Circulating Osteopontin levels are associated with insulin resistance and inflammation in type 2 diabetes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 780-806-Determinants of Insulin Resistance & Associated Metabolic Disturbances
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-791
Giuseppe Daniele*, Teresa Vanessa Fiorentino, Francesco Andreozzi, Rodolfo Guardado Mendoza, Amalia Gastaldelli, Deidre Winnier, Christopher Jenkinson, Devjit Tripathy and Franco Folli
University of Texas Health Science Center, San Antonio, TX
Obesity and type 2 diabetes are associated to insulin resistance and low-grade inflammation. Osteopontin (OPN) is a multifunctional protein expressed in activated macrophages and T-cells, osteoclasts, hepatocytes, smooth muscle and endothelial cells. OPN plays a role in inflammatory disorders, such as rheumatoid arthritis, atherosclerosis, diabetic vascular diseases, and hepatic inflammation. Plasma OPN levels are increased in obese as compared to lean subjects. The aim of the study was to compare the circulating concentrations of OPN in normal glucose tolerance (control subjects) and type 2 diabetic subjects and its relation with insulin sensitivity, insulin secretion and inflammatory state. In a cross-sectional study, 20 type 2 diabetic patients treated with metformin and/or sulfonylurea and 18 control subjects were studied. All subjects received: OGTT, euglycemic hyperinsulinemic clamp, DEXA scan and measurement of plasma OPN, TNF-α, IL-6, MCP-1 and fractalkine (FRK). Type 2 diabetics exhibited significantly increased circulating OPN concentrations as compared with control subjects (6.1±1.2 vs. 3.1±0.7 ng/ml, P=0.04). Type 2 diabetics showed higher circulating concentrations of proinflammatory cytokines than control subjects (TNF-α: 14.1±2.2 vs. 9.0±0.7 pg/ml, P=0.02, MCP-1: 420.4±42.4 vs. 224.6±23.5 pg/ml, P<0.001, fractalkine: 44.8±8.3 vs. 34.2±13.4, P=0.04). Significant positive correlations were found among OPN levels, fasting plasma glucose (r=0.45, P=0.005), 1 hour OGTT plasma glucose (r=0.37, P=0.02), 2 hours OGTT plasma glucose (r=0.36, P=0.02) and fasting insulin (r=0.42, P=0.008). Consistently, negative correlations were found between OPN levels and M/I value (r= -0.41, P=0.01) and disposition index (r= -0.32, P=0.04). The area under the ROC curve for OPN levels as a predictor of M value less than 4 (insulin resistant state) was 0.79 (95% CI, 0.63-0.94; p=0.004). Adipose tissue insulin resistance index (fasting FFA x fasting insulin) was higher in type 2 diabetes subjects as compared to control subjects (4.1±0.9 vs. 3.0±0.5, P=0.03) and it was positively correlated with OPN levels (r= 0.33, P=0.04). Higher OPN levels are associated with insulin resistance, reduced insulin secretion and worse inflammatory state. These findings reveal a potential therapeutic impact of targeting OPN that could improve metabolic regulation and cardiovascular risk in type 2 diabetic patients

Nothing to Disclose: GD, TVF, FA, RG, AG, DW, CJ, DT, FF

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