<p>Breastfeeding is inversely associated with cardiometabolic disease incidence in prospective studies; however, the metabolic pathways underlying these associations remain largely unknown. Here, we derive a plasma metabolomic score of lifetime total duration of breastfeeding using elastic net regularized regression in Nurses’ Health Studies (<i>n</i> = 4349) and replicate in the Women’s Health Initiative (n = 2088). Data include 181 untargeted plasma metabolites profiled by liquid chromatography mass spectrometry using blood samples collected in mid-life, and self-reported lifetime total duration of breastfeeding. We then examine the associations between the metabolite-based breastfeeding score and risk of T2D and CVD using multivariable Cox regression models and replicated in two external cohorts. The metabolite-based breastfeeding score comprised of 5 metabolites (i.e., C54:2 triglyceride, C56:2 triglyceride, C56:3 triglyceride, cotinine, indole-3-propionate), which show a modest but statistically significant correlation with lifetime total duration of breastfeeding. The metabolite-based breastfeeding score significantly inversely associate with T2D incidence (HR = 0.76, 95%CI = 0.71-0.82) and with CVD incidence (HR = 0.88, 95%CI = 0.84-0.93) independent of T2D and CVD risk factors. We identify plasma metabolite profiles in mid-life associated with breastfeeding duration, which is also linked to CVD and T2D risk.</p>

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Plasma metabolomic signature of breastfeeding and risk of cardiometabolic diseases

  • Anna Birukov,
  • Nan Lin,
  • Jennifer Mongiovi,
  • Cristina Razquin,
  • Fenglei Wang,
  • Zhila Semnani-Azad,
  • Anne-Julie Tessier,
  • Marta Guasch-Ferré,
  • Sylvia H. Ley,
  • JoAnn E. Manson,
  • Rachel G. Sinkey,
  • Bernhard Haring,
  • Aladdin H. Shadyab,
  • Raji Balasubramanian,
  • Miguel A. Martínez-González,
  • Kathryn M. Rexrode,
  • Frank B. Hu,
  • Cuilin Zhang,
  • Oana A. Zeleznik,
  • Naoko Sasamoto

摘要

Breastfeeding is inversely associated with cardiometabolic disease incidence in prospective studies; however, the metabolic pathways underlying these associations remain largely unknown. Here, we derive a plasma metabolomic score of lifetime total duration of breastfeeding using elastic net regularized regression in Nurses’ Health Studies (n = 4349) and replicate in the Women’s Health Initiative (n = 2088). Data include 181 untargeted plasma metabolites profiled by liquid chromatography mass spectrometry using blood samples collected in mid-life, and self-reported lifetime total duration of breastfeeding. We then examine the associations between the metabolite-based breastfeeding score and risk of T2D and CVD using multivariable Cox regression models and replicated in two external cohorts. The metabolite-based breastfeeding score comprised of 5 metabolites (i.e., C54:2 triglyceride, C56:2 triglyceride, C56:3 triglyceride, cotinine, indole-3-propionate), which show a modest but statistically significant correlation with lifetime total duration of breastfeeding. The metabolite-based breastfeeding score significantly inversely associate with T2D incidence (HR = 0.76, 95%CI = 0.71-0.82) and with CVD incidence (HR = 0.88, 95%CI = 0.84-0.93) independent of T2D and CVD risk factors. We identify plasma metabolite profiles in mid-life associated with breastfeeding duration, which is also linked to CVD and T2D risk.