Associations of circulating very-long-chain saturated fatty acids and incident type 2 diabetes: a pooled analysis of prospective cohort studies

BACKGROUND: Saturated fatty acids (SFAs) of different chain lengths have unique metabolic and biological effects, and a small number of recent studies suggest that higher circulating concentrations of the very-long-chain SFAs (VLSFAs) arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are associated with a lower risk of diabetes. Confirmation of these findings in a large and diverse population is needed. OBJECTIVE: We investigated the associations of circulating VLSFAs 20:0, 22:0, and 24:0 with incident type 2 diabetes in prospective studies. METHODS: Twelve studies that are part of the Fatty Acids and Outcomes Research Consortium participated in the analysis. Using Cox or logistic regression within studies and an inverse-variance-weighted meta-analysis across studies, we examined the associations of VLSFAs 20:0, 22:0, and 24:0 with incident diabetes among 51,431 participants. RESULTS: There were 14,276 cases of incident diabetes across participating studies. Higher circulating concentrations of 20:0, 22:0, and 24:0 were each associated with a lower risk of incident diabetes. Pooling across cohorts, the RR (95% CI) for incident diabetes comparing the 90th percentile to the 10th percentile was 0.78 (0.70, 0.87) for 20:0, 0.84 (0.77, 0.91) for 22:0, and 0.75 (0.69, 0.83) for 24:0 after adjustment for demographic, lifestyle, adiposity, and other health factors. Results were fully attenuated in exploratory models that adjusted for circulating 16:0 and triglycerides. CONCLUSIONS: Results from this pooled analysis indicate that higher concentrations of circulating VLSFAs 20:0, 22:0, and 24:0 are each associated with a lower risk of diabetes.

  • Fretts A M
  • Imamura F
  • Marklund M
  • Micha R
  • Wu J H Y
  • Murphy R A
  • Chien K L
  • McKnight B
  • Tintle N
  • Forouhi N G
  • Qureshi W T
  • Virtanen J K
  • Wong K
  • Wood A C
  • Lankinen M
  • Rajaobelina K
  • Harris T B
  • Djousse L
  • Harris B
  • Wareham N J
  • Steffen L M
  • Laakso M
  • Veenstra J
  • Samieri C
  • Brouwer I A
  • Yu C I
  • Koulman A
  • Steffen B T
  • Helmer C
  • Sotoodehnia N
  • Siscovick D
  • Gudnason V
  • Wagenknecht L
  • Voutilainen S
  • Tsai M Y
  • Uusitupa M
  • Kalsbeek A
  • Berr C
  • Mozaffarian D
  • Lemaitre R N


  • Am J Clin Nutr
Apr 1;109(4):1216-1223