Incident Early-and Later-Onset Type 2 Diabetes and Risk of Early-and Later-Onset Cancer: Prospective Cohort Study

OBJECTIVE We evaluated prospectively the association between incident early-onset (diag-nosed before 40 years of age) and later-onset type 2 diabetes and early-onset (di-agnosed before 50 years of age) and later-onset cancer risk. RESEARCH DESIGN AND METHODS We prospectively followed 228,073 eligible participants in the Nurses’ Health Studies for up to 38 years. Hazard ratios (HRs) and 95% CI were estimated using Cox models. RESULTS We documented 18,290 type 2 diabetes, 6,520 early-onset cancer, and 36,907 later-onset cancer cases during follow-up. In fully adjusted analyses, early-onset type 2 diabetes was associated with increased risk of early-onset total cancer (HR [95% CI] 1.47 [1.06–2.04]), diabetes-related cancer (2.11 [1.38–3.23]), and obe-sity-related cancer (1.75 [1.08–2.82]), and the risk elevations were restricted to those with a BMI at 18 years of age of ‡21 kg/m² (total cancer: 1.75 [1.20–2.56]; diabetes-related cancer: 2.43 [1.50–3.94]; and obesity-related cancer: 1.84 [1.05–3.22]). Early-onset type 2 diabetes was associated with higher risk of later-onset diabetes-related and obesity-related cancer specifically among individuals with higher BMI at 18 years of age. Later-onset type 2 diabetes was associated with a higher risk of later-onset total cancer (1.15 [1.11–1.20]), diabetes-related cancer (1.17 [1.12–1.22]), and obesity-related cancer (1.18 [1.13–1.24]). In analyses based on refined timing, the HRs attenuated substantially with aging. CONCLUSIONS Incident early-onset type 2 diabetes was associated with increased risk of early-onset total cancer and diabetes-and obesity-related cancer, especially in those with higher BMI at 18 years of age. The impact of early-onset type 2 diabetes on cancer risk may be inherently stronger than that of later-onset type 2 diabetes.