Submitted to: Obesity Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2003
Publication Date: 12/1/2003
Citation: Elosua, R., Demissie, S., Cupples, L.A., Meigs, J.B., Wilson, P.W., Schaefer, E.J., Corella, D., Ordovas, J.M. 2003. Obesity modulates the association between apolipoprotein E genotype and fasting insulinemia and glucose in men. The Framingham Offspring Study. Obesity Research. 11(12):1502-1508. Interpretive Summary: Lipoproteins are particles carrying cholesterol and fats in the bloodstream. Its atherogenicity may be modulated by their serum levels and these are determined in part by genetic factors. Apolipoprotein E is found in most blood lipoproteins. This protein plays a key role in the metabolism of these particles, especially those containing dietary fat. Previously, we have shown that different forms of the apolipoprotein E (APOE) gene determine blood lipid levels and this translates into future risk of heart disease. In addition to blood lipids, another risk factor for heart disease is blood glucose, which is tightly associated with diabetes. In this work we demonstrate that the APOE gene does not affect blood glucose levels on people with normal body weight, but it plays a significant role on those subjects who are overweight or obese. In summary, the excess risk for diabetes and heart disease due to the APOE gene can be removed by normalizing body weight. Our data underscore the importance of controlling obesity in order to achieve healthier aging.
Technical Abstract: Obesity, insulin resistance and apolipoprotein E (APOE) genotype have all been associated with coronary heart disease. We examined the interaction between obesity and APOE genotype in determining fasting insulin and glucose levels. During 1991-1995, 3,799 subjects underwent a clinical examination, and fasting insulin and glucose measurement. APOE genotypes were determined on 3,500 participants. Participants taking oral hypoglycemic drug or insulin preparations, or with the rare APOE 2/4 genotype were excluded. Finally, 2,929 individuals were included in the present analysis. In men, we observed a statistically significant interaction between obesity and APOE genotype on insulin and glucose level (p=0.003 and 0.008, respectively). Obese men with the APOE4 genotype presented with higher levels of insulin and glucose than obese men in the other genotype groups. No association between genotype and insulin or glucose in non-obese men was observed. Obesity was associated with higher insulin levels in the three APOE genotypes groups, whereas obesity was directly associated with glucose in those with the APOE4 genotype. In women, the interaction between APOE genotype and obesity on fasting insulin and glucose was not statistically significant. Obesity was associated with higher levels of fasting insulin and glucose. APOE genotype was not associated with insulin or glucose. Obesity modulates the association between APOE genotype and fasting insulin and glucose levels in men. While weight control is important in all people, it may be especially important in APOE4 men to modify potentially elevated fasting insulin and glucose levels.