A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants in Relation to Risk of Type 1 Diabetes

Background The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes. Methodology/ Principal Findings The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p′-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p′-DDE (OR 0.56, 95% CI 0.29, 1.08). Conclusions The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes.

[1]  L. Nyström,et al.  Epidemiology of diabetes mellitus in Sweden. Results of the first year of a prospective study in the population age group 15-34 years. , 2009, Acta medica Scandinavica.

[2]  E. Budtz-Jørgensen,et al.  Elimination half-lives of polychlorinated biphenyl congeners in children. , 2008, Environmental science & technology.

[3]  Å. Lernmark,et al.  Maternal Enterovirus Infection during Pregnancy as a Risk Factor in Offspring Diagnosed with Type 1 Diabetes between 15 and 30 Years of Age , 2008, Experimental diabetes research.

[4]  I. Hertz-Picciotto,et al.  Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development. , 2008, Basic & clinical pharmacology & toxicology.

[5]  L. Costa.  Contaminants in Fish: Risk-Benefit Considerations , 2007, Arhiv za higijenu rada i toksikologiju.

[6]  A. Glynn,et al.  Dietary intake estimations of organohalogen contaminants (dioxins, PCB, PBDE and chlorinated pesticides, e.g. DDT) based on Swedish market basket data. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[7]  W. Hanneman,et al.  Disruption of estrogen-regulated gene expression by dioxin: downregulation of a gene associated with the onset of non-insulin-dependent diabetes mellitus (type 2 diabetes) , 2004, Human & experimental toxicology.

[8]  P. Bingley,et al.  The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes , 2004, The Lancet.

[9]  G. Eisenbarth,et al.  Immunopathogenesis and immunotherapeutic approaches to type 1A diabetes , 2004, Expert opinion on biological therapy.

[10]  L. Hagmar,et al.  Exposure to CB-153 and p,p'-DDE and male reproductive function. , 2004, Human reproduction.

[11]  C. Trautwein,et al.  Dioxin Increases C/EBPβ Transcription by Activating cAMP/Protein Kinase A* , 2004, Journal of Biological Chemistry.

[12]  L. C. Stene,et al.  Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. , 2003, The American journal of clinical nutrition.

[13]  E. Gale.  The rise of childhood type 1 diabetes in the 20th century. , 2002, Diabetes.

[14]  N. Bunce,et al.  Linking dioxins to diabetes: epidemiology and biologic plausibility. , 2002, Environmental health perspectives.

[15]  J. Ilonen,et al.  Estimation of genetic risk for type 1 diabetes. , 2002, American journal of medical genetics.

[16]  S. Smith.  Peroxisome proliferator-activated receptors and the regulation of mammalian lipid metabolism. , 2001, Biochemical Society transactions.

[17]  M. Longnecker,et al.  Environmental contaminants as etiologic factors for diabetes. , 2001, Environmental health perspectives.

[18]  A. Green,et al.  Trends in the incidence of childhood-onset diabetes in Europe 1989–1998 , 2001, Diabetologia.

[19]  H. Adami,et al.  Serum concentrations of organochlorines in men: a search for markers of exposure. , 2000, The Science of the total environment.

[20]  L. Hagmar,et al.  Influence of the consumption of fatty Baltic Sea fish on plasma levels of halogenated environmental contaminants in Latvian and Swedish men , 2000 .

[21]  C. Beaufort.  Variation and trends in incidence of childhood diabetes in Europe , 2000, The Lancet.

[22]  J. Tuomilehto,et al.  Worldwide increase in incidence of Type I diabetes – the analysis of the data on published incidence trends , 1999, Diabetologia.

[23]  G. Dahlquist,et al.  Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group. , 1999, Diabetes care.

[24]  S. Holladay.  Prenatal immunotoxicant exposure and postnatal autoimmune disease. , 1999, Environmental health perspectives.

[25]  J. Tuomilehto,et al.  Record-high incidence of Type I (insulin-dependent) diabetes mellitus in Finnish children , 1999, Diabetologia.

[26]  P. Bingley,et al.  Rising incidence of insulin dependent diabetes in children aged under 5 years in the Oxford region: time trend analysis , 1997, BMJ.

[27]  L. Hagmar,et al.  Monitoring of Polychlorinated Biphenyls in Human Blood Plasma: Methodological Developments and Influence of Age, Lactation, and Fish Consumption , 1997, Archives of environmental contamination and toxicology.

[28]  G. Dahlquist,et al.  Maternal Enteroviral Infection During Pregnancy as a Risk Factor for ChildHood IDDM: A Population-Based Case-Control Study , 1995, Diabetes.

[29]  F. Matsumura,et al.  2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced changes in glucose transporting activity in guinea pigs, mice, and rats in vivo and in vitro. , 1994, Journal of biochemical toxicology.

[30]  A. Staines,et al.  Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population. , 1992, BMJ.

[31]  F. Matsumura,et al.  Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on serum insulin and glucose levels in the rabbit. , 1988, Journal of environmental science and health. Part. B, Pesticides, food contaminants, and agricultural wastes.

[32]  P Rubinstein,et al.  Diabetes mellitus and autoimmunity in patients with the congenital rubella syndrome. , 1985, Reviews of infectious diseases.

[33]  J. Stockman,et al.  Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study , 2011 .

[34]  Y. Chong,et al.  Exposure to persistent organic pollutants in utero and related maternal characteristics on birth outcomes: a multivariate data analysis approach. , 2009, Chemosphere.

[35]  J. Stockman.  The Rising Incidence of Childhood Type 1 Diabetes and Reduced Contribution of High-Risk HLA Haplotypes , 2006 .

[36]  L. Hagmar,et al.  Environmental Health: a Global Access Science Source Inter-population Variations in Concentrations, Determinants of and Correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (cb-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-dde): a Cross-sectional Study of 3161 Men and Women from In , 2022 .