Abstract
Aims/hypothesisThe 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.MethodsIn 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.ResultsThe 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/interpretationBased 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.
Highlights
Dietary factors, such as whole-grain intake, have been related to a lower mortality from type 2 diabetes [1], and soluble fibre has been shown to reduce HbA1c and fasting plasma glucose in individuals diagnosed with type 2 diabetes [2]
Inclusion in the register was based on the following diagnostic criteria: (1) registration in the National Patient Register with a diagnosis of diabetes; (2) registration of chiropody in the Danish National Health Service Register (NHSR); (3) five blood-glucose measurements in a 1 year period in the Danish NHSR; (4) two blood-glucose measurements per year for five consecutive years in NHSR; (5) purchase of oral glucose-lowering drugs in the Danish National Prescription Registry (DNPR) [16] and (6) purchase of prescribed insulin recorded in DNPR
The case-cohort study population included 1183 individuals diagnosed with type 2 diabetes, a randomly selected subcohort of 841, and 342 deceased cases in the sampled deceased group
Summary
Dietary factors, such as whole-grain intake, have been related to a lower mortality from type 2 diabetes [1], and soluble fibre has been shown to reduce HbA1c and fasting plasma glucose in individuals diagnosed with type 2 diabetes [2]. Enterolactone, a phytoestrogen metabolite produced by the gut microbiota after ingestion of dietary lignans, has been studied widely for its protective effects in chronic disease [6]. The main dietary sources include seeds, whole grains, nuts and fibre-rich fruits and vegetables, with smaller amounts found in coffee, tea, wine and beer [7]. The metabolism of lignans into enterolignans (enterodiol and enterolactone) is affected by several factors including smoking, obesity, dietary sources of lignans [6], gut microbiota [8] and use of antibiotics [9]
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