Dietary Insulin Load and Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803 (Alliance)

Abstract

Background: Evidence suggests that diets inducing postprandial hyperinsulinemia may be associated with increased cancerrelated mortality. The goal of this study was to assess the influence of postdiagnosis dietary insulin load and dietary insulin index on outcomes of stage III colon cancer patients. Methods: We conducted a prospective observational study of 1023 patients with resected stage III colon cancer enrolled in an adjuvant chemotherapy trial who reported dietary intake halfway through and six months after chemotherapy. We evaluated the association of dietary insulin load and dietary insulin index with cancer recurrence and survival using Cox proportional hazards regression adjusted for potential confounders; statistical tests were two-sided. Results: High dietary insulin load had a statistically significant association with worse disease-free survival (DFS), comparing the highest vs lowest quintile (adjusted hazard ratio [HR] ¼ 2.77, 95% confidence interval [CI] ¼ 1.90 to 4.02, P trend < .001). High dietary insulin index was also associated with worse DFS (highest vs lowest quintile, HR ¼ 1.75, 95% CI ¼ 1.22 to 2.51, P trend ¼ .01). The association between higher dietary insulin load and worse DFS differed by body mass index and was strongest among patients with obesity (HR ¼ 3.66, 95% CI ¼ 1.88 to 7.12, P interaction ¼ .04). The influence of dietary insulin load on cancer outcomes did not differ by mutation status of KRAS, BRAF, PIK3CA, TP53, or microsatellite instability. Conclusions: Patients with resected stage III colon cancer who consumed a high-insulinogenic diet were at increased risk of recurrence and mortality. These findings support the importance of dietary management following resection of colon cancer, and future research into underlying mechanisms of action is warranted. Postdiagnosis lifestyle behaviors, including diet and physical activity, may be important risk factors for cancer recurrence and death in colon cancer patients (1-3). The exact mechanisms through which these factors influence outcomes are unknown, but epidemiological evidence suggests that insulin may play a role (4,5). Moreover, insulin signaling involves downstream pathways that are relevant for colon cancer pathogenesis and response to treatment (eg, KRAS/NRAS, BRAF, PIK3CA) (6,7). Insulin secretion is strongly influenced by diet, with carbohydrate-rich diets inducing postprandial hyperinsulinemia (8,9). Dietary glycemic load-an indicator of the body's plasma glucose response to different foods-has been

Dietary Intake in Association with All-Cause Mortality and Colorectal Cancer Mortality among Colorectal Cancer Survivors: A Systematic Review and Meta-Analysis of Prospective Studies

“…Among a total of 175 full-text reports, 130 papers were additionally excluded due to an different exposure and/or outcome ( n = 82), unrelated study design ( n = 20), studies with uncertain information regarding RR or HR ( n = 19), overlap ( n = 2), or studies without original data (abstracts or reviews) ( n = 7). As a result, 45 studies were included in the final systematic review and meta-analysis [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ].…”

“…Exposure data related to prediagnostic intake only were available in 21 studies [ 17 , 18 , 19 , 20 , 28 , 29 , 34 , 35 , 36 , 39 , 40 , 41 , 42 , 43 , 46 , 49 , 50 , 55 , 56 , 57 , 59 ], exposure data related to postdiagnostic intake only were available in 20 studies [ 16 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 31 , 32 , 33 , 37 , 38 , 44 , 45 , 47 , 48 , 51 , 54 , 58 , 60 ], and 4 studies included both prediagnostic and postdiagnostic dietary intake [ 26 , 30 , 52 , 53 ]. Outcome data related to all-cause mortality only were available in 16 studies [ 16 , 20 , 21 , 22 , 24 , …”

Post-diagnosis dietary insulinemic potential and survival outcomes among colorectal cancer patients

“…Both the insulin index and glycemic index assess the postprandial (short-term) effects of the diet, unlike the EDIH score which predicts integrated insulin exposure (i.e., both fasting and non-fasting), based on habitual (long-term) dietary intake [18]. Post-diagnosis insulin index and insulin load have been linked to higher risk of dying from colorectal cancer [32,33]. Higher dietary insulin load and insulin index after diagnosis of colorectal cancer were associated with increased risk of colorectal cancer-specific and overall mortality [33].…”

Targeting Adipokines in Obesity-Related Tumors

“…Moreover, clinical research has found that the risk of recurrence and death will increase in patients with stage III colon cancer after consumption of a high-insulin diet, which indicates that cultivation of healthy dietary habits after colorectal cancer surgery is very important, and a diet rich in carbohydrates, protein and lipids that can stimulate insulin secretion should be avoided. Control of insulin levels is helpful for the treatment and prognosis of tumors (130).…”