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Although numerous studies have explored the relation of insulin-like growth factor (IGF)-I and IGF-binding protein (BP) 3 with cancer and cardiovascular disease, only two previous studies are known to have looked at the association of IGF-I and IGF-BP3 with risk of mortality. The objective of this US study was to examine the risk of all-cause, heart disease, and cancer mortality associated with IGF-I and IGF-BP3 levels using data from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES III Mortality Study (n = 6,061) (1988-2000). The authors constructed proportional hazards models with age as the time scale to determine the association of baseline IGF-I and IGF-BP3 levels with subsequent mortality. After adjustment for baseline measures, there was no increased risk of all-cause, heart disease, or cancer mortality for the lower quartiles of IGF-I compared with the highest quartile. The adjusted relative hazard of all-cause mortality for the lowest quartile of IGF-BP3 compared with the highest quartile was 1.57 (95% confidence interval: 0.98, 2.52), and the trend for risk was significant (p = 0.0364), but there was no increased risk of heart disease or cancer mortality. Results suggest that the association of IGF-I and IGF-BP3 with mortality may differ from associations with incidence of disease.

Although abnormal glucose tolerance is a well-established risk factor for cardiovascular disease, its relation to cancer risk is less certain. Therefore, the authors performed a prospective cohort study using data from the Second National Health and Nutrition Examination Survey and the Second National Health and Nutrition Examination Survey Mortality Study to determine this relation. This analysis focused upon a nationally representative sample of 3,054 adults aged 30-74 years who underwent an oral glucose tolerance test at baseline (1976-1980). Deaths were identified by searching national mortality files through 1992. Adults were classified as having either previously diagnosed diabetes (n = 247), undiagnosed diabetes (n = 180), impaired glucose tolerance (n = 477), or normal glucose tolerance (n = 2250). There were 195 cancer deaths during 40,024 person-years of follow-up. Compared with those having normal glucose tolerance, adults with impaired glucose tolerance had the greatest adjusted relative hazard of cancer mortality (relative hazard = 1.87, 95% confidence interval (CI): 1.06, 3.31), followed by those with undiagnosed diabetes (relative hazard = 1.31, 95% CI: 0.48, 3.56) and diabetes (relative hazard = 1.13, 95% CI: 0.49, 2.62). These data suggest that, in the United States, impaired glucose tolerance is an independent predictor for cancer mortality.

Diabetes is a well-established cause of cardiovascular disease (CVD) and all-cause mortality. The burden of death attributable to diabetes in the United States is not well quantified, particularly with regard to age. The authors analyzed data from the Second National Health and Nutrition Examination Survey (NHANES II) (1976-1980) and the NHANES II Mortality Study, in which a nationally representative cohort of 9,250 adults aged 30-75 years was followed for 12-16 years, to determine all-cause and cause-specific mortality. Overall, between 1976 and 1980, the prevalence of diagnosed diabetes was 4.3%. By 1992, the relative hazard of all-cause mortality was 1.9 (95% confidence interval: 1.5, 2.3), and the population attributable risk (PAR) was 3.6%. The relative hazard of CVD mortality was 2.3 (95% confidence interval: 1.8, 2.8), and the PAR was 5.2%. Including participants with undiagnosed diabetes in the estimates increased the PAR for all-cause mortality to 5.1% and that for CVD mortality to 6.8%. Women had a higher prevalence of diagnosed diabetes than men and a greater relative hazard of death than nondiabetic women, leading to a higher PAR for women (3.8% for all causes and 7.3% for CVD) versus men (3.3% for all causes and 3.8% for CVD). These data suggest that diabetes accounts for at least 3.6% of all deaths and 5.2% of CVD deaths in US adults. Improvements in diabetes prevention and treatment should produce noticeable effects on US life expectancy.