Abstract

Introduction: The promotion of evidence-based diets is an important s trategy to mitigate the global health and economic burden of diabetes. Higher flavonoid intakes are associated with a lower risk of obesity and diabetes. Less clear are associations of the flavonoid subclasses with diabetes, the mediating impact of body fat, and the identification of subpopulations that may receive the greatest benefit. Hypothesis: Higher flavonoid intakes will be associated with lower body fat at baseline and a lower risk of diabetes during follow-up. Methods: Incident diabetes was assessed in 54,787 participants of the Danish Diet, Cancer, and Health Study followed-up for 23 years. Dietary intake and objective measures of body fat were assessed at baseline; habitual flavonoid intake was calculated using the Phenol-Explorer database and body fat was objectively assessed using bioelectrical impedance. Incidence of diabetes was obtained using Danish National Patient and Prescription Registries. Cross-sectional associations between flavonoid intakes and body fat were assessed using multivariable-adjusted linear regression models. Non-linear associations between flavonoid intake and incident diabetes were examined using restricted cubic splines based on multivariable-adjusted Cox proportional hazards models. Results: Among 54,787 participants without diabetes at baseline (median [IQR] age of 56 [52 - 60] years; (47.3%) men), 6,700 individuals were diagnosed with diabetes. Participants in the highest total flavonoid intake quintile (median, 1,202 mg/d) had a 1.52 kg lower body fat (95% CI: -1.74, -1.30) and a 19% lower risk of diabetes [HR (95% CI): 0.81 (0.75, 0.87)] after multivariable adjustments and compared to participants in the lowest intake quintile (median, 174 mg/d). Body fat mediated 51.6% of the association between flavonoid intake and incident diabetes. Neither smoking status, BMI, nor sex appeared to modify the association between total flavonoid intake and incident diabetes. However, the difference (flavonoid intake quintile 5 - quintile 1) in the 20-year estimated absolute risk of diabetes was greatest for current smokers (males: 2.19%, females: 1.65%) and those with a BMI ≥30 kg/m 2 (males: 5.56%, females: 4.59%), likely owing to the higher prevalence of diabetes in these “at risk” subgroups. Moderate to high intakes of flavonols, flavanol monomers, flavanol oligo+polymers, and anthocyanins, and the individual compounds within these subclasses, were associated with a lower risk of diabetes. Conclusion: In this Danish prospective cohort study, we observed that higher flavonoid intakes were cross-sectionally associated with lower body fat, and longitudinally associated with a lower risk of diabetes. Our results suggest that promoting a diet abundant in flavonoid-rich foods may help to ameliorate diabetes risk, in part through a reduction in body fat.

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