA, sex, breastfeeding duration and birth order, those who had seven or more infections during their first year of life were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.028, HR 9.166 [95% CI 1.277, 65.81]) compared with those who had no infections. Those who had their first viral infection aged between 6 and 12 months were less likely to develop at least one positive type 1 diabetes-related antibody (p=0.043, HR 0.828 [95% CI 0.690, 0.994]) or multiple antibodies (p=0.0351, HR 0.664 [95% CI 0.453, 0.972]). Those who had ever had an unspecified bacterial infection were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.013, HR 1.412 [95% CI 1.075, 1.854]), to develop multiple antibodies (p=0.037, HR 1.652 [95% CI 1.030, 2.649]) and to develop clinical type 1 diabetes (p=0.011, HR 2.066 [95% CI 1.182, 3.613]). Conclusions/interpretation We found weak support for the assumption that viral infections early in life may initiate the autoimmune process or later development of type 1 diabetes. In contrast, certain bacterial infections appeared to increase the risk of both multiple autoantibodies and clinical type 1 diabetes.Peer reviewe

Association between family history, early growth and the risk of beta cell autoimmunity in children at risk for type 1 diabetes

Aims/hypothesis The aim of this work was to examine the relationship between family history of type 1 diabetes, birthweight, growth during the first 2 years and development of multiple beta cell autoantibodies in children with a first-degree relative with type 1 diabetes and HLA-conferred disease susceptibility. Methods In a secondary analysis of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), clinical characteristics and development of beta cell autoantibodies were compared in relation to family history of type 1 diabetes (mother vs father vs sibling) in 2074 children from families with a single affected family member. Results Multiple autoantibodies (>= 2 of 5 measured) developed in 277 (13%) children: 107 (10%), 114 (16%) and 56 (18%) born with a mother, father or sibling with type 1 diabetes, respectively (p <0.001). The HR for time to multiple autoimmunity was 0.54 (95% CI 0.39, 0.75) in offspring of affected mothers (n = 107/1046,p <0.001) and 0.81 (95% CI 0.59, 1.11) (n = 114/722,p = 0.19) in offspring of affected fathers, compared with participants with a sibling with type 1 diabetes (comparator groupn = 56/306). The time to the first autoantibody present (to insulin, GAD, tyrosine phosphatase-related insulinoma-associated 2 molecules, islet cell or zinc transporter 8) was similar in the three groups. Height velocity (zscore/year) in the first 24 months was independently associated with developing multiple antibodies in the total cohort (HR 1.31 [95% CI 1.01, 1.70],p = 0.04). A higher birthweight in children born to an affected mother vs affected father or an affected sibling was not related to the risk of multiple autoimmunity. Conclusions/interpretation The risk of developing multiple autoantibodies was lower in children with maternal type 1 diabetes. For the whole group, this risk of developing multiple autoantibodies was independent of birthweight but was greater in those with increased height velocity during the first 2 years of life. However, the risk associated with paternal type 1 diabetes was not linked to differences in birthweight or early growth.Peer reviewe

Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD65. Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD65 autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD65, but not with control antigens, compared with placebo subjects. GAD65-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD65 enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD65-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD65 immunity

Association between family history, early growth and the risk of beta cell autoimmunity in children at risk for type 1 diabetes

Aims/hypothesisThe aim of this work was to examine the relationship between family history of type 1 diabetes, birthweight, growth during the first 2 years and development of multiple beta cell autoantibodies in children with a first-degree relative with type 1 diabetes and HLA-conferred disease susceptibility.MethodsIn a secondary analysis of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), clinical characteristics and development of beta cell autoantibodies were compared in relation to family history of type 1 diabetes (mother vs father vs sibling) in 2074 children from families with a single affected family member.ResultsMultiple autoantibodies (>= 2 of 5 measured) developed in 277 (13%) children: 107 (10%), 114 (16%) and 56 (18%) born with a mother, father or sibling with type 1 diabetes, respectively (p Conclusions/interpretationThe risk of developing multiple autoantibodies was lower in children with maternal type 1 diabetes. For the whole group, this risk of developing multiple autoantibodies was independent of birthweight but was greater in those with increased height velocity during the first 2 years of life. However, the risk associated with paternal type 1 diabetes was not linked to differences in birthweight or early growth.</div

IUP – konsekvenser för lärare i praktiken.

Abstract Arbetets titel: IUP – konsekvenser för lärare i praktiken. Arbetets art: Examensarbete om 10 poäng, 51-60 p, i det allmänna utbildningsområdet för lärarprogrammet. Författare Lukas Ludvigsson, Mikael Hansson Handledare Carl E Olivestam Tidpunkt Vårterminen 2006 Bakgrund Regeringens mål med IUP är att skolan i större utsträckning skall arbeta mot målen i läroplanen och kursplanerna. Anledningen till att IUP infördes var att regeringen ville nå en högre måloriente-ring, enligt läroplanen, i arbetet med eleverna. Syfte Vi har gjort en undersökning om vilka konsekvenser införandet av IUP har haft för lärare i undervisningen, baserat på deras egna åsikter. Vi har även undersökt vilka praktiska konsekvenser IUP har haft för lärarnas dagliga arbete, och vad de tycker om detta. Material och Metod Vår uppsats är baserad på material i form av litteratur om IUP, samt resultat från en undersökning. Som metod har vi valt att använda oss av en kvantitativ enkät genomförd med lärare som arbetar med IUP. Slutsatser Lärarna är i det stora hela positiva till införandet av IUP. Däremot anser de att det krävs mer tid för dem att arbeta med de individuella utvecklingsplanerna. Majoriteten av lärarna ansåg också att arbetsbelastningen har ökat jämfört med tidigare arbetssätt samt att arbetet med IUP kräver mer resurser än tidigare. En klar majoritet av lärarna anser också att införandet av IUP innebär en ökad kontakt med föräldrarna, vilket de tycker är positivt för elevernas utveckling

Materials for future power sources

Proton exchange membrane fuel cells and lithium polymer batteries are important as future power sources in electronic devices, vehicles and stationary applications. The development of these power sources involves finding and characterising materials that are well suited r the application. The materials investigated in this thesis are the perfluorosulphonic ionomer NafionTM (DuPont) and metal oxides incorporated into the membrane form of this material. The ionomer is used as polymer electrolyte in proton exchange membrane fuel cells (PEMFC) and the metal oxides are used as cathode materials in lithium polymer batters (LPB). Crystallinity in cast Nafion films can be introduced by ion beam exposure or aging. Spectroscopic investigations of the crystallinity of the ionomer indicate that the crystalline regions contain less water than amorphous regions and this could in part explain the drying out of the polymer electrolyte membrane in a PEMFC. Spectroscopic results on the equilibrated water uptake and the state of water in thin cast ionomer films indicate that there is a full proton transfer from the sulphonic acid group in the ionomer when there is one water molecule per sulphonate group. The LPB cathode materials, lithium manganese oxide and lithium cobalt oxide, were incorporated in situ in Nafion membranes. Other manganese oxides and cobalt oxides were incorporated in situ inside the membrane. Ion-exchange experiments from HcoO2 to LiCoO2 within the membrane were also successful. Fourier transform infrared spectroscopy, Raman spectroscopy and X-ray diffraction were used for the characterisation of the incorporated species and the Nafion film/membrane

Subsyndromal Depression in Very Old Persons

Bakgrund: Subsyndromal depression (SSD) eller subklinisk depression är ett vanligt affektivt tillstånd som kan beskrivas som depressivitet under gränsen för vad som kallas syndromal eller egentlig depressiv episod. Förekomsten av SSD har rapporterats vara ungefär 10 % i populationen, eller ungefär 2-3 gånger högre än förekomsten av syndromal depression. SSD jämfört med icke-depression (ND) är associerat med en lägre aktivitetsförmåga (ADL, Activities of Daily Living), lägre kognitiv funktion, lägre subjektiv hälsa, sämre psykiska utfall och en högre dödlighet. Emellertid har flertalet studier om SSD hos äldre gjorts i åldersgruppen yngre äldre (60-80 års ålder), medan få studier har undersökt SSD hos äldre äldre personer (80+ års ålder). Eftersom många aspekter (t ex multisjukdom, skörhet, funktionsförmågor och socialt beroende) generellt förändras mellan yngre äldre och äldre äldre åldrar, så finns det ett behov av ökad kunskap om SSD hos äldre äldre. Syftet med denna avhandling var att beskriva SSD, eller det komplexa området mellan syndromal depression och normalt åldrande, hos äldre äldre personer. Metod: studie 1 baserades på kvalitativa intervjuer (n=27), medan studier 2-4 till stor del baserades på data från en prospektiv observationsstudie av en kohort, ”Elderly in Linköping Screening Assessment” (ELSA85). ELSA85 hade en populationsbaserad design där man följde personer från 85 års ålder i tre uppföljande mätvågor. Depressivitet mättes med 15- frågeversionen av Geriatric Depression Scale (GDS-15), som också användes för att definiera SSD i studierna. Resultat: Analysen av de kvalitativa intervjuerna (studie 1) resulterade i fyra teman (livet går ned och kroppen sviktar, att klara sig själv, att hänga med, och att ta en dag i taget), vilka tillsammans gav en helhetsbild av SSD i de högsta åldrarna. I en jämförelse mellan SSD, ND och syndromal depression, så skiljde sig SSD kvalitativt från syndromal depression, men däremot inte tydligt från ND. En tvärsnittsanalys av data från baslinjen av studien (studie 2) identifierade associerade faktorer till SSD bland äldre äldre personer, och enligt analysen med multipel logistisk respektive linjär regression så var det fyra domäner (sociodemografiska faktorer, sviktande fysisk funktion, neuropsykiatriska faktorer och existentiella faktorer) som var signifikant associerade med SSD. I en fem års longitudinell uppföljning (studie 3) visades att direkta hälso- och sjukvårdskostnader per överlevnadsmånad och person var förhöjd hos personer med SSD jämfört med ND med ett storleksförhållande 1.45 (€634 vs €436), vilket var en signifikant skillnad även när man kontrollerade för somatisk multisjukdom. I en åtta års longitudinell uppföljning visades att dödligheten var förhöjd (dödsintensitet eller Hazard ratio (HR))=1.33) för personer med SSD jämfört med ND, liksom sjuklighet avseende personlig ADL (P-ADL), instrumentell ADL (IADL), ensamhet, subjektiv hälsa, och depressivitet. Däremot var inte kognitiv snabbhet, exekutiva funktioner eller global kognitiv funktion signifikant försämrade när man hade kontrollerat för relevanta variabler. Slutsatser: SSD hos äldre äldre personer ser olika ut hos olika personer, och personal i hälso- och sjukvården bör vara uppmärksamma på även andra depressiva tecken förutom de klassiska symtomen i diagnosregistren. SSD hos äldre äldre är associerat med förhöjda sjukvårdskostnader, förhöjd sjuklighet och dödlighet. Med tanke på den höga förekomsten av SSD och den demografiska utvecklingen med ökande antal äldre äldre personer i samhället, så indikerar fynden behovet av att utveckla kliniska och samhälleliga strategier för att förebygga SSD och associerade negativa utfall

Begreppet arbetsförmåga : en litteraturgenomgång

Begreppet arbetsförmåga har en mycket central betydelse i sjukförsäkringssammanhang. I studien undersöks hur begreppet används i den vetenskapligt publicerade litteraturen. En omfattande litteratursökning följdes av en kvalitativ analys av det funna materialet. Tre grunddimensioner av begreppet arbetsförmåga identifieras och beskrivs: en fysisk, en psykisk och en social. Vidare analyseras begreppets karaktär av relationsbegrepp och visas på att olika förekommande sätt att mäta arbetsförmåga behövs. En konklusion är att litteraturens definitioner och operationaliseringar av begreppet arbetsförmåga ofta är fragmentariska eller oprecisa. Behovet av tydligare definitioner, inte minst med avseende på behovet att kunna bedöma och mäta arbetsförmåga, är stort