Comparing the prognostic value of the old and new sarcopenia criteria from the Asian Working Group on Sarcopenia in older adults with type 2 diabetes: Which set is more appropriate?

BACKGROUND: This study aimed to compare the prevalence of sarcopenia according to the old and new Asian Working Group on Sarcopenia (AWGS) operational criteria and explore the effects of sarcopenia on adverse outcomes in older adults with type 2 diabetes (T2D). METHODS: A total of 386 patients with T2D aged ≥ 60 years were recruited in retrospective cohort study. Sarcopenia was assessed with different versions of the AWGS consensus, including the AWGS2014, AWGS2019H (muscle mass adjusted for height), and AWGS2019B (muscle mass adjusted for body mass index). The median follow-up period was 47 months. The composite primary endpoint was the first occurrence of cardiovascular disease (CVD), fragility fracture, and all-cause mortality and the secondary outcomes included the three separate components of the primary outcome. RESULTS: In this study, the prevalence of sarcopenia under different criteria was significantly different, with AWGS2019H having the highest prevalence of 31.3%. The agreement among sarcopenia criteria was unsatisfactory. By Cox regression analysis, all three AWGS definitions of sarcopenia were associated with the composite outcome of all-cause mortality, fracture and CVD (hazard ratio [HR], 2.69 vs. HR, 2.63; vs. HR, 2.23; model 3). Further exploratory analysis, sarcopenia defined by the AWGS2019H criteria was an independent risk factor for death, incident CVD, and fractures. While AWGS2014 criteria was an increased risk factor of death and CVD. The AWGS2019B criteria were only associated with incident fractures. CONCLUSION: All three AWGS definitions of sarcopenia were associated the composite primary endpoint. Additionally, the AWGS2019H criteria may be a better independent risk factor for negative health outcomes.

Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses.

BACKGROUND: Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. METHODS: We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. FINDINGS: In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09-6.32] in EIMDS, and 4.31 [1.39-13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05-1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. INTERPRETATION: Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes.

Sarcopenic obesity predicts negative health outcomes among older patients with type 2 diabetes: The Ageing and Body Composition of Diabetes (ABCD) cohort study.

BACKGROUND AND AIMS: The definition of and diagnostic criteria for sarcopenic obesity (SO) remain unclear, hindering the assessment of its prevalence as well as its clinical relevance to negative health outcomes, especially in diabetic patients, who are more prone to body composition changes. The aim of this study was to investigate the prevalence of SO and its impact on negative health outcomes among elderly patients with type 2 diabetes (T2DM) from the Ageing and Body Composition of Diabetes (ABCD) cohort. METHODS: This retrospective cohort study included 386 elderly patients with T2DM (177 males and 209 females, mean age of 67.91 ± 6.10 years). SO was defined as the coexistence of sarcopenia defined by the 2019 Asian Working Group for Sarcopenia up-to-date consensus and obesity identified by five alternative measurements as follows: body mass index (BMI)≥28 kg/m2 (BMI28), BMI≥25 kg/m2 (BMI25), body fat percentage (BF%)≥25% for men or 35% for women, visceral fat area (VFA)≥100 cm2, or android fat mass (AF) higher than the sex-specific median. The primary endpoint was all-cause death or fragility fracture, and the secondary endpoint was a composite of cardiovascular diseases (CVDs). Cox proportional hazards regression analysis was used to estimate the association between SO and negative health outcomes. RESULTS: The prevalence of SO was 0.2% (BMI28), 2.5% (BMI25), 9.8% (AF), and 18.7% (BF% or VFA) among elderly patients with T2DM, according to the different obesity surrogate markers. During a mean follow-up period of 3.46 ± 1.15 years, 50 patients reached the primary endpoint, and 33 patients had incident CVD. SO classified using BF% was significantly associated with the primary endpoint [hazard ratio (HR) = 2.94, 95% CI = 1.25-6.92] and incident CVD (HR = 6.02, 95% CI = 1.56-23.15), even after comprehensive adjustment for bone-, comorbidity-, and diabetes-specific confounding variables. When SO was classified using BMI25, VFA and AF, similar results were found for adverse outcomes. However, SO classified using BMI25 resulted in misclassification of SO for 61 participants, 19 of whom experienced adverse events during follow-up, and SO classified using VFA or AF was not significantly associated with incident CVD. CONCLUSIONS: SO is not uncommon in geriatric patients with T2DM, and its prevalence varies widely depending on the diverse surrogate indices of body fat excess. Furthermore, SO may be a better independent risk factor for negative health outcomes when classified using BF%.

Renal fat fraction is significantly associated with the risk of chronic kidney disease in patients with type 2 diabetes.

Backgrounds: Ectopic fat deposition is closely related to chronic kidney disease (CKD). Currently, there are few population studies that have been conducted to determine the relationship between renal parenchyma fat deposition and the risk of CKD among patients with type 2 diabetes mellitus (T2DM). Therefore, we employed magnetic resonance imaging (MRI) to detect renal parenchyma fat content in individuals with T2DM, expressed as renal fat fraction (FF), to explore whether renal FF is an important risk factor for CKD in patients with T2DM. Methods: In this cross-sectional study, 189 subjects with T2DM were enrolled. CKD was defined as the estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2. Measurement of the renal FF was performed on a 3.0-T MRI (MAGNETOM Skyra, Siemens, Erlangen, Germany). Binary logistic regression was used to determine the association between tertiles of renal FF and risk of CKD. Receiver-operator characteristic (ROC) curves were constructed to evaluate the sensitivity and specificity of renal FF in detecting CKD in T2DM patients. Results: The patients were divided into three groups according to tertiles of the renal FF level (2.498 - 7.434). As renal FF increases, patients tend to be older, and more abdominally obese, with a decreased eGFR (p<0.05). After adjustment for potential confounders, patients in the highest tertile of renal FF had a significantly increased risk of CKD than those in the lowest tertile (odds ratio (OR) = 3.98, 95% confidence interval (CI) = 1.12 - 14.09, p = 0.032), and the area under the ROC curve for this model was 0.836 (0.765-0.907). Conclusions: The renal FF is significantly independently associated with CKD in patients with T2DM.

Neutrophil Extracellular Traps Induce Glomerular Endothelial Cell Dysfunction and Pyroptosis in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Neutrophil extracellular traps (NETs) are a network structure composed of loose chromatin and embedded with multiple proteins. Here, we observed increased NETs deposition in the glomeruli of DKD patients and diabetic mice (streptozotocin-induced or db/db mice). After NETs were degraded with DNase I, diabetic mice exhibited attenuated glomerulopathy and glomerular endothelial cells (GECs) injury. We also observed alleviated glomerulopathy and GECs injury in peptidylarginine deiminase 4-knockout mice with streptozotocin-induced diabetes. In vitro, NETs-induced GECs pyroptosis was characterized by pore formation in the cell membrane, dysregulation of multiple genes involved in cell membrane function, and increased expression of pyroptosis-related proteins. Strengthening the GECs surface charge by oleylamine significantly inhibited NETs-induced GECs pyroptosis. These findings suggest that the GECs charge-related pyroptosis is involved in DKD progression, which is promoted by NETs.

Association between fat mass and mortality: analysis of Mendelian randomization and lifestyle modification.

BACKGROUND: The association between fat mass and mortality has been equivocally shown to be linear, J-shaped, and U-shaped. We aimed to clarify this relationship based on Mendelian randomization (MR) analysis and lifestyle modification. METHODS: This prospective analysis included 449,831 participants from UK Biobank. Linear MR analysis was used to estimate the linear relationship between fat mass and mortality. We assessed whole body fat mass by bioimpedance analysis at baseline and categorized subjects into five equal groups based on fat mass index (FMI). The association between FMI and mortality were investigated among whole population and in subgroups stratified by individual lifestyle factors, including diet, physical activity, smoking, alcohol, sleep and psychological health. FINDINGS: Linear MR analyses indicated a positive association between genetically predicted fat mass and all-cause mortality (HR 1.10, 95 % CI 1.08-1.12, P < 0.001). The association between FMI and all-cause mortality was manifested as J-shaped (HRs across FMI categories: 1.04, 1.00, 1.07, 1.21, 1.54), which was significantly modified by the number of low-risk lifestyle factors (P for interaction<0.001). When evaluating individual lifestyle factors, we observed a nonlinear relationship between FMI and all-cause mortality among participants who had high-risk lifestyle factors, while a linear relationship was observed among participants who had low-risk lifestyle factors, especially for those with adequate physical activity (HRs across FMI categories: 0.95, 1.00, 1.05, 1.17, 1.44) and who never smoked (0.96, 1.00, 1.03, 1.14, 1.51). INTERPRETATION: Genetically determined fat mass is causally and linearly associated with mortality. The J-shape association between anthropometric FMI and mortality is caused by high-risk lifestyle factors.

Lifestyle and chronic kidney disease: A machine learning modeling study.

Background: Individual lifestyle varies in the real world, and the comparative efficacy of lifestyles to preserve renal function remains indeterminate. We aimed to systematically compare the effects of lifestyles on chronic kidney disease (CKD) incidence, and establish a lifestyle scoring system for CKD risk identification. Methods: Using the data of the UK Biobank cohort, we included 470,778 participants who were free of CKD at the baseline. We harnessed the light gradient boosting machine algorithm to rank the importance of 37 lifestyle factors (such as dietary patterns, physical activity (PA), sleep, psychological health, smoking, and alcohol) on the risk of CKD. The lifestyle score was calculated by a combination of machine learning and the Cox proportional-hazards model. A CKD event was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2, mortality and hospitalization due to chronic renal failure, and self-reported chronic renal failure, initiated renal replacement therapy. Results: During a median of the 11-year follow-up, 13,555 participants developed the CKD event. Bread, walking time, moderate activity, and vigorous activity ranked as the top four risk factors of CKD. A healthy lifestyle mainly consisted of whole grain bread, walking, moderate physical activity, oat cereal, and muesli, which have scored 12, 12, 10, 7, and 7, respectively. An unhealthy lifestyle mainly included white bread, tea >4 cups/day, biscuit cereal, low drink temperature, and processed meat, which have scored -12, -9, -7, -4, and -3, respectively. In restricted cubic spline regression analysis, a higher lifestyle score was associated with a lower risk of CKD event (p for linear relation < 0.001). Compared to participants with the lifestyle score < 0, participants scoring 0-20, 20-40, 40-60, and >60 exhibited 25, 42, 55, and 70% lower risk of CKD event, respectively. The C-statistic of the age-adjusted lifestyle score for predicting CKD events was 0.710 (0.703-0.718). Conclusion: A lifestyle scoring system for CKD prevention was established. Based on the system, individuals could flexibly choose healthy lifestyles and avoid unhealthy lifestyles to prevent CKD.

Early-phase insulin hypersecretion associated with weight loss outcome after LSG: a prospective cohort study in Asian patients with BMI ≥28 kg/m2.

BACKGROUND: Obesity has become a global problem that poses a serious threat to human health. Laparoscopic sleeve gastrectomy (LSG) is an effective long-term treatment. However, the weight loss of some patients after LSG is still insufficient. It is necessary to investigate the factors associated with inadequate weight loss after LSG. OBJECTIVE: The objective of this study was to explore whether preoperative insulin secretion could be associated with weight loss after LSG in patients with obesity. SETTING: This is a single-center prospective cohort study conducted in a university hospital. METHODS: Patients from a prospective database who underwent LSG were analyzed. All 178 participants underwent a 75-g oral glucose tolerance test (OGTT) to assess preoperative insulin and c-peptide secretion before LSG. The areas under the curve (AUCs) for glucose, insulin, and c-peptide were determined in the OGTT. The percentage of excess weight loss (%EWL) and the percentage of total weight loss (%TWL) were used to estimate the effect of weight loss after LSG. Regression models were used to assess the correlation between preoperative insulin and c-peptide secretion with %EWL ≥75% and TWL ≥35% at 12 months after LSG. RESULTS: The AUCs of insulin and c-peptide were significantly lower in the %EWL ≥75% and %TWL ≥35% groups at 0-30 minutes, 0-60 minutes, and 0-120 minutes during the OGTT. At 30, 60, and 120 minutes during the OGTT, c-peptide levels were significantly lower in the %EWL ≥75% group and %TWL ≥35% group. The preoperative c-peptide level at 30 minutes during the OGTT (C30) was significantly negatively correlated with %EWL (ß = -.37, P < .001) and %TWL (ß = -.28, P = .011). Univariate logistic regression analysis showed that preoperative C30 was associated with %EWL ≥75% and %TWL ≥35% after LSG. According to multiple logistic regression analysis, patients with a low preoperative C30 had an 8-fold higher %TWL ≥35% after LSG than those with a high C30 (odds ratio: 8.41 [95% confidence interval: 1.46-48.58], P = .017). Similarly, patients with a low preoperative C30 had a 7-fold higher EWL% ≥75% after LSG than patients with a high C30 (odds ratio: 7.25 [95% confidence interval: 1.11-47.50], P = .039). CONCLUSIONS: The rate of weight loss after LSG is low among patients with preoperative hyperinsulinemia. The preoperative c-peptide level at 30 minutes during the OGTT is associated with weight loss after LSG.

Heightened Cardiovascular Risk in Hypertension Associated With Renin-Independent Aldosteronism Versus Renin-Dependent Aldosteronism: A Collaborative Study.

Background While both renin-dependent and renin-independent aldosterone secretion contribute to aldosteronism, their relative associations with cardiovascular disease (CVD) risk has not been investigated. Methods and Results A total of 2909 participants from the FOS (Framingham Offspring Study) with baseline, serum aldosterone concentration, and plasma renin concentration who attended the sixth examination cycle and were followed up until 2014 and who were free of CVD were included. We further recruited 2612 hypertensive participants from the CONPASS (Chongqing Primary Aldosteronism Study). Captopril challenge test was performed to confirm renin-dependent or -independent aldosteronism in CONPASS. Among 1433 hypertensive subjects of FOS, when compared with those with serum aldosterone concentration <10 ng dL-1 (normal aldosterone), participants who had serum aldosterone concentration ≥10 ng dL-1 and plasma renin concentration ≤15 mIU L-1 (identified as renin-independent aldosteronism) showed a higher risk of CVD (hazard ratio, 1.40 [95% CI, 1.08-1.82]), while those who had serum aldosterone concentration ≥10 ng dL-1 and plasma renin concentration >15 mIU L-1 (identified as renin-dependent aldosteronism) showed an unchanged CVD risk. In CONPASS, renin-independent aldosteronism carried a significantly higher risk of CVD than normal aldosterone (odds ratio, 2.57 [95% CI, 1.13-5.86]), while the CVD risk remained unchanged in renin-dependent aldosteronism. Elevation of the urinary potassium-to-sodium excretion ratio, reflective of mineralocorticoid receptor activity, was only observed in participants with renin-independent aldosteronism. Conclusions Among patients with hypertension, renin-independent aldosteronism is more closely associated with CVD risk than renin-dependent aldosteronism.

Perirenal Fat Thickness Is Significantly Associated With the Risk for Development of Chronic Kidney Disease in Patients With Diabetes.

Perirenal fat is adjacent to kidneys and active in metabolism and adipokine secretion. We aimed to investigate whether perirenal fat is an independent predictor for chronic kidney disease (CKD) and compared it with total, subcutaneous, or visceral fat in patients with diabetes. Perirenal fat thickness (PRFT) was measured by computed tomography, and total body fat (TBF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were assessed by DEXA. In cross-sectional analysis, patients with higher PRFT had a lower estimated glomerular filtration rate (eGFR). Multiple linear regression analysis showed a negative correlation between PRFT and eGFR after confounders adjustment. No association between eGFR and TBF, SAT, or VAT was observed. Longitudinally, 190 patients with type 2 diabetes mellitus (T2DM) without CKD at baseline were followed for 2 years. A total of 29 participants developed CKD. After VAT-based multivariate adjustment, each SD (per-SD) increment in baseline PRFT was associated with a higher incidence of CKD (hazard ratio 1.67, 95% CI 1.04-2.68), while TBF, SAT, and VAT were not. Furthermore, PRFT predicted CKD, with a C-statistic (95% CI) of 0.668 (0.562, 0.774), which was higher than that of TPF [0.535 (0.433, 0.637)], SAT [0.526 (0.434, 0.618)], and VAT [0.602 (0.506, 0.698)]. In conclusion, with perirenal fat there was a higher predictive value for CKD than with total, subcutaneous, or visceral fat in T2DM.

Relationship Between the TyG Index and Diabetic Kidney Disease in Patients with Type-2 Diabetes Mellitus.

BACKGROUND: Diabetic kidney disease (DKD) lacks a simple and relatively accurate predictor. The Triglyceride-Glucose (TyG) Index is a proxy of insulin resistance, but the association between the TyG Index and DKD is less certain. We investigated if the TyG Index can predict DKD onset effectively. MATERIALS AND METHODS: Cross-sectional and longitudinal analyses were undertaken. In total, 1432 type-2 diabetes mellitus (T2DM) patients were included in the cross-sectional analysis. The TyG Index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into three tertiles. Associations of the TyG Index with microalbuminuria and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were calculated. Longitudinally, 424 patients without DKD at baseline were followed up for 21 (range, 12-24) months. The main outcome was DKD prevalence as defined with eGFR <60 mL/min/1.73 m2 or continuously increased urinary microalbuminuria: creatinine ratio (>30 mg/mL) over 3 months. Cox regression was used to analyze the association between the TyG Index at baseline and DKD. Receiver operating characteristics curve (ROC) analysis was used to assess the sensitivity and specificity of the TyG Index in predicting DKD. RESULTS: In cross-sectional analysis, patients with a higher TyG Index had a higher risk of microalbuminuria (OR = 2.342, 95% CI = 1.744-3.144, p < 0.001), and eGFR <60 mL/min/1.73 m2 (1.696, 95% CI =1.096-2.625, p = 0.018). Longitudinally, 94 of 424 participants developed DKD. After confounder adjustment, patients in the high tertile of the TyG Index at baseline had a greater risk to developing DKD than those in the low tertile (HR = 1.727, 95% CI = 1.042-2.863, p = 0.034). The area under the ROC curve was 0.69 (0.63-0.76). CONCLUSION: The TyG Index is a potential predictor for DKD in T2DM patients. CLINICAL TRIAL: Clinical Trials identification number = NCT03692884.

Low-dose colchicine in type 2 diabetes with microalbuminuria: A double-blind randomized clinical trial.

BACKGROUND: Neutrophil-related chronic inflammation (NRCI) may contribute to the pathogenesis of diabetic kidney disease (DKD). We evaluated whether blocking NRCI with low-dose colchicine prevents DKD. METHODS: A double-blind, randomized, placebo-controlled study was conducted. A total of 160 patients with type 2 diabetes (T2D) and microalbuminuria (urinary albumin creatinine ratio [UACR] 30 to 300 mg/g Cr) who received angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) for at least 3 months were included. Subjects were 1:1 randomized to a placebo or colchicine group (0.5 mg/day). RESULTS: The primary end point was the incidence of overt nephropathy (UACR > 300 mg/g Cr). During the 36 months, 38 patients (51.4%) in colchicine group and 39 (54.1%) in the control group developed overt nephropathy (hazard ratio, 1.066; 95% confidence interval, 0.679-1.673; P = .78). Compared with placebo, colchicine modestly lowered levels of NRCI parameters (P values <.05 for high-sensitivity C-reactive protein, white blood cell counts, neutrophil counts, and neutrophil-to-lymphocyte ratio), whereas the changes of UACR and estimated glomerular filtration rate (eGFR) were similar between the two groups. There were no significant differences between the two groups in drug-related adverse events, including infection, gastrointestinal symptoms, and limb numbness. CONCLUSIONS: In patients with T2D with microalbuminuria, low-dose colchicine effectively and safely lowered NRCI but did not prevent the incidence of overt nephropathy.

Age-Related Changes in Body Composition and Bone Mineral Density and Their Relationship with the Duration of Diabetes and Glycaemic Control in Type 2 Diabetes.

PURPOSE: To investigate age-related changes in body composition (BC) and bone mineral density (BMD) in type 2 diabetes (T2D) and analyse whether diabetes duration or glycaemic control affects these factors. PATIENTS AND METHODS: We enrolled 1474 hospitalized T2D patients (817 males and 657 females; 45-85 years). BC and BMD were assessed by dual-energy X-ray absorptiometry (DEXA). Patients were stratified into age groups: 45-54, 55-64, 65-74, and ≥75 years. Continuous variables were compared using t-tests or one-way analysis of variance (ANOVA), and categorical variables were compared using chi-square tests. Effects of age, diabetes duration, and haemoglobin A1C (HbA1c) on BC and BMD were assessed with multiple linear regression models. RESULTS: In T2D, in females, changes in fat mass index (FMI) were positively correlated with age, while changes in lean mass index (LMI) were unrelated to age. Changes in FMI or LMI in males were unrelated to age. For regional BC distribution, changes in visceral adipose tissue (VAT) were positively correlated with age for both males and females, while changes in appendage lean mass (ALM) were negatively correlated with age. For BMD, changes in total BMD (TBMD) in males were not correlated with age, while changes in lumbar spine BMD (LBMD) were positively correlated with age, and femoral neck BMD (FNBMD) was negatively correlated with age. Changes in BMD in all parts of females were negatively correlated with age. In addition, changes in BC and BMD were unrelated to diabetes duration, and HbA1c was mainly associated with decreases in lean mass but had little effect on other BC and BMD parameters. CONCLUSION: In T2D, changes in BC and BMD were associated with age but not diabetes duration. A higher HbA1c is associated with lower lean mass.

Optimal Cut-Offs of Body Mass Index and Waist Circumference to Identify Obesity in Chinese Type 2 Diabetic Patients.

PURPOSE: The prevalence of general obesity (commonly defined by body mass index (BMI) in kg/m2) and abdominal obesity (commonly assessed by waist circumference (WC)) has increased rapidly in China. The aim of this study was to investigate the diagnostic accuracy of traditional cut-offs for BMI or WC to identify general or abdominal obesity in Chinese type 2 diabetic patients and propose optimal cut-offs. PATIENTS AND METHODS: BMI and WC were obtained from 1539 type 2 diabetic patients. Body fat percentage and visceral fat area measured by dual-energy x-ray absorptiometry were set as the gold standard to identify general and abdominal obesity. We assessed the diagnostic power of traditional cut-offs for BMI and WC to define obesity, and analyzed receive operating characteristic (ROC) curves to obtain the optimal cut-offs to identify obesity in Chinese type 2 diabetic patients. RESULTS: In Chinese type 2 diabetic patients, the optimal BMI was 25 kg/m2 with the best trade-off between sensitivity and specificity (men: 74.6% (95% CI: 70.7-78.2%) and 65.1% (95% CI: 59.7-70.3%), AUC 0.78 (95% CI: 0.75-0.81), p<0.05; women: 65.8% (95% CI: 60.3-71.0%) and 80.3% (95% CI: 75.7-84.3%), AUC 0.80 (95% CI: 0.77-0.83), p<0.05) in both genders. The optimal WC was 93 cm in men and 90 cm in women with the best trade-off between sensitivity and specificity (men: 87.2% (95% CI: 84.3-89.8%) and 80.2% (95% CI: 74.9-84.8%), AUC 0.91 (95% CI: 0.88-0.92), p<0.05; women: 81.0% (95% CI: 76.9-84.6%) and 88.7% (95% CI: 83.9-92.4%), AUC 0.92 (95% CI: 0.90-0.94), p<0.05). CONCLUSION: For the Chinese patients with type 2 diabetes, the optimal cut-offs for BMI or WC to identify general or abdominal obesity need to be reconsidered.

Serum cell-free DNA and progression of diabetic kidney disease: a prospective study.

AIMS: Cell-free DNA (cfDNA) is associated with diabetes and cardiovascular diseases. Our study was to evaluate whether serum cfDNA could predict the progression of diabetic kidney disease (DKD). METHODS: In this prospective study, a total of 160 patients with DKD were enrolled, and the kidney function was followed up by measurement of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) for three consecutive years. At baseline, concentrations of serum cfDNA were measured. DKD progression was defined as two-continuous decrease in eGFR and changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at last follow-up. Regression models were used to analyze associations of serum cfDNA with the DKD progression. RESULTS: In total, 131 patients finished all the follow-up visits. At the end of the study, 64 patients showed decreased eGFR and 29 patients had changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at follow-up. At baseline, the progression group had higher serum cfDNA levels than the non-progression group (960.49 (816.53, 1073.65) ng/mL vs 824.51 (701.34, 987.06) ng/mL, p=0.014). Serum cfDNA levels were significantly negatively associated with the 1.5-year eGFR change (r=-0.219 p=0.009) and 3-year eGFR change (r=-0.181, p=0.043). Multivariate logistic analyses showed that after adjustment of age, gender, body mass index, fast plasma glucose, smoking, triglycerides, total cholesterol, duration of diabetes, systolic blood pressure, diabetic retinopathy, eGFR, high sensitivity C-reactive protein, angiotensin receptor blocker/ACE inhibitor usage, with the increase of one SD of serum cfDNA levels, the risk of DKD progression increased by 2.4 times (OR, 2.46; 95% CI 1.84 to 4.89). CONCLUSION: Serum cfDNA is closely associated with DKD, and it might be a predictor of DKD progression in patients with type 2 diabetes.

Peripheral monocyte count is an independent predictor of all-cause mortality in type 2 diabetes with macro-vascular complications.

The relationship between monocyte count and mortality seemed to be varied in different diseases, and it remains unclear in type 2 diabetes (T2D). We conducted a prospective study to investigate whether monocyte count predict all-cause mortality in patients with T2D.In this prospective study, a total of 1073 patients with T2D were enrolled at baseline and 880 patients completed the follow up. The median follow-up time was 47 months. At baseline, clinical characteristics including height, weight, waist circumference, blood pressure were recorded. Biochemical parameters including counts of white blood cells (WBCC), neutrophil (NC) and monocyte (MC), lipid profiles, glycated hemoglobin (HbA1c), serum creatinine were measured. Charlson comorbidity index (CCI) was calculated based on age and comorbidities. Participants were stratified into low, median, and high tertiles according to the baseline MC. Regression models were used to analyze the associations of peripheral MC and the all-cause mortality.Compared to the survived subjects, the baseline MC was significantly higher in patients who deceased during the follow-up (0.45 ±â€Š0.16 vs 0.37 ±â€Š0.15 × 10/L, P = .003). In the multivariate Cox hazard models, subjects in higher MC tertile showed higher risks of all-cause mortality (low tertile as the reference, hazard ratio [HR] 95%CI 2.65 [0.84,8.31] and 3.73 [1.14,12.24] for middle and high MC tertile, respectively) after adjusted for gender, body mass index, CCI, duration of T2D, history of hypertension and metabolic syndrome, drugs, levels of high-sensitivity C-reactive protein, systolic blood pressure, HbA1c, WBCC, and NC. In T2D patients with macro-vascular complications at baseline, 1-SD increment of MC resulted in 1.92-fold higher risk of all-cause mortality. However, the relationship disappeared in subjects without macro-vascular complications at baseline (1.13 [0.72, 1.78], P = .591).Peripheral monocyte count is an independent predictor of all-cause mortality in T2D, especially for subjects with macro-vascular complications.

[Clinical practice and evaluation of management of patients based on clinical pathway of emergency respiratory and cardiac arrest].

OBJECTIVE: To explore the effect of clinical pathway of emergency respiratory and cardiac arrest on management of patients with sudden respiratory and cardiac arrest. METHODS: The clinical data of patients with sudden respiratory and cardiac arrest admitted to Huashan North Hospital Affiliated to Fudan University from 1 year before to 1 year (started in July 2017) after the implementation of clinical pathway of emergency respiratory and cardiac arrest were retrospectively analyzed. The patients who managed by clinical pathway of emergency respiratory and cardiac arrest (from July 2017 to June 2018) were served as observational group, and those manually managed by 2015 American Heart Association cardiopulmonary resuscitation and cardiovascular emergency guide update and the procession in the management of emergency key diseases (from July 2016 to June 2017) were set as control group. The gender, age, underlying disease, the initiation time of cardiopulmonary resuscitation (CPR), the first time of defibrillation, the completion time of endotracheal intubation, the time of venous access, the usage time of the first dose of adrenaline, the usage time of vasoactive drugs, the completion rate of high quality CPR, the success rate of return of spontaneous circulation (ROSC) and the table procedure of clinical pathway were compared between the two groups. RESULTS: There was no statistically significant difference in gender, age or underlying disease between the two groups. Compared with the control group, the clinical pathway could effectively guide the decision-making of the emergency medical staffs, significantly reduce the variation in the procession of the resuscitation, the first time of defibrillation, the completion time of the deep vein catheterization, the usage time of norepinephrine and the completion time of the blood specimen delivery were significantly shortened [the first time of defibrillation (minutes): 1.28±0.86 vs. 2.93±1.61, the completion time of deep vein catheter (minutes): 15.13±2.73 vs. 17.25±3.02, the usage time of norepinephrine (minutes): 15.43±2.80 vs. 17.88±1.67, the completion time of blood specimen delivery (minutes): 7.81±1.42 vs. 9.00±1.03, all P < 0.05]. There was no statistically significant difference in the initiation time of CPR, the completion time of tracheal intubation, the time of peripheral venous access, the usage time of the first dose of adrenaline or sodium bicarbonate, or the success rate of ROSC between the two groups. However, the usage time of the first dose of adrenaline and sodium bicarbonate was shortened in the observation group [the usage time of the first dose of adrenaline (minutes): 3.81±1.22 vs. 4.00±1.32, the usage time of the first does of sodium bicarbonate (minutes): 8.94±3.49 vs. 11.19±3.54, both P > 0.05], and the success rate of ROSC was relatively increased as compared with those in the control group [15.04% (17/113) vs. 12.50% (12/96), P > 0.05]. CONCLUSIONS: The clinical pathway of emergency respiratory and cardiac arrest could effectively guide the clinical decision-making of the emergency medical staffs, significantly reduce the variation in the procession of the resuscitation, improve the quality of the resuscitation, and ensure medical safety of emergency department.

Prevalence of low lean mass in patients with adult growth hormone deficiency with or without low-dose growth hormone therapy.

OBJECTIVE: The importance of muscle mass has been emphasized in various studies, and growth hormone (GH) deficiency is tightly associated with lean mass loss. Therefore, we aimed to investigate the prevalence of low lean mass in patients with adult growth hormone deficiency (AGHD) who received or did not receive GH therapy. METHODS: In this retrospective study, we included patients diagnosed with AGHD by using the insulin tolerance test (ITT) in our hospital. Patients without completed follow-up data were excluded, and data for 56 patients were analysed. Twenty-six patients who had received GH therapy for more than 6 months, based on the medical record, were included in the GH group and received recombinant human growth hormone (rhGH) at a dose of 0.5 IU/d. Thirty patients who had not previously received GH treatment were included in the non-GH group. Many anthropometric and blood biochemical indicators were measured. Body composition was measured on a dual-energy X-ray-absorptiometry (DXA) scanner. Low lean mass was defined as a skeletal muscle index (SMI) <7.0 kg/m2 in males or 5.7 kg/m2 in females. Statistical analyses were performed using GraphPad Prism 5.0. RESULTS: Compared to the non-GH group, the patients who received GH therapy had significantly lower total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and fasting plasma glucose (FPG). The percentage of patients with low lean mass in GH and non-GH groups was 30.77% and 60%, respectively. The percentage of total lean was lower in the GH group than in the non-GH group, but the difference in total lean mass was not statistically significant. Conversely, patients with GH treatment had significantly lower fat mass and percentage than non-GH-treated patients (P < 0.05). The GH group had significantly higher serum levels of both IGF-1 and IGFBP3. Moreover, both IGF-1 and IGFBP3 were significantly correlated with SMI (r2  = 0.275, P = 0.003, and r2  = 0.138, P = 0.005, respectively). CONCLUSIONS: Our data showed that AGHD patients who received low-dose GH treatment had a lower prevalence of low lean mass than those who did not receive GH treatment. Patients with GH treatment had significantly lower cardiovascular risk factors, especially the lipid profile.

The appropriate remodeling of extracellular matrix is the key molecular signature in subcutaneous adipose tissue following Roux-en-Y gastric bypass.

AIMS: We sought to reveal the key molecular signature in subcutaneous adipose tissue (scAT) following Roux-en-Y gastric bypass (RYGB), through bioinformatics analysis and further verification in vivo. MAIN METHODS: We obtained a transcriptome data of scAT from RYGB and sham-operated rats from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were screened and the DEGs-related Gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Also, the protein-protein interaction (PPI) network was constructed among the DEGs. Furthermore, we established an experimental rat model to verify the bioinformatics findings. KEY FINDINGS: Using the method of bioinformatics, a total of 602 genes were found to be differentially expressed in scAT between the RYGB group and the sham-operated group. GO analysis showed that DEGs were significantly enriched in extracellular matrix(ECM) -associated functions or processes. KEGG pathway analysis revealed that the protein digestion and absorption pathway and ECM-receptor interaction pathway were the most significantly enriched pathways. The genes encoding ECM components and ECM remodeling-related proteins interact substantially in the PPI network. Then the results of rat experimental verified that the gene expression levels of ECM components(Collagen I and III) and ECM cross-linking related proteins(lysyl oxidase and lysyl oxidase-like 1) decreased and ECM dagradation-related proteins increased in scAT following RYGB. These beneficial results were positively associated with improved insulin resistance (IR). SIGNIFICANCE: Appropriate ECM remodeling, primarily the reduction of ECM deposition and cross-linking and the increase of ECM dagradation, may be the key molecular signature in scAT following RYGB.

Gender-specific association of serum uric acid levels and cardio-ankle vascular index in Chinese adults.

BACKGROUND: Little is known about the relationship between serum uric acid (SUA) and cardio-ankle vascular index (CAVI) in Chinese population. Therefore, we aimed to investigate the gender difference in the association of SUA and CAVI in a southwestern Chinese population. METHODS: Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014 in Chongqing. The data included completed anthropometry and blood biochemical indicators. The CAVI were recorded using an automatically VaseraVS-1000 vascular screening system. RESULTS: We found females with hyperuricemia (HUA) had significantly higher CAVI than women with normal SUA (8.45 ± 1.40 vs 7.67 ± 1.15, P<0.05). Then we defined high CAVI as CAVI≥9 m/s, and compared the percentage of high CAVI, we found women with HUA had higher percentage of high CAVI than women with normal SUA (26.83% vs 9.38%, P<0.05). Those differences were not significant in males. Also, the logistic regression analysis found age and hypertension were major independent risk factors associated with high CAVI in both genders. HUA and hyperglycemia were independently associated with high CAVI in females with an OR of 3.65, 95%CI (1.37-9.73) and 3.02, 95%CI (1.38-6.63) respectively. However, these significant associations were not be found in males. CONCLUSIONS: Our data showed positive associations between elevated SUA levels and higher CAVI risk in the inland Chinese females, but not in males. The reason for the gender differences were still unclear, sex hormones may play a role. Further prospective studies including detailed personal information and multicenter were required.