Background It is unknown whether the risk for obesity-related cancers between metabolically unhealthy and healthy overweight/obese adults. Methods Data on body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and random blood glucose in Framingham Heart Study adults (n=3763) ages 55-69 were used to estimate risks of obesity-related cancers (n=385) including post-menopausal breast, female reproductive, colon, liver, gallbladder, pancreas, and kidney cancers, as well as esophageal adenocarcinomas. Multivariable-adjusted Cox proportional hazards models were used to estimate risk for obesity-related cancers associated with body fat and metabolic health (as defined by glucose levels) among subjects in three risk groups (vs. referent group with normal-weight/normal glucose): normal-weight/elevated glucose; overweight/normal glucose; and overweight/elevated glucose. Results Overweight adults (BMI≥25 or WHtR≥0.51 (men) and ≥0.57 (women)) with elevated glucose (≥125 mg/dL) had a statistically significant two-fold increased risk of developing obesity-related cancer while overweight adults with normal glucose had a 50% increased risk. Normal-weight adults with elevated glucose had no excess cancer risk. The effects of BMI and WHtR were independent of one another. Finally, overweight women with elevated blood glucose had a 2.6-fold increased risk (95% CI: 1.4-4.9) of female reproductive (cervical, endometrial, uterine cancers) and post-menopausal breast cancers while overweight women with normal glucose levels had only a 70% increased risk (95% CI: 1.1-2.5). Conclusion These results suggest that cancer risk may be lower among metabolically-healthy overweight/obese older adults than among overweight/obese adults with metabolic dysfunction. Impact Metabolic dysfunction and obesity act synergistically to increase cancer risk.

Midlife weight gain was a strong cancer risk factor. This excess risk was somewhat stronger among those with concurrent metabolic dysfunction.

Background/Objective: Obesity has been associated with risk of developing certain cancers. A limited number of studies have examined effects of various anthropometric measures of body composition on cancer risk. The aim of this study was to estimate the sex-specific effects of various anthropometric measures on risk of obesity-related cancers (ObCa). Subjects/Methods: Data on body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and hip circumference (HC) among 3,818 45–69 year-olds in the Framingham Offspring Study were included. Cox proportional hazards models were used to estimate adjusted risks of 16 obesity-related cancers, with the most common being postmenopausal breast, endometrial, and colon cancers. Results: Obesity as measured by BMI in both men and women was a predictor of ObCa; those in the highest quintile (Q5) of BMI (≥30.3 in women; >31.1 kg/m 2 in men) had more than twice the risk of ObCa (HR=2.07; 95% CI: 1.06–4.07 (women) and HR=2.25; 95% CI: 1.08–4.69 (men)). Waist-related measures (WC, WHtR) were stronger predictors of ObCa in men than in women and HC confounded the relations between waist size and cancer risk. After adjusting for HC, men in Q5 of WC had more than a three-fold increased risk of ObCa (HR:=3.22; 95% CI: 1.39–7.45). Comparable effects in women were weak and non-statistically significant. Results were similar for WHtR. Finally, a J-shaped relation was found between HC and ObCa after adjusting for WC among men but not in women. Conclusion: These results suggest that obesity as measured by BMI is a predictor of obesity-related cancer risk in men and women. These results suggest that waist and hip circumference measures are inter-related and confound the independent effects of each measure. Among men, a large waist size and a small hip size are independent predictors of cancer risk.

Context Testosterone deficiency prevalence increases with age, comorbidities, and obesity. Objective To inform clinical guidelines for testosterone deficiency management and development of targets for nonpharmacologic intervention trials for these men, we determined serum testosterone in never-smoking, lean men without select comorbidities in nationally representative surveys. Design, Setting, Participants We used cross-sectional data for never-smoking, lean men ≥20 years without diabetes, myocardial infarction, congestive heart failure, stroke, or cancer, without use of hormone-influencing medications, and participated in morning sessions of National Health and Nutrition Examination Survey (NHANES) III (phase I 1988–1991) or continuous NHANES (1999–2004). By age, we determined median total testosterone (ng/mL) measured previously by a Food and Drug Administration-approved immunoassay and median estimated free testosterone concentration. Results In NHANES III, in never-smoking, lean men without comorbidities, median (25th, 75th percentile) testosterone was 4% to 9% higher than all men—20 to 39 years: 6.24 (5.16, 7.51), 40 to 59: 5.37 (3.83, 6.49), and ≥60: 4.61 (4.01, 5.18). In continuous NHANES, in never-smoking, lean men without comorbidities, levels were 13% to 24% higher than all men—20 to 39 years: 6.26 (5.32, 7.27), 40 to 59: 5.86 (4.91, 6.55), and ≥60: 4.22 (3.74, 5.73). In never-smoking, lean men without comorbidities, median estimated free testosterone was similar to (NHANES III) or slightly higher than (continuous NHANES) in all men. Conclusions These nationally representative data document testosterone levels (immunoassay) in never-smoking, lean men without select comorbidities 30 and 15 to 20 years ago. This information can be incorporated into guidelines for testosterone deficiency management and used to develop targets for nonpharmacologic intervention trials for testosterone deficiency.