We speculated that a diet with a high glycemic index (GI) or a diet wi
th a low nutrient density (nutrient-to-calorie ratio) would enhance co
lon carcinogenesis, presumably via increased insulin resistance. Forty
-eight Sprague-Dawley (SD) rats received an azoxymethane injection (20
mg/kg) and were randomized into five groups given an AIN-76 diet cont
aining 1) 65% starch by weight, 2) 65% glucose (GI = 100), 3) 65% fruc
tose (GI = 23), 4) 82% starch, or 5) 39% oil and 39% sucrose. The nutr
ient density of Diets 4 and 5 was one-half that of Diets 1-3. Promotio
n was assessed by the multiplicity (number of crypts) of aberrant cryp
t foci (ACF), an early marker of colon carcinogenesis. Insulin resista
nce was estimated by the FIRI index (blood insulin x blood glucose), b
y plasma triglycerides, and by visceral fat. To confirm the results in
another rat strain, the experiment was duplicated in 48 Fischer (F344
) rats. Results show that 1) the ACF multiplicity was not different in
glucose- and fructose-fed rats (p > 0.7): diets with contrasting GI h
ad the same effect on ACF growth; 2) diets of low nutrient density inc
reased visceral fat (p < 0.05) but reduced the ACF size in F344 rats (
p < 0.001, no reduction in SD rats); and 3) indirect insulin resistanc
e markers (FIRI index, blood triglycerides, and visceral fat) did nor
correlate with ACF multiplicity. These results do not support the hypo
thesis that diets with a high GI or low nutrient density or diets that
increase some indirect insulin resistance markers can promote colon c
arcinogenesis in F344 or SD rats.