Lower urinary concentrations of lignan metabolites are associated with a higher risk for type 2 diabetes, new prospective data from the Nurses' Health Study (NHS) suggest.
Lignans are plant-synthesized chemicals commonly found in fiber-containing foods. Results from the study, believed to be the first to prospectively examine urinary concentrations of lignan metabolites in relation to type 2 diabetes risk, were published online February 18 in Diabetes Care by Qi Sun, MD, assistant professor of medicine at Brigham and Women's Hospital and Harvard Medical School, Boston.
"Our findings further endorse the recommendations that promote consumption of a plant-based diet, [including] whole grains, fruits, vegetables, red wine, and coffee, for primary prevention of diabetes," Dr. Sun told Medscape Medical News.
High Metabolites, Low Diabetes Risk
Dr. Sun and colleagues analyzed data for 1107 study subjects who did not have type 2 diabetes, cardiovascular disease, or cancer at baseline but who developed diabetes during follow-up. These included 452 from the original NHS, which enrolled 121,700 women aged 30 to 55 years in 1976, and 655 from a second cohort (NHS II) of 116,686 women enrolled in 1989 at ages 25 to 42.
Blood and urine samples were collected in 2000–2001 for NHS and in 1995–2000 for NHS II. Follow-up continued through 2008 for NHS and 2007 for NHS II.
Each subject from both cohorts was matched randomly by age at sample collection, month of sample collection, fasting status (more than 8 hours or not), first morning urine (yes or no), race, menopausal status, and hormone-replacement therapy for the NHS II cohort with a study subject who did not develop type 2 diabetes during follow-up. Dietary consumption was assessed by food frequency questionnaires.
Those who went on to develop type 2 diabetes had lower baseline urinary levels of the 2 major lignan metabolites enterodiol and enterolactone than did the controls, with an approximately 2-fold difference for enterolactone. These lignan metabolites, produced via metabolism by intestinal microbiota, are more biologically active than the lignans themselves, Dr. Sun and colleagues explain.
Prior to adjustment for factors other than those used to match the cases and controls, there was a significantly reduced risk for type 2 diabetes among those in the highest quartile for both enterolignans compared with the lowest quartile (P < .0001 for both cohorts).
After further adjustment for diabetes risk factors — particularly body mass index (BMI) — the relationship remained significant for the 2 metabolites in the NHS II cohort (P = .003) but not in NHS (P = .24). Higher enterolignan levels correlated with a lower BMI for both cohorts, the authors note.
There was a dose-response relationship, with a significant linear trend for the association between enterolactone levels and diabetes risk (P for linearity = .007) and for the 2 metabolites combined (P for linearity = .009).
In general, the association between higher enterolactone concentrations and reduced diabetes risk was greater among the subjects who were overweight or obese, the authors note.
And, after further adjustment for overall diet quality, there was still a significant association between enterolactone and diabetes risk.
Still Many Unanswered Questions
The mechanisms for the putative effects of lignans aren't well understood, but in vitro studies suggest that antioxidation might play a role. Also, enterolactone activates a specific estrogen receptor in vitro and in mice, and some evidence suggests that this receptor could play a role in maintaining body weight and insulin sensitivity.
"Further studies are needed to replicate these findings and to explore potential mechanisms underlying the observed association," Dr. Sun and his colleagues conclude.
Beyond the general category of plant-based foods, this study can't provide many more specifics regarding which particular foods contain the greatest lignan concentrations. In fact, one foodstuff known to have a high lignan concentration, flaxseed, could not be assessed by the food diaries.
"Almost all plant-based foods contain lignans, the food precursors of enterolignans, with various contents. We cannot precisely ascribe the enterolignans to specific foods. Based on the composition of diet, food sources of enterolignans may vary substantially from population to population," Dr. Sun told Medscape Medical News.
Another yet-unanswered question is whether consuming probiotics, which influence the gut microbiota that metabolize lignans, might reduce the risk for type 2 diabetes.
"It is currently unknown whether probiotics can specifically promote the bacteria that are producing the enterolignans. It is certainly an important question that should be addressed in future research. Yogurt intake has been consistently associated with lower type 2 diabetes risk," Dr. Sun noted.
In the next step of this research, he told Medscape Medical News, "we plan to evaluate the interrelations among lignan food sources, gut microbiota, enterolignans, and cardiometabolic risk factors."
This study was funded by research grants from the National Institutes of Health. The authors have reported no relevant financial relationships.
Diabetes Care. Published online February 18, 2014. Abstract
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Cite this: Plant-Based Food Component May Reduce Diabetes Risk - Medscape - Feb 24, 2014.