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To explore the relationship between social isolation and health behaviors and ulcer severity in patients with diabetic foot.A cross-sectional study was conducted with 160 patients suffering from type 2 diabetes mellitus combined with diabetic foot. The patients received treatment at the Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University between September 2020 and December 2021. Patient information was collected, including the scores for Lubben Social Network Scale and the Wagner classification of foot ulcers. Analysis was conducted to study the characteristics of the patients' health behaviors, including whether they received information and education on diabetic foot, whether there were delays in their attempt to access medical service, the frequency of foot examinations, etc. In addition, patient demographic data were collected, including sex, age, education, and employment status. According to their scores for Lubben Social Network Scale, the patients were divided into a social isolation group (The findings suggest that, compared with the non-social-isolation group, the social isolation group had a higher proportion of diabetic foot patients with Wagner grade 3-5 diabetic foot ulcers (Social isolation is correlated to health behaviors and ulcer severity in patients with diabetic foot. Giving more attention to the problem of social isolation of diabetic foot patients and increasing their ties with the social environment and the members of their social network may have a positive effect on improving the delays in diabetic foot patients' attempt to access medical service, which is particularly important for follow-up treatment.

Background To investigate the influence of diabetes duration and glycemic control, assessed by glycated hemoglobin (HbA1c) levels, on risk of incident dementia. Methods The present study is a prospective study of 461 563 participants from the UK Biobank. The age at diabetes diagnosis was determined by self-report. Diabetes duration was calculated as baseline age minus age at diagnosis. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (CIs). Results During a median follow-up of 8.1 years, 2 233 dementia cases were recorded. As compared with normoglycemic individuals, individuals with diabetes had higher risk of all-cause dementia, and the risk increased with increasing duration of diabetes; compared with participants with diabetes duration of Conclusions Diabetes duration appeared to be associated with the risk of incident dementia due to factors beyond glycemic control. Clinicians should consider not only glycemic control but also diabetes duration in dementia risk assessments for patients with diabetes.

Background: Wealth and income are potential modifiable risk factors for dementia, but whether wealth status, which is composed of a combination of debt and poverty, and assessed by wealth and income, is associated with cognitive impairment among elderly adults remains unknown. Objective: To examine the associations of different combinations of debt and poverty with the incidence of dementia and cognitive impairment without dementia (CIND) and to evaluate the mediating role of depression in these relationships. Methods: We included 15,565 participants aged 51 years or older from the Health and Retirement Study (1992–2012) who were free of CIND and dementia at baseline. Dementia and CIND were assessed using either the modified Telephone Interview for Cognitive Status (mTICS) or a proxy assessment. Cox models with time-dependent covariates and mediation analysis were used. Results: During a median of 14.4 years of follow-up, 4,484 participants experienced CIND and 1,774 were diagnosed with dementia. Both debt and poverty were independently associated with increased dementia and CIND risks, and the risks were augmented when both debt and poverty were present together (the hazard ratios [95% confidence intervals] were 1.35 [1.08–1.70] and 1.96 [1.48–2.60] for CIND and dementia, respectively). The associations between different wealth statuses and cognition were partially (mediation ratio range: 11.8–29.7%) mediated by depression. Conclusion: Debt and poverty were associated with an increased risk of dementia and CIND, and these associations were partially mediated by depression. Alleviating poverty and debt may be effective for improving mental health and therefore curbing the risk of cognitive impairment and dementia.

AIMS To assess the associations of diabetes duration and glycaemic control (defined by plasma glycated haemoglobin [HbA1c] level) with the risks of cardiovascular disease (CVD) and all-cause mortality and to determine whether the addition of either or both to the established CVD risk factors can improve predictions. MATERIALS AND METHODS A total of 435 679 participants from the UK Biobank without CVD at baseline were included. Cox models adjusting for classic risk factors (sociodemographic and anthropometric characteristics, lipid profiles and medication use) were used, and predictive utility was determined by the C-index and net reclassification improvement (NRI). RESULTS Compared with participants without diabetes, participants with longer diabetes durations and poorer glycaemic control had a higher risk of fatal/nonfatal CVD. Among participants with diabetes, the fully-adjusted hazard ratios (HRs) for diabetes durations of 5 to

OBJECTIVE The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines lowered the hypertension threshold from a SBP/DBP level of at least 140/90 mmHg to at least 130/80 mmHg. The cardiovascular impact of isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) under the new definition remains unclear. METHODS We used data from the UK Biobank study, which is a prospective population-based cohort study. Participants were categorized into five groups: normal BP, normal high BP, ISH, IDH and systolic and diastolic hypertension. The primary endpoint for this study was the composite of nonfatal myocardial infarction (MI), nonfatal ischaemic stroke, nonfatal haemorrhagic stroke and cardiovascular disease (CVD) death. We also explored the results for the above-mentioned CVD outcomes separately. Baseline BP measurements were obtained twice after the participant had been at rest for at least 5 min in a seated position. RESULTS We included 385 955 participants who were not taking antihypertensive medications, were free of CVD at baseline and had available data on BP measurements. During a median follow-up of 8.1 years, 8959 CVD events were recorded, including 4729 nonfatal MIs, 2287 nonfatal ischaemic strokes, 813 nonfatal haemorrhagic strokes, and 1826 CVD deaths. According to the hypertension threshold of at least 130/80 mmHg by the American College of Cardiology/American Heart Association guidelines, both ISH (hazard ratio 1.39; 95% confidence interval 1.27, 1.15) and IDH (hazard ratio 1.28; 95% confidence interval 1.15, 1.43) were significantly associated with a higher overall CVD risk than normal BP. ISH was associated with most CVD risk, except for ischaemic stroke, while the excess CVD risk associated with IDH appeared to be driven mainly by MI and CVD death. We found heterogeneity by sex and age regarding the effects of IDH on overall CVD risk, with significant associations in younger adults (age

Greater lipid variability may cause adverse health events among diabetic patients. We aimed to examine the effect of lipid variability on the risk of diabetic microvascular outcomes among type 2 diabetes mellitus patients.We assessed the association between visit-to-visit variability (measured by variability independent of mean) in high-density lipoprotein (HDL) cholesterol, low-density lipoprotein-cholesterol (LDL), triglyceride, and remnant cholesterol (RC) measurements among participants involved in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and the risk of incident microvascular outcomes, including nephropathy, neuropathy, and retinopathy. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders.There were 2400, 2470, and 2468 cases of nephropathy, neuropathy, and retinopathy during a follow-up period of 22 600, 21 542, and 26 701 person-years, respectively. Higher levels of HDL, triglyceride, and RC variability were associated with an increased risk of incident nephropathy and neuropathy. Compared with the lowest quartile, the fully adjusted HRs (95% CI) for the highest quartile of HDL, triglyceride, and RC variability for nephropathy risk were 1.57 (1.22, 2.01), 1.50 (1.18, 1.92), and 1.40 (1.09, 1.80), respectively; and for neuropathy, the corresponding risks were 1.36 (1.05, 1.75), 1.47 (1.14, 1.91), and 1.35 (1.04, 1.74), respectively. Null association was observed between LDL variability and all microvascular complications. Additionally, all associations of variability in the other lipids with retinopathy risk were null.Among individuals with type 2 diabetes mellitus, HDL, triglyceride, and RC variability were associated with increased risks of nephropathy and neuropathy but not retinopathy.ClinicalTrials.gov., no. NCT00000620.背景: 较大的血脂变异性可能会导致糖尿病患者的不良健康事件。我们旨在2型糖尿病(T2DM)患者中研究血脂变异性对糖尿病微血管结果风险的影响。 方法: 我们评估了ACCORD研究参与者在高密度脂蛋白胆固醇(HDL), 低密度脂蛋白胆固醇(LDL), 甘油三酯和残余胆固醇(RC)测量中的随访间变异性(通过独立于平均值的变异性来衡量)与发生微血管病变(包括神经病变, 肾病和视网膜病变)的风险之间的关系。使用COX比例风险模型估计危险比(HR)和95%可信区间(CI), 并对潜在混杂因素进行了校正。 结果: 在22600人-年, 21542人-年和26701人-年的随访期内, 分别有2400例肾病, 2470例神经病变和2468例视网膜病变。HDL, 甘油三酯和RC变异性越高, 发生肾病和神经病变的风险就越高。与最低四分位数相比, 高密度脂蛋白, 甘油三酯和RC变异性对肾病风险的完全校正后的HR(95%CI)分别为1.57(1.22, 2.01), 1.50(1.18, 1.92)和1.40(1.09, 1.80)；对于神经病变, 相应的风险分别为1.36(1.05, 1.75), 1.47(1.14, 1.91)和1.35(1.04, 1.74)。在LDL变异性和所有微血管并发症之间无明显关联。此外, 其他血脂的变异性与视网膜病变风险之间无明显关联。 结论: 在T2DM患者中, HDL, 甘油三酯和RC变异性与肾病和神经病变的风险增加有关, 但与视网膜病变无关。.

Context The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear. Objective To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes. Design, Setting, and Patients This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality. Results A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was 7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was Conclusions A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.

The patterns of the association between high-density lipoprotein cholesterol (HDL-C) concentrations and mortality among the elderly are still unclear.To examine the association of HDL-C concentrations with mortality and to identify the optimal HDL-C concentration range that predicts the lowest risk of all-cause mortality among the elderly.This was a nationwide, community-based, prospective cohort study.This study included 7766 elderly individuals (aged ≥65 years; mean age: 74.4 years) from the Health and Retirement Study. Cox proportional hazards models and Cox models with penalized smoothing splines were used to estimate hazard ratios (HRs) with 95% CI for all-cause and cause-specific mortality.During a median follow-up of 5.9 years, 1921 deaths occurred. After a full adjustment for covariates, a nonlinear (P0.001 for nonlinearity) association was found between HDL-C and all-cause mortality [minimum mortality risk at 71 mg/dL (1.84 mM)]; the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration61 mg/dL (1.58 mM; HR: 1.18; 95% CI: 1.05 to 1.33) and with HDL-C concentration87 mg/dL (2.25 mM; HR: 1.56; 95% CI: 1.17 to 2.07) than in the group with HDL-C concentrations ranging from 61 to 87 mg/dL (1.58 to 2.25 mM). Nonlinear associations of HDL-C concentrations with both cardiovascular and noncardiovascular mortality were also observed (both P0.001 for nonlinearity).Among the elderly, nonlinear associations were found between HDL-C and all-cause and cardiovascular mortality. The single optimal HDL-C concentration and range were 71 mg/dL and 61 to 87 mg/dL, respectively.

"High-density Lipoprotein Cholesterol and All-cause and Cause-specific Mortality Among the Elderly" Supplementary materials

OBJECTIVE: To analyze the characteristics of pathogenic microorganisms in the infected bone tissues in patients with diabetic foot osteomyelitis (DFO) using 16S rRNA high-throughput sequencing to facilitate rapid and accurate detection of pathogens and effective infection control. METHODS: Between September, 2016 and April, 2017, 16 patients with DFO were admitted in our department and infected bone specimens were obtained during debridement. The pathogenic microorganisms in the specimens were identified using both 16S rRNA high-throughput sequencing and automatic blood culture analyzer, and the characteristics of the microflora were analyzed based on 16S rRNA sequencing data in comparison with the results of blood culture. RESULTS: The results of 16S rRNA sequencing showed that bone tissues of DFO contained diverse and uniformly distributed pathogenic organisms, among which 20 (87%) dominant genera were identified with Prevotella as the most abundant pathogen. Both 16S rRNA sequencing and routine culture results suggested the domination of gram-negative bacteria among the pathogens in DFO bone tissues. 16S rRNA sequencing, compared with routine culture, yielded a higher positivity rate (100% vs 88.24%) and detected a greater average number of pathogens (12.56 vs 1.50) and a higher proportion of gram-negative bacteria (67.16% vs 50.00%) in the samples. 16S rRNA sequencing detected nearly all the pathogens identified by routine culture except for Escherichia coli, Serratia marcescens and Enterobacter cloaca, and identified 13 genera that failed to be detected by routine culture, including the obligate or strict anaerobes Anaerococcus, Veillonella, Bacteroides, Fusobacterium, Porphyromonas, Finegoldia, Prevotella, Peptostreptococcus, Parvimonas, Peptoniphilus and Bulleidia. Routine culture did not detect any anaerobes in the samples but identified multidrug-resistant strains in as many as 58.33% of the pathogens. CONCLUSIONS: 16S rRNA high-throughput sequencing is capable of demonstrating the diversity and abundance of microflora in DFO bone tissues, where diverse and uniformly distributed pathogens can be detected with a discrete distribution of the dominant genera, most of which are gram-negative. Compared with routine culture method, 16S rRNA sequencing allows more convenient and accurate identification of the pathogens (especially gram-negative bacteria and anaerobes), and can be useful in clinical decision on appropriate treatment of DFO.

To investigate foot biomechanics characteristic of patients with type 2 diabetes mellitus.This study was conducted among 303 patients with type 2 diabetes. The whole foot was divided into 10 regions, namely the first toe (T1); the second to fifth toes (T2-5); the first, second, third, fourth, and fifth metatarsals (M1, M2, M3, M4, and M5, respectively); midfoot (MF), and the heel medial (HM). Foot arch index, foot angle and maximum peak pressure (MPP) of the 10 regions were measured using a Footscan gait system.The maximum peak pressure of 10 regions decreased in the order of M3M2HMM4HLM1M5T1MLT2-5 for the left foot, and in the order of M3M2HMM4HLM1M5T1MLT2-5 for the right foot. The MPP in M1 region was higher in the right than in the left foot (P0.05). The MPP in M3, M4, M5, and MF was higher in the left than in the right foot (P0.05). The percentage of high-risk foot (defined by a total plantar pressure ≥70 N/cmDiabetic patients have obvious alterations in foot biomechanics with abnormalities of the plantar pressure, and the percentage of high-risk foot increases in overweight and obese patients, suggesting the need of body weight control in these patients when administering offloading treatment for prevention of diabetic foot ulcer.

To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells.After the HCT116 cells were pretreated with specific ERK inhibitor (U0126) or specific siRNA and exposed to 10 mmol/L sodium butyrate (NaBT) for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy.The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the U0126-blocked export of SphK2.ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.