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08.04.2019 | Article | Ausgabe 6/2019 Open Access

Diabetologia 6/2019

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

Diabetologia > Ausgabe 6/2019
Anne K. Eriksen, Cecilie Kyrø, Natalja P. Nørskov, Kirsten Frederiksen, Knud-Erik Bach Knudsen, Kim Overvad, Rikard Landberg, Anne Tjønneland, Anja Olsen
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The online version of this article (https://​doi.​org/​10.​1007/​s00125-019-4854-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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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.


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.


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 (log2) (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.


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.

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