We speculated that a diet with a high glycemic index (GI), or a diet with a low nutrient density (nutrient-to-calorie ratio), would enhance colon carcinogenesis, presuma-bly via increased insulin resistance. Forty-eight female Sprague -Dawley rats (SD) received an azoxymethane injection (20mg /kg) and were randomized to 5 groups given an AIN76 diet containing (1) 65% starch by wt. (2) 65% glucose, GI=100, (3) 65% fructose, GI=23, (4) 82% starch, or (5) 39% oil and 39% sucrose. The nutrient density was halved in 45 diets compared to 13 diets. Promotion was assessed by the multi-plicity (number of crypts) of aberrant crypt foci (ACF), an early marker of colon carcinogenesis. Insulin resistance was estimated by (blood insulin x blood glucose), by plasma triglycerides, and by visceral fat. To confirm the results in another rat strain, the whole experiment was duplicated in 48 female Fischer F344 rats. Results show that: (i) ACF multiplicity was not different in glucose- and fructose-fed rats (p>0.7): diets with contrasting GI had the same effect on ACF growth. (ii) Diets of low nutrient density increased visceral fat (p<0.05), but reduced the ACF size in F344 (p<0.001, no reduction in SD). (iii) Indirect insulin resistance markers (FIRI index, blood triglycerides, visceral fat) did not correlate with ACF multiplicity. These results do not support the hypothesis that diets with a high glycemic index, or of low nutrient density, or diets that increase some indirect insulin resistance markers, can promote colon carcinogenesis in female rats
