Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of type 2 diabetes mellitus (T2DM). 423,503 UK adults from the UK Biobank (UKB) and 13,800 Chinese adults from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. The exposures of interest were social isolation and loneliness. Social isolation was evaluated based on the number of household members, frequency of social activities, contact with others, and marriage status (CHARLS only). Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others (UKB only). The primary endpoint was incident T2DM. The two-sample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB (n = 463,010) and the European Bioinformatics Institute (n = 655,666). The UKB cohort study documented 15,072 T2DM cases during a mean follow-up of 13.5 years, and the CHARLS cohort study recorded 1,249 T2DM cases during a mean follow-up of 5.8 years. Social isolation and loneliness showed significant associations with an elevated risk of T2DM in both UKB (social isolation [most vs least]: HR 1.17, 95% CI 1.11–1.23; loneliness [yes vs no]: HR 1.21, 95% CI 1.13–1.30) and CHARLS cohorts (social isolation [yes vs no]: HR 1.22, 95% CI 1.06–1.40; loneliness [yes vs no]: HR 1.21, 95% CI 1.07–1.36). These associations remained significant after accounting for baseline glucose status and genetic susceptibility to T2DM. Two-sample MR analyses determined that feeling lonely (OR 1.04, 95% CI 1.02–1.06) and engaging in fewer leisure/social activities (OR 1.03, 95% CI 1.02–1.05) were associated with increased T2DM risk, whereas more contact with friends or family (OR 0.99, 95% CI 0.98–0.99) was associated with reduced T2DM risk. Social isolation and loneliness are each associated with an elevated risk of T2DM, with MR analyses suggesting potential causal links. These associations remain significant after considering genetic susceptibility to T2DM. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of T2DM prevention strategies. CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-008) and National Natural Science Foundation of China (No. 72103187).

Background: The triglyceride-glucose (TyG) index and the stress hyperglycaemia ratio (SHR) are both positively associated with cardiovascular (CV) risk in patients with coronary heart disease. However, the prognostic value of these two biomarkers has not been well elucidated in patients with chronic total occlusion (CTO). Therefore, this study aims to evaluate the association of the TyG index and the SHR with long-term prognosis in patients with CTO. Methods: This prospective cohort study consecutively included 2740 angina patients with CTO from January 2017 to December 2018 at Fuwai Hospital. The outcomes are a composite of CV death and target vessel myocardial infarction (TVMI) and major CV cerebrovascular adverse events (MACCEs, including all-cause death, nonfatal MI, ischaemia-driven target vessel revascularization, and stroke). The association between biomarkers and prognosis was analysed by multivariable Cox proportional hazard models, and the predictive value was determined by a receiver-operating characteristic (ROC) curve. Results: During the follow-up with a median time of 3 years, 179 (6.5%) cases of MACCEs and 47 (1.7%) cases of CV death or TVMI were recorded. Patients with a high TyG index (> 9.10) and a high SHR (> 0.87) showed a significantly increased risk of CV death/TVMI (TyG index: HR 4.23, 95% CI 1.58–11.37; SHR: HR 5.14, 95% CI 1.89–13.98) and MACCEs (TyG index: HR 2.47, 95% CI 1.54–3.97; SHR: HR 2.91, 95% CI 1.84–4.60) compared with those with a low Tyg index and a low SHR (TyG < 8.56, SHR < 0.76). The area under the curve (AUC) values were 0.623 (TyG index) and 0.589 (SHR) for CV death/TVMI and 0.659 (TyG index) and 0.624 (SHR) for MACCEs. Furthermore, patients with both a high TyG index and a high SHR showed the highest risk of clinical outcomes among patients with different levels of these two biomarkers, and the AUC for the TyG-SHR combination was larger than the TyG index alone in predicting MACCE risk. Conclusions: The study revealed that a high TyG index and a high SHR were significantly correlated with poor prognosis in patients with CTO and suggested that these two biomarkers are reliable in predicting long-term prognosis in CTO patients.

Background: Inflammation plays a crucial role in the pathogenesis and progression of coronary artery disease (CAD). The neutrophil to lymphocyte ratio (NLR) is a novel inflammatory biomarker and its association with clinical outcomes in CAD patients with different glycemic metabolism after percutaneous coronary intervention (PCI) remains undetermined. Therefore, this study aimed to investigate the effect of NLR on the prognosis of patients undergoing PCI with or without type 2 diabetes mellitus (T2DM). Methods: We consecutively enrolled 8,835 patients with CAD hospitalized for PCI at Fuwai hospital. NLR was calculated using the following formula: neutrophil (*10⁹/L)/lymphocyte (*10⁹/L). According to optimal cut-off value, study patients were categorized as higher level of NLR (NLR-H) and lower level of NLR (NLR-L) and were further stratified as NLR-H with T2DM and non-T2DM, and NLR-L with T2DM and non-T2DM. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as all-cause mortality, myocardial infarction (MI), stroke and target vessel revascularization. Results: A total of 674 (7.6%) MACCEs were recorded during a median follow-up of 2.4 years. The optimal cut-off value of NLR was 2.85 determined by the surv_cutpoint function. Compared to those in the NLR-H/T2DM groups, patients in the NLR-L/non-T2DM, NLR-H/non-T2DM and NLR-L/T2DM groups were at significantly lower risk of 2-year MACCEs [adjusted hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.52 to 0.87, P = 0.003; adjusted HR: 0.62, 95%CI: 0.45 to 0.85, P = 0.003; adjusted HR: 0.77, 95%CI: 0.61 to 0.97, P = 0.025; respectively]. Remarkably, patients in the NLR-L/non-T2DM group also had significantly lower risk of a composite of all-cause mortality and MI than those in the NLR-H/T2DM group (adjusted HR: 0.57, 95%CI: 0.35 to 0.93, P = 0.024). Multivariable Cox proportional hazards model also indicated the highest risk of MACCEs in diabetic patients with higher level of NLR than others (P for trend = 0.009). Additionally, subgroup analysis indicated consistent impact of NLR on MACCEs across different subgroups. Conclusions: Presence of T2DM with elevated NLR is associated with worse clinical outcomes in CAD patients undergoing PCI. Categorization of patients with elevated NLR and T2DM could provide valuable information for risk stratification of CAD patients.

Background: Stress hyperglycemia was positively associated with poor prognosis in individuals with acute myocardial infarction (AMI). However, admission glucose and stress hyperglycemia ratio (SHR) may not be the best indicator of stress hyperglycemia. We performed this study to evaluate the comparative prognostic value of different measures of hyperglycemia (fasting SHR, fasting plasma glucose [FPG], and hemoglobin A1c [HbA1c]) for in-hospital mortality in AMI patients with or without diabetes. Methods: In this prospective, nationwide, multicenter China Acute Myocardial Infarction (CAMI) registry, 5,308 AMI patients including 2081 with diabetes and 3227 without diabetes were evaluated. Fasting SHR was calculated using the formula [(first FPG (mmol/l))/(1.59×HbA1c (%)-2.59)]. According to the quartiles of fasting SHR, FPG and HbA1c, diabetic and non-diabetic patients were divided into four groups, respectively. The primary endpoint was in-hospital mortality. Results: Overall, 225 (4.2%) patients died during hospitalization. Individuals in quartile 4 had a significantly higher rate of in-hospital mortality compared with those in quartile 1 in diabetic cohort (9.7% vs. 2.0%; adjusted odds ratio [OR] 4.070, 95% CI 2.014–8.228) and nondiabetic cohort (8.8% vs. 2.2%; adjusted OR 2.976, 95% CI 1.695–5.224). Fasting SHR was also correlated with higher in-hospital mortality when treated as a continuous variable in diabetic and nondiabetic patients. Similar results were observed for FPG either as a continuous variable or a categorical variable. In addition, fasting SHR and FPG, rather than HbA1c, had a moderate predictive value for in-hospital mortality in patients with diabetes (areas under the curve [AUC] for fasting SHR: 0.702; FPG: 0.689) and without diabetes (AUC for fasting SHR: 0.690; FPG: 0.693). The AUC for fasting SHR was not significantly different from that of FPG in diabetic and nondiabetic patients. Moreover, adding fasting SHR or FPG to the original model led to a significant improvement in C-statistic regardless of diabetic status. Conclusions: This study indicated that, in individuals with AMI, fasting SHR as well as FPG was strongly associated with in-hospital mortality regardless of glucose metabolism status. Fasting SHR and FPG might be considered as a useful marker for risk stratification in this population. Trial registration: ClinicalTrials.gov NCT01874691.

Study Objective: To prospectively examine the association between sleep quality and incident cancer risk in the elderly. Methods: A total of 10,036 participants aged ≥50 years free of cancer at baseline from the English Longitudinal Study of Ageing at wave 4 (2008) were included, and followed up until 2016. The primary endpoint was new onset physician-diagnosed cancer. Sleep quality was assessed by four questions regarding the frequency of sleep problems and overall subjective feeling of sleep quality in the last month, with higher score denoting poorer sleep quality. The multivariable Cox regression model was used to calculate hazard ratio (HR) with 95% confidence interval (CI) for incident cancer risk according to sleep quality. Results: At 8-year follow-up, a total of 745 (7.4%) participants developed cancer. Compared with good sleep quality at baseline, HR (95% CI) for incident cancer risk was 1.328 (1.061, 1.662) for intermediate quality, 1.586 (1.149, 2.189) for poor quality. Similarly, compared with maintaining good sleep quality in the first 4 years, HR (95% CI) for incident cancer risk was 1.615 (1.208, 2.160) for maintaining intermediate quality and 1.608 (1.043, 2.480) for maintaining poor quality. The exclusion of participants with family history of cancer or abnormal sleep duration yielded consistent results. Conclusions: Poor sleep quality is positively associated with the long-term risk of developing cancer in an elderly cohort. Both medical staffs and the general public should pay more attention to improving sleep hygiene.

The occurrence and development of coronary heart disease (CHD) are closely linked to fluctuations in blood glucose levels. While the efficacy of intensified treatment guided by HbA1c levels remains uncertain for individuals with diabetes and CHD, this review summarizes the findings and conclusions regarding HbA1c in the context of CHD. Our review showed a curvilinear correlation between regulated level of HbA1c and therapeutic effectiveness of intensified glycemic control among patients with type 2 diabetes and coronary heart disease. It is necessary to optimize the dynamic monitoring indicators of HbA1c, combine genetic profiles, haptoglobin phenotypes for example and select more suitable hypoglycemic drugs to establish more appropriate glucose-controlling guideline for patients with CHD at different stage of diabetes.