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.

Abstract

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 (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.

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.

• Authors: Anne K Eriksen, Cecilie Kyrø, Natalja P Nørskov, Kirsten Frederiksen, Knud-Erik Bach Knudsen, Kim Overvad, Rikard Landberg, Anne Tjønneland, Anja Olsen
• Journal: Diabetologia (Diabetologia) Vol. 62 Issue 6 Pg. 959-969 (06 2019) ISSN: 1432-0428 [Electronic] Germany
• PMID: 30963187 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lignans
• 4-Butyrolactone
• 2,3-bis(3'-hydroxybenzyl)butyrolactone

Topics

• 4-Butyrolactone (analogs & derivatives, blood, metabolism)
• Aged
• Case-Control Studies
• Cohort Studies
• Diabetes Mellitus, Type 2 (blood, metabolism, mortality, pathology)
• Female
• Humans
• Lignans (blood, metabolism)
• Male
• Middle Aged
• Neoplasms (blood, metabolism, mortality, pathology)
• Prognosis
• Random Allocation