CONTEXT:The relationship between the consumption of different beverages and the risk of microvascular complications in individuals with type 2 diabetes (T2D) is unclear. OBJECTIVE:To investigate the association of individual beverage consumption, including artificially sweetened beverages (ASBs), sugar-sweetened beverages (SSBs), tea, coffee, natural juice, and yogurt, with the risk of microvascular complications in adults with T2D. METHODS:This cohort study included 6676 participants with T2D who were free of macrovascular and microvascular complications at baseline in the UK Biobank. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:During a median follow-up of 11.7 years, 1116 cases of composite microvascular complications were documented. After multivariable adjustment, a linear dose-response relationship was demonstrated between the consumption of ASBs and SSBs and the risk of microvascular complications. Compared with nonconsumers, those who consumed ≥2.0 units/day of ASBs and SSBs had an HR (95% CI) of 1.44 (1.18-1.75) and 1.32 (1.00-1.76) for composite microvascular complications, respectively. In addition, higher tea consumption was associated with a lower risk of diabetic retinopathy, with an HR (95% CI) of 0.72 (0.57-0.92) for whom consuming ≥4.0 units/day. There was no significant association between individual beverage consumption and the risk of diabetic neuropathy. No significant association was observed between the consumption of coffee, natural juice, or yogurt and the risks of microvascular complications. Moreover, substituting half units/day of ASBs or SSBs with tea or coffee was associated with a 16% to 28% lower risk of microvascular complications. CONCLUSION:Higher consumption of ASBs and SSBs was linearly associated with an increased risk of microvascular complications in adults with T2D.

OBJECTIVE:To prospectively evaluate the association between modifiable lifestyle factors and peripheral artery disease (PAD) among individuals with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS:We included 14,543 individuals with T2D from the UK Biobank. We defined a weighted healthy lifestyle score using nonsmoking, regular physical activity, high-quality diet, moderate alcohol consumption, optimal waist-to-hip ratio, and adequate sleep duration, and categorized into unfavorable, intermediate, and favorable lifestyles. We created a genetic risk score (GRS) using 19 single nucleotide polymorphisms previously found to be associated with PAD. We modeled the association between lifestyle score and PAD, overall and stratified by PAD genetic susceptibility. RESULTS:After a median 13.5 years of follow-up, 628 incident cases of PAD were documented. A linear inverse association between the weighted lifestyle score and PAD was observed, with a hazard ratio (HR) (95% CI) of 0.27 (0.19, 0.38) for favorable compared with unfavorable lifestyle (Ptrend < 0.0001). An estimated 58.3% (45.0%, 69.1%) of PAD in this population could be potentially avoidable if all participants attained a favorable lifestyle. Moreover, the PAD GRS was associated with increased PAD risk (HR [95% CI] per SD increment: 1.13 [1.03, 1.23]). A favorable lifestyle was able to partially mitigate the excess risk of PAD associated with higher GRS, albeit as a nonsignificant interaction. Several biomarkers in the lipid metabolism, hepatic/renal function, and systemic inflammation pathways collectively explained 13.3% (8.5%, 20.1%) of the association between weighted lifestyle score and PAD. CONCLUSIONS:A favorable lifestyle was associated with lower risk of PAD among individuals with T2D, independent of genetic predisposition to PAD.

ScopeAmong patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association.Methods and resultsThis study includes 5405 participants with T2D who provided at least one 24‐h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A, C‐reactive protein, and body mass index collectively explain 26.9% (12.8%, 48.5%) of the association between UPF intake and the risk of overall CVD.ConclusionHigher UPF intakes are associated with increased hazards of CVD among individuals with T2D, and the association is partly mediated through worsening biomarkers of renal function, lipid metabolism, inflammation, and body weight.

Background The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particularly individual BA subtypes, with chronic kidney disease (CKD) in patients of newly diagnosed type 2 diabetes. Methods In this cross-sectional study, we included 1234 newly diagnosed type 2 diabetes who participated in an ongoing prospective study, the Dongfeng-Tongji cohort. Circulating primary and secondary unconjugated BAs and their taurine- or glycine-conjugates were measured using ultraperformance liquid chromatography-tandem mass spectrometry. CKD was defined as eGFR < 60 ml/min per 1.73 m 2 . Logistic regression model was used to compute odds ratio (OR) and 95% confidence interval (CI). Results After adjusting for multiple testing, higher levels of total primary BAs (OR per standard deviation [SD] increment: 0.78; 95% CI: 0.65–0.92), cholate (OR per SD: 0.78; 95% CI: 0.66–0.92), chenodeoxycholate (OR per SD: 0.81; 95% CI: 0.69–0.96), glycocholate (OR per SD: 0.81; 95% CI: 0.68–0.96), and glycochenodeoxycholate (OR per SD: 0.82; 95% CI: 0.69–0.97) were associated with a lower likelihood of having CKD in patients with newly diagnosed type 2 diabetes. No significant relationships between secondary BAs and odds of CKD were observed. Conclusions Our findings showed that higher concentrations of circulating unconjugated primary BAs and their glycine-conjugates, but not taurine-conjugates or secondary BAs, were associated with lower odds of having CKD in patients with type 2 diabetes.

Context: Younger onset of type 2 diabetes (T2D) was associated with higher risks of vascular complications and mortality. Objective: To prospectively assess risk profiles for incident T2D stratified by age at onset. Methods: A total of 471 269 participants free of T2D at baseline were included from the UK Biobank. Approximately 70 clinical, lipid, lipoprotein, inflammatory, and metabolic markers, and genetic risk scores (GRSs) were analyzed. Stratified Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into 4 groups (<= 50.0, 50.1-60.0, 60.1-70.0, and >70.0 years). Results: During 11 years of follow-up, 15 805 incident T2D were identified. Among clinical risk factors, obesity had the highest HR at any age, ranging from 13.16 (95% CI, 9.67-17.91) for 50.0 years and younger to 4.13 (3.78-4.51) for older than 70.0 years. Other risks associated with T2D onset at age 50.0 years and younger included dyslipidemia (3.50, 2.91-4.20), hypertension (3.21, 2.71-3.80), cardiovascular disease (2.87, 2.13-3.87), parental history of diabetes (2.42, 2.04-2.86), education lower than college (1.89, 1.57-2.27), physical inactivity (1.73, 1.43-2.10), smoking (1.38, 1.13-1.68), several lipoprotein particles, inflammatory markers, liver enzymes, fatty acids, amino acids, as well as GRS. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <.05), and some were not significant for onset at age older than 70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B. Conclusion: Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasizes the necessity of promoting primary prevention among younger individuals. Moreover, obesity should be prioritized.

RATIONALE & OBJECTIVE:Chronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study. STUDY DESIGN:Observational cohort study. SETTING & PARTICIPANTS:A total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy. EXPOSURE:Levels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy. OUTCOME:Incident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records. ANALYTICAL APPROACH:Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. RESULTS:We identified 2,269 CKD cases over a median follow-up period of 13.1 years via linkage with the electronic health records. After adjusting for covariates and correcting for multiple testing, 90 of 142 biomarkers were significantly associated with incident CKD. In general, higher concentrations of very-low-density lipoprotein (VLDL) particles were associated with a higher risk of CKD whereas higher concentrations of high-density lipoprotein (HDL) particles were associated with a lower risk of CKD. Higher concentrations of cholesterol, phospholipids, and total lipids within VLDL were associated with a higher risk of CKD, whereas within HDL they were associated with a lower risk of CKD. Further, higher triglyceride levels within all lipoprotein subclasses, including all HDL particles, were associated with greater risk of CKD. We also identified that several amino acids, fatty acids, and inflammatory biomarkers were associated with risk of CKD. LIMITATIONS:Potential underreporting of CKD cases because of case identification via electronic health records. CONCLUSIONS:Our findings highlight multiple known and novel pathways linking circulating metabolites to the risk of CKD. PLAIN-LANGUAGE SUMMARY:The relationship between individual lipoprotein particle subclasses and lipid-related traits and risk of chronic kidney disease (CKD) in general population is unclear. Using data from 91,532 participants in the UK Biobank, we evaluated the associations of metabolites measured using nuclear magnetic resonance testing with the risk of CKD. We identified that 90 out of 142 lipid biomarkers were significantly associated with incident CKD. We found that very-low-density lipoproteins, high-density lipoproteins, the lipid concentration and composition within these lipoproteins, triglycerides within all the lipoprotein subclasses, fatty acids, amino acids, and inflammation biomarkers were associated with CKD risk. These findings advance our knowledge about mechanistic pathways that may contribute to the development of CKD.

Context: Few studies have examined the relationship between vitamin D and the risk of recurrent cardiovascular (CV) events in people with coronary heart disease (CHD). Objective: This study aimed to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentration and the vitamin D receptor (VDR) polymorphisms with the risk of recurrent CV events in individuals with established CHD. Methods: A total of 22 571 participants with CHD were included from the UK Biobank. Recurrent CV events, including myocardial infarction (MI), heart failure (HF), stroke, and CV disease mortality, were identified from electronic health records. Cox proportional-hazard models were used to calculate hazard ratios (HRs) and 95% CIs. Results: The median (interquartile range) of serum 25(OH)D concentration was 44.8 nmol/L (range, 30.3-61.4 nmol/L), and 58.6% of participants had 25(OH)D below 50 nmol/L. During a median follow-up of 11.2 years, a total of 3998 recurrent CV events were documented. After multivariable adjustment, there was a nonlinear inverse relationship between serum 25(OH)D and recurrent CV events (P nonlinearity <.01), and the decreasing risk gradually leveled off at around 50 nmol/L. Compared with participants with serum 25(OH)D less than 25.0 nmol/L, the HRs (95% CIs) for participants with serum 25(OH)D of 50.0 to 74.9 nmol/L were 0.64 (0.58-0.71) for recurrent CV events, 0.78 (0.65-0.94) for MI, 0.66 (0.57-0.76) for HF, and 0.66 (0.52-0.84) for stroke. In addition, these associations were not modified by genetic variants in the VDR. Conclusion: In people with established CHD, higher serum 25(OH)D concentrations were nonlinearly associated with a lower risk of recurrent CV events, with a potential threshold around 50 nmol/L. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of recurrent CV events among individuals with CHD.

Emerging evidence revealed that pyrethroids and circulating lipid metabolites are involved in incident type 2 diabetes (T2D). However, the pyrethroid-associated lipid profile and its potential role in the association of pyrethroids with T2D remain unknown. Metabolome-wide association or mediation analyses were performed among 1006 pairs of T2D cases and matched controls nested within the prospective Dongfeng-Tongji cohort. We identified 59 lipid metabolites significantly associated with serum deltamethrin levels, of which eight were also significantly associated with serum fenvalerate (false discovery rate [FDR] < 0.05). Pathway enrichment analysis showed that deltamethrin-associated lipid metabolites were significantly enriched in the glycerophospholipid metabolism pathway (FDR = 0.02). Furthermore, we also found that several deltamethrin-associated lipid metabolites (i.e., phosphatidylcholine [PC] 32:0, PC 34:4, cholesterol ester 20:0, triacylglycerol 52:5 [18:2]), and glycerophosphoethanolamine-enriched latent variable mediated the association between serum deltamethrin levels and T2D risk, with the mediated proportions being 44.81%, 15.92%, 16.85%, 16.66%, and 22.86%, respectively. Serum pyrethroids, particularly deltamethrin, may lead to an altered circulating lipid profile primarily in the glycerophospholipid metabolism pathway represented by PCs and lysophosphatidylcholines, potentially mediating the association between serum deltamethrin and T2D. The study provides a new perspective in elucidating the potential mechanisms through which pyrethroid exposure might induce T2D.

BACKGROUND:The association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and mortality among patients with metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) remains unclear.OBJECTIVE:The aim was to evaluate the association between serum 25(OH)D concentrations and mortality among individuals with MAFLD/NAFLD.METHODS:The study included 4651 individuals with fatty liver disease (FLD; 3964 had MAFLD and 3968 had NAFLD) from NHANES III. Fatty liver disease was identified by ultrasonographic detection of hepatic steatosis. Mortality was ascertained by linkage to the National Death Index up to 31 December 2019. Cox proportional hazards models were used to estimate the HRs and 95% CIs, with adjustment of potential confounders.RESULTS:Of 4651 individuals with FLD, 3427 individuals (69.7%) had both MAFLD and NAFLD. During median follow-ups of 25.8 and 26.1 y, we identified 1809 and 1665 deaths among 3964 participants with MAFLD and 3968 participants with NAFLD, respectively. Compared with participants with serum 25(OH)D concentrations ≤30.0 nmol/L, the multivariable-adjusted HRs and 95% CIs of all-cause mortality were 0.62 (0.43, 0.89) for participants with MAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.001) and 0.63 (0.42, 0.95) for participants with NAFLD having serum 25(OH)D >75.0 nmol/L (P-trend = 0.002). A nonlinear inverse association was observed between serum 25(OH)D concentrations and all-cause mortality among participants with MAFLD (Poverall < 0.001; Pnonlinear = 0.003) or NAFLD (Poverall < 0.001; Pnonlinear = 0.009), with a threshold effect at ∼50.0 nmol/L. The inverse association was stronger among participants with MAFLD aged <60 y (P-interaction = 0.001).CONCLUSIONS:This study suggested a nonlinear inverse association between serum 25(OH)D concentrations and all-cause mortality among patients with MAFLD/NAFLD, with a threshold effect at ∼50.0 nmol/L of serum 25(OH)D.

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.

BACKGROUND:Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism. OBJECTIVES:We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). METHODS:A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped. RESULTS:During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%-129% higher risk of CVD among individuals with T2D. CONCLUSIONS:A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D.

BACKGROUND:Air pollution and type 2 diabetes (T2D) are both associated with an increased risk of ischemic heart disease (IHD). Little is known about the combined effects of multiple air pollutants on IHD risk, especially among individuals with T2D. We sought to assess the association of combined exposure to multiple air pollutants with incident IHD and examine the modification effect of T2D. METHODS:This study included 388780 individuals (20036 individuals with T2D) free of cardiovascular disease and cancer from the UK Biobank. The combined exposure to multiple air pollutants, including particulate matter (PM) with diameters ≤ 2.5 μm (PM2.5), PM with diameters between 2.5 and 10 µm (PMcoarse), PM with diameters ≤ 10 μm (PM10), nitrogen dioxide (NO2), and nitrogen dioxides (NOx), was assessed by creating a weighted air pollution score (APS), with a higher APS representing a higher level of air pollution exposure. Hazard ratios (HR) and 95 % confidence intervals (CI) for incident IHD were assessed by multivariable-adjusted Cox proportional hazard models. RESULTS:During a median of 12.9 years of follow-up, 27333 incident IHD cases were observed. Compared with the lowest tertile of the APS, the multivariable-adjusted HR (95 % CI) of IHD risk for the highest tertile was 1.13 (1.03-1.23) among individuals with T2D, while the HR was 1.06 (1.03-1.10) among individuals without T2D. Additionally, the associations between APS and IHD incidence showed a linear relationship among individuals with T2D (nonlinearity: P = 0.37), whereas a non-linear relationship was observed among individuals without T2D (nonlinearity: P = 0.02). For the joint analysis, individuals in the highest tertile of APS and with T2D had a 54 % higher risk of IHD compared to individuals in the lowest tertile of APS and without T2D, with a significant additive interaction (Pinteraction < 0.01). The proportion of relative excess risk was 17 % due to the interaction in categorical analyses. CONCLUSIONS:The combined exposure to multiple air pollutants has been associated with an elevated risk of incident IHD, and the association is more pronounced among individuals with T2D.

Context :Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. Objective We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. Methods: This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c >= 7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable linear regression models were used to estimate beta values and 95% CI. Results: After multivariable adjustment including demographic and lifestyle factors, medical history, and total intracranial volume, those with prediabetes had smaller total and subcortical gray matter volumes than participants with NGM, while atrophy of total and subcortical gray matter was more pronounced in those with T2D (all P trend < .05). Moreover, participants with T2D had larger volumes of white matter and WMH (both P trend < .05). For brain microstructure, participants with prediabetes had lower FA values in commissural fibers (beta -0.04; 95% CI -0.08, -0.003). Global and tract-specific microstructural abnormalities of white matter were observed in participants with T2D, especially for T2D with HbA1c >= 7% (all P trend < .05), except for FA values in projection fibers. Conclusion: These findings suggest that interventions for hyperglycemia at an earlier stage may help protect brain health.

BACKGROUND AND AIMS:Very high levels of high-density lipoprotein cholesterol (HDL-C) have been paradoxically linked to increased mortality risk. The present study aimed to examine associations of HDL-C and varied sizes of the HDL particle (HDL-P) with mortality risk stratified by hypertension. METHODS AND RESULTS:This prospective cohort study included 429 792 participants (244 866 with hypertension and 184 926 without hypertension) from the UK Biobank. During a median follow-up of 12.7 years, 23 993 (9.8%) and 8142 (4.4%) deaths occurred among individuals with and without hypertension, respectively. A U-shaped association of HDL-C with all-cause mortality was observed in individuals with hypertension after multivariable adjustment, whereas an L-shape was observed in individuals without hypertension. Compared with individuals with normal HDL-C of 50-70 mg/dL, those with very high HDL-C levels (>90 mg/dL) had a significantly higher risk of all-cause mortality among individuals with hypertension (hazard ratio, 1.47; 95% confidence interval, 1.35-1.61), but not among those without hypertension (1.05, 0.91-1.22). As for HDL-P, among individuals with hypertension, a larger size of HDL-P was positively whereas smaller HDL-P was negatively associated with all-cause mortality. After additional adjustment for larger HDL-P in the model, the U-shaped association between HDL-C and mortality risk was altered to an L-shape among individuals with hypertension. CONCLUSIONS:The increased risk of mortality associated with very high HDL-C existed only in individuals with hypertension, but not in those without hypertension. Moreover, the increased risk at high HDL-C levels in hypertension was likely driven by larger HDL-P.

AIMS:To examine the association of a healthy sleep pattern with the risk of recurrent cardiovascular events among patients with coronary heart disease (CHD). METHODS AND RESULTS:This prospective cohort study included 21 193 individuals with CHD from the UK Biobank. A healthy sleep score was generated based on a combination of chronotype, sleep duration, insomnia, and excessive daytime sleepiness. Cox proportional hazards regression models were applied to estimate the associations between healthy sleep score and recurrent cardiovascular events. During a median of 11.1 years of follow up, we documented 3771 recurrent cardiovascular events, including 1634 heart failure cases and 704 stroke cases. After multivariable adjustment, including lifestyle factors, medical history, and CHD duration, sleep 7-8 h/day, never/rarely insomnia, and no frequent daytime sleepiness were each significantly associated with a 12-22% lower risk of heart failure. In addition, compared with participants who had a healthy sleep score of 0-1, the multivariable-adjusted HR (95% CI) for participants with a healthy sleep score of 4 was 0.86 (0.75, 0.99) for recurrent cardiovascular events, 0.71 (0.57, 0.89) for heart failure, and 0.72 (0.51, 1.03) for stroke. CONCLUSIONS:Adherence to a healthy sleep pattern was significantly associated with a lower risk of recurrent cardiovascular events among patients with CHD, especially for heart failure. These findings indicate that healthy sleep behaviours could be beneficial in the prevention of cardiovascular event recurrence.

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 remains unclear. This study 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 diseases (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, 1394 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 2872 ASCVD, 852 heart failure, 1548 CKD, and 1776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risks of ASCVD (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. Conclusion: 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.

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.

Aims: To quantify associations of different metrics of long-term glycemic variability (GV) with multiple adverse diabetes-related outcomes.Methods: We searched PubMed and Embase from database inception to 23 August 2021. GV was based on measurements of HbA1c or fasting plasma glucose (FPG) and calculated by standard deviation (SD), coefficient of variance (CV) or other metrics. Outcomes included mortality, cardiovascular disease (CVD), renal disease, pe-ripheral neuropathy, retinopathy, dementia and cancer. Random-effects meta-analyses were adopted to pool the relative risks (RRs).Results: Seventy-five articles with 2,051,701 participants were included. When comparing top with bottom quartiles, HbA1c variabilities were associated with all-cause mortality (RRCV = 1.63, 95 % CI 1.37-1.92; RRSD = 1.87, 1.55-2.26), CVD (RRCV = 1.38, 1.07-1.78; RRSD = 1.34, 1.12-1.59), renal disease (RRCV = 1.43, 1.18-1.74; RRSD = 1.44, 1.24-1.67), and peripheral neuropathy (RRCV = 1.84, 1.40-2.43; RRSD = 1.98, 1.51-2.61), but not retinopathy. FPG variabilities were associated with all-cause mortality (RRCV = 1.59, 1.43-1.78; RRSD = 1.67, 1.26-2.20), renal disease (RRCV = 1.77, 1.32-2.38), and retinopathy (RRCV = 1.92, 1.10-3.35), but not CVD and peripheral neuropathy. Associations of GV with Alzheimer's disease (RRHbA1c-CV = 1.38, 1.13-1.70; RRFPG-CV = 1.32, 1.07-1.63) and cancer (RRHbA1c-SD = 2.19, 1.52-3.17; RRFPG-CV = 3.64, 2.21-5.98) were each found sig-nificant in one study.Conclusions: Long-term GV was associated with multiple adverse diabetes-related outcomes, while the strength of associations varied. The findings support the use of long-term GV for diabetes management in clinical practice.