Associations between persistent organic pollutants and type 1 diabetes in youth.

Adolescent Case-Control Studies Child Diabetes Mellitus, Type 1 / epidemiology Dichlorodiphenyl Dichloroethylene Environmental Pollutants / adverse effects Glucose Humans Hydrocarbons, Chlorinated / analysis Insulin Insulin Resistance Persistent Organic Pollutants Pesticides Polychlorinated Biphenyls RNA, Messenger

Organochlorine Pesticides Persistent Organic Pollutants Polychlorinated Biphenyls Type 1 Diabetes Youths

Journal

Environment international

ISSN: 1873-6750

Titre abrégé: Environ Int

Pays: Netherlands

ID NLM: 7807270

Informations de publication

Date de publication:
05 2022

Historique:

received: 26 11 2021

revised: 08 02 2022

accepted: 07 03 2022

pubmed: 19 3 2022

medline: 27 4 2022

entrez: 18 3 2022

Statut: ppublish

Résumé

Diabetes affects millions of people worldwide with a continued increase in incidence occurring within the pediatric population. The potential contribution of persistent organic pollutants (POPs) to diabetes in youth remains poorly known, especially regarding type 1 diabetes (T1D), generally the most prevalent form of diabetes in youth. We investigated the associations between POPs and T1D in youth and studied the impacts of POPs on pancreatic β-cell function and viability in vitro. We used data and plasma samples from the SEARCH for Diabetes in Youth Case Control Study (SEARCH-CC). Participants were categorized as Controls, T1D with normal insulin sensitivity (T1D/IS), and T1D with insulin resistance (T1D/IR). We assessed plasma concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides and estimated the odds of T1D through multivariable logistic regression. In addition, we performed in vitro experiments with the INS-1E pancreatic β-cells. Cells were treated with PCB-153 or p,p'-DDE at environmentally relevant doses. We measured insulin production and secretion and assessed the mRNA expression of key regulators involved in insulin synthesis (Ins1, Ins2, Pdx1, Mafa, Pcsk1/3, and Pcsk2), glucose sensing (Slc2a2 and Gck), and insulin secretion (Abcc8, Kcnj11, Cacna1d, Cacna1b, Stx1a, Snap25, and Sytl4). Finally, we assessed the effects of PCB-153 and p,p'-DDE on β-cell viability. Among 442 youths, 112 were controls, 182 were classified with T1D/IS and 148 with T1D/IR. The odds ratios (OR) of T1D/IS versus controls were statistically significant for p,p'-DDE (OR 2.0, 95% confidence interval (CI) 1.0, 3.8 and 2.4, 95% CI 1.2, 5.0 for 2nd and 3rd tertiles, respectively), trans-nonachlor (OR 2.5, 95% CI 1.3, 5.0 and OR 2.3, 95% CI 1.1, 5.1 for 2nd and 3rd tertiles, respectively), and PCB-153 (OR 2.3, 95% CI 1.1, 4.6 for 3rd tertile). However, these associations were not observed in participants with T1D/IR. At an experimental level, treatment with p,p'-DDE or PCB-153, at concentrations ranging from 1 × 10 These results support a potential role of POPs in T1D etiology and demonstrate a high sensitivity of pancreatic β-cells to POPs.

Sections du résumé

BACKGROUND

OBJECTIVES

We investigated the associations between POPs and T1D in youth and studied the impacts of POPs on pancreatic β-cell function and viability in vitro.

METHODS

We used data and plasma samples from the SEARCH for Diabetes in Youth Case Control Study (SEARCH-CC). Participants were categorized as Controls, T1D with normal insulin sensitivity (T1D/IS), and T1D with insulin resistance (T1D/IR). We assessed plasma concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides and estimated the odds of T1D through multivariable logistic regression. In addition, we performed in vitro experiments with the INS-1E pancreatic β-cells. Cells were treated with PCB-153 or p,p'-DDE at environmentally relevant doses. We measured insulin production and secretion and assessed the mRNA expression of key regulators involved in insulin synthesis (Ins1, Ins2, Pdx1, Mafa, Pcsk1/3, and Pcsk2), glucose sensing (Slc2a2 and Gck), and insulin secretion (Abcc8, Kcnj11, Cacna1d, Cacna1b, Stx1a, Snap25, and Sytl4). Finally, we assessed the effects of PCB-153 and p,p'-DDE on β-cell viability.

RESULTS

Among 442 youths, 112 were controls, 182 were classified with T1D/IS and 148 with T1D/IR. The odds ratios (OR) of T1D/IS versus controls were statistically significant for p,p'-DDE (OR 2.0, 95% confidence interval (CI) 1.0, 3.8 and 2.4, 95% CI 1.2, 5.0 for 2nd and 3rd tertiles, respectively), trans-nonachlor (OR 2.5, 95% CI 1.3, 5.0 and OR 2.3, 95% CI 1.1, 5.1 for 2nd and 3rd tertiles, respectively), and PCB-153 (OR 2.3, 95% CI 1.1, 4.6 for 3rd tertile). However, these associations were not observed in participants with T1D/IR. At an experimental level, treatment with p,p'-DDE or PCB-153, at concentrations ranging from 1 × 10

CONCLUSION

These results support a potential role of POPs in T1D etiology and demonstrate a high sensitivity of pancreatic β-cells to POPs.

Identifiants

DOI: 10.1016/j.envint.2022.107175 PMID: 35303528

pubmed: 35303528

pii: S0160-4120(22)00101-5

doi: 10.1016/j.envint.2022.107175

pii:

doi:

Substances chimiques

Environmental Pollutants 0

Hydrocarbons, Chlorinated 0

Insulin 0

Pesticides 0

RNA, Messenger 0

Dichlorodiphenyl Dichloroethylene 4M7FS82U08

Polychlorinated Biphenyls DFC2HB4I0K

Glucose IY9XDZ35W2

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng