Review Article

Dietary Polyphenols, Mediterranean Diet, Prediabetes, and Type 2 Diabetes: A Narrative Review of the Evidence

Table 2

Prospective studies evaluating polyphenol intake on the risk of type 2 diabetes.

First author, publication year, study name, locationSexFollow-up (years)Age at baseline (years) (mean)Number of cases/participantsExposure assessment and case ascertainmentTypes of polyphenols analyzedRelative risk (95% CI) (highest versus lowest category)Adjustment for covariates

Knekt 2002, The FMCHES, FinlandBoth1839.3 ± 15.8526/9878FFQ > 100 items/identified from Social Insurance Institution FinlandQuartiles of dietary intake of major flavonoid subclasses (total flavonoid intake 24.2 mg/d)Q4 versus Q1 0.98 (0.78, 1.24)Sex and age
Song 2005, WHS, United StatesF8.8≥45 (53)1614/38,018131-item semiquantitative validated FFQ/self-report and confirmed with supplementary questionnaire about symptoms, American Diabetes Criteriamg/d quintiles of dietary intake of total or individual flavonols and flavones and flavonoid-rich foodsQ5 versus Q1 (median intake mg/d: 47.2 versus 8.85) of total flavonoids 0.92 (0.78, 1.09)Age, BMI, energy, total fat, smoking, exercise, alcohol use, history of hypertension, high cholesterol, family history of diabetes, fiber intake, glycemic load, magnesium
Nettleton 2006, Iowa Women’s Health Study, United StatesF1855–69 (61)3395/35,816Validated 127-item FFQ/self-reported were determined by the following question: “Were you diagnosed for the first time by a doctor as having sugar diabetes?”mg/d quintiles of flavonoid and flavonoid sourcesQ5 versus Q1 (median intake mg/d: 680.4 versus 90.4) of total flavonoids 0.97 (0.86, 1.10)Age, energy, education level, BMI, waist:hip ratio, activity level, smoking status, multivitamin use, and hormone therapy
Kataja-Tuomola 2011, ATBC, FinlandM10.250–69 (57.5)660/25,505Validated FFQ 275 food items/self-reported or medical diagnosis and Social Insurance Institution FinlandQuintiles of flavonols and flavonesNonsignificant associations for kaempferol, luteolin, myricetin, quercetinAge, supplementation, BMI, cigarettes smoked daily, smoking years, blood pressure, total cholesterol, high-density lipoprotein cholesterol, leisure-time physical activity, and daily intake of alcohol and energy
Wedick 2012, NHS, NHSII, HPFS, United StatesF (NHS)2430–55 (50)6878/70,359131-item semiquantitative validated FFQ/self-report and confirmed with supplementary questionnaire about symptoms, the National Diabetes Group criteriamg/d quintiles of dietary intake of major flavonoid subclassesQ5 versus Q1 (median intake mg/d: 718.1 versus 105.2) of total flavonoids 0.85 (0.79, 0.92)Age, BMI, smoking status, alcohol intake, multivitamin use, physical activity, family history of diabetes, postmenopausal status and hormone use, ethnicity, total energy, intakes of red meat, fish, whole grains, coffee, high-calorie sodas, and trans fat
F (NHSII)1625–42 (36)3084/89,201Same as abovemg/d quintiles of dietary intake of major flavonoid subclassesQ5 versus Q1 (median intake mg/d: 770.3 versus 112.1) of total flavonoids 0.99 (0.89, 1.11)Same as above plus oral contraceptive use
M (HPFS)2040–75 (53)2649/41,334Same as abovemg/d quintiles of dietary intake of major flavonoid subclassesQ5 versus Q1 (median intake mg/d: 624.3 versus 112.5) of total flavonoids 0.92 (0.81, 0.94)Same as above except postmenopausal status and hormone use and oral contraceptive use
Zamora-Ros 2013, Epic-InterAct, 8 European countriesBoth3.99 million person-years of follow-up52.4 (9.1)12,403/16,154Country-specific FFQ/self-report and linkage to primary and secondary care registers, hospital and mortality datamg/d quintiles of dietary flavonoids, types of flavonoids and lignans intakeQ5 versus Q1 (median intake mg/d: 817.5 versus 126.8) of total flavonoids 0.90 (0.77, 1.04)Age, sex, and total energy intake, educational level, physical activity, smoking status, BMI, alcohol intake, intakes of red meat, processed meat, sugar-sweetened soft drinks, and coffee, intakes of fiber, vitamin C, and magnesium
Jacques 2013, Framingham Offspring Cohort, United StatesBoth11.954.2 (53.8, 54.5)308/2915Validated FFQ/fasting glucose concentrations and/or a medical and medication use history obtained by a physician at each study examination6 flavonoid classes and total flavonoidsHR per 2.5-fold difference in flavonoid intake (cumulative mean flavonoid intake) 0.89 (0.75, 1.05)Sex, age, cardiovascular disease, current smoker (y/n), BMI, and cumulative mean energy intake, vegetable and fruit intake
Zamora-Ros 2014, EPIC-InterAct, United StatesBoth3.99 million person-years of follow-up52.4 (9.1)12,403/16,154Country-specific FFQ/self-report and linkage to primary and secondary care registers, hospital and mortality datamg/d quintiles of dietary flavanol and flavonol intakeQ5 versus Q1 of sum of flavanols and flavonols (median intake in mg/d: 713.6 versus 97.6). Inverse associations between all flavan-3-ol monomers, proanthocyanidin dimers and trimers (Q5 versus Q1 0.81 (0.71, 0.92) and 0.91 (0.80, 1.04), resp.)Age, sex, and total energy intake, educational level, physical activity, smoking status, BMI, alcohol intake, intakes of red meat, processed meat, sugar-sweetened soft drinks, and coffee, intakes of fiber, vitamin C, and magnesium
Tresserra-Rimbau 2016, PREDIMED, SpainBoth5.5155–80314/3430Validated 137-item FFQ/fasting plasma glucose ≥7 mmol/L or 2 h plasma glucose ≥11.1 mmol/L after a 75 g oral glucose load, confirmed by a second test using the same criteria, the American Diabetes Association criteriaTotal polyphenols, flavonoids, stilbenes, lignansT3 versus T1 (mean intake 1002 versus 600) of total polyphenols 0.72 (0.52, 0.99)Age, sex, recruitment center, intervention group. Smoking, BMI, physical activity, dyslipidemia, hypertension, education level, total energy intake, alcohol intake, adherence to the Mediterranean diet, and fasting glucose
Ding 2016, NHS, NHS2, HPFS, United StatesF (NHS)830–55 (50)3671/63,115131-item semiquantitative validated FFQ/self-report and confirmed with supplementary questionnaire about symptoms, the National Diabetes Group criteriamg/d quintiles of isoflavone consumptionQ5 versus Q1 (median intake mg/d: 2.78 versus 0.17) of isoflavones 0.97 (0.88, 1.07)Age, race, family history of T2D, baseline disease status, BMI, physical activity, overall dietary pattern (alternate Healthy Eating Index score, in quintiles), total energy intake and smoking status and menopausal status, postmenopausal hormone use
F (NHSII)825–42 (36)3920/79,061Same as abovemg/d quintiles of isoflavone consumptionQ5 versus Q1 (median intake mg/d: 5.73 versus 0.17) of isoflavones 0.85 (0.76, 0.95)Same as above
M (HPFS)840–75 (53)742/21,281Same as abovemg/d quintiles of isoflavone consumptionQ5 versus Q1 (median intake mg/d: 5.09 versus 0.31) of isoflavones 0.80 (0.62, 1.02)Same as above except postmenopausal status and hormone use

ATBC, α-Tocopherol, β-Carotene Cancer Prevention Study; WHS, Women’s Health Study; FFQ, food frequency questionnaire; NHS, Nurses’ Health Study; HPFS, Health Professionals Follow-up Study; PREDIMED, Prevención con Dieta Mediterránea; EPIC, The European Prospective Investigation into Cancer and Nutrition; FMCHES, Finnish Mobile Clinic Health Examination Survey.