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Two Biomarkers That Link to Severe Heart Disease and Insulin Resistance

Oxidized LDL (oxLDL) cholesterol and fructosamine are associated with severe heart disease in women….

Insulin resistance is known to increase risk for cardiovascular diseases. However some patients with insulin resistance appear to experience only moderate symptoms of coronary blockage while others suffer severe coronary atherosclerotic and continue to progress after stent placement or bypass surgery. A group of researchers at UNC School of Medicine attempted to investigate “whether the severity of atherosclerosis is associated not only with lipoprotein concentrations, weight, blood pressure, biomarkers of inflammation and IR an animal model but also changes in parameters that measure protein glycation.” The team chose pigs as study subjects because pigs also develop coronary artery and aortic atherosclerosis and insulin resistance in a similar fashion with human.

The team fed pigs with a high fat and salt diet over a year until all pigs became insulin resistance. All pigs developed coronary and aortic atherosclerosis but only about half of the pigs developed the severe form of the disease. According to the study, “atherosclerosis severity was not associated with increases in body weight, backfat, insulin or glucose levels, insulin resistance, blood pressure, or biomarkers of inflammation.” However, oxLDL and fructosamine (the two variables that have been associated with increased oxidative protein glycation) levels were observed to be higher in animals with severe and diffused distal coronary atherosclerosis phenotype as compared to animal with moderate diseases. This suggests to the researchers that increased protein glycation may have enhanced the severity of atherosclerosis development in insulin resistant pigs.

Furthermore, the correlation between oxLDL and fructosamine, and several forms of heart diseases is found to be more common in female pigs. Fourteen of the 20 pigs that developed severe atherosclerosis were females. Fourteen of the 17 pigs that did not develop severe atherosclerosis were male.

Even though, the exact mechanism that explains this correlation is unknown but it is proposed that increases in the secretion of cell surface receptor RAGE under these conditions may have contributed to severe atherosclerosis and abnormal protein glycation. Nevertheless, the author believed that they have a “unique animal model that very much mimics what we see in humans. [Their] model is a good predictor of diet-induced atherosclerosis in females.” The authors suggest future studies investigating the abnormal biochemical reactions in the cellular pathways involved in glycated proteins and severe coronary disease.

Practice Pearls:

  • Insulin resistance is known to increase risk for cardiovascular diseases, but some patients appear to suffer from more severe form of heart diseases than others.
  • Oxidized LDL and fructosamine levels were observed to be higher in animals with severe coronary atherosclerosis.
  • The correlation between oxLDL and fructosamine and severe form of heart diseases is found to be more common in female pigs.

Nichols TC, Merricks EP. “Oxidized LDL and Fructosamine Associated with Severity of Coronary Artery Atherosclerosis in Insulin Resistant Pigs Fed a High Fat/High NaCl Diet.” PLoS One. 2015 Jul 6; 10(7):e0132302. doi: 10.1371/journal.pone.0132302.