Predicted lean body mass, fat mass, and heart failure in patients with type 2 diabetes mellitus.

BACKGROUND: High body mass index (BMI) is associated with a higher risk of heart failure (HF) in patients with new-onset type 2 diabetes mellitus (T2DM). However, limited studies have investigated the independent association between fat mass or lean body mass and HF risk among T2DM patients with cardiovascular disease (CVD) or high CVD risk. OBJECTIVES: To investigate the association between fat mass index (FMI, kg/m2) or lean BMI (LBMI, kg/m2) and HF risk. METHODS: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional-hazards models were applied to evaluate the association of FMI, LBMI, and BMI with HF risk. Discordant analysis was performed to compare the magnitude of this associations. RESULTS: HF occurred in 356 participants (3.7%). After adjusting for confounding factors, higher FMI values were independently associated with HF risk (HR: 1.72, 95% CI: 1.15-2.57, each 1 SD increase in FMI); LBMI was a protective risk factor for HF (HR: 0.58, 95% CI: 0.38-0.87,). After further adjusting for FMI, the association between BMI and HF risk (HR, 0.97; 95% CI, 0.67-1.42) disappeared. Compared with concordant values below the medians, discordant FMI above the median with BMI below yielded an HR of 1.78 (95% CI: 1.14-2.78) for HF. In contrast, BMI above the median with FMI below was not associated with HF risk (HR: 1.09, 95% CI: 0.57-2.09). CONCLUSIONS: The risk of HF conferred by higher BMI was primarily driven by the association between FMI and HF. After adjusting for BMI, LBMI played a protective role.

ALP-assisted chemical redox cycling signal amplification for ultrasensitive fluorescence detection of DNA methylation.

Affinity assays allow direct detection of DNA methylation events without requiring a special sequence. However, the signal amplification of these methods heavily depends on nanocatalysts and bioenzymes, making them suffer from low sensitivity. In this work, alkaline phosphatase (ALP)-assisted chemical redox cycling was employed to amplify the sensitivity of fluorescence affinity assays for DNA methylation detection using Ru@SiO2@MnO2 nanocomposites as fluorescent probes. In the ALP-assisted chemical redox cycling reaction system, ALP hydrolyzed 2-phosphate-L-ascorbic acid trisodium salt (AAP) to produce AA, which could reduce MnO2 nanosheets to form Mn2+, making the fluorescence recovery of Ru@SiO2 nanoparticles possible. Meanwhile, AA was oxidized to dehydroascorbic acid (DHA), which was re-reduced by tris(2-carboxyethyl) phosphine (TCEP) to trigger a redox cycling reaction. The constantly generated AA could etch large amounts of MnO2 nanosheets and greatly recover Ru@SiO2 fluorescence, amplifying the signal of the fluorescence assay. Employing the proposed ALP-assisted chemical redox cycling signal amplification strategy, a sensitive affinity assay for DNA methylation detection was achieved using ALP encapsulated liposomes that were linked with the 5mC antibody (Ab) to bind with methylated sites. A detection limit down to 2.9 fM was obtained for DNA methylation detection and a DNA methylation level as low as 0.1% could be distinguished, which was superior to conventional affinity assays. Moreover, the affinity assays could detect DNA methylation more specifically and directly, implying their great potential for the analysis of tumor-specific genes in liquid biopsy.

Association between accelerometer-derived physical activity and incident cardiac arrest.

AIMS: Studies on objectively measured physical activity (PA) have investigated acute cardiovascular outcomes but not cardiac arrest (CA). Our study aimed to investigate the dose-response relationship between accelerometer-measured PA and CA by intensity of PA. METHODS AND RESULTS: This prospective cohort study included 98 893 UK Biobank participants whose PA data were measured using wrist-worn accelerometers. Total PA volume was measured using the average overall acceleration. Minutes per week of light PA (LPA), moderate PA (MPA), and vigorous PA (VPA) were recorded. The incident CA was identified using diagnostic codes linked to hospital encounters and death records. Cox proportional hazard models with restricted cubic splines were used to study the associations, including sex differences. During the follow-up period (median: 7.31 years; interquartile range: 6.78-7.82 years), 282 incident CAs (0.39 per 1000 person-years) occurred. Total PA was inversely related to CA risk. The CA risk decreased sharply until the time spent in MPA or VPA reached ∼360 min or 20 min per week, respectively, after which it was relatively flat. The LPA was not associated with CA risk. Subgroup analyses showed a more pronounced association between PA and a reduced risk of CA in women compared to men. CONCLUSION: Accelerometer-measured PA, particularly MPA and VPA, was associated with a lower CA risk. Furthermore, a stronger association was observed in women than men.

Association of the cumulative triglyceride-glucose index with major adverse cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and is associated with major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). However, the long-term effect of the TyG index on the incidence of MACEs remains unclear. We aimed to investigate the association between the cumulative TyG index and the risk of MACEs in patients with T2DM. METHODS: This post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial assessed patients' (T2DM > 3 months) cumulative TyG index and MACE data from the study database. Five fasting blood glucose and triglyceride measurements, at baseline and the first four visits, were taken from 5695 participants who had not experienced MACEs. Cumulative exposure to the TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to determine the association between the cumulative TyG index and MACEs. The incremental predictive value of the cumulative TyG index was further assessed. RESULTS: Over a median follow-up of 5.09 years, 673 (11.82%) MACEs occurred, including 256 (4.50%) cardiovascular disease (CVD) deaths, 288 (5.06%) non-fatal myocardial infarctions (MIs), and 197 (3.46%) strokes. The risk of developing MACEs increased with the cumulative TyG index quartile. After adjusting for multiple potential confounders, the hazard ratios for the very high cumulative TyG index group versus the low group were 1.59 (95% confidence interval [CI], 1.17-2.16), 1.97 (95% CI 1.19-3.26), and 1.66 (95% CI 1.02-2.70) for overall MACEs, CVD death, and non-fatal MI, respectively. Restricted cubic spline analysis also showed a cumulative increase in the risk of MACEs with an increase in the magnitude of the cumulative TyG index. The addition of the cumulative TyG index to a conventional risk model for MACEs improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value. CONCLUSIONS: In patients with T2DM, the cumulative TyG index independently predicts the incidence of MACEs, and monitoring the long-term TyG index may assist with optimized-for-risk stratification and outcome prediction for MACEs. Trial registration URL: http://www. CLINICALTRIALS: gov . Unique identifier: NCT00000620.

Down-conversion luminescence and temperature sensing characteristics of LaSrGaO4 :Er3.

Erbium(III) ion (Er3+ ) has abundant energy levels that can emit light covering a quite broad wavelength range in many hosts. Here we synthesized LaSrGaO4 :Er3+ phosphors by a high-temperature solid-state method. Upon excitation at the ultraviolet (UV) band, LaSrGaO4 :Er3+ phosphors could emit green, red and near-infrared emission simultaneously. The temperature dependent emission characteristics of the as-prepared samples was then studied and two kinds of luminescent ratiometric thermometry were constructed. The first one is on the basis of two green emission bands that stems from the 2 H11/2 → 4 I15/2 and 4 S3/2 → 4 I15/2 transitions of Er3+ . The intensity ratio between these two emission bands was found to follow well with the Boltzmann distribution, and its maximum relative sensitivity was calculated to be 0.84% K-1 at 299 K. The other one depends on the 4 F9/2 → 4 I15/2 transition of Er3+ and self-luminescence of the host LaSrGaO4 , considering that these two emission lines have different temperature response. The relative sensitivity of this type of luminescence intensity ratio (LIR) thermometry could reach 1.86% K-1 at 299 K, we have successfully developed materials with one of the largest relative sensitivities to date, which provides some basis for the subsequent development of a new type of non-contact temperature sensor.

Atherogenic index of plasma is associated with major adverse cardiovascular events in patients with type 2 diabetes mellitus.

BACKGROUND: Previous studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM). METHODS: This was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors. RESULTS: AIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084-1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205-1.474, P < 0.001; Model 2: HR = 1.171, 95% CI 1.030-1.333, P = 0.016; Model 3: HR = 1.194, 95% CI 1.049-1.360, P = 0.007), all-cause mortality (Model 1: HR = 1.184, 95% CI 1.077-1.303, P < 0.001), cardiovascular death (Model 1: HR = 1.422, 95% CI 1.201-1.683, P < 0.001; Model 3: HR = 1.264, 95% CI 1.015-1.573, P = 0.036), and nonfatal myocardial infarction (Model 1: HR = 1.447, 95% CI 1.255-1.669, P < 0.001; Model 2: HR = 1.252, 95% CI 1.045-1.499, P = 0.015; Model 3: HR = 1.284, 95% CI 1.071-1.539, P = 0.007). Subgroup stratified analyses showed that AIP might interact with sex, a classical risk factor of cardiovascular events. CONCLUSIONS: This study showed that AIP might be a strong biomarker that could be used to predict the risk of cardiovascular events in patients with T2DM. TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000620.

HMGB1 impairs endothelium-dependent relaxation in diabetes through TLR4/eNOS pathway.

Endothelium-dependent relaxation (EDR) is an initial key step leading to various vascular complications in patients with diabetes. However, the underlying mechanism of EDR impairment in diabetes is not fully understood. Present study defined the role of high-mobility group protein (HMGB1) in EDR related to diabetes. Serum level of HMGB1 was increased in diabetic patients and in db/db mice. Serum HMGB1 level was also positively correlated with HbA1c and negatively correlated with nitric oxide (NO) in diabetic patients. Results from wire myograph showed that recombinant HMGB1 (rHMGB1) was capable of impairing EDR of aortas from wild-type (WT) mice by an eNOS-dependent mechanism. Consistently, HMGB1 inhibitor glycyrrhizin acid (GA) decreased the serum level of HMGB1 and rescued EDR impairment partly in db/db mice. Furthermore, rHMGB1 mediated EDR impairment was abolished in aortas of TLR4-/- mice. In addition, high-glucose-induced HMGB1 upregulation and secretion in endothelial cells. In conclusion, HMGB1 contributes to the EDR impairment through TLR4/eNOS pathway in the setting of diabetes. GA as the HMGB1 inhibitor could attenuate EDR impairment in an animal model of diabetes.

Turning waste into treasure: chicken eggshell membrane derived fluorescent carbon nanodots for the rapid and sensitive detection of Hg2+ and glutathione.

Herein, a green, economical, and waste-utilization approach is reported for the synthesis of water-soluble carbon nanodots (C-Dots) with a high fluorescence quantum yield of 19.5%. As a common protein-rich waste, eggshell membrane was selected as a cost-effective and ideal precursor to prepare C-Dots using the microwave method. The as-prepared C-Dots showed a maximum emission at 375 nm with an excitation wavelength at 235 nm. The fluorescent C-Dots were adopted as a sensitive probe for the rapid detection of Hg2+ and glutathione (GSH) based on the fluorescence off and on (turn-off-on) strategy. This was ascribed to the fact that Hg2+ could effectively quench the fluorescence of the C-Dots and GSH was able to prevent fluorescence quenching owing to the specific binding between Hg2+ and GSH. The designed method exhibited a high sensitivity and selectivity towards the detection of Hg2+ and GSH. Under the optimized conditions, the method showed a good linear relationship with Hg2+ concentration in the range from 100 nM to 50 µM with a detection limit of 32.0 nM. For GSH detection, it displayed a linear range from 50 nM to 10 µM with a detection limit of 9.8 nM. Moreover, this method was successfully applied to detect GSH in human serum samples. The eggshell derived fluorescent C-Dots pave the way for economical environmental and biological analyses.

Waist circumference is associated with major adverse cardiovascular events in male but not female patients with type-2 diabetes mellitus.

BACKGROUND: Although studies have shown that waist circumference (WC) is positively associated with an increased risk of cardiovascular diseases among the normal population, few studies have investigated WC in patients with type-2 diabetes mellitus (T2DM). METHODS: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The Cox proportional hazards models was used to investigate the relationship between WC and major adverse cardiovascular events (MACEs) in T2DM patients with cardiovascular disease (CVD) or high risk factors of CVD. RESULTS: A total of 10,251 T2DM patients (6299 men [61.4%], 3952 women [38.6%]) were included in our analysis. The mean age was 64.0 ± 7.53 years. After a mean follow-up at 9.2 ± 2.4 years later, 1804 patients (event rate of 23 per 1000 person-years) had developed MACEs. MACEs rates in men and women were 18.0 and 26.0 events per 1000 person-years, respectively. After multivariable adjustment, each increase in WC of 1 SD increased the risk of MACEs (HR: 1.10, 95% CI 1.04-1.17; P < 0.01) in men, with a non-significant increase in MACEs (HR: 1.04, 95% CI 0.95-1.13; P = 0.40) in women. Compared with those in the first quartile of WC, male patients in the fourth quartile of WC had a hazard ratio (HR) of 1.24 (95% CI 1.05-1.46) for MACEs; female patients in the fourth quartile of WC had an HR of 1.22 (95% CI 0.96-1.56) for MACEs. CONCLUSIONS: Higher WC is associated with increased risks of MACEs in male but not female T2DM patients. Trial registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000620).

Association between Radiation Exposure and Endothelium-Dependent Vasodilation: Results from Clinical and Experimental Studies.

PURPOSE: The association between occupational radiation exposure and endothelium-dependent vasodilation (EDV) remains unclear. This study evaluated the association between radiation exposure and EDV among fluoroscopy-guided interventional procedure specialists and explored the possible mechanisms. MATERIALS AND METHODS: Brachial flow-mediated dilation was compared in 21 interventional cardiologists (the radiation group) and 15 noninterventional cardiologists (the nonradiation group). Animal radiation experiments were also performed to observe the impact of radiation on EDV. RESULTS: Flow-mediated dilation in both the left (radiation group, 3.63% vs. nonradiation group, 6.77%; P < .001) and right brachial arteries (5.36% vs. 7.33%, respectively; P = .04) and serum nitric oxide (NO) level (343.69 vs. 427.09 µmol/L, respectively; P = .02) were significantly reduced in the radiation group compared to those in the nonradiation group. EDV was significantly impaired in acetylcholine concentrations of 3 × 10-6 mol/L and 10-5 mol/L (60.09% vs.74.79%, respectively; P = .03; and 62.73% vs. 80.56%, respectively; P = .002), and reactive oxygen species levels in the aorta intima and media layers were significantly increased in mice after a single x-ray exposure, which could be partly rescued by pretreatment with folic acid (P < .05). CONCLUSIONS: Radiation exposure can lead to impairment of flow-mediated vasodilation in human or EDV in mice. In mice acutely exposed to radiation, folic acid alleviated radiation-induced EDV impairment by possible reduction of reactive oxidative species.

Transcatheter Closure of Large Coronary-Cameral Fistulas Using the Patent Ductus Arteriosus Occluder or Amplatzer Vascular Plugs.

Transcatheter closure (TCC) has emerged as the first-line treatment for coronary artery fistulas. However, limited data exist regarding the long-term outcomes and technical aspects of this procedure. We aimed to report the long-term outcomes and technical aspects of TCC of large coronary-cameral fistulas (CCFs).All patients with large CCFs who underwent attempted TCC using the patent ductus arteriosus (PDA) occluder or Amplatzer vascular plug (AVP), from June 2002 to December 2017, were retrospectively reviewed. A total of 23 patients with large CCFs underwent attempted TCC using the PDA occluder or AVP. Most CCFs originated from the right coronary artery and drained predominantly into the right heart chamber. Procedural success was achieved in 21 (91.3%) patients. Devices were deployed using the arteriovenous loop in 15, transarterial approach in 4, and arterio-artery loop approach in 2 patients. Procedural complications included coronary spasm in one and side branch occlusion in one patient. Among these 21 patients with successful device implantation, follow-up angiograms or computed tomography angiograms were obtained in 14 (66.7%) patients at a median of 11.0 (range, 9.8-16.3) months. Late complications included thrombosis of residual fistula segment without myocardial infarction (MI) in one, coronary thrombosis resulting in MI in one, and recanalization necessitating re-intervention in one patient. No death and device embolization occurred.TCC of large CCFs using the PDA occluder or AVP is an effective therapy in anatomically suitable candidates, with favorable long-term outcomes. Given that potentially hazardous complications may occur late after the procedure, long-term periodic evaluation is mandatory.

Association of predicted lean body mass and fat mass with cardiovascular events in patients with type 2 diabetes mellitus.

BACKGROUND: Previous studies have found that predicted fat mass and lean body mass may act differently on adverse events. However, the cardiovascular prognostic value of lean body mass and fat mass in patients with type 2 diabetes mellitus (T2DM) has not yet been investigated. We sought to investigate the relation between predicted lean body mass or fat mass and the risk of cardiovascular disease in patients with T2DM. METHODS: We conducted a post hoc analysis of data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to investigate the relation between the predicted lean body mass or fat mass and major adverse cardiovascular events in patients with T2DM. We used sex-specific quartiles of predicted lean body mass index (BMI; kg/m2) and fat mass index (kg/m2). We defined a major adverse cardiovascular event as a composite of nonfatal myocardial infarction, nonfatal stroke or death from cardiovascular causes. RESULTS: After a mean follow-up period of 8.8 years, we found that a major cardiovascular event occurred in 1801 of 10 251 patients (17.8%). Predicted lean BMI was not associated with major cardiovascular events (p = 0.34). Compared with patients in the first quartile (incidence rate 16.4%; 17.2%, 17.5% and 19.8% for the second, third and four quartiles, respectively) of predicted fat mass index, those in the fourth quartile had a hazard ratio of 1.53 (95% confidence interval 1.23-1.91). INTERPRETATION: In patients with T2DM, we found that predicted fat mass had a strong positive association with a higher risk of a major adverse cardiovascular event. Increasing lean body mass did not have a protective role. Trial registration: ClinicalTrials.gov., no. NCT00000620.

Self-Luminescence of Perovskite-Like LaSrGaO4 via Intrinsic Defects and Anomalous Luminescence Analysis of LaSrGaO4:Mn2.

A series of deep red phosphors with perovskite-like oxide LaSrGaO4 as host are synthesized by a high temperature solid state method, and the luminescence properties and mechanisms have been investigated in detail. LaSrGaO4 presents self-luminescence at 722 nm, and it is proved that the self-luminescence comes from two kinds of electronic defects and three kinds of vacancy defects, which are anti-occupation defects La Sr•, strontium gap defects Sr i••, the oxygen interstitial defects O i″, substitution defects Sr La', and strontium vacancy defects V Sr″. In addition, when Mn2+ ions are doped in LaSrGaO4, interestingly, the shape of the emission spectra of LaSrGaO4:Mn2+ is the same as that of LaSrGaO4, and the emission intensities are enhanced greatly. Luminescence of Mn2+ ions has been confirmed by doping Mg2+ into LaSrGaO4 and measuring the lifetimes of host LaSrGaO4, LaSrGaO4:Mg2+, and LaSrGaO4:Mn2+ for comparison. The mechanisms of host self-luminescence and Mn2+ luminescence are discussed by detecting the luminescence centers with the low temperature spectra, calculating the forbidden bandwidth with the diffuse reflectance spectra, and calculating the trap depths with the thermoluminescence spectra and further depicted by establishing the transition model. LaSrGaO4:Mn2+ can emit strong deep red light about 722 nm, so the phosphor will have a good application prospect in the field of plant lighting.

Platelet reactivity-adjusted antiplatelet therapy in patients with percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

Numerous number of evidences show that high on-treatment platelet reactivity is a well-known risk factor for adverse events in patients after percutaneous coronary intervention (PCI). Controversial situations still exist regarding the effectiveness of tailoring antiplatelet therapy according to platelet function monitoring. The PubMed, Embase, and Cochrane Central databases were searched for randomized trials comparing platelet reactivity-adjusted antiplatelet therapy with conventional antiplatelet therapy in patients undergoing PCI. The primary end point was all-cause mortality, major adverse cardiac events (MACE) including cardiovascular (CV) death, nonfatal myocardial infarction (MI), definite/probable stent thrombosis (ST), revascularization, and stroke or transient ischemic attack (TIA). The safety end point was defined as major bleeding events. We derived pooled risk ratios (RRs) with fixed-effect models. Six studies enrolling 6347 patients were included. Compared with conventional treatment, tailoring antiplatelet failed to reduce all-cause mortality (RR: 0.89, 95% confidence interval [CI]: 0.63-1.24, P = 0.48), MACE (RR: 1.02, 95% CI: 0.92-1.14, P = 0.69), MI (RR: 1.07, 95% CI: 0.95-1.21, P = 0.24), CV death (RR: 0.69, 95% CI: 0.40-1.19, P = 0.09), ST (RR: 0.83, 95% CI: 0.50-1.38, P = 0.23), stroke or TIA (RR: 1.08, 95% CI: 0.55-2.12, P = 0.83), revascularization (RR: 0.96, 95% CI: 0.69-1.33, P = 0.79), and major bleeding events (RR: 0.79, 95% CI: 0.53-1.17, P = 0.24). Compared with traditional antiplatelet treatment, tailoring antiplatelet therapy according to platelet reactivity testing failed to reduce all-cause mortality, MACE, and major bleeding events in patients undergoing PCI.

Exploring the association between regional fat distribution and atrial fibrillation risks: a comprehensive cohort study.

Background: The contribution of total fat mass and regional fat distribution to the risk of AF has rarely been studied. Methods: This prospective cohort study(N=494,063) evaluated the association of total fat mass measured by fat percentage (FP) and regional fat measured by arm fat percentage (AFP), trunk fat percentage (TFP), and leg fat percentage (LFP) with incident AF. A subgroup (N = 25,581) underwent MRI, which allowed us to further assess whether visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) of the trunk fat exert different effects on AF incidence. Results: Over, a median 12.9 ± 1.86 years of follow-up, 29,658 participants (cumulative rate: 6.0%) developed AF. Each 1-standard deviation (SD) increase in LFP was associated with a 16% lower risk of AF (HR: 0.84, 95% CI: 0.82, 0.85). The association between FP and AF was weaker than that between LFP and AF (HR: 0.90, 95% CI: 0.89, 0.92). AFP and TFP only had a marginal association with a lower incidence of AF. Both the VAT and ASAT showed a U-shaped relationship with incident AF. Conclusions: Fat mass, mainly leg fat mass, was associated with a lower risk of AF. ASAT did not exert protective effects.

Glycemic variability evaluated by HbA1c rather than fasting plasma glucose is associated with adverse cardiovascular events.

Background: Although studies have shown that glycemic variability is positively associated with an increased risk of cardiovascular disease, few studies have compared hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) variability with adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Methods: This was a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Cox proportional hazards models were used to explore the relationship between HbA1c or FPG variability and the incidence of major adverse cardiovascular events (MACEs). Results: In total, 9,547 patients with T2DM were enrolled in this study. During the median 4.6 ± 1.5 years follow-up period, 907 patients developed MACEs. The risk of MACEs increased in the HbA1c variability group in each higher quartile of HbA1c variability (P < 0.01). Compared with those in the first quartile of HbA1c variability, patients in the fourth quartile had a hazard ratio of 1.37 (Model 2, 95% confidence interval: 1.13-1.67) for MACEs. Higher FPG variability was not associated with a higher risk of MACEs in patients with T2DM (P for trend=0.28). A U-shaped relationship was observed between HbA1c and FPG variability, and MACEs. Glucose control therapy modified the relationship between HbA1c and MACEs; participants with higher HbA1c variability receiving intensive glucose control were more likely to develop MACEs (P for interaction <0.01). Conclusion: In adults with T2DM, the relationship between glycemic variability evaluated using HbA1c and FPG was U-shaped, and an increase in HbA1c variability rather than FPG variability was significantly associated with MACEs. The relationship between HbA1c variability and MACEs was affected by the glucose control strategy, and a higher HbA1c variability was more strongly associated with MACEs in patients receiving an intensive glucose control strategy.

Cumulative blood pressure predicts risk of stroke in individuals with type 2 diabetes.

AIMS: To determine whether cumulative blood pressure (BP) could predict stroke in individuals with type 2 diabetes (T2D). METHODS: BP levels at baseline and the initial three visits were obtained from individuals participating in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial who had not experienced a stroke. Cumulative elevations in BP were assessed by adding the weighted mean BP values at various time intervals. The association of cumulative BP with stroke was evaluated by a multivariate-adjusted Cox proportional hazard model analysis. RESULTS: Overall, 8282 participants were included (62.10% males and 37.90% females; mean age, 62.73 years). With a median follow-up period of 6.36 years, 324 (3.91%) and 305 (3.68%) patients had any and nonfatal stroke events, respectively. Only baseline systolic BP (SBP) independently predicted any stroke after adjustment for potential confounders, whereas cumulative SBP and pulse pressure independently predicted elevated stroke events. A strong dose-response relationship between cumulative BP and stroke was identified, and conventional risk factors combined with cumulative SBP improved prediction efficiency. CONCLUSION: Cumulative SBP independently predicts stroke in individuals with T2D and provides an incremental predictive value for stroke compared with baseline BP assessments. TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT00000620).

Depression is associated with heart failure in patients with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of heart failure (HF). Depression, a common comorbidity of T2DM, may further increase the risk of heart failure (HF). We investigated the association between depression and incident HF in patients with T2DM. Methods and results: Depressive symptoms were assessed in the ACCORD Health-Related Quality of Life study participants at baseline, 12, 36, and 48 months using the nine-item Patient Health Questionnaire (PHQ-9). The severity of depressive symptoms was categorized as none (0-4 points), mild (5-9 points), or moderate-severe (10-24 points). Cox regression with PHQ-9 as a time-dependent covariate was used to assess the association between depression and incident HF. During the median follow-up of 8.1 years, 104 participants developed HF (incidence: 7.1/1,000 person-years). Half of the participants with moderate-severe depression were relieved and a significant percentage of participants without depression or with mild depression worsened to mild or moderate-severe depression during the follow-up period, respectively. Each unit increase in the PHQ-9 score was associated with a 5% higher risk of HF (hazard ratio [HR]:1.05, 95% confidence interval [CI]: 1.01-1.10). Patients with depression ever (HR: 2.23, 95% CI: 1.25-3.98) or persistent depression (HR: 2.13, 95% CI: 1.05-4.44) had a higher risk of HF than those without depression ever. Conclusion: Depressive symptoms change greatly in T2DM patients, depressive symptoms are an independent risk factor for HF. These results reinforce the importance of continuous evaluation and management of mental health status in T2DM patients with high HF risk.

Device-measured physical activity and type 2 diabetes mellitus risk.

Objectives: We investigated how device-measured physical activity (PA) volume (PA energy expenditure [PAEE]) and intensity (fraction of PAEE from moderate-to-vigorous PA [FMVPAEE]) were associated with the incidence of type 2 diabetes mellites (T2DM). Methods: This population-based prospective cohort study included 90,044 participants. The primary exposures were PAEE and FMVPAEE. The secondary exposures were energy expenditure exerted during light, moderate, and vigorous PA and their fraction of PAEE. Results: Each 1-SD increase in PAEE was associated with a 17% lower risk of T2DM (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.78-0.98). Each 1-SD increase in FMVPAEE was associated with a 21% lower incidence of T2DM (HR: 0.79, 95% CI: 0.74-0.83). Achieving the same PA volume (KJ/kg/day) through vigorous PA (HR: 0.88, 95% CI: 0.85-0.91) was more effective in preventing T2DM than moderate PA (HR: 0.97, 95% CI: 0.96-0.98) and light PA (HR: 0.99, 95% CI: 0.98-1.00). Conclusion: A higher PA volume is associated with a lower incidence of T2DM. Achieving the same PA volumes through higher-intensity PA is more effective than low-intensity PA in reducing T2DM incidence.

Relationship Between Regional Adiposity Distribution and Incident Heart Failure in General Populations without Cardiovascular Disease.

BACKGROUND: Obesity is associated with a high risk of heart failure. However, the contribution of regional fat distribution evaluated using bioimpedance analysis toward heart failure risk in the general population without cardiovascular disease has rarely been studied. METHODS: This study included 483,316 participants without heart failure and cardiovascular disease from the UK Biobank study. The regional fat mass was determined by bioimpedance analysis and calculated by dividing the square of height in meters (kg/m2). This study evaluated the association of regional fat mass (arm fat index [AFI], trunk fat index [TFI], and leg fat index [LFI]) with the risk of incident heart failure and whether regional fat mass adds a further prognostic value for heart failure besides body mass index (BMI) in a large prospective cohort study. RESULTS: During the median 12.1 years, 3134 incident heart failure cases occurred. After adjustment for BMI and other confounding factors, each 1-standard deviation increase in LFI was associated with a 21% lower heart failure risk even after adjusting for BMI and other confounding factors (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.73-0.85). However, we did not observe heart failure-associated risks with AFI and TFI (HR 1.04; 95% CI, 0.99-1.09; HR 0.97, 95% CI, 0.91-1.04, respectively). Subgroup analysis demonstrated that the protective role of LFI was more prominent in the elderly and female participants (P < .01). CONCLUSION: Regional fat measurement other than BMI can improve heart failure risk stratification; leg fat plays a protective role, yet arm and trunk fat do not, in the general population without cardiovascular disease.