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We examined the effect of intrauterine diabetes exposure (IDE) on the incidence of diabetic end-stage renal disease (ESRD) in Pima Indians with type 2 diabetes.Individuals were followed from their first diabetic examination until December 2006, death, ESRD, or age of 45 years.Among the 1,850 diabetic participants, 102 had IDE. ESRD developed in 57, 5 of whom had IDE. Cumulative incidence of ESRD by age 45 was 19.3% in participants with IDE and 5.1% in those without; the age- and sex-adjusted incidence rate ratio was 4.12 (95% CI 1.54–11.02). After additional adjustment for age at diabetes onset, ESRD incidence was similar in the two groups (incidence rate ratio 1.38, 95% CI 0.45–4.24).IDE increases the age- and sex-adjusted incidence of ESRD fourfold in young adults with type 2 diabetes, mediated primarily by the earlier onset of type 2 diabetes in those with IDE.