Objectives: Substantial evidence associates persistent organic pollutants (POP) with metabolic disturbances related to diabetes, but longitudinal studies with repeated measures are scarce. We aimed to characterize the association between background exposures to POPs with repeated measures of glucose homeostasis over 23-years. Methods: Within the Coronary Artery Risk Development in Young Adults study (year 0 ages: 18-30 years), we measured POPs in serum obtained in 1987-88 (follow-up year 2) in 90 non-diabetic controls and 90 cases diabetes-free at year 2 who became diabetic by year 20. We analyzed 32 POPs detectable in ≥75% of participants and created summary scores for 32 POPs, 23 polychlorinated biphenyls (PCB), and 8 organochlorine pesticides (OCP). Dependent variables were measures of glucose homeostasis at years 0-25 (up to 8 examinations). We explored associations using repeated measures regression adjusted for race, sex, concurrent body mass index (BMI), examination center and period, separately for cases and controls. Results: The associations between the three summary scores and measures of glucose homeostasis were present for observations at ages 40-55 years, and particularly between 48-55 years: the 23 PCB summary was associated with HbA1c (never-diabetics: slope [value per unit of summary score], β=0.008, p=0.02; diabetics: β=0.03, p=0.07), fasting glucose (never-diabetics: β=0.24, p=0.003; diabetics: β=1.10, p=0.03), and insulin sensitivity% (never-diabetics: β=-2.82, p<0.001, diabetics: β=-0.31, p=0.30). No associations were observed at younger ages. Conclusions: Glucose homeostasis may worsen after decades of exposure to PCBs and OCPs at background environmental levels, independent of BMI and after participants reached the 5th decade of life.