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Higher LDL Levels Linked to Increased Risk of Impaired Fasting Glucose

Higher concentrations of low-density lipoprotein (LDL) that has been modified by oxidation is associated with an increased incidence of abdominal obesity, high fasting glucose levels and high triglyceride levels and the metabolic syndrome. Studies in cellular and animal models have suggested that oxidized LDL (small fraction of LDL, the so called “bad” cholesterol, that has undergone oxidation) contributes to processes that lead to the incidence of diabetes and the metabolic syndrome. However, this association has not been tested in humans, according to background information in the article. Oxidized LDL is only a minor fraction of LDL, ranging from 0.001 percent in healthy individuals to approximately 5 percent in patients with acute coronary events.

Paul Holvoet, Ph.D., of Katholieke Universiteit Leuven, Belgium, and colleagues conducted a study to determine the association between the concentration of oxidized LDL and the incidence 5 years later of metabolic syndrome and its components. The study included 1,889 participants (41 percent African American; 56 percent women) who were between the ages of 18 and 30 years at the time of recruitment in 1985 and 1986 and were seen both at year 15 (2000-2001, ages 33-45 years) and year 20 examinations (2005-2006), when oxidized LDL was measured.

The researchers found that oxidized LDL showed a graded relation to incident metabolic syndrome, with participants in the group (i.e., the 20 percent of the study population) with the highest levels being 3.5 times more likely to develop the metabolic syndrome than participants in the group (i.e., the 20 percent of the study population) with the lowest levels. A similar relationship was found for components of metabolic syndrome, with those with the highest oxidized LDL levels having about twice the risk for abdominal obesity and high fasting glucose and triglyceride measurements.

“A novel finding of this study is that oxidized LDL was associated with incident metabolic syndrome. As yet, it is not possible to conclude whether oxidized LDL is a marker related to mechanistic underlying factors on the pathway to the development of metabolic syndrome, or whether it is by itself a functional intermediary in this pathway. However, the strong association of oxidized LDL with the incidence of metabolic syndrome is consistent with a causal role,” the authors write.
JAMA. 2008;299[19]:2287-2293.

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