STUDY BACKGROUND: Despite widespread agreement that excess weight increases the risk of cardiovascular disease and type 2 diabetes, medical practitioners still lack a meaningful clinical metric. We expected that weight gain would lead to a decrease in quality-adjusted life years and an increase in life years lost associated with diabetes and cardiovascular disease. Methods: We developed a disease stimulus model to assess the annual risk profile of diabetes and cardiovascular disease and compared individuals with a BMI of 25-25-<30 kg/m2 (overweight), 30-<35 kg/m2 (obese), or 35 kg/m2 and above (overweight) to individuals with an ideal BMI (18.5-<25 kg/m2). Mortality rates were compared to those with ideal BMI (18.5-<25 kg/m2). Study data were obtained from 3992 non-Hispanic white subjects participating in the National Nutrition and Screening Survey (2003-10), with full risk factor assessment and fasting blood glucose concentration data available. After confirming the validity of the model predictions, we compared the correlations between different weight groups and years of life lost and years of healthy life lost. Findings: Weight gain was significantly and positively associated with risk factors for cardiovascular disease and type 2 diabetes. Weight gain had the greatest effect on years of life lost in younger individuals, and this effect diminished with increasing age. Years of life lost in obese men ranged from 0.8 years (95% CI 0.2-1.4) in the 60-79 age group to 5.9 years (4.4-7.4) in the 20-39 age group, and for severely obese men ranged from 0.9 years (0-1.8) in the 60-79 age group, rising to 8.4 years (7.0-9.8) in the 20-39 age group. In contrast, the loss of life expectancy observed in the overweight group was decreasing or even negligible. Similar findings were found among women, with 6.1 (4.6-7.6) years of life lost in the severely obese group at ages 20-39 and 0.9 (0.1-1.7) years at ages 60-79. The healthy life years lost were two to four times greater than the overall life years lost in all age groups and weight categories. Figure: Loss of healthy life-years versus life-years lost versus ideal BMI controls for each BMI group in men and women Conclusion: Our study suggests that both healthy life-years and overall life-years lost show that weight gain is harmful for cardiovascular disease and diabetes. This will provide useful health management measures for clinicians when dealing with their patients.