Table 2.
Longitudinal studies exploring the association between PFAS and glucose metabolism/diabetes mellitus.
| Author, year and reference | Study Design | Population | n. of subjects | PFAS plasma concentration (ng/mL) | Observation period | Main Results |
|---|---|---|---|---|---|---|
| Leonard RC, 2008 (18). | Retrospective cohort | Workers in polymer production plant (DuPont Washington Works) | 6027 | n.a. | Mean (SD): Males 26 (15); F 16 (10) years | Mortality associated with diabetes significantly increases in workers in polymer production plant. |
| Lundin JI, 2009 (24). | longitudinal | Workers in polymer production plant (3M Company plant, Minnesota) | 3993 | n.a. | Mean 31.3 years | A work history of only moderate-exposure was associated with the risk of dying from diabetes mellitus. |
| Steenland K, 2015 (25). | Cohort | Workers in polymer production plant (DuPont Washington Works) | 3713 | Median (SD) PFOA: 325 (920) |
10 years | Very modest positive trend using the categorical trend test for T2DM. |
| Domazet SL, 2016 (26). | Cohort | Danish children (European Youth Health Study) | 201/202 | Median (IQR) PFOS M 44.5 (35.4-55.7); F 39.9 (34.3-49.3); PFOA M 9.70 (7.7-12.1), F 9.0 (7.4-11.2) |
6-12 years | PFOA exposure in childhood was associated with decreased β-cell function at 15 years of age. |
| Fleisch AF, 2017 (27). | Cohort | US children (Project Viva) | 665 | Range in the 4th quartile PFOA (8.0–22.4); PFOS (34.9–168.0); PFNA (1.0–2.6); PFHxS (3.8–43.2) |
Median 7.7 years | Children with higher PFAS concentrations had lower HOMA-IR, especially females. |
| Matilla-Santander N, 2017 (28). | Cohort | Spanish pregnant women (INMA study) | 1204 | Range in the 4th quartile PFOS Q4: (7.81-38.58); PFOA: (3.30-31.64); PFHxS: (0.82-11.00); PFNA: (0.90-5.51) |
From the 1st trimester to delivery | Serum PFOS/PFHxS was associated with impaired glucose tolerance and with GDM. |
| Jensen RC, 2018 (29). | Cohort | Danish pregnant women (Odense Child Cohort) | 318 | Median (5th–95th percentile) PFOS: 8.31 (4.08–16.26); PFOA: 1.71 (0.69–4.19); PFHxS: 0.30 (0.08–0.60); PFNA: 0.66 (0.37–1.58); PFDA: 0.26 (0.15–0.53) |
Between the 11th and 28th gestational weeks | In women with high risk for GDM, a two-fold increase in PFHxS concentration was associated with increased FBG, fasting INSULIN and HOMA-IR; a doubling in PFNA concentration was associated with higher fasting insulin and HOMA-%β. |
| Mancini FR, 2018 (30). | Cohort | French women (E3n Cohort Study) | 71270 | Estimated mean dietary exposure to PFOS 0.49 (0.18) ng/kg body weight/day; PFOA 0.86 (0.73) ng/kg body weight/day | Over 15 years of follow-up | Inverse U-shape association was found when considering PFOA and T2DM; PFOS was nonlinearly associated with T2DM only in women with BMI ≤ 25 kg/m2. |
| Wang H, 2018 (31). | Cohort | Chinese pregnant women (Tangshan City) | 560 | Range min-max PFOS: (0.8-114.6); PFOA: (1.2-77.7) |
From the 1st trimester to OGTT (mid-pregnancy) | PFOA was positively associated with HOMA-IR and blood glucose level at 1 h and 2 h of OGTT; PFOS tended to be negatively associated with FBG and OGTT blood glucose. |
| Alderete TL, 2019 (32). | Cohort | Overweight Hispanic children (8-14 ys) included in the SOLAR project | 40 | Geometric mean (SD) PFHxS: 1.65 (2); PFOS: 12.22 (1.91); PFOA: 2.78 (1.29) |
1-3 years | The increase in PFOA and PFHxS concentrations was associated with an increase in 2-hour glucose levels. The increase in PFHxS concentrations was also associated with an increase in the glucose area under the curve. |
| Rahman ML, 2019 (33). | Cohort | Pregnant women (NICHD Fetal Growth Study) | 2334 | Geometric mean (95%CI) PFOS: 5.21 (5.07-5-35); PFOA: 1.99 (1.93-2.04); PFHxS: 0.76 (0.73-0.78); PFNA: 0.80 (0.78-0.82); PFDA: 0.27 (0.26-0.28) |
Between 8-13 weeks to delivery | PFNA, PFOA, PFHpA, PFDoDA showed significant positive associations with GDM among women with a family history of T2DM. |
| Zhang C, 2015 (34). | Prospective case-control | Pregnant women (LIFE study) | 258 | Geometric mean (range) PFOA non-GDM: 3.07 (2.83–3.12); PFOA GDM: 3.94 (3.15–4.93) |
From pre-conception to >24 weeks of gestation | Positive association between serum PFOA and GDM. |
| Sun Q, 2018 (35). |
Prospective case-control study | US women (Nurses’ Health Study II) | 793 cases and 793 controls | Mean (IQR) in cases PFOS: 35.7 (26.4–48.3); PFOA: 4.96 (3.70–6.67) |
Follow-up: 6:7 ± 3:7 y | Higher plasma concentrations of PFOS and PFOA were associated with an elevated risk of T2DM. |
| Liu X, 2019 (36). |
Prospective nested case-control | Chinese pregnant women (Beijing) | 439 | Median (IQR) long chain PFOS: 4.16 (2.79–6.39); long chain PFOA 2.29 (1.78–3.12) |
From the 1st prenatal care visit to 24-28 gestational weeks | Short-chain PFCAs exposure and both GDM risk and impaired glucose homeostasis in pregnant women. |
| Yu G, 2021 (37). |
Cohort | Pregnant women who participated in the Shanghai Birth Cohort | 2747 | Median (IQR): PFOA: 11.55 (5.93); PFOS: 9.40 (6.90); PFNA: 1.65 (1.07) |
24 - 28 weeks | Environmental exposure to PFAS may affect glucose homeostasis in pregnancy and increase the risk of GDM, especially in normal weight women. |
| Valvi D, 2021 (38). | Cohort | Farohese Islan born individuals | 699 | Median (min-max): PFOS 31.5 (7.23-106.1); PFOA 5.06 (1.31-17.3); PFHxS 0.92 (0.19-55.2); PFNA 0.69 (0.12-2.88) |
28 years | Associations were stronger for PFOS and suggested decreased insulin sensitivity and increased β-cell function. |
| Charles D, 2020 (39). | Nested case-control study | Norwegan Women and Cancer Study | 46 T2DM vs. 85 non- T2DM | Median (5th–95th percentile) in cases: PFOA: 2.32 (1.00, 4.13); PFOS: 20.1 (10.3, 37.9); PFNA: 0.38 (0.18, 1.06) | Nearly 4 years | No significant associations between pre-diagnostic PFAS concentrations and T2DM incidence. |
| Girardi P, 2021 (40). | longitudinal case-control | Male employees for a factory that produced PFOA and PFOS | 462 | Geometric Mean (min-max): PFOA: 4048 ng/mL (19–91,900) |
31.7 years | Increased relative risk for mortality from diabetes consequences in the cohort of workers for a factory that produced PFOA and PFOS as compared to the cohort of workers from the metalworking factory. |
| Cardenas A, 2019 (41). | Cohort from a randomized controlled study | Participants from the Diabetes Prevention Program (DPP) trial and Diabetes Prevention Program Outcomes Study (DPPOS) | 957 | Geometric Mean (IQR): PFOA 4.82 (3.20); PFOS 18.42 (16.90); PFHxS: 2.41 (2.40); PFNA: 0.53 (0.40) |
15 years | A doubling in baseline branched PFOA concentration was associated with a 14% increase in diabetes risk for the placebo but not in the lifestyle intervention group. |
BMI, Body Mass Index; FBG, Fasting Blood Glucose; GDM, Gestational Diabetes Mellitus; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; HOMA-%β, Homeostatic Model Assessment for β-cell function; OGTT, Oral Glucose Tolerance Test; T2DM, Type 2 diabetes mellitus. PFDA, perfluorodecanoic acid; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid.