Associations of serum 25-hydroxyvitamin D and vitamin D receptor polymorphisms with risks of cardiovascular disease and mortality among patients with chronic kidney disease: a prospective study.

BACKGROUND: Evidence regarding the relationships of serum 25-hydroxyvitamin D [25(OH)D] with cardiovascular diseases (CVD) and mortality among patients with chronic kidney disease (CKD) is limited and inconsistent. OBJECTIVES: This study aimed to investigate the associations between serum 25(OH)D and CVD incidence and mortality among patients with CKD. METHODS: This prospective study included 21,507 participants with CKD and free of CVD in the UK Biobank. Incidences of total and subtypes of CVD and mortality were ascertained via electronic health records. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) for CVD incidence and mortality. RESULTS: The median serum 25(OH)D concentration was 44.0 nmol/L (interquartile range: 30.1, 60.6 nmol/L). After multivariable adjustment, compared with CKD patients with serum 25(OH)D concentrations of <25 nmol/L, those with serum 25(OH)D ≥75 nmol/L had HRs (95% CIs) of 0.80 (0.71, 0.90) for total CVD incidence, 0.82 (0.69, 0.97) for ischemic heart disease, 0.56 (0.41, 0.77) for stroke, 0.64 (0.46, 0.88) for myocardial infarction, 0.62 (0.49, 0.80) for heart failure, 0.60 (0.43, 0.85) for CVD mortality, and 0.62 (0.52, 0.74) for all-cause mortality. In addition, these associations were not modified by vitamin D receptor polymorphisms, with no significant interaction detected. CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risks of total and subtypes of CVD incidence and mortality among individuals with CKD. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of CVD and mortality in patients with CKD.

Diagnosis of pulmonary tuberculosis with 3D neural network based on multi-scale attention mechanism.

This paper presents a novel multi-scale attention residual network (MAResNet) for diagnosing patients with pulmonary tuberculosis (PTB) by computed tomography (CT) images. First, a three-dimensional (3D) network structure is applied in MAResNet based on the continuity and correlation of nodal features on different slices of CT images. Secondly, MAResNet incorporates the residual module and Convolutional Block Attention Module (CBAM) to reuse the shallow features of CT images and focus on key features to enhance the feature distinguishability of images. In addition, multi-scale inputs can increase the global receptive field of the network, extract the location information of PTB, and capture the local details of nodules. The expression ability of both high-level and low-level semantic information in the network can also be enhanced. The proposed MAResNet shows excellent results, with overall 94% accuracy in PTB classification. MAResNet based on 3D CT images can assist doctors make more accurate diagnosis of PTB and alleviate the burden of manual screening. In the experiment, a called Grad-CAM was employed to enhance the class activation mapping (CAM) technique for analyzing the model's output, which can identify lesions in important parts of the lungs and make transparent decisions.

Associations of Habitual Calcium Supplementation With Risk of Cardiovascular Disease and Mortality in Individuals With and Without Diabetes.

OBJECTIVE: To prospectively examine the associations of habitual calcium supplementation with cardiovascular disease (CVD) events and mortality in individuals with and without diabetes. RESEARCH DESIGN AND METHODS: The main analysis included 434,374 participants from the UK Biobank. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Interactions of calcium supplement use with diabetes status were tested on multiplicative and additive scales. RESULTS: Over a median follow-up of 8.1 and 11.2 years, 26,374 incident CVD events and 20,526 deaths were documented, respectively. After multivariable adjustment, habitual calcium supplementation was significantly associated with higher risks of CVD incidence (HR 1.34; 95% CI 1.14, 1.57), CVD mortality (HR 1.67; 95% CI 1.19, 2.33), and all-cause mortality (HR 1.44; 95% CI 1.20, 1.72) in participants with diabetes, whereas no significant association was observed in participants without diabetes (HR 0.97 [95% CI 0.92, 1.03] for CVD incidence; HR 1.05 [95% CI 0.90, 1.23] for CVD mortality; HR 1.02 [95% CI 0.96, 1.09] for all-cause mortality). Significant multiplicative and additive interactions were found between habitual calcium supplementation and diabetes status on risks of CVD events and mortality (all Pinteraction < 0.05). In contrast, no significant interactions were observed between dietary or serum calcium and diabetes status. CONCLUSIONS: Habitual use of calcium supplements was significantly associated with higher risk of CVD events and mortality in people with diabetes but not in people without diabetes. Further studies are needed to balance potentially adverse effects of calcium supplement against likely benefits, particularly among patients with diabetes.

Associations of Nut Consumption with All-Cause Mortality among Individuals with Type 2 Diabetes.

BACKGROUND: Nuts are energy-dense, high-fat foods, and whether nut consumption influences mortality risk among individuals with type 2 diabetes (T2D) remains unclear. OBJECTIVES: This study aimed to investigate the associations of nut consumption with all-cause mortality among adults with T2D and to further explore the potential mediation effects of cardiometabolic biomarkers. METHODS: The current analysis included 5090 US participants with T2D from the National Health and Nutrition Examination Survey (1999-2014). Cox proportional hazards models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: After 35,632 person-y of follow-up, 1174 deaths were documented. Higher nut consumption was significantly associated with a lower risk of all-cause mortality among individuals with T2D. After multivariable adjustment including lifestyles and dietary factors, diabetes duration, and glycated hemoglobin, compared with participants who did not consume nuts, the HR (95% CI) for those who consumed nuts over 3.5 ounce equivalent (oz.eq)/wk was 0.64 (0.50, 0.82; P-trend < 0.001) for all-cause mortality. A linear dose-response relationship was observed between nut consumption and all-cause mortality among individuals with T2D (Poverall=0.004, Pnonlinearity=0.35). In substitution analyses, replacing one serving of red and processed meat, refined grains, eggs, and dairy foods with one serving of nuts was associated with a 18% to 22% lower risk of all-cause mortality. In addition, mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.7% and 9.1% of the relationship between nut consumption with all-cause mortality, respectively. CONCLUSIONS: Higher nut consumption was significantly associated with lower all-cause mortality among individuals with T2D. These findings indicate a potential benefit of nut consumption in the prevention of premature death among individuals with T2D.

Remimazolam versus propofol in combination with esketamine for surgical abortion: A double-blind randomized controlled trial.

Remimazolam is a new benzodiazepine with a short half-life, good efficacy, and safety profiles in general anesthesia. Combining esketamine with propofol (P + E) could reduce propofol consumption and injection pain. It is, however, unclear if a low dose of remimazolam co-administrated with esketamine (R + E) is comparable to the increasingly used P + E for surgical abortion with general anesthetic. We conducted a double-blind randomized controlled trial to compare the efficacy and safety of R + E and P + E. Two hundred patients scheduled for a surgical abortion were randomized to receive remimazolam 0.3 mg/kg plus esketamine 0.3 mg/kg (R + E), and propofol 2 mg/kg plus esketamine 0.3 mg/kg (P + E). Sedative effectiveness was evaluated by measuring the time to lose consciousness (LOC), recovery time, and successful sedation rate. Safety was assessed by hemodynamics and adverse events during and postoperation. The time to LOC and recovery time in R + E was 5 s shorter and 1 min longer than that in P + E, respectively (both p < 0.001). Success sedation rate did not differ between groups (p = 0.73). Bradycardia incidence and injection site pain were less frequent in the R + E group than that in the P + E group. More rash was observed in the R + E group compared with the P + E group (32% vs. 5%, p < 0.001), but all were mild (only chest rash) and resolved subsequently. Low dose of remimazolam when combined with esketamine has favorable profiles with rapid onset and recovery, but mild hemodynamic side effects and adverse events. It can be used as an alternative for surgical abortion with general anesthetic.

Dexmedetomidine alleviates propofol-induced pyroptosis of hippocampal neurons through NLRP3 inflammasome pathway.

Propofol is neurotoxic to trigger neuronal pyroptosis and dexmedetomidine possesses the ability to suppress proptosis. This study expounded on the protective functions of dexmedetomidine on propofol-induced pyroptosis of primary hippocampal neurons via NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway. At first, primary hippocampal neurons underwent separation and identification and were treated with different concentrations of propofol (1, 10, and 100 µM). The toxicity of propofol in the neurons was evaluated. Prior to propofol treatment, the neurons were treated with different concentrations of dexmedetomidine (0.01, 0.1, 1, 5, and 10 µM). The viability of neurons with different treatments was detected. The mRNA expressions of homeobox A5 (HOXA5) and NLRP3 were identified. The protein levels of intracellular HOXA5, NLRP3, the N-terminal fragment of gasdermin D (GSDMD-N), and cleaved-caspase-1 and the concentrations of interleukin (IL)-1ß and IL-18 were examined. Subsequently, the binding of HOXA5 to the NLRP3 promoter was detected. Joint experiments were conducted with pcDNA3.1-HOXA5 or pcDNA3.1-NLRP3 in dexmedetomidine-treated neurons. Dexmedetomidine pretreatment attenuated propofol-induced pyroptosis of hippocampal neurons, increased cell viability, and repressed NLRP3, GSDMD-N, and cleaved-caspase-1 protein levels and IL-1ß and IL-18 concentrations. Dexmedetomidine pretreatment inhibited intracellular HOXA5 expression, and HOXA5 bound to the NLRP3 promoter region to promote NLRP3 expression. Overexpressing HOXA5 or NLRP3 reversed anti-pyroptosis role of dexmedetomidine pretreatment in hippocampal neurons. Dexmedetomidine pretreatment suppressed NLRP3 expression by downregulating HOXA5 expression, inhibiting propofol-induced pyroptosis in primary hippocampal neurons.

Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study.

BACKGROUND: The influence of overall lifestyle behaviors on diabetic microvascular complications remains unknown. In addition, the potential mediating biomarkers underlying the association is unclear. This study aimed to examine the associations of the combined lifestyle factors with risks of total and individual microvascular complications among patients with type 2 diabetes (T2D) and to explore the potential mediation effects of metabolic biomarkers. METHODS AND FINDINGS: This retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95% confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend ≤0.01). Further, the population-attributable fraction (95% CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle (<4 low-risk factors) ranged from 25.3% (10.0%, 39.4%) to 39.0% (17.7%, 56.8%). In addition, albumin, HDL-C, triglycerides, apolipoprotein A, C-reactive protein, and HbA1c collectively explained 23.20% (12.70%, 38.50%) of the associations between overall lifestyle behaviors and total diabetic microvascular complications. The key limitation of the current analysis was the potential underreporting of microvascular complications because the cases were identified via electronic health records. CONCLUSIONS: Adherence to overall healthy lifestyle behaviors was associated with a significantly lower risk of microvascular complications in patients with T2D, and the favorable associations were partially mediated through improving biomarkers of glycemic control, systemic inflammation, liver function, and lipid profile.

Association of Combined Healthy Lifestyles With Cardiovascular Disease and Mortality of Patients With Diabetes: An International Multicohort Study.

OBJECTIVE: To prospectively examine the associations of combined lifestyle factors with incident cardiovascular disease (CVD) and mortality in patients with diabetes. PATIENTS AND METHODS: Patients with prevalent diabetes were included from 5 prospective, population-based cohorts in China (Dongfeng-Tongji cohort and Kailuan study), the United Kingdom (UK Biobank study), and the United States (National Health and Nutrition Examination Survey and National Institutes of Health-AARP Diet and Health Study). Healthy lifestyle scores were constructed according to non-current smoking, low to moderate alcohol drinking, regular physical activity, healthy diet, and optimal body weight; the healthy level of each lifestyle factor was assigned 1 point, or 0 for otherwise, and the range of the score was 0 to 5. Cox proportional hazards models were used to estimate hazard ratios for incident CVD, CVD mortality, and all-cause mortality adjusting for sociodemographic, medical, and diabetes-related factors, and outcomes were obtained by linkage to medical records and death registries. Data were collected from October 18, 1988, to September 30, 2020. RESULTS: A total of 6945 incident CVD cases were documented in 41,350 participants without CVD at baseline from the 2 Chinese cohorts and the UK Biobank during 389,330 person-years of follow-up, and 40,353 deaths were documented in 101,219 participants from all 5 cohorts during 1,238,391 person-years of follow-up. Adjusted hazard ratios (95% CIs) comparing patients with 4 or 5 vs 0 or 1 healthy lifestyle factors were 0.67 (0.60 to 0.74) for incident CVD, 0.58 (0.50 to 0.68) for CVD mortality, and 0.60 (0.53 to 0.68) for all-cause mortality. Findings remained consistent across different cohorts, subgroups, and sensitivity analyses. CONCLUSION: The international analyses document that adherence to multicomponent healthy lifestyles is associated with lower risk of CVD and premature death of patients with diabetes.

Proton Pump Inhibitor Use and Risks of Cardiovascular Disease and Mortality in Patients With Type 2 Diabetes.

CONTEXT: Proton pump inhibitors (PPIs) are widely used drugs for gastric acid-related diseases and may affect the gut microbiome. OBJECTIVE: We aimed to evaluate the associations of PPI use with risks of cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2D). METHODS: We analyzed the associations of PPI use with risks of coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), stroke, and all-cause mortality in 19 229 adults with T2D using data from the UK Biobank study. RESULTS: During a median follow-up of 10.9 to 11.2 years, we documented 2971 CAD, 1827 MI, 1192 HF, and 738 stroke cases, along with 2297 total deaths. PPI use was significantly associated with higher risks of CAD (hazard ratio [HR], 1.27; 95% CI, 1.15-1.40), MI (HR, 1.34; 95% CI, 1.18-1.52), HF (HR, 1.35; 95% CI, 1.16-1.57), and all-cause mortality (HR, 1.30; 95% CI, 1.16-1.45). No statistically significant association was observed between PPI use and stroke (HR, 1.11; 95% CI, 0.90-1.36). The results were consistent in the subgroup analyses stratified by factors including indications of PPI, antidiabetic medication use, and antiplatelet drug use. Analyses in a 1:1 propensity score-matched cohort of PPI users vs nonusers yielded similar results. CONCLUSION: Our data suggest that PPI use is associated with higher risks of CVD events and mortality among patients with T2D. The benefits and risks of PPI use should be carefully balanced among patients with T2D, and monitoring of adverse CVD events during PPI therapy should be enhanced.

Associations of healthy dietary patterns with mortality among people with prediabetes.

PURPOSE: To examine the associations of healthy dietary patterns with cardiometabolic biomarkers and all-cause mortality among individuals with prediabetes. METHODS: This cohort study included 8363 adults with prediabetes from the National Health and Nutrition Examination Survey 1999-2014. Healthy dietary patterns including Alternate Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet score (AMED), Dietary Approaches to Stop Hypertension score (DASH), and Healthy Eating Index-2015 (HEI-2015) were calculated based on 24-h dietary recall data. Mortality status was obtained by linkage to National Death Index records. Cardiometabolic biomarkers, including blood glucose, insulin, HbA1c, C-reactive protein (CRP), and lipids, were measured at recruitment. RESULTS: During 61,991 person-years of follow-up, 991 deaths occurred. Comparing the extreme quartiles, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were 0.65 (0.49, 0.85) for AHEI-2010 (P-trend = 0.002), 0.68 (0.50, 0.92) for AMED (P-trend = 0.004), 0.72 (0.53, 0.98) for DASH (P-trend = 0.03), and 0.78 (0.58, 1.05) for HEI-2015 (P-trend = 0.08). Besides, the HRs (95% CIs) for all-cause mortality per 20-percentile increment in scores were 0.78 (0.67, 0.90) for AHEI-2010 (P = 0.001), 0.73 (0.62, 0.86) for AMED (P < 0.001), 0.84 (0.69, 1.02) for DASH (P = 0.08), and 0.86 (0.74, 1.00) for HEI-2015 (P = 0.04). In addition, higher dietary scores were associated with favorable blood glucose, insulin, HOMA-IR, blood lipids, and CRP (all P-trend < 0.05). The high-density lipoprotein cholesterol and CRP explained 1.53-9.21% of the associations between dietary patterns and all-cause mortality (P < 0.05). CONCLUSIONS: Diets with higher AHEI-2010, AMED, DASH, and HEI-2015 were associated with improved cardiometabolic factors and lower all-cause mortality among individuals with prediabetes. These findings suggest that multiple healthy dietary patterns instead of a one-size-fits-all diet plan might be beneficial and acceptable for individuals with prediabetes.

Biomimetic-compartmented nanoprobe for in-situ imaging of iron storage and release from ferritin in cells.

Ferritin plays an important role in regulating the homeostasis of iron in cells by storing/releasing iron. Current methods usually explored the determination of iron content, but in-situ imaging of the iron storage/release from ferritin in cells cannot be achieved. Hence, an engineered self-assembled biomimetic-compartmented nanoprobe (APO@CDs) has been constructed. The protein shell of APO (apoferritin) acted as ion channel module to control iron ions entering/exiting ferritin cavity; the inner core of CDs (carbon dots) acted as signal module for iron ions response. Compared with CDs, the response sensitivity and specificity to iron ions (Fe3+) have been improved by using APO@CDs, and the cytotoxicity was significantly reduced. Additionally, compared with cells containing APO@CDs alone, the normalized fluorescence gray value of Fe3+-treated cells was significantly decreased (0.275), indicating that Fe3+ has effectively entered the ferritin. Furtherly, that of Fe3+-treated cells incubated with deferoxamine (DFO) was significantly enhanced (0.712), showing that Fe3+ was released from ferritin under the mediation of DFO. The results demonstrate that APO@CDs can be successfully applied to in-situ imaging of iron storage/release from ferritin in cells, providing a potential platform for the in-situ dynamic study of the iron storage/release in biomedical field.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study.

OBJECTIVE: Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. In this study we aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with risk of diabetic microvascular complications. RESEARCH DESIGN AND METHODS: This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Median serum 25(OH)D concentration was 40.7 nmol/L (interquartile range 27.5, 56.4). During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, in comparisons with participants with 25(OH)D <25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications.

Photoassisted Electrochemical Hydrogen Evolution Reaction of MFe2O4@Ultrathin Black Phosphorus Amorphous-Crystalline Interface.

Exploring highly active, stable, and low-cost catalysts for photoelectrochemical hydrogen evolution reaction (PE-HER) is vital in the field of energy conversion. Herein, we construct a new amorphous crystalline interface that amorphous iron-based spinel oxide (A-MFe2O4 (M = Ni, Co, Zn)) is uniformly anchored on the crystalline exfoliated black phosphorus (C-EBP) nanosheets via electrochemical and solvothermal strategies. Among these A-MFe2O4@C-EBP catalysts, more oxygen defects of A-NiFe2O4@C-EBP interface provide a larger effective electrochemical active area of 32.33 mF cm-2 as well as a turnover frequency of 0.44 s-1 and allow for an optimum equilibrium of the hydrogen-containing adsorption intermediates. Furthermore, A-NiFe2O4@C-EBP exhibits significant PE-HER performance with an overpotential of 42 mV at 10 mA cm-2 under visible-light irradiation. Density functional theory (DFT) calculations show that the amorphous-crystalline composite structure causes a large number of oxygen defects enhancing the intrinsic activity of A-NiFe2O4@C-EBP, which A-NiFe2O4@C-EBP significantly improves its adsorption capacity for H* for HER and has the lowest Gibbs free energy change for HER. This study not only provides a superior multifunctional amorphous-crystalline interface catalysts but also helps to understand the catalytic mechanism of PE-HER.

Associations of combined healthy lifestyles with cancer morbidity and mortality among individuals with diabetes: results from five cohort studies in the USA, the UK and China.

AIMS/HYPOTHESIS: Cancer has contributed to an increasing proportion of diabetes-related deaths, while lifestyle management is the cornerstone of both diabetes care and cancer prevention. We aimed to evaluate the associations of combined healthy lifestyles with total and site-specific cancer risks among individuals with diabetes. METHODS: We included 92,239 individuals with diabetes but without cancer at baseline from five population-based cohorts in the USA (National Health and Nutrition Examination Survey and National Institutes of Health [NIH]-AARP Diet and Health Study), the UK (UK Biobank study) and China (Dongfeng-Tongji cohort and Kailuan study). Healthy lifestyle scores (range 0-5) were constructed based on current nonsmoking, low-to-moderate alcohol drinking, adequate physical activity, healthy diet and optimal bodyweight. Cox regressions were used to calculate HRs for cancer morbidity and mortality, adjusting for sociodemographic, medical and diabetes-related factors. RESULTS: During 376,354 person-years of follow-up from UK Biobank and the two Chinese cohorts, 3229 incident cancer cases were documented, and 6682 cancer deaths were documented during 1,089,987 person-years of follow-up in the five cohorts. The pooled multivariable-adjusted HRs (95% CIs) comparing participants with 4-5 vs 0-1 healthy lifestyle factors were 0.73 (0.61, 0.88) for incident cancer and 0.55 (0.46, 0.67) for cancer mortality, and ranged between 0.41 and 0.63 for oesophagus, lung, liver, colorectum, breast and kidney cancers. Findings remained consistent across different cohorts and subgroups. CONCLUSIONS/INTERPRETATION: This international cohort study found that adherence to combined healthy lifestyles was associated with lower risks of total cancer morbidity and mortality as well as several subtypes (oesophagus, lung, liver, colorectum, breast and kidney cancers) among individuals with diabetes.

Associations of New-Onset Atrial Fibrillation With Risks of Cardiovascular Disease, Chronic Kidney Disease, and Mortality Among Patients With Type 2 Diabetes.

OBJECTIVE: Atrial fibrillation (AF) frequently occurs in patients with type 2 diabetes (T2D); however, the longitudinal associations of new-onset AF with risks of adverse health outcomes in patients with T2D remain unclear. In this study, we aimed to determine the associations of new-onset AF with subsequent risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), and mortality among patients with T2D. RESEARCH DESIGN AND METHODS: We included 16,551 adults with T2D, who were free of cardiovascular disease (CVD) and CKD at recruitment from the UK Biobank study. Time-varying Cox regression models were used to assess the associations of incident AF with subsequent risks of incident ASCVD, heart failure, CKD, and mortality. RESULTS: Among the patients with T2D, 1,394 developed AF and 15,157 remained free of AF during the follow-up. Over median follow-up of 10.7-11.0 years, we documented 2,872 cases of ASCVD, 852 heart failure, and 1,548 CKD and 1,776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risk of ASCVD (hazard ratio [HR] 1.85; 95% CI 1.59-2.16), heart failure (HR 4.40; 95% CI 3.67-5.28), CKD (HR 1.68; 95% CI 1.41-2.01), all-cause mortality (HR 2.91; 95% CI 2.53-3.34), and CVD mortality (HR 3.75; 95% CI 2.93-4.80) compared with those without incident AF. CONCLUSIONS: Patients with T2D who developed AF had significantly increased risks of developing subsequent adverse cardiovascular events, CKD, and mortality. Our data underscore the importance of strategies of AF prevention to reduce macro- and microvascular complications in patients with T2D.

Vitamin D status, genetic factors, and risks of cardiovascular disease among individuals with type 2 diabetes: a prospective study.

BACKGROUND: The presence of a threshold effect has been proposed, suggesting that beneficial effects from vitamin D supplementation may only be present when the vitamin D concentration is below a particular threshold. OBJECTIVES: We investigated the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and genetic factors with risks of total and subtypes of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. METHODS: This prospective study included 15,103 individuals with T2D who were initially free of CVD and had serum 25(OH)D measurements in the UK Biobank. Incidences of total and subtypes of CVD, including ischemic heart disease (IHD) and stroke, were ascertained via electronic health records. Weighted genetic risk scores (GRSs) were constructed for IHD and stroke. RESULTS: The mean serum 25(OH)D concentration was 43.4 nmol/L (SD: 20.4 nmol/L), and 65.7% of participants had a vitamin D concentration below 50 nmol/L. During a median of 11.2 years of follow-up, 3534 incident CVD events were documented. Compared with individuals with 25(OH)D concentrations <25 nmol/L, participants with 25(OH)D concentrations ≥75 nmol/L had HRs (95% CIs) of 0.75 (0.64, 0.88) for CVD, 0.69 (0.56, 0.84) for IHD, and 0.74 (0.52, 1.06) for stroke. Participants with 25(OH)D concentrations ≥50 nmol/L and low GRSs, as compared with individuals with 25(OH)D concentrations <25 nmol/L and high GRSs, had a 50% (39%, 65%) lower risk of IHD. No significant interactions were demonstrated between serum 25(OH)D concentrations and the GRSs and genetic variants in vitamin D receptors (VDR). CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risks of total CVD and IHD among patients with T2D, regardless of their genetic susceptibility and the genetic variants in VDR. Risk reductions tended to plateau at serum 25(OH)D levels around 50 nmol/L. These findings suggest that maintaining an adequate vitamin D status and avoiding deficiency may help to prevent CVD complications among patients with T2D.

Associations of exposure to lead and cadmium with risk of all-cause and cardiovascular disease mortality among patients with type 2 diabetes.

The aim of this paper is to investigate the associations of lead and cadmium exposure with all-cause and cardiovascular disease (CVD) mortality among adults with type 2 diabetes (T2D). The prospective cohort study included participants with T2D (n = 7420 for blood lead; n = 5113 for blood cadmium) from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014. Death outcomes were ascertained through linkage with the National Death Index records. The geometric mean (interquartile range) concentrations of blood lead and cadmium were 19.6 (11.8, 35.0) µg/L and 0.39 (0.21, 0.60) µg/L, respectively. During 72,279 and 37,017 person-years of followup, 2818 all-cause deaths (including 832 CVD deaths) for blood lead and 1237 all-cause deaths (including 319 CVD deaths) for blood cadmium were documented, respectively. Comparing extreme quartiles, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality were 1.51 (1.25, 1.82) for blood lead (Ptrend < 0.001) and 1.58 (1.22, 2.03) for blood cadmium (Ptrend < 0.001); and the HRs (95% CIs) of CVD mortality were 2.27 (1.54, 3.34) for blood lead (Ptrend < 0.001) and 1.78 (1.04, 3.03) for blood cadmium (Ptrend = 0.07). In the joint analysis, compared with participants in the lowest tertiles of blood lead and cadmium, participants in the highest tertiles had a HR (95% CI) of 2.09 (1.35, 3.24) for all-cause mortality. Exposure to lead and cadmium alone or in combination was significantly associated with higher risk of mortality among patients with T2D. These findings imply that minimizing exposure to lead and cadmium may aid in the prevention of premature death among individuals with diabetes.

Retraction of "Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis".

[This retracts the article DOI: 10.1515/biol-2021-0072.].

Associations of Serum Carotenoids With Risk of Cardiovascular Mortality Among Individuals With Type 2 Diabetes: Results From NHANES.

OBJECTIVE: Although carotenoids have been suggested to exhibit antioxidant properties, some experimental studies reported that ß-carotene may show pro-oxidant effects under certain conditions. Current evidence regarding the cardiovascular effects of carotenoids among patients with type 2 diabetes (T2D) is scarce. This study aimed to prospectively examine the associations of individual serum carotenoid concentrations with cardiovascular mortality among adults with T2D. RESEARCH DESIGN AND METHODS: This analysis included 3,107 individuals with T2D from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001-2006. Cardiovascular mortality was ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During an average of 14 years of follow-up, 441 cardiovascular deaths occurred. After multivariate adjustment including lifestyles, dietary factors, glucose control, and other major carotenoids, higher serum ß-carotene concentrations were significantly associated with an elevated risk of cardiovascular mortality in a dose-response manner. When extreme quartiles of ß-carotene were compared, the multivariable-adjusted HR was 2.47 (95% CI 1.62, 3.76) for cardiovascular mortality (Ptrend = 0.002); and per one-unit increment in natural log-transformed serum ß-carotene was associated with a 46% higher risk of cardiovascular mortality (P = 0.001). Other individual carotenoids (α-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin) were not significantly associated with the risk of cardiovascular mortality. Consistent results were observed when stratifying by age, sex, race, BMI, smoking status, diabetes duration, and glycated hemoglobin A1c levels. CONCLUSIONS: Higher concentrations of serum ß-carotene, but not other individual carotenoids, were significantly associated with an increased risk of cardiovascular mortality among individuals with T2D. Our findings, if replicated, underscore the need to estimate the optimal serum ß-carotene concentrations in individuals with T2D.