Associations between persistent organic pollutants and type 1 diabetes in youth

Details

• Alternative Title:
  Environ Int
• Personal Author:
  Bresson, Sophie E. ; Isom, Scott ; Jensen, Elizabeth T. ; Huber, Sandra ; Oulhote, Youssef ; Rigdon, Joseph ; Lovato, James ; Liese, Angela D. ; Pihoker, Catherine ; Dabelea, Dana ; Ehrlich, Shelley ; Ruzzin, Jérôme
• Description:
  Background:
  
  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.
  
  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 × 10−15 M to 5 × 10−6 M, impaired the ability of pancreatic β-cells to produce and secrete insulin in response to glucose. These failures were paralleled by impaired Ins1 and Ins2 mRNA expression. In addition, among different targeted genes, PCB-153 significantly reduced Slc2a2 and Gck mRNA expression whereas p,p’-DDE mainly affected Abcc8 and Kcnj11. While treatment with PCB-153 or p,p’-DDE for 2 days did not affect β-cell viability, longer treatment progressively killed the β-cells.
  
  Conclusion:
  
  These results support a potential role of POPs in T1D etiology and demonstrate a high sensitivity of pancreatic β-cells to POPs.
  
  
• Subjects:
  Adolescent Case-Control Studies Child Diabetes Mellitus, Type 1 Dichlorodiphenyl Dichloroethylene Environmental Pollutants Glucose Humans Hydrocarbons, Chlorinated Insulin Insulin Resistance Persistent Organic Pollutants Pesticides Polychlorinated Biphenyls RNA, Messenger

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• Keywords:
  Organochlorine Pesticides Type 1 Diabetes Youths
• Source:
  Environ Int. 163:107175
• Pubmed ID:
  35303528
• Pubmed Central ID:
  PMC11696922
• Document Type:
  Journal Article
• Funding:
  UC4 DK108173/DK/NIDDK NIH HHSUnited States/ ; U18 DP002710/DP/NCCDPHP CDC HHSUnited States/ ; U18 DP006134/DP/NCCDPHP CDC HHSUnited States/ ; U18 DP006138/DP/NCCDPHP CDC HHSUnited States/ ; UL1 TR000154/TR/NCATS NIH HHSUnited States/ ; U18 DP002714/DP/NCCDPHP CDC HHSUnited States/ ; U01 DP000248/DP/NCCDPHP CDC HHSUnited States/ ; U01 DP000244/DP/NCCDPHP CDC HHSUnited States/ ; UL1 TR000062/TR/NCATS NIH HHSUnited States/ ; EP-C-15-002/EPA/EPAUnited States/ ; UL1 TR001425/TR/NCATS NIH HHSUnited States/ ; U01 DP000250/DP/NCCDPHP CDC HHSUnited States/ ; U18 DP002708/DP/NCCDPHP CDC HHSUnited States/ ; P30 DK057516/DK/NIDDK NIH HHSUnited States/ ; HIR 10-001/HX/HSRD VAUnited States/ ; U01 DP000247/DP/NCCDPHP CDC HHSUnited States/ ; U18 DP006131/DP/NCCDPHP CDC HHSUnited States/ ; U18 DP006136/DP/NCCDPHP CDC HHSUnited States/ ; U18 DP002709/DP/NCCDPHP CDC HHSUnited States/ ; U18 DP006133/DP/NCCDPHP CDC HHSUnited States/ ; U18 DP006139/DP/NCCDPHP CDC HHSUnited States/ ; UL1 TR000077/TR/NCATS NIH HHSUnited States/ ; R01 DK127208/DK/NIDDK NIH HHSUnited States/ ; UL1 TR000423/TR/NCATS NIH HHSUnited States/ ; U01 DP000246/DP/NCCDPHP CDC HHSUnited States/ ; U01 DP000254/DP/NCCDPHP CDC HHSUnited States/
• Volume:
  163
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:4f1370991708c4fdfe3557403b0a2e018ba5407b7ef04d0c972ad9403be6071a6d597511f9e67797d64dbbb8709cb7009be6603dbd8aabea4d246add86de5e71
• Download URL:
  https://stacks.cdc.gov/view/cdc/175280/cdc_175280_DS1.pdf
• File Type:
  [PDF - 1.22 MB ]