Biomarkers of exposure to dietary carbohydrates with an application in gastroenterology

Non enzymatic glycated proteins in the blood, the product of the non enzymatic reaction of a reducing sugar with the reactive amino acid of a target protein, are an integrated measure of blood glucose over days to weeks. There are few epidemiological studies in non diabetic subjects on the effect of diet and other behavioral risk factors on markers of protein glycation, and on the association of these markers with disease. We compared the correlation of HbA_1c and fructosamine with dietary carbohydrate intake in 59 diabetic and non diabetic subjects. Fructosamine was more strongly correlated with dietary sugar (r = 0.26, p = 0.05) than HbA_1c (r = 0.001, p = 0.99). To study the relationship between serum fructosamine and diet in a population sample of non diabetic subjects, we measured diet with a validated semiquantitative food frequency questionnaire in a population sample of 252 subjects (137 men and 115 women) without diabetes and with fasting serum glucose <126mg/100m1. Serum fructosamine was positively associated (p < 0.10) with dietary glycemic load, intake of polyunsaturated fats and alcohol; and negatively associated with intake of monounsaturated fats, and with physical activity. The findings of this study support the hypothesis that carbohydrate, and above all high glycemic index carbohydrate, is important in determining the fructosamine level, a measure of glycated serum proteins. In many epidemiological studies dietary sugar has been found to be associated with colorectal cancer, but glycated hemoglobin (HbA_1c) has not been found associated with incident colorectal cancer or adenoma, a precursor of colorectal cancer. We compared non diabetic subjects with the first occurrence of adenomatous polyps removed after a complete colonoscopy (153 cases) with subjects with normal colonoscopy (84 controls). In these subjects the risk of colorectal adenoma increased with the level of fructosamine (χ2 for linear trend, p = 0.09), and with increasing levels of serum triglycerides and cholesterol, and decreased with increasing levels of fasting serum insulin. Fasting serum glucose was not associated with adenomatous colorectal polyps. These results show that the risk of colorectal adenoma increases with the level of fructosamine, an indicator of glucose variation in the blood, and of a high glycemic load diet.