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Endothelial dysfunction increases risk for type 2 diabetes. We examined whether variation in the gene for E-selectin (SELE), a biomarker of endothelial dysfunction, was associated with levels of E-selectin or diabetes quantitative traits (including fasting levels of insulin and hemoglobin A(1c)) in 719 nondiabetic participants of the Nurses' Health Study or with risk of diabetes in 602 incident (over 10 years of follow-up) cases and 655 control women matched for age, race, and fasting status. Variation in three single nucleotide polymorphisms previously associated with cardiovascular disease risk and having effects on E-selectin function, S128R, G98T, and L554F, was not significantly (p > 0.05) associated with levels of E-selectin or diabetes quantitative traits, or with risk of incident diabetes in the primary analysis. Among women with low levels of subclinical inflammation (C-reactive protein levels below the population median), S128R R allele carriers had a diabetes risk factor-adjusted relative risk of incident diabetes of 1.71 (95% confidence interval, 1.04 to 2.81) relative to those with the SS genotype. Apart from an association in this subgroup, we conclude that the E-selectin variants we examined are not important genetic risk factors for type 2 diabetes in women.

Objective: Efficient detection of impaired glucose tolerance (IGT) is needed to implement type 2 diabetes prevention interventions., Research Design and Methods: We assessed the capacity of the metabolic syndrome (MetS) to identify IGT in a cross-sectional analysis of 3,326 Caucasian Framingham Offspring Study (FOS), 1,168 Caucasian and 1,812 Mexican-American San Antonio Heart Study (SAHS), 1,983 Mexico City Diabetes Study (MCDS), and 452 Caucasian, 407 Mexican-American, and 290 African-American Insulin Resistance Atherosclerosis Study (IRAS) men and women aged 30-79 years who had a clinical examination and an oral glucose tolerance test (OGTT) during 1987-1996. Those with diabetes treatment or fasting plasma glucose > or =7.0 mmol/l were excluded (MetS was defined by Third Report of the National Cholesterol Education Program's Adult Treatment Panel criteria and IGT as 2-h postchallenge glucose [2hPG] > or =7.8 mmol/l). We calculated positive (PPV) and negative predictive values (NPV), population attributable risk percentages (PAR%), age- and sex-adjusted odds ratios (ORs), and areas under the receiver operating characteristic curve (AROCs) associated with MetS traits., Results: Among FOS, SAHS, and MCDS subjects, 24-43% had MetS and 15-23% had IGT (including 2-5% with 2hPG > or =11.1 mmol/l). Among those with MetS, OR for IGT were 3-4, PPV were 0.24-0.41, NPV were 0.84-0.91, and PAR% were 30-40%. Among subjects with MetS defined by impaired fasting glucose (IFG) and any two other traits, OR for IGT were 9-24, PPV were 0.62-0.89, NPV were 0.78-0.87, and PAR% were 3-12%. Among IRAS subjects, 24-34% had MetS and 37-41% had IGT. Among those with MetS, ORs for IGT were 3-6, PPVs were 0.57-0.73, and NPVs were 0.67-0.72. In logistic regression models, IFG, large waist, and high triglycerides were independently associated with IGT (AROC 0.71-0.83) in all study populations., Conclusions: The MetS, especially defined by IFG, large waist, and high triglycerides, efficiently identifies subjects likely to have IGT on OGTT and thus be eligible for diabetes prevention interventions.