Coffee is among the most consumed beverages worldwide. Coffee consumption has been associated with lower risk of type 2 diabetes mellitus (T2D), but underlying mechanisms are not well understood. We aimed to study the role of classic and novel-T2D biomarkers with anti- or pro-inflammatory activity in the association between habitual coffee intake and T2D risk. Furthermore, we studied differences by coffee types and smoking status in this association. Using two large population-based cohorts, the UK-Biobank (UKB; n = 145,368) and the Rotterdam Study (RS; n = 7111), we investigated associations of habitual coffee consumption with incident T2D and repeated measures of insulin resistance (HOMA-IR), using Cox proportional hazards and mixed effect models, respectively. Additionally, we studied associations between coffee and subclinical inflammation biomarkers including C-reactive protein (CRP) and IL-13, and adipokines, such as adiponectin and leptin, using linear regression models. Next, we performed formal causal mediation analyses to investigate the role of coffee-associated biomarkers in the association of coffee with T2D. Finally, we evaluated effect modification by coffee type and smoking. All models were adjusted for sociodemographic, lifestyle and health-related factors. During a median follow-up of 13.9 (RS) and 7.4 (UKB) years, 843 and 2290 incident T2D cases occurred, respectively. A 1 cup/day increase in coffee consumption was associated with 4% lower T2D risk (RS, HR = 0.96 [95%CI 0.92; 0.99], p = 0.045; UKB, HR = 0.96 [0.94; 0.98], p < 0.001), with lower HOMA-IR (RS, log-transformed β = -0.017 [-0.024;-0.010], p < 0.001), and with lower CRP (RS, log-transformed β = -0.014 [-0.022;-0.005], p = 0.002; UKB, β = -0.011 [-0.012;-0.009], p < 0.001). We also observed associations of higher coffee consumption with higher serum adiponectin and IL-13 concentrations, and with lower leptin concentrations. Coffee-related CRP levels partially mediated the inverse association of coffee intake with T2D incidence (average mediation effect RS β = 0.105 (0.014; 0.240), p = 0.016; UKB β = 6.484 (4.265; 9.339), p < 0.001), with a proportion mediated by CRP from 3.7% [-0.012%; 24.4%] (RS) to 9.8% [5,7%; 25.8%] (UKB). No mediation effect was observed for the other biomarkers. Coffee-T2D and coffee-CRP associations were generally stronger among consumers of ground (filtered or espresso) coffee and among never and former smokers. Lower subclinical inflammation may partially mediate the beneficial association between coffee consumption and lower T2D risk. Consumers of ground coffee and non-smokers may benefit the most. KEYWORDS (MESH TERMS): coffee consumptions; diabetes mellitus, type 2; inflammation; adipokines; biomarkers; mediation analysis; follow-up studies.

Although there is some evidence that total dietary antioxidant capacity (TDAC) is inversely associated with the presence of obesity, no longitudinal studies have been performed investigating the effect of TDAC on comprehensive measures of body composition over time. In this study, we included 4595 middle-aged and elderly participants from the Rotterdam Study, a population-based cohort. We estimated TDAC among these individuals by calculating a ferric reducing ability of plasma (FRAP) score based on data from food-frequency questionnaires. Body composition was assessed by means of dual X-ray absorptiometry at baseline and every subsequent 3–5 years. From these data, we calculated fat mass index (FMI), fat-free mass index (FFMI), android-to-gynoid fat ratio (AGR), body fat percentage (BF%) and body mass index (BMI). We also assessed hand grip strength at two time points and prevalence of sarcopenia at one time point in a subset of participants. Data were analyzed using linear mixed models or multinomial logistic regression models with multivariable adjustment. We found that higher FRAP score was associated with higher FFMI (0.091 kg/m² per standard deviation (SD) higher FRAP score, 95% CI 0.031; 0.150), lower AGR (−0.028, 95% CI −0.053; −0.003), higher BMI (0.115, 95% CI 0.020; 0.209) and lower BF% (−0.223, 95% CI −0.383; −0.064) across follow-up after multivariable adjustment. FRAP score was not associated with hand grip strength or sarcopenia. Additional adjustment for adherence to dietary guidelines and exclusion of individuals with comorbid disease at baseline did not change our results. In conclusion, dietary intake of antioxidants may positively affect the amount of lean mass and overall body composition among the middle-aged and elderly.

Background: Population-based data on sex-specific cardiovascular risk profiles and mortality risks according to location of arteriosclerosis remain scarce. Objectives: To study sex-specific cardiovascular risk profiles and mortality risks associated with arteriosclerosis at multiple sites. Methods: From the population-based Rotterdam Study, 2,357 participants (mean age 69 years,