Pre-diagnostic plasma enterolactone concentrations are associated with lower mortality among individuals with type 2 diabetes: A case-cohort study in the Danish Diet, Cancer and Health cohort

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Anne Kirstine Eriksen, Cecilie Kyrø, Natalja P Nørskov, Kirsten Frederiksen, Knud Erik Bach Knudsen, Kim Overvad, Rikard Landberg, Anne Tjønneland, Anja Olsen

Aims/hypothesis: The phytoestrogen enterolactone is a gut microbiota-derived metabolite of plant lignans with suggested beneficial properties for health. In the current study, we investigated the association between pre-diagnostic plasma enterolactone concentrations and mortality among individuals diagnosed with type 2 diabetes.

Methods: In a population of people diagnosed with diabetes, nested within the Danish Diet, Cancer and Health cohort, we conducted a case-cohort study including a random sample of n = 450 cases (deceased) and a randomly selected subcohort of n = 850 (in total n = 617 deaths). Information on diagnosis, vital status and cause of death was obtained from Danish registers. Cox proportional hazard models with special weighting were applied to assess all-cause and cause-specific mortality.

Results: The median enterolactone concentration of the current population was low, 10.9 nmol/l (5th percentile to 95th percentile: 1.3–59.6), compared with previously reported concentrations from the Diet, Cancer and Health cohort. Pre-diagnostic enterolactone concentrations were associated with lower all-cause mortality when assessed linearly per doubling in concentration (log 2 ) (HR 0.91 [95% CI 0.85, 0.96]) and according to quartiles (HR 0.63 [95% CI 0.48, 0.84]) for the highest quartile of enterolactone compared with the lowest quartile. For cause-specific mortality, only death from diabetes (registered as underlying cause of death) reached statistical significance.

Conclusions/interpretation: Based on this large cohort of people with diabetes with detailed and complete baseline and follow-up information, pre-diagnostic enterolactone concentrations were inversely associated with mortality. To our knowledge, this is the first study on enterolactone and type 2 diabetes mortality. Our findings call for further exploration of enterolactone in type 2 diabetes management.

Original languageEnglish
JournalDiabetologia
Volume62
Issue number6
Pages (from-to)959-969
Number of pages11
ISSN0012-186X
DOIs
Publication statusPublished - 2019

    Research areas

  • Case-cohort, Enterolactone, Mortality, Prognosis, Type 2 diabetes

ID: 217115668