ABSTRACT: BACKGROUND:A diet high in trans-fatty acids (TFA) induces insulin resistance in rodent models and primates. However, previous epidemiological studies on the association between TFAs, based primarily on self-reported intake from the diet, and diabetes in humans have yielded conflicting results. Herein we examined the associations of objectively measured plasma TFA concentrations with diabetes in a large population-based study among US adults. METHODS:We included 3801 participants aged ?20?years from the National Health and Nutrition Examination Survey 1999-2000 and 2009-10. Four major TFAs, namely palmitelaidic acid (C16:1 n-7t), elaidic acid (C18:1 n-9t), vaccenic acid (C18:1 n-7t), and linolelaidic acid (C18:2 n-6t, 9t), were measured in fasting plasma using gas chromatography-mass spectrometry. Diabetes was defined by self-reported physician diagnosis, plasma fasting glucose ?126?mg/dL, or HbA1c ?6.5%. RESULTS:After adjustment for other major risk factors, the odds ratios (95% confidence intervals) of diabetes comparing the highest with lowest quintile of plasma TFAs was 2.19 (1.27-3.79) for total TFAs (Ptrend ?=?0.01), 2.34 (1.48-3.72) for elaidic acid (Ptrend ?=?0.0004), 1.33 (0.82-2.15) for linolelaidic acid (Ptrend ?=?0.18), 1.58 (0.97-2.58) for palmitelaidic acid (Ptrend ?=?0.02), and 1.64 (0.95-2.84) for vaccenic acid (Ptrend ?=?0.08). In addition, total TFAs, elaidic acid, palmitelaidic acid, and vaccenic acid were significantly associated with fasting glucose, fasting insulin, the insulin resistance index, and HbA1c. CONCLUSIONS:In a nationally representative population, plasma TFAs, in particular elaidic acid, were positively associated with diabetes and biomarkers of glucose metabolism.