Outside pregnancy, acute caffeine consumption is associated with insulin resistance. We investigated if during pregnancy plasma concentrations of caffeine and its metabolite, paraxanthine, were associated with insulin resistance. Caffeine, paraxanthine, glucose, and insulin were measured and insulin resistance estimated by homeostasis model assessment (HOMA) in banked samples from 251 fasting subjects at mean gestational age of 20.3 ± 2.0 weeks. Analysis of covariance and adjusted logistic regression were performed. Most (96.4%) women had caffeine and/or paraxanthine present. Caffeine concentrations in the upper two quartiles (>266 ng/mL) were associated with threefold higher odds of having higher insulin resistance estimated by log HOMA ≥75th percentile (third quartile odds ratio [OR], 3.02; 95% confidence interval [CI]: 1.21 to 7.54 and fourth quartile OR, 2.95; 95% CI: 1.19 to 7.31). Paraxanthine concentrations in the upper quartile (>392 ng/mL) were also associated with threefold higher odds of having higher insulin resistance (OR, 3.04; 95% CI: 1.28 to 7.25). Adjusted mean HOMA in the first caffeine-to-paraxanthine ratio quartile was 1.5 ± 2.2 versus 1.3 ± 2.3 in the fourth quartile ( P < 0.01). Both high caffeine and paraxanthine concentrations were associated with insulin resistance, but slow versus fast metabolism did not make an important difference.
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