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

TY - JOUR

T1 - Pre-diagnostic plasma enterolactone concentrations are associated with lower mortality among individuals with type 2 diabetes

T2 - A case-cohort study in the Danish Diet, Cancer and Health cohort

AU - Eriksen, Anne Kirstine

AU - Kyrø, Cecilie

AU - Nørskov, Natalja P

AU - Frederiksen, Kirsten

AU - Knudsen, Knud Erik Bach

AU - Overvad, Kim

AU - Landberg, Rikard

AU - Tjønneland, Anne

AU - Olsen, Anja

N1 - (Ekstern)

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

KW - Case-cohort

KW - Enterolactone

KW - Mortality

KW - Prognosis

KW - Type 2 diabetes

U2 - 10.1007/s00125-019-4854-9

DO - 10.1007/s00125-019-4854-9

M3 - Journal article

C2 - 30963187

AN - SCOPUS:85064220670

SN - 0012-186X

VL - 62

SP - 959

EP - 969

JO - Diabetologia

JF - Diabetologia

IS - 6

ER -