Serum Adiponectin and Ghrelin, Metabolic Syndrome and Diabetes Status in Cuban Americans

Purpose: Metabolic syndrome (MetS) is associated with the development of cardiovascular disease (CVD) and type 2 diabetes. Decreases in circulating adiponectin and ghrelin have been associated with MetS. Our primary aim was to evaluate the relationship of MetS with adiponectin and ghrelin for Cuban Americans with and without type 2 diabetes. Methods: Cross-sectional study of 367 adults, self identified as Cuban extraction and randomly recruited from a mailing list of Broward and Miami-Dade counties. Fasted whole blood for adiponectin (ADPN) was collected using K3EDTA tubes and measured by ELISA. Ghrelin was assayed with fasted blood plasma by Enzyme Immunometric Assay. MetS and 10-year risk for coronary heart disease (CHD) were determined using the ATP III criteria. Results: Adiponectin (F=51.8, R2 =0.21 p<0.001) and ghrelin (F=12.77, R 2 =0.06, p<0.001) differed by diabetes status (ANOVA) not age and gender. In stepwise linear regression models triglyceride levels ≥ 150 mg/dL negatively corresponded (coefficient = -0.23) with ghrelin levels for persons without diabetes (F=7.45, R2 =0.053, p=0.007); abdominal obesity and fasting plasma glucose predicted high sensitivity C-reactive protein (hs-CRP) for persons with and without diabetes (F=16.3, R2 = 0.144, p <0.001). Conclusion: Low ghrelin levels were associated with MetS regardless of diabetes status. High adiponectin levels were related to a low probability for those without diabetes only. There was a positive association of hs-CRP with BMI, MetS and number of MetS components.

Multiparameter flow cytometric analysis of C -reactive protein binding to human-derived cell lines and peripheral blood monocytes

C-reactive protein (CRP), a normally occurring human plasma protein may become elevated as much as 1,000 fold during disease states involving acute inflammation or tissue damage. Through its binding to phosphorylcholine in the presence of calcium, CRP has been shown to potentiate the activation of complement, stimulate phagocytosis and opsonize certain microorganisms. Utilizing a flow cytometric functional ligand binding assay I have demonstrated that a monocyte population in human peripheral blood and specific human-derived myelomonocytic cell lines reproducibly bind an evolutionarily conserved conformational pentraxin epitope on human CRP through a mechanism that does not involve its ligand, phosphorylcholine. ^ A variety of cell lines at different stages of differentiation were examined. The monocytic cell line, THP-1, bound the most CRP followed by U937 and KG-1a cells. The HL-60 cell line was induced towards either the granulocyte or monocyte pathway with DMSO or PMA, respectively. Untreated HL-60 cells or DMSO-treated cells did not bind CRP while cells treated with PMA showed increased binding of CRP, similar to U-937 cells. T cell and B-cell derived lines were negative. ^ Inhibition studies with Limulin and human SAP demonstrated that the binding site is a conserved pentraxin epitope. The calcium requirement necessary for binding to occur indicated that the cells recognize a conformational form of CRP. Phosphorylcholine did not inhibit the reaction therefore the possibility that CRP had bound to damaged membranes with exposed PC sites was discounted. ^ A study of 81 normal donors using flow cytometry demonstrated that a majority of peripheral blood monocytes (67.9 ± 1.3, mean ± sem) bound CRP. The percentage of binding was normally distributed and not affected by gender, age or ethnicity. Whole blood obtained from donors representing a variety of disease states showed a significant reduction in the level of CRP bound by monocytes in those donors classified with infection, inflammation or cancer. This reduction in monocyte populations binding CRP did not correlate with the concentration of plasma CRP. ^ The ability of monocytes to specifically bind CRP combined with the binding reactivity of the protein itself to a variety of phosphorylcholine containing substances may represent an important bridge between innate and adaptive immunity. ^