Markers of Developing Metabolic Syndrome

September 6th, 2007 by Marc Uemura and Kelly Okazaki

Boston, MA: A. recent study published in the journal, Circulation, on August 13, 2007 evaluated the possible association between 8 different biological markers and the development of Metabolic Syndrome (MetS) over a period averaging 2.9 years. These bio-markers came from 4 different pathways – inflammation (C-reactive protein), hemostasis (plasminogin activator inhibitor-1, fibrinogen), neurohormonal activity (aldosterone, rennin, B-type natiuretic peptide, N-type proatrial natiuretic peptide) and endothelial function (homocysteine). However, because the exact mechanisms involved in the development of MetS are not well understood, the specific markers which can indicate MetS development/progression have not been identified even though numerous studies have demonstrated biomarkers that have been potentially associated to MetS related problems. (One salient example of this is elevated C Reactive Protein and its association with diabetes).

Therefore, the authors in this paper sought to combine a panel of biomarkers which have known associations but not causation to MetS in order to better predict its development. This prospective study evaluated the relationship between the risk factors of MetS as defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, such as increased waist circumference, systolic and diastolic blood pressures, plasma glucose, triglycerides, and HDL cholesterol and changes in the 8 bio-markers in a subset of Framingham Offspring Study participants who lacked MetS and other cardiovascular risks at the onset of data collection.

Two of the tested makers, Plasminogen activator inhibitor-1 (PAI-1) and aldosterone, were significantly associated with the development of MetS which may provide insight into the mechanisms leading to MetS. The authors felt that the best use of the markers may lie in gaining insight into the pathophysiology of metabolic syndrome rather than predicting its development.

There are data to suggest that PAI-1 may play a role in MetS. The authors hypothesize that PAI-1 may be involved in adipose tissue regulation and development. In support of the role of PAI-1 in metabolic syndrome, they cite a lack of insulin resistance and obesity in PAI-1 knockout mice.

Unlike PAI-1, the association between aldosterone and MetS is not as clearly supported in the literature. The authors propose that aldosterone may mediate adipogenesis via an increased rate of adipocyte differentiation.

While the two markers in combination are not reliable predictors for the development of MetS and are of limited diagnostic use, the authors go on to indicate that all possible biomarkers have not yet been evaluated. Thus, other, better biomarkers may exist.

Erik Ingelsson, Michael J. Pencina, Geoffrey H. Tofler, Emelia J. Benjamin, Katherine J. Lanier, Paul F. Jacques, Caroline S. Fox, James B. Meigs, Daniel Levy, Martin G. Larson, Jacob Selhub, Ralph B. D’Agostino, Sr, Thomas J. Wang, and Ramachandran S. Vasan .Multimarker Approach to Evaluate the Incidence of the Metabolic Syndrome and Longitudinal Changes in Metabolic Risk Factors: The Framingham Offspring Study.. Circulation 2007: 116, 984-992