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Title: A clustering analysis of lipoprotein diameters in the metabolic syndrome

Author
item FRAZIER-WOOD, ALEXIS - University Of Alabama
item GLASSER, STEPHEN - University Of Alabama
item GARVEY, W - University Of Alabama
item KABAGAMBE, EDMOND - University Of Alabama
item BORECKI, INGRID - Washington University
item TIWARI, HEMANT - University Of Alabama
item TSAI, MICHAEL - University Of Minnesota
item HOPKINS, PAUL - University Of Utah
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ARNETT, DONNA - University Of Alabama

Submitted to: Lipids in Health and Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/19/2011
Publication Date: 12/19/2011
Citation: Frazier-Wood, A.C., Glasser, S., Garvey, W.T., Kabagambe, E.K., Borecki, I.B., Tiwari, H.K., Tsai, M.Y., Hopkins, P.N., Ordovas, J.M., Arnett, D.K. 2011. A clustering analysis of lipoprotein diameters in the metabolic syndrome. Lipids in Health and Disease. 10:237.

Interpretive Summary: The presence of smaller low-density lipoproteins (LDL) has been associated with the risk of hardening of the arteries, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-density lipoprotein (VLDL), low- and high-density lipoprotein (HDL) particle diameters with components of the metabolic syndrome (MetS). Our objective was to explore the relationship of VLDL, LDL and HDL diameters to MetS and its features, and by grouping individuals by their diameters of VLDL, LDL and HDL particles, to capture information across all three lipoproteins into a unified phenotype. For this purpose we used nuclear magnetic resonance spectroscopy measurements on fasting plasma samples from a population sample of 1,036 adults. We identified eight discrete groups. Two groups (N = 251) were enriched with individuals meeting criteria for the MetS, and were characterized by the smallest LDL/HDL diameters. One group was additionally distinguished by large VLDL, and had significantly higher blood pressure, fasting glucose, triglycerides (TG), and waist circumference (WC). However, large VLDL, in the absence of small LDL and HDL particles, did not associate with MetS features. In conclusion, we have shown that small LDL diameters are associated with IR and the MetS, but, in addition, the occurrence of these in conjunction with a shift to overall larger VLDL diameter may identify those with the highest fasting glucose, TG and WC within the MetS. This information contributes to the identification of those most at risk for incident type II diabetes and cardiometabolic disease.

Technical Abstract: The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle diameters with components of the metabolic syndrome (MetS), although this has been the focus of less research. We aimed to explore the relationship of VLDL, LDL and HDL diameters to MetS and its features, and by clustering individuals by their diameters of VLDL, LDL and HDL particles, to capture information across all three fractions of lipoprotein into a unified phenotype. We used nuclear magnetic resonance spectroscopy measurements on fasting plasma samples from a general population sample of 1,036 adults (mean +/- SD, 48.8 +/- 16.2 y of age). Using latent class analysis, the sample was grouped by the diameter of their fasting lipoproteins, and mixed effects models tested whether the distribution of MetS components varied across the groups. Eight discrete groups were identified. Two groups (N = 251) were enriched with individuals meeting criteria for the MetS, and were characterized by the smallest LDL/HDL diameters. One of those two groups, one was additionally distinguished by large VLDL, and had significantly higher blood pressure, fasting glucose, triglycerides, and waist circumference (WC; P less than .001). However, large VLDL, in the absence of small LDL and HDL particles, did not associate with MetS features. These associations held after additionally controlling for VLDL, LDL and HDL particle concentrations. While small LDL diameters remain associated with IR and the MetS, the occurrence of these in conjunction with a shift to overall larger VLDL diameter may identify those with the highest fasting glucose, TG and WC within the MetS. If replicated, the association of this phenotype with more severe IR-features indicated that it may contribute to identifying of those most at risk for incident type II diabetes and cardiometabolic disease.