Background: We aimed to assess the impact of healthy cardiovascular health (CVH) on diabetic complications, mortality, and life expectancy among people with type 2 diabetes and to explore whether inflammation marker mediate these associations. Methods: This prospective cohort study included 33,236 participants (aged 40–72) with type 2 diabetes from the UK Biobank with annual follow-up from 2006 to 2010 to 2020. Type 2 diabetes was ascertained from self-report, glycated hemoglobin ≥ 6.5%, hospital inpatient registry, or glucose-lowering medication use. Information on mortality was derived from the national death registry. Favorable CVH metrics consisted of non-smoker, regular physical activity, a healthy diet, non-overweight, untreated resting blood pressure < 120/<80 mm Hg, and untreated total cholesterol < 200 mg/dL. Participants were categorized into three groups according to the number of favorable CVH metrics: unfavorable (0 or 1); intermediate (any 2 or 3); and favorable (4 or more). Inflammation marker, as measured by C-reactive protein (CRP), was assessed at baseline and categorized as low (≤ 3 mg/L) and high (> 3 mg/L). Data were analyzed using Cox regression models, flexible parametric survival models, and mediation models. Results: During the follow-up (median: 11.7 years), 3133 (9.4%) cases of diabetes complications and 4701 (14.1%) deaths occurred. Compared to unfavorable CVH, favorable CVH was associated with a reduced risk of diabetes complications (HR, 0.35; 95% CI, 0.26–0.47) and all-cause mortality (HR, 0.53; 95% CI, 0.43–0.65). In participants with unfavorable CVH, life expectancy at age 45 had a significantly reduction of 7.20 (95% CI, 5.48–8.92) years compared to those with a favorable CVH. Among people with type 2 diabetes, the proportions of diabetes complications and all-cause mortality that would be reduced by promoting the favorable CVH was 61.5% and 39.1%, respectively. CRP level mediated 14.3% and 29.7% of the associations between CVH and diabetic complication and all-cause mortality, respectively. Conclusion: A favorable CVH was associated with lower risk of diabetes complications and mortality risk, and was associated with a longer life expectancy among people with type 2 diabetes. This association may be in part accounted for by inflammatory processes. Our findings highlight the importance of favorable CVH for the prevention of diabetic complications and all-cause mortality among people with type 2 diabetes, and underscores the need to monitor inflammation among people with unfavorable CVH.

Background: Constipation was associated with incidence of dementia and cognitive decline. Laxatives are the mainstay of constipation management and are commonly used among older populations for both treatment and prevention of constipation. However, the association between use of laxatives and incident dementia, and whether laxatives use may modify the effect of genetic predisposition on dementia remains unclear. Methods: We applied 1:3 propensity score matching to balance the baseline characteristics of the laxative users versus non-users and to reduce potential confounders using multi-variates adjusted Cox hazards regression models. We categorized genetic risk into three groups (low, middle, and high) through a genetic risk score of common genetic variants. Information on laxatives use was assessed at baseline and categories into four varieties, including bulk forming laxatives, softeners and emollients, osmotic laxatives, and stimulant laxatives. Results: Of 486,994 participants, there were 14,422 laxatives users in UK Biobank. After propensity score matching, participants with use of laxatives (n = 14,422) and matched non-laxative (n = 43,266) exposed individuals were enrolled. Over follow-up to 15 years, there were 1377 participants developed dementia (539 for Alzheimer’s disease, and 343 for vascular dementia). The use of laxatives had greater risk of dementia (HR, 1.72; 95% CI:1.54–1.92), Alzheimer’s disease (HR, 1.36; 95% CI: 1.13–1.63), and vascular dementia (HR, 1.53; 95% CI: 1.23–1.92). Compared to non-laxative exposed participants, those with use of softeners and emollients drugs, stimulant laxatives, and osmotic laxatives were associated with 96% (HR, 1.96; 95 CI: 1.23–3.12; P = 0.005), 80% (HR, 1.80; 95% CI: 1.37–2.37; P < 0.001), and 107% (HR, 2.07; 95% CI: 1.47–2.92; P < 0.001) higher risk of developed incident dementia, respectively. In joint effect analysis, compared to participants with low/middle genetic susceptibility and non-laxatives use, the HR (95% CIs) of dementia was 4.10 (3.49–4.81) for those with high genetic susceptibility plus use of laxatives. There was an additive interaction between laxatives use and genetic susceptibility on dementia (RERI: 0.736, 95% CI: 0.127 to 1.246; AP: 0.180, 95% CI: 0.047 to 0.312). Conclusions: Use of laxatives was associated with higher risk of dementia and modify the effect of genetic susceptibility on dementia. Our findings suggested that attention should be paid to the relationship between laxatives use and dementia, especially in people at high genetic susceptibility.

Background: The associations between sugary beverages and genetic predisposition to depression risk remain unclear. Aims: This study aimed to investigate the associations of sugar‐sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with depression and to assess whether these associations were modified by genetic predisposition. Methods: We used data from the UK Biobank of 180 599 individuals aged 39–72 years who were depression‐free at baseline. Dietary intake of SSBs, ASBs and NJs was accessed by a 24‐hour dietary recall between 2009 and 2012. The Polygenic Risk Score for depression was estimated and categorised as low (lowest tertile), intermediate (tertile 2) and high (highest tertile). Cox proportional hazard and substitution models were conducted to evaluate hazard ratios (HRs) and 95% CIs. Results: Over the 12‐year follow‐up, 4915 individuals developed depression. Higher consumption (>2 units/day) of SSBs (HR: 1.26, 95% CI 1.12 to 1.43) and ASBs (HR: 1.40, 95% CI 1.23 to 1.60) were both associated with an increased risk of depression. However, moderate consumption (>0–1 units/day) of NJs was associated with a lower risk of depression (HR: 0.89, 95% CI 0.83 to 0.95). Furthermore, genetic predisposition did not modify these associations (p interaction>0.05). In substitution models, the HRs for depression risk were 0.94 (95% CI 0.89 to 0.99) and 0.89 (95% CI 0.85 to 0.94), respectively, when 1 unit/day of SSBs or ASBs was replaced by an equivalent intake of NJs. Conclusions: Higher consumption of SSBs and ASBs was associated with an increased risk of depression; in contrast, moderate consumption of NJs was inversely associated with a lower risk of depression. In theory, substituting SSBs and ASBs with NJs would suppose a reduction of depression risk.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), has infected hundreds of millions of people and caused millions of deaths. Looking for valid druggable targets with minimal side effects for the treatment of COVID-19 remains critical. After discovering host genes from multiscale omics data, we developed an end-to-end network method to investigate drug-host gene(s)-coronavirus (CoV) paths and the mechanism of action between the drug and the host factor in a directional network. We also inspected the potential side effect of the candidate drug on several common comorbidities. We established a catalog of host genes associated with three CoVs. Rule-based prioritization yielded 29 Food and Drug Administration (FDA)-approved drugs via accounting for the effects of drugs on CoVs, comorbidities, and drug-target confidence information. Seven drugs are currently undergoing clinical trials as COVID-19 treatment. This catalog of druggable host genes associated with CoVs and the prioritized repurposed drugs will provide a new sight in therapeutics discovery for severe COVID-19 patients.