C-reactive protein partially mediates the inverse association between coffee consumption and risk of type 2 diabetes: The UK Biobank and the Rotterdam study cohorts.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ß = -0.017 [-0.024;-0.010], p < 0.001), and with lower CRP (RS, log-transformed ß = -0.014 [-0.022;-0.005], p = 0.002; UKB, ß = -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 ß = 0.105 (0.014; 0.240), p = 0.016; UKB ß = 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. CONCLUSIONS: 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.

Associations between Phytoestrogens, Glucose Homeostasis, and Risk of Diabetes in Women: A Systematic Review and Meta-Analysis.

Phytoestrogens might have advantageous effects on diabetes in women. We performed a systematic review and meta-analysis to determine the effect of phytoestrogens on glucose homeostasis and the risk of type 2 diabetes (T2D) among women. Randomized controlled trials (RCTs) and prospective observational studies that assessed associations of phytoestrogens (supplementation, dietary intake, or biomarkers) with fasting glucose or insulin, homeostatic model assessment of insulin resistance (HOMA-IR), or with the risk of T2D were included. We identified 18 RCTs (n = 1687 individuals) investigating the effect of phytoestrogen supplementation on glucose homeostasis and 9 prospective population-based studies (n = 212,796 individuals) examining the association between phytoestrogen intake and the risk of T2D. Compared with placebo, phytoestrogen supplementation resulted in improvements in fasting glucose and HOMA-IR: the pooled mean differences of changes were -0.12 mmol/L (95% CI: -0.20, -0.03 mmol/L) and -0.24 mmol/L (95% CI: -0.45, -0.03 mmol/L), respectively. Although there was no significant decrease in insulin concentrations with overall phytoestrogen supplementation, the pooled mean difference in changes was -0.99 pmol/L (95% CI: -4.65, 2.68 pmol/L). However, the results of RCTs varied by type of phytoestrogens: soy-derived isoflavones and genistein improved glucose homeostasis, whereas isoflavone mix and daidzein had no effect or were associated with an adverse glycemic profile. Higher dietary phytoestrogen intake was associated with a 10% lower risk of developing T2D in observational studies (pooled RR: 0.90; 95% CI: 0.85, 0.96; for the highest compared with the lowest quantiles). Results were similar when the analyses were restricted to only medium- and high-quality studies. Overall, phytoestrogens may have a positive influence on glycemia and could be used for diabetes prevention in women. However, for some individual types of phytoestrogens, such as mixed isoflavones, caution is needed in recommending their use in women, because their use could lead to an adverse glycemic profile in women.