Dataset Information

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.

SUBMITTER: Eriksen AK

PROVIDER: S-EPMC6509069 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

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.

Eriksen Anne K AK Kyrø Cecilie C Nørskov Natalja P NP Frederiksen Kirsten K Bach Knudsen Knud-Erik KE Overvad Kim K Landberg Rikard R Tjønneland Anne A Olsen Anja A

Diabetologia 20190408 6

<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>In a population of people diagnosed with diabetes, nested within the Danish Diet, Cancer and Health cohort, we conducted a case-cohort study includ ...[more]

PMID: 30963187

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Project description:Lignans are plant-based phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast carcinogenesis. Retrospective studies have observed decreased breast cancer risk associated with high circulating enterolactone concentrations, a biomarker of lignan intake, but results from prospective studies are conflicting. To prospectively examine this association, we measured plasma enterolactone levels in 802 breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses' Health Study II cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known breast cancer risk factors, to calculate relative risks (RR) and 95 % confidence intervals (CI). Compared to women with enterolactone concentrations ?4 nmol/L, the multivariate-adjusted RRs for breast cancer were 1.18 (95 % CI 0.86-1.62), 0.91 (95 % CI 0.66-1.25), and 0.96 (95 % CI 0.70-1.33) for women with enterolactone levels in the second to the fourth quartiles, respectively; P trend = 0.60. Results were similar across tumors defined by estrogen and progesterone receptor status. Among premenopausal women with follicular estradiol levels below the median (<47 pg/mL), women in the highest category of enterolactone levels had a 51 % lower breast cancer risk compared to those in the lowest category (95 % CI 0.27-0.91); P trend = 0.02. No association was observed among women with high-follicular estradiol levels (?47 pg/mL), (comparable RR = 1.39, 95 % CI 0.73-2.65; P interaction = 0.02). We did not observe an overall association between plasma enterolactone and breast cancer risk in a large nested case-control study of US women. However, a significant inverse association was observed among premenopausal women with low-follicular estradiol levels, suggesting that enterolactone may be important in a low-estrogen environment. This should be confirmed in future studies.

Project description:BackgroundDyslipidemia is reported in 27 - 43% of children and adolescents with overweight/obesity and tracks into adulthood, increasing the risk of cardiovascular morbidity. Cut-off values for fasting plasma lipid concentrations are typically set at fixed levels throughout childhood. The objective of this cross-sectional study was to generate fasting plasma lipid references for a Danish/North-European White population-based cohort of children and adolescents, and investigate the prevalence of dyslipidemia in this cohort as well as in a cohort with overweight/obesity.MethodsA population-based cohort of 2141 (1275 girls) children and adolescents aged 6 - 19 (median 11.5) years was recruited from 11 municipalities in Denmark. Additionally, a cohort of children and adolescents of 1421 (774 girls) with overweight/obesity aged 6 - 19 years (median 11.8) was recruited for the study. Height, weight, and fasting plasma lipid concentrations were measured on all participants. Smoothed reference curves and percentiles were generated using the Generalized Additive Models for Location Scale and Shape package in the statistical software R.ResultsIn the population-based cohort, plasma concentrations of total cholesterol (TC) (P < 0.05), low-density lipoprotein cholesterol (LDL) (P < 0.005), and high-density lipoprotein cholesterol (HDL) (P < 0.005) were higher in the youngest compared to the oldest tertile. Fasting plasma levels of triglycerides (TG) (P < 0.005) increased with age in both sexes. In boys, non-HDL was lower in the oldest compared to the youngest tertile (P < 0.0005). Concentrations of TC, LDL, non-HDL, and TG were higher (P < 0.05), and HDL lower (P < 0.05) in the cohort with overweight/obesity in both sexes and for all ages except for TC in the youngest girls. The overall prevalence of dyslipidemia was 6.4% in the population-based cohort and 28.0% in the cohort with overweight/obesity. The odds ratio for exhibiting dyslipidemia in the cohort with overweight/obesity compared with the population-based cohort was 6.2 (95% CI: 4.9 - 8.1, P < 2*10-16).ConclusionFasting plasma lipid concentrations change during childhood and adolescence and differ with sex and age. Children and adolescents with obesity have increased concentrations of circulating lipids and exhibit an increased prevalence of dyslipidemia.Trial registrationThe study is part of The Danish Childhood Obesity Biobank; ClinicalTrials.gov ID-no.: NCT00928473 retrospectively registered on June 25th 2009.

Dataset Information

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.

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

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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