title: Urinary Excretion of Select Dietary Polyphenol Metabolites Is Associated with a Lower Risk of Type 2 Diabetes in Proximate but Not Remote Follow-Up in a Prospective Investigation in 2 Cohorts of US Women.
abstract: BACKGROUND
  Polyphenols are phytochemicals that possess antioxidant and anti-inflammatory properties and improve glucose metabolism in animal experiments, although data from prospective epidemiologic studies examining polyphenol intakes in relation to type 2 diabetes (T2D) risk are inconsistent.
  
  
  OBJECTIVE
  We examined urinary excretion of select flavonoid and phenolic acid metabolites, as biomarkers of intake, in relation to T2D risk.
  
  
  METHODS
  Eight polyphenol metabolites (naringenin, hesperetin, quercetin, isorhamnetin, catechin, epicatechin, caffeic acid, and ferulic acid) were quantified in spot urine samples by liquid chromatography/mass spectrometry among 1111 T2D case-control pairs selected from the Nurses' Health Study (NHS) and NHSII.
  
  
  RESULTS
  Higher urinary excretion of hesperetin was associated with a lower T2D risk after multivariate adjustment: the OR comparing top vs. bottom quartiles was 0.68 (95% CI: 0.49, 0.96), although a linear trend was lacking (P = 0.30). The other measured polyphenols were not significantly associated with T2D risk after multivariate adjustment. However, during the early follow-up period [≤ 4.6 y (median) since urine sample collection], markers of flavanone intakes (naringenin and hesperetin) and flavonol intakes (quercetin and isorhamnetin) were significantly associated with a lower T2D risk. The ORs (95% CIs) comparing extreme quartiles were 0.61 (0.39, 0.98; P-trend: 0.03) for total flavanones and 0.55 (0.33, 0.92; P-trend: 0.04) for total flavonols (P-interaction with follow-up length: ≤ 0.04). An inverse association was also observed for caffeic acid during early follow-up only: the OR was 0.52 (95% CI: 0.32, 0.84; P-trend: 0.03). None of these markers was associated with T2D risk during later follow-up. Metabolites of flavan-3-ols and ferulic acid were not associated with T2D risk in either period.
  
  
  CONCLUSIONS
  These results suggest that specific flavonoid subclasses, including flavanones and flavonols, as well as caffeic acid, are associated with a lower T2D risk in relatively short-term follow-up but not during longer follow-up. Substantial within-person variability of the metabolites in single spot urine samples may limit the ability to capture associations with long-term disease risk.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Nutrition and qisun@hsph.harvard.edu.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Division of Preventive and Behavioral Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA;
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Wedick
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA;
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.affiliation: Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China;
authors.forename: An
authors.initials: A
authors.lastname: Pan
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Townsend
authors.affiliation: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; and.
authors.forename: Aedin
authors.initials: A
authors.lastname: Cassidy
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI.
authors.forename: Adrian A
authors.initials: AA
authors.lastname: Franke
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA;
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA;
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Nutrition and Saw Swee Hock School of Public Health and Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore;
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002109:Caffeic Acids / Q000652:urine; D016022:Case-Control Studies; D002392:Catechin / Q000652:urine; D003373:Coumaric Acids / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D044950:Flavanones / Q000652:urine; D005500:Follow-Up Studies; D006569:Hesperidin / Q000652:urine; D006801:Humans; D062385:Hydroxybenzoates / Q000652:urine; D008875:Middle Aged; D015596:Nutrition Assessment; D059808:Polyphenols / Q000652:urine*; D011446:Prospective Studies; D011794:Quercetin / Q000031:analogs & derivatives / Q000652:urine; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D002109:Caffeic Acids; D003373:Coumaric Acids; D044950:Flavanones; D062385:Hydroxybenzoates; D059808:Polyphenols; C047368:3-methylquercetin; D002392:Catechin; D011794:Quercetin; C004999:ferulic acid; D006569:Hesperidin; C005273:naringenin; C017616:phenolic acid; C013015:hesperetin; C040048:caffeic acid; C028610:flavanone
keywords: diabetes; nutrition; polyphenol; urinary biomarker; women