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 (diagnosed before 40 years of age) and later-onset type 2 diabetes and early-onset (diagnosed 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 obesity-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.