Table 1

Prospective studies documenting associations between EDC exposure and diabetes risk

ReferencePopulationOutcome and comparisonEffect estimate (95% CI)
PCBs
 Vasiliu et al., 2006 (21)1,384 subjects without diabetes in the Michigan polybrominated biphenyls cohort followed for 25 yearsIncident diabetes in women with the highest vs. lowest serum PCB levelsIDR: 2.33 (1.25–4.34)*
 Wang et al., 2008 (22)378 subjects and 370 matched referents from the Yucheng poisoning in Taiwan in the 1970sIncident diabetes in women who consumed rice bran oil laced with PCBs as well as a subgroup who developed chloracne, a manifestation of dioxin-like PCB exposureOR: 2.1 (1.1–4.5)*; Chloracne OR: 5.5 (2.1–13.4)*
 Turyk et al., 2009 (27)471 Great Lakes sport fish consumers without diabetes followed from 1994/1995 to 2005Incident diabetes among the highest vs. lowest tertile of PCB levelsTotal PCBs IRR: 1.8 (0.6–5.0); PCB 118 IRR: 1.3 (0.5–3.0)
 Wu et al., 2013 (23)Two case-control studies of women without diabetes from the NHS and a meta-analysis of pooled data with six additional prospective studiesIncident diabetes after pooling of data and comparing highest PCB exposure group with the referentPooled OR: 1.70 (1.28–2.27)*
 Rignell-Hydbom et al., 2009 (26)Case-control study of women age 50–59 years in southern SwedenIncident diabetes in 39 patients and matched control subjects after ≥6 years of follow-up comparing the highest quartile of PCB levels with the referentOR: 1.6 (0.61–4.0)
 Lee et al., 2010 (25)90 patients and control subjects in a nested case-control study followed for ∼18 yearsIncident diabetes comparing second sextile or quartile with the referent for a summary measure of 16 POPs, including 12 PCBs as well as individual PCBsPCB sum OR: 5.3*; PCB 187 OR: 2.8 (1.1–7.4)*
 Lee et al., 2011 (24)725 participants from the PIVUS studyIncident diabetes comparing a summary measure of 14 PCBs across quintiles with the referentQuintile 2 OR: 4.5 (0.9–23.5); Quintile 3 OR: 5.1 (1.0–26.0); Quintile 4 OR: 8.8 (1.8–42.7)*; Quintile 5 OR: 7.5 (1.4–38.8)*; Ptrend < 0.01
 Song et al., 2016 (29)Meta-analysis of 13 cross-sectional and 8 prospective studies published before 8 March 2014 examining links between PCBs and diabetes riskPooled diabetes risk in the highest vs. lowest exposure groups for PCBsRR: 2.39 (1.86–3.08)*
OC pesticides
 Wu et al., 2013 (23)Two case-control studies of women without diabetes from the NHS and a meta-analysis of pooled data with six additional prospective studiesIncident diabetes comparing highest tertile of plasma HCB levels in NHS and highest to lowest exposure group in pooled prospective studiesNHS OR: 3.14 (1.28–7.67)*; Pooled OR: 2.00 (1.13–3.53)*
 Turyk et al., 2009 (27)471 Great Lakes sport fish consumers without diabetes followed from 1994/1995 to 2005Incident diabetes comparing tertiles of serum DDE levels with the referentTertile 2 IRR: 5.5 (1.2–25.1)*; Tertile 3 IRR: 7.1 (1.6–31.9)*
 Rignell-Hydbom et al., 2009 (26)Case-control study of women age 50–59 years in southern SwedenIncident diabetes in 39 patients and matched control subjects after ≥6 years of follow-up comparing the highest quartile of DDE levels with the referentOR: 5.5 (1.2–25)*
 Lee et al., 2010 (25)90 patients and control subjects in a nested case-control study followed for ∼18 yearsIncident diabetes comparing second sextile with the referent for summary measure of 16 POPs (including 3 OC pesticides) or second quartile with the referent for trans-nonachlorSum OR: 5.4 (1.6–18.4)*; Trans-nonachlor OR: 4.3 (1.5–12.6)*
 Lee et al., 2011 (24)725 participants from the PIVUS studyIncident diabetes comparing quintiles of OC pesticides or summary measure of three OC pesticides with the referentQuintile 5 sum OC pesticides OR: 3.4 (1.0–11.7); Ptrend = 0.03; Quintile 4 trans-nonachlor OR: 4.2 (1.3–13.3)*; Ptrend = 0.03
 Van Larebeke et al., 2015 (28)973 participants of the Flemish Environment and Health SurveyRisk of incident diabetes calculated for a doubling of serum or comparing 90th percentile with 10th percentile of levels for HCB (men and women) or DDE (men only)Doubled HCB OR: 1.61 (1.07–2.42)*; 90th vs. 10th percentile HCB OR: 6.27*; Doubled DDE OR: 1.66 (1.09–2.53)*; 90th vs. 10th percentile DDE OR: 5.39*
 Starling et al., 2014 (35)13,637 women from the Agricultural Health StudyIncident diabetes for ever use of the OC pesticide dieldrinHR: 1.99 (1.12–3.54)*
 Song et al., 2016 (29)Meta-analysis of 11 cross-sectional and 6 prospective studies published before 8 March 2014 examining links among various pesticides and diabetes riskPooled diabetes risk in the highest vs. lowest exposure groups for pesticidesRR: 2.30 (1.81–2.93)*
Chemical constituents of air pollution
 Brook et al., 2016 (41)65 adults with metabolic syndrome and insulin resistance from the Air Pollution and Cardiometabolic Diseases China StudyChange in HOMA-IR per SD increase in personal-level black carbon or PM2.5 exposure during the fourth and fifth days of assessmentDay 4 black carbon: 0.18 (0.01–0.36)*; Day 5 black carbon: 0.22 (0.04–0.39)*; Day 4 PM2.5: 0.18 (0.02–0.34)*; Day 5 pm2.5: 0.22 (0.08–0.36)*
 Weinmayr et al., 2015 (43)3,607 individuals from the Heinz Nixdorf Recall Study in Germany followed for an average of 5.1 yearsIncident diabetes relative IQR increase in PM10, PM2.5, traffic-specific PM10, and traffic-specific PM2.5 as well as comparison of living <100 m vs. 200 m from a busy roadPM10 RR: 1.20 (1.01–1.42)*; PM2.5 RR: 1.08 (0.89–1.29); Traffic PM10 RR: 1.11 (0.99–1.23); Traffic PM2.5 RR: 1.10 (0.99–1.23); <100 m RR: 1.37 (1.04–1.81)*
 To et al., 2015 (93)29,549 women from the Canadian National Breast Screening StudyChange in diabetes prevalence per 10 μg/m3 increase in PM2.5 exposurePRR: 1.28 (1.16–1.41)*
 Park et al., 2015 (46)5,839 subjects in the Multi-Ethnic Study of Atherosclerosis cohortPrevalent and incident diabetes risk per IQR increase in residential concentrations of PM2.5 or NOxPrevalent DM PM2.5 OR: 1.09 (1.00–1.17)*; Prevalent DM NOx OR: 1.18 (1.01–1.38)*; Incident DM PM2.5 HR: 1.02 (0.95–1.10); Incident DM NOx HR: 1.00 (0.86–1.16)
 Pope et al., 2015 (48)669,046 participants from the American Cancer Society Cancer Prevention Study IIRisk of diabetes-associated death on death certificates per 10 μg/m3 increase in PM2.5HR: 1.13 (1.02–1.26)*
 Brook et al., 2013 (49)2.1 million adults from the 1991 Canadian Census Mortality Follow-up StudyDiabetes-associated mortality per 10 μ/m3 increase in PM2.5HR: 1.49 (1.37–1.62)*
 Thiering et al., 2013 (42)Fasting blood from 397 10-year-old children in two prospective German birth cohort studiesChange in HOMA-IR per 2-SD increase in ambient NO2 and PM10 and for every 500 m to nearest major roadNO2: 17.0% (5.0–30.3%)*; PM10: 18.7% (2.9–36.9%)*; Road proximity: 7.2% (0.8–14.0%)*
 Coogan et al., 2012 (44)3,992 black women living in Los Angeles followed for 10 yearsIncident diabetes per IQR increase in NOx or 10 μg/m3 increase in PM2.5NOx IRR: 1.25 (1.07–1.46)*; PM2.5 IRR: 1.63 (0.78–3.44)
 Coogan et al., 2016 (47)43,003 participants in the Black Women’s Health Study followed from 1995 to 2011Incident diabetes per IQR increase in NO2 by using both land use repression and dispersion modelsLand use HR: 0.96 (0.88–1.06); Dispersion HR: 0.94 (0.80–1.10)
 Krämer et al., 2010 (45)1,775 women without diabetes age 54–55 followed for 16 years in West GermanyIncident diabetes per IQR increase in exposure on the basis of data from monitoring stations, emission inventories, or land use regression models as well as distance from busy road (<100 m) relative to education statusMonitored PM10 HR: 1.16 (0.81–1.65); Monitored NO2 HR: 1.34 (1.02–1.76)*; Inventory traffic PM HR: 1.15 (1.04–1.27)*; Inventory traffic NO2 HR: 1.15 (1.04–1.27)*; Land use soot HR: 1.27 (1.09–1.48)*; Land use NO2 HR: 1.42 (1.16–1.73)*; <100 m/low education HR: 2.54 (1.31–4.91)*; <100 m/high education HR: 0.92 (0.58–1.47)
 Schneider et al., 2008 (50)22 people with type 2 diabetes living in North CarolinaChanges in vascular parameters per 10 μ/m3 increase in PM2.5 accounting for lag period (in days)Lag 0 FMD: −17.3 (−34.6 to 0.0)*; Lag 1 SAEI: −17.0 (−27.5 to −6.4)*; Lag 3 SAEI: −15.1 (−29.3 to −0.9)*
 O’Donnell et al., 2011 (51)9,202 patients hospitalized with ischemic strokeRisk of ischemic stroke among patients with diabetes per 10 μg/m3 increase in PM2.511% (1–22%)*
 Brook et al., 2013 (40)25 healthy adults from rural Michigan brought to an urban location for 5 consecutive daysChange in HOMA-IR per 10 μg/m3 increase in PM2.50.7 (0.1–1.3)*
BPA
 Sun et al., 2014 (60)971 incident type 2 diabetes case-control pairs from the NHS and NHS IIIncident diabetes after adjusting for BMI comparing highest with the referent quartile of urinary BPA levelsNHS OR: 0.81 (0.48–1.38); NHS II OR: 2.08 (1.17–3.69)*
 Bi et al., 2016 (61)2,209 middle-aged and elderly subjects without diabetes followed for 4 yearsIncident diabetes risk in highest quartile vs. lowest quartile of urinary BPA level for each 10-point increase in a diabetes genetic risk scoreOR: 1.89 (1.31–2.72)*
 Hu et al., 2015 (62)121 patients with type 2 diabetes followed for 6 yearsIncident chronic kidney disease in patients with diabetes comparing highest with referent tertile of urinary BPA levelOR: 6.65 (1.47–30.04)*
 Song et al., 2016 (29)Meta-analysis of five cross-sectional and prospective studies published before 8 March 2014 examining links between BPA and diabetes riskPooled diabetes risk in the highest vs. lowest exposure groups for BPARR: 1.45 (1.13–1.87)*
Phthalates
 Sun et al., 2014 (60)971 incident type 2 diabetes case-control pairs from the NHS and NHS IIIncident diabetes after adjusting for BMI comparing highest with the referent quartile of urinary phthalate levelsNHS DEHP OR: 1.34 (0.77–2.30); NHS butyl phthalates OR: 0.91 (0.50–1.68); NHS total phthalates OR: 0.87 (0.49–1.53); NHS II DEHP OR: 1.91 (1.04–3.49)*; NHS II butyl phthalates OR: 3.16 (1.68–5.95)*; NHS II total phthalates OR: 2.14 (1.19–3.85)*
 Watkins et al., 2016 (70)250 children of women enrolled in the Early Life Exposure in Mexico to Environmental Toxicants cohortChange in insulin secretion as assessed by a C-peptide index per IQR increase in either in utero MEP levels for pubertal boys or peripubertal DEHP for prepubertal girlsPubertal boys: −17% (−29 to −3.3%)*; Prepubertal girls: 20% (2.5–41%)*
 Song et al., 2016 (29)Meta-analysis of four cross-sectional and prospective studies published before 8 March 2014 examining links between phthalates and diabetes riskPooled diabetes risk in the highest vs. lowest exposure groups for BPARR: 1.48 (0.98–2.25)
  • Data are from studies from around the world (Supplementary Fig. 1). DM, diabetes; FMD, flow-mediated dilatation; IDR, incidence density ratio; PRR, prevalence rate ratio; SAEI, small-artery elasticity index.

  • *P < 0.05.