Abstract
BackgroundWe examined the role of the insulinemic potential of diet and lifestyle in the development of cancers of the digestive system, using two plasma C-peptide-based indices: the empirical dietary index for hyperinsulinemia (EDIH) and empirical lifestyle index for hyperinsulinemia (ELIH).MethodsWe used Cox regression to analyze data on 45 816 men (Health Professionals Follow-up Study, 1986–2012) and 74 191 women (Nurses’ Health Study, 1984–2012) to examine associations between EDIH and ELIH scores and digestive system cancers. We computed the diet-only score (EDIH) from food-frequency questionnaires administered every 4 years. The lifestyle score (ELIH) included diet, body mass index, and physical activity. Outcomes included incident cancer of the digestive system (mouth, throat, esophagus, stomach, small intestine, and colorectum) and its accessory organs (pancreas, gallbladder, and liver). P values were two-sided.ResultsWe found direct associations between higher insulinemic potential of diet or lifestyle and risk of developing digestive system cancers in both men and women. The pooled multivariable hazard ratios (HRs) for participants comparing the highest to lowest EDIH quintile were: HR = 1.27, 95% confidence interval (CI) = 1.15 to 1.40, Ptrend < .001 for digestive system cancers; HR = 1.30, 95% CI = 1.17 to 1.45, Ptrend < .001 for digestive tract cancers (excluding accessory organs); and HR = 1.15, 95% CI = 0.93 to 1.41, Ptrend = .48 for digestive accessory organ cancers. The same associations were stronger with the lifestyle score: HR = 1.47, 95% CI = 1.23 to 1.76, Ptrend < .001 for digestive system cancers; HR = 1.49, 95% CI = 1.14 to 1.95, Ptrend = .001 for digestive tract cancers; and HR = 1.43, 95% CI = 1.17 to 1.73, Ptrend < .001 for digestive accessory organ cancers.ConclusionsThe findings suggest that interventions to reduce the insulinemic potential of diet and lifestyle may be a means of preventing digestive system cancer.
Highlights
NSAIDs=non-steroidal anti-inflammatory drugs; Empirical dietary index for hyperinsulinemia (EDIH)=empirical dietary index for hyperinsulinemia. *EDIH scores were adjusted for total energy intake using the residual method
Lower scores indicate insulin sensitive diets, and higher scores indicate hyperinsulinemic diets. †Heterogeneity for risk was tested using duplication method cause-specific Cox regression analyses ‡All analyses were adjusted for the following potential confounding variables: race, family history of cancer, history of endoscopy, multivitamin use, total alcohol intake, physical activity, pack-years of smoking, regular aspirin use, regular NSAIDs use, BMI, and for menopausal status, and postmenopausal hormone use in women. §The p-value for linear trend across EDIH quintiles was the p-value of the ordinal variable constructed by assigning quintile medians to all participants in the quintile
Lower scores indicate insulin sensitive diets, and higher scores indicate hyperinsulinemic diets. †Heterogeneity for risk was tested using duplication method cause-specific Cox regression analyses ‡All analyses were adjusted for the following potential confounding variables: race, family history of cancer, history of endoscopy, multivitamin use, total alcohol intake, physical activity, pack-years of smoking, regular aspirin use, regular NSAIDs use, and for menopausal status, and postmenopausal hormone use in women. §The p-value for linear trend across EDIH quintiles was the p-value of the ordinal variable constructed by assigning quintile medians to all participants in the quintile
Summary
NSAIDs=non-steroidal anti-inflammatory drugs; EDIH=empirical dietary index for hyperinsulinemia.
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