Article

Childhood vaccination and type 1 diabetes.

Danish Epidemiology Science Centre, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
New England Journal of Medicine (Impact Factor: 54.42). 05/2004; 350(14):1398-404. DOI: 10.1056/NEJMoa032665
Source: PubMed

ABSTRACT A link between childhood vaccinations and the development of type 1 diabetes has been proposed.
We evaluated a cohort comprising all children born in Denmark from January 1, 1990, through December 31, 2000, for whom detailed information on vaccinations and type 1 diabetes was available. Using Poisson regression models, we estimated rate ratios according to vaccination status, including the trend associated with the number of doses, among all children and in a subgroup of children who had siblings with type 1 diabetes. Given recent claims of clustering of cases of diabetes two to four years after vaccination, we also estimated rate ratios during the period after vaccination.
Type 1 diabetes was diagnosed in 681 children during 4,720,517 person-years of follow-up. The rate ratio for type 1 diabetes among children who received at least one dose of vaccine, as compared with unvaccinated children, was 0.91 (95 percent confidence interval, 0.74 to 1.12) for Haemophilus influenzae type b vaccine; 1.02 (95 percent confidence interval, 0.75 to 1.37) for diphtheria, tetanus, and inactivated poliovirus vaccine; 0.96 (95 percent confidence interval, 0.71 to 1.30) for diphtheria, tetanus, acellular pertussis, and inactivated poliovirus vaccine; 1.06 (95 percent confidence interval, 0.80 to 1.40) for whole-cell pertussis vaccine; 1.14 (95 percent confidence interval, 0.90 to 1.45) for measles, mumps, and rubella vaccine; and 1.08 (95 percent confidence interval, 0.74 to 1.57) for oral poliovirus vaccine. The development of type 1 diabetes in genetically predisposed children (defined as those who had siblings with type 1 diabetes) was not significantly associated with vaccination. Furthermore, there was no evidence of any clustering of cases two to four years after vaccination with any vaccine.
These results do not support a causal relation between childhood vaccination and type 1 diabetes.

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Although the majority of the sibling pairs with T1D were discordant for DN, its presence in one sibling doubles and presence of ESRD triples the risk of DN in the other diabetic sibling. An encouraging observation was that although the proportion of children to be diagnosed with T1D at the age of 4 or under is increasing, they seem to have a decreased risk of DN or at least delayed onset. Väitöstyön tarkoituksena oli tutkia tyypin 1 diabeteksen (T1D) sekä diabeettisen nefropatian (DN) kasautumista perheissä. Ensimmäisen osatyön tavoitteena oli tutkia monotsygoottisten että ditsygoottisten kaksosten konkordanssia T1D:n suhteen sekä määrittää geneettisten tekijöiden ja ympäristötekijöiden suhteellista osuutta T1D:n synnyssä. Toisen osatyön tarkoitus oli määrittää T1D:sta sairastavien sisarusten kumulatiivinen sairastumisriski T1D:een pitkän seuranta-ajan kuluessa. Tavoitteena oli myös selvittää riskiin vaikuttavia tekijöitä, erityisesti indeksipotilaan (probandin) sairastumisiän vaikutusta sekä eri syntymäkohorttien välisiä eroja. Kolmannen osatyön päämääränä oli tutkia, onko perheen toisella diabeetikkosisaruksella kohonnut riski sairastua diabeettiseen nefropatiaan, jos aiemmin sairastuneella sisaruksella on jo todettu tämä tauti. Tarkoituksena oli myös selvittää, vaikuttaako diabeettisen nefropatian vaikeusaste (dialyysi ja munuaisensiirto) sisarusriskiin sekä sitä, onko diabetekseen sairastumisiällä vaikutusta nefropatiariskiin. Viimeisessä osatyön tarkoitus oli tutkia T1D:ta sairastavien henkilöiden lasten diabetesriskiä longitudinaalisesti ja sitä, eroaako diabeetikkomiesten ja -naisten lasten diabetesriski. Lisäksi tutkittiin, vaikuttaako diabeetikkovanhemman sairastumisikä lapsen riskiin ja erityisesti, onko sairastumisiän vaikutus samanlainen sekä diabeetikkomiesten että diabeetikkonaisten lapsilla. Myös lasten syntymäkohortin vaikutusta tutkittiin. Kolme laajaa, väestöpohjaista aineistoa oli käytössä. Ensimmäinen aineisto sisälsi kaikki Suomessa vuosina 1958-86 syntyneet kaksosparit (nuorten kaksosten kohortti, n=22646 paria)). Toinen aineisto koostui vuosina 1965-79 T1D:een alle 18-vuotiaina sairastuneista diabeetikoista (n=5144) ja heidän sisaruksistaan (n=10168) ja kolmas aineisto koostui em. diabeetikoista ja heidän lapsistaan (n=5291). Monotsygoottisista kaksospareista 27.3 % oli konkordantteja T1D:n suhteen (molemmilla T1D), kun taas ditsygoottisista kaksospareista vain 3.8 %. Rakenneyhtälömallituksessa parhaiten sopiva malli selitti sairastumiseen liittyvää vaihtelua sekä geneettisin että yksilöllisin ympäristötekijöin ja heritabiliteetin estimaatiksi saatiin 88 %. Identtiset kaksoset sairastuivat hyvin samanikäisinä. Pisin sairastumisväli identtisillä konkordanteilla pareilla oli 6.9 vuotta. 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