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Abstract Background: Relative fat mass (RFM) represents a newly developed sex-specific anthropometric formula to estimate total body fat percentage. Nonetheless, research examining the correlation between RFM and the risk of diabetes remains scarce. This research assessed the link between RFM and DM risk within the Japanese demographic. Methods: From 2004 to 2015, 15,462 Japanese individuals without diabetes underwent physical evaluations at Murakami Memorial Hospital. The relationship between RFM and the onset of diabetes was analyzed separately using Cox proportional-hazards regression models. This study employed Cox proportional hazards regression incorporating cubic spline functions and smooth curve fitting to detect non-linear associations between RFM and new cases of diabetes, categorized by sex. Sensitivity analyses were performed to confirm the robustness of the link between RFM and incident diabetes. Results: After controlling for confounding factors, a significant positive correlation between RFM and diabetes risk was found in women (HR: 1.13, 95%CI: 1.04–1.24, P = 0.0061), while the association in men was not statistically significant (HR: 1.05, 95%CI: 0.98–1.13, P = 0.1511). Additionally, a non-linear relationship between RFM and the incidence of diabetes was detected in both genders. The RFM threshold was identified at 39.23 for women and 23.08 for men. For women, HR was 1.11 (95%CI: 1.01–1.21) below the threshold and 1.39 (95%CI: 1.17–1.65) above it. In men, an RFM above 23.08 was positively related to diabetes risk (HR: 1.16, 95%CI: 1.06–1.28, P = 0.0012), whereas an RFM below this point did not show a significant association (HR: 0.98, 95%CI: 0.91–1.06, P = 0.5899). Conclusion: Our findings suggest a non-linear relationship and threshold effect between RFM and the risk of diabetes. These findings imply that maintaining RFM at lower levels may be beneficial in mitigating the onset of DM.

Abstract Background Relative fat mass (RFM) is a newly developed, sex-specific anthropometric formula designed to estimate total body fat percentage. However, research investigating the correlation between RFM and the risk of non-alcoholic fatty liver disease (NAFLD) remains limited. This study evaluates the association between RFM and the risk of NAFLD within the Japanese population. Methods This study including 14,250 Japanese adults who underwent physical examinations at Murakami Memorial Hospital between 2004 and 2015. We employed binary logistic regression to elucidate the direct relationship between RFM levels and the incidence of NAFLD. Additionally, a generalized additive model (GAM) coupled with smooth curve fitting techniques was utilized to map the non-linear association. Results The cohort had an average age of 43.53 ± 8.89 years, with a male majority of 52.00%. NAFLD was identified in 17.59% of the participants. After adjusting for confounding factors, a significant positive correlation between RFM and NAFLD risk was observed (OR: 1.15, 95%CI: 1.10–1.21, P

Abstract Despite the clear association between remnant cholesterol (RC)and diabetes risk, no study to date has examined the relationship between RC and reversal of prediabetes to normoglycemia. This retrospective cohort study included a total of 15,023 patients with prediabetes who underwent a physical examination between 2010 and 2016. The link between initial RC levels and the reversion from prediabetes to normoglycemia was analyzed using the Cox proportional-hazards regression model. Additionally, the study explored the possible relationship between RC and the probability of returning normoglycemia by applying Cox proportional hazards regression models with cubic spline functions. To address competing risks, a multivariate Cox regression analysis was undertaken, treating the onset of diabetes as a competing risk event for reversing prediabetes to normoglycemia. Additionally, the study incorporated extensive subgroup analyses alongside multiple sensitivity analyses, enhancing the reliability and robustness of the results. After adjusting for covariates, the findings indicated that RC was inversely associated with the likelihood of reverting to normoglycemia (per 5 mg/dL increase, HR = 0.918, 95% CI 0.909–0.927). The analysis also revealed a nonlinear relationship between RC and normoglycemia reversion, with an inflection point at 51.08 mg/dL. For RC values below this inflection point (RC

Abstract The available evidence on the connection between excessive alcohol consumption and diabetes is controversial. Therefore, the primary objective of this investigation was to examine the connection between excessive alcohol consumption and incident diabetes in a Japanese population through the utilization of propensity score matching (PSM) analysis. Our retrospective cohort study encompassed a sample of 15,464 Japanese individuals who were initially free of diabetes between the years 2004 and 2015. The study utilized comprehensive medical records of individuals who underwent a physical examination. Employing a one:one PSM analysis, the current research included 2298 individuals with and without excessive alcohol consumption. Furthermore, a doubly robust estimation method was employed to ascertain the connection between excessive alcohol consumption and diabetes. The findings revealed that individuals with excessive alcohol consumption exhibited a 73% higher likelihood of developing diabetes (HR = 1.73, 95% CI 1.08–2.77). Furthermore, upon adjusting for variables, the PSM cohort demonstrated that individuals with excessive alcohol consumption had a 78% increased risk of developing diabetes in comparison to those with non-excessive alcohol consumption (HR = 1.78, 95% CI 1.08–2.93). Individuals with excessive alcohol consumption were found to have a 73% higher risk of developing diabetes compared to those with non-excessive alcohol consumption, even after controlling for propensity score (HR = 1.73, 95% CI 1.08–2.78). Participants in the PSM cohort with excessive alcohol consumption had a 73% higher risk of developing diabetes than those with non-excessive alcohol consumption after controlling for confounding factors. These findings underscore the importance of alcohol consumption guidelines aimed at reducing excessive drinking. Clinicians should be vigilant in screening for alcohol use in patients, particularly those at risk for diabetes, and provide appropriate counseling and resources to support alcohol reduction.

BackgroundThe triglyceride-glucose (TyG) index, recognized for its cost-efficiency and simplicity, serves as an accessible indicator of insulin resistance. Yet, its correlation with the risk of prediabetes and diabetes (Pre-DM/DM) in the Chinese demographic remains uncertain. Consequently, our study explored the association between the TyG index and the development of Pre-DM/DM within the Chinese population.MethodsThe retrospective cohort study was carried out utilizing data from a health screening initiative. The study included 179541 adults over 20 who underwent medical examinations at the Rich Healthcare Group over a period spanning from 2010 to 2016. The correlation between the TyG index and Pre-DM/DM risk was investigated using Cox regression analysis. Furthermore, Cox proportional hazards regression with cubic spline functions and smooth curve fitting was incorporated to explore their non-linear connection.ResultsThe mean age of study participants was 41.18 ± 12.20 years old, and 95255 (53.05%) were male. During a median follow-up of 3.01 years, 21281 (11.85%) participants were diagnosed with Pre-DM/DM. After adjusting the potential confounding factors, the results showed that the TyG index was positively correlated with incident Pre-DM/DM (HR: 1.67, 95%CI: 1.62-1.71, P< 0.001). Additionally, a non-linear association was observed between the TyG index and the onset of Pre-DM/DM, with an inflection point identified at 8.73. Hazard ratios (HR) to the left and right of this inflection point were 1.95 (95%CI: 1.86-2.04) and 1.34 (95%CI: 1.27-1.42), respectively. Furthermore, sensitivity analyses confirmed the stability of these findings.ConclusionThe TyG index exhibited a non-linear positive relationship with the risk of Pre-DM/DM. These findings imply that maintaining the TyG index at a lower, specified threshold may be beneficial in mitigating the onset of Pre-DM/DM.

Abstract Objective The connection between triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and stroke risk is controversial. Our goal was to explore this relationship in individuals aged 45 and older enrolled in the China Health and Retirement Longitudinal Study (CHARLS). Methods Our analysis encompassed 10,164 participants from the CHARLS cohorts. We applied the Cox proportional-hazards regression model to evaluate the potential correlation between the TG/HDL-C ratio and stroke incidence. Using a cubic spline function and smooth curve fitting within the Cox model allowed us to unearth a possible non-linear pattern in this relationship. We also conducted thorough sensitivity and subgroup analyses to deepen our understanding of the TG/HDL-C ratio’s impact on stroke risk. Results Adjusting for various risk factors, we observed a significant link between the TG/HDL-C ratio and increased stroke risk in individuals aged 45 and above (HR: 1.03, 95% CI 1.00–1.05, P = 0.0426). The relationship appeared non-linear, with an inflection at a TG/HDL-C ratio of 1.85. Ratios below this threshold indicated a heightened stroke risk (HR: 1.28, 95% CI 1.06–1.54, P = 0.0089), while ratios above it did not show a significant risk increase (HR: 1.01, 95% CI 0.98–1.04, P = 0.6738). Sensitivity analysis confirmed the robustness of these findings. Notably, non-smokers exhibited a stronger correlation between the TG/HDL-C ratio and stroke risk compared to past and current smokers. Conclusion Our investigation revealed a significant, yet non-linear, association between the TG/HDL-C ratio and the incidence of stroke among individuals aged 45 and above. Specifically, we found that stroke risk increased in correlation with TG/HDL-C ratio below the threshold of 1.85. These insights may guide healthcare providers in advising and developing more effective strategies for stroke prevention in this demographic.

Abstract Objective The connection between total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio and stroke risk is controversial. This study aims to examine the connection between the TC/HDL-C ratio and stroke in middle-aged and older individuals who are part of the China Health and Retirement Longitudinal Study (CHARLS). Methods This study conducted a retrospective cohort analysis, enrolling a total of 10,184 participants who met the designated criteria from CHARLS between 2011 and 2012. We then used the Cox proportional-hazards regression model to analyze the relationship between the TC/HDL-C ratio and stroke risk. Using a Cox proportional hazards regression model with cubic spline functions and smooth curve fitting, we were able to identify the non-linear relationship between the TC/HDL-C ratio and stroke occurrence. The sensitivity and subgroup analyses were also performed to investigate the connection between TC/HDL-C ratio and stroke. Results This study revealed a statistically significant association between the TC/HDL-C ratio and stroke risk in subjects aged 45 years or older after adjusting for risk factors (HR: 1.05, 95%CI 1.00–1.10, P = 0.0410). Furthermore, a non-linear connection between the TC/HDL-C ratio and stroke risk was detected, with a TC/HDL-C ratio inflection point of 3.71. We identified a significant positive connection between the TC/HDL-C ratio and stroke risk, when the TC/HDL-C ratio was less than 3.71 (HR: 1.25, 95%CI 1.07–1.45, P = 0.0039). However, their connection was not significant when the TC/HDL-C ratio exceeded 3.71 (HR: 1.00, 95%CI 0.94–1.06, P = 0.9232). The sensitivity analysis and subgroup analyses revealed that our findings were well-robust. Conclusion Our study demonstrated a positive, non-linear connection between the TC/HDL-C ratio and stroke risk in middle-aged and older individuals. There was a significant positive connection between the TC/HDL-C ratio and stroke risk, when the TC/HDL-C ratio was less than 3.71. The current research can be used as a guideline to support clinician consultation and optimize stroke prevention measures for middle-aged and older adults.

Abstract There is limited research on the association between the alanine aminotransferase to high-density lipoprotein cholesterol ratio (ALT/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD). The purpose of the current research was to look into the connection between the ALT/HDL-C ratio and the risk of NAFLD in lean Chinese individuals. Between January 2010 and December 2014, 11,975 non-obese people participated in this prospective cohort research. The relationship between the ALT/HDL-C ratio and the risk of developing NAFLD was assessed using the Cox proportional-hazards regression model, Cox proportional hazards regression with cubic spline functions and smooth curve fitting, sensitivity analysis, and subgroup analyses. The ALT/HDL-C ratio’s potential value as a NAFLD prognostic marker was to be evaluated using the receiver operating characteristic curve analysis. A total of 5419 (45.253%) women comprised the research's participant population, and the research participants’ average age was 43.278 ± 14.941 years. The ALT/HDL-C ratio was 11.607 (7.973–17.422) at the median (interquartile ranges). 2087 (17.428%) patients had NAFLD diagnoses throughout a median follow-up of 24.967 months. The study's findings demonstrated a positive connection between the ALT/AHDL-C ratio and the incident NAFLD (HR = 1.037, 95% CI: 1.031–1.042) when adjusting for relevant factors. The ALT/HDL-C ratio and NAFLD risk had a nonlinear connection, with 12.963 as the ratio's inflection point. Effect sizes (HR) were 1.023 (95% CI: 1.017–1.029) and 1.204 (95% CI: 1.171–1.237), respectively, on the right and left sides of the inflection point. The sensitivity analysis also showed how reliable our findings were. According to subgroup analysis, those with BMI

Abstract Objective In patients experiencing acute ischemic stroke, there is ongoing debate surrounding the connection between chronic hyperglycemic status and their initial clinical outcomes. Our objective was to examine the connection between glycated hemoglobin (HbA1c) levels and adverse clinical outcomes at both 3-months adverse clinical outcomes in individuals with acute ischemic stroke (AIS) with and without diabetes. Methods The present prospective cohort study involved 896 AIS patients without diabetes and 628 with diabetes treated at a South Korean hospital from January 2010 to December 2016. The target independent variable is HbA1c. The outcome variable is a modified Rankin scale score ≥ 3. A binary logistic regression model was applied to assess the connection between HbA1c levels and 3-month poor clinical outcomes in AIS patients with and without diabetes. Additionally, a generalized additive model and smoothed curve fitting were utilized to explore potential nonlinear associations between HbA1c levels and 3-month adverse clinical outcomes in AIS patients with and without diabetes. Results The binary logistic regression model could not identify any statistically significant connection between HbA1c and 3-month adverse clinical outcomes in AIS patients, both those with and without diabetes, after correcting for various factors. However, a nonlinear relationship emerged between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. The inflection point for HbA1c was determined to be 6.1%. For HbA1c values ≤ 6.1%, an inverse association was observed between HbA1c and 3-month adverse clinical outcomes in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with an 87% reduction in 3-month adverse clinical outcomes (OR = 0.13, 95% CI: 0.02–0.81). Conversely, when HbA1c exceeded 6.1%, a positive association between HbA1c and 3-month adverse clinical outcomes became apparent in diabetic AIS patients, and each 1% increase in HbA1c in AIS patients with DM was associated with a 23% increase in 3-month adverse clinical outcomes (OR = 1.23, 95%CI: 1.03–1.47). However, it’s important to note that no significant linear or nonlinear relationships were observed between HbA1c levels and 3-month adverse clinical outcomes in AIS patients without diabetes. Conclusion Our findings suggest a nonlinear connection and threshold effect between HbA1c and 3-month adverse clinical outcomes in AIS patients with diabetes. AIS patients with diabetes had a lower risk of 3-month adverse clinical outcomes when their HbA1c control was close to 6.1%. Our findings may aid treatment decision-making and potentially guide interventions to optimize glycemic control in AIS patients.

Background Neuroinflammatory responses are closely associated with poststroke prognosis severity. This study aimed to develop a predictive model, combining inflammation‐derived markers and clinical indicators, for distinguishing functional outcomes in patients with subacute ischemic stroke. Methods and Results Based on activities of daily living assessments, ischemic stroke participants were categorized into groups with little effective (LE) recovery and obvious effective (OE) recovery. Initial biocandidates were identified by overlapping differentially expressed proteins from proteomics of clinical serum samples (5 LE, 5 OE, and 6 healthy controls) and differentially expressed genes from an RNA sequence of the ischemic cortex in middle cerebral artery occlusion mice (n=3). Multidimensional validations were conducted in ischemia–reperfusion models and a clinical cohort (15 LE, 11 OE, and 18 healthy controls). Models of robust biocandidates combined with clinical indicators were developed with machine learning in the training data set and prediction in another test data set (15 LE and 11 OE). We identified 194 differentially expressed proteins (LE versus healthy controls) and 174 differentially expressed proteins (OE versus healthy controls) in human serum, and 5121 differentially expressed genes (day 3) and 5906 differentially expressed genes (day 7) in middle cerebral artery occlusion mice cortex. Inflammation‐derived biomarkers TIMP1 (tissue inhibitor metalloproteinase‐1) and galactosidase‐binding protein LGLAS3 (galectin‐3) exhibited robust increases under ischemic injury in mice and humans. TIMP1 and LGALS3 coupled with clinical indicators (hemoglobin, low‐density lipoprotein cholesterol, and uric acid) were developed into a combined model for differentiating functional outcome with high accuracy (area under the curve, 0.8). Conclusions The combined model is a valuable tool for evaluating prognostic outcomes, and the predictive factors can facilitate development of better treatment strategies.

Abstract Objective Current literature is deficient in robust evidence delineating the correlation between the triglyceride glucose-body mass index (TyG-BMI) and the incidence of stroke. Consequently, this investigation seeks to elucidate the potential link between TyG-BMI and stroke risk in a cohort of middle-aged and senior Chinese individuals. Methods This study employs longitudinal data from four waves of the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011, 2013, 2015, and 2018, encompassing 8,698 participants. The CHARLS cohort was assembled using a multistage probability sampling technique. Participants underwent comprehensive evaluations through standardized questionnaires administered via face-to-face interviews. Our analytic strategy involved the application of Cox proportional hazards regression models to investigate the association between TyG-BMI and the risk of stroke. To discern potential non-linear relationships, we incorporated Cox proportional hazards regression with smooth curve fitting. Additionally, we executed a battery of sensitivity and subgroup analyses to validate the robustness of our findings. Results Our study utilized a multivariate Cox proportional hazards regression model and found a significant correlation between the TyG-BMI and the risk of stroke. Specifically, a 10-unit increase in TyG-BMI corresponded to a 4.9% heightened risk of stroke (HR = 1.049, 95% CI 1.029–1.069). The analysis also uncovered a non-linear pattern in this relationship, pinpointed by an inflection point at a TyG-BMI value of 174.63. To the left of this inflection point—meaning at lower TyG-BMI values—a 10-unit hike in TyG-BMI was linked to a more substantial 14.4% rise in stroke risk (HR 1.144; 95% CI 1.044–1.253). Conversely, to the right of the inflection point—at higher TyG-BMI values—each 10-unit increment was associated with a smaller, 3.8% increase in the risk of stroke (HR 1.038; 95% CI 1.016–1.061). Conclusions In the middle-aged and elderly Chinese population, elevated TyG-BMI was significantly and positively associated with stroke risk. In addition, there was also a specific non-linear association between TyG-BMI and stroke (inflection point 174.63). Further reduction of TyG-BMI below 174.63 through lifestyle changes and dietary control can significantly reduce the risk of stroke.

Abstract The available evidence on the connection between high-density lipoprotein cholesterol (HDL-C) levels and the reversion from prediabetes (Pre-DM) to normoglycemia is currently limited. The present research sought to examine the connection between HDL-C levels and the regression from Pre-DM to normoglycemia in a population of Chinese adults. This historical cohort study collected 15,420 Pre-DM patients in China who underwent health screening between 2010 and 2016. The present research used the Cox proportional hazards regression model to investigate the connection between HDL-C levels and reversion from Pre-DM to normoglycemia. The Cox proportional hazards regression model with cubic spline functions and smooth curve fitting was employed to ascertain the nonlinear association between HDL-C and reversion from Pre-DM to normoglycemia. Furthermore, a set of sensitivity analyses and subgroup analyses were employed. Following the adjustment of covariates, the findings revealed a positive connection between HDL-C levels and the likelihood of reversion from Pre-DM to normoglycemia (HR 1.898, 95% CI 1.758–2.048, P

Abstract Early identification is crucial to effectively intervene in individuals at high risk of developing pre-diabetes. This study aimed to create a personalized nomogram to determine the 5-year risk of pre-diabetes among Chinese adults. This retrospective cohort study included 184,188 participants without prediabetes at baseline. Training cohorts (92,177) and validation cohorts (92,011) were randomly assigned (92,011). We compared five prediction models on the training cohorts: full cox proportional hazards model, stepwise cox proportional hazards model, multivariable fractional polynomials (MFP), machine learning, and least absolute shrinkage and selection operator (LASSO) models. At the same time, we validated the above five models on the validation set. And we chose the LASSO model as the final risk prediction model for prediabetes. We presented the model with a nomogram. The model's performance was evaluated in terms of its discriminative ability, clinical utility, and calibration using the area under the receiver operating characteristic (ROC) curve, decision curve analysis, and calibration analysis on the training cohorts. Simultaneously, we also evaluated the above nomogram on the validation set. The 5-year incidence of prediabetes was 10.70% and 10.69% in the training and validation cohort, respectively. We developed a simple nomogram that predicted the risk of prediabetes by using the parameters of age, body mass index (BMI), fasting plasma glucose (FBG), triglycerides (TG), systolic blood pressure (SBP), and serum creatinine (Scr). The nomogram's area under the receiver operating characteristic curve (AUC) was 0.7341 (95% CI 0.7290–0.7392) for the training cohort and 0.7336 (95% CI 0.7285–0.7387) for the validation cohort, indicating good discriminative ability. The calibration curve showed a perfect fit between the predicted prediabetes risk and the observed prediabetes risk. An analysis of the decision curve presented the clinical application of the nomogram, with alternative threshold probability spectrums being presented as well. A personalized prediabetes prediction nomogram was developed and validated among Chinese adults, identifying high-risk individuals. Doctors and others can easily and efficiently use our prediabetes prediction model when assessing prediabetes risk.

Abstract Objective The relationship between the non-high-density lipoprotein to high-density lipoprotein ratio (non-HDL-c/HDL-c ratio) and changes in glycemic status as well as the development of type 2 diabetes mellitus (T2DM) has been well established. However, there is a lack of evidence concerning the association between the non-HDL-c/HDL-c ratio and the reversal of normoglycemia in individuals with impaired fasting glucose (IFG). Therefore, this study aimed to examine the connection between the non-HDL-c/HDL-c ratio and the likelihood of reverting to normoglycemia among people with IFG. Methods This retrospective cohort study examined data collected from 15,524 non-selective participants with IFG at the Rich Healthcare Group in China between January 2010 and 2016. The Cox proportional-hazards regression model was used to investigate the connection between the baseline non-HDL-c/HDL-c ratio and the probability of reverting to normoglycemia. We were able to discover the non-linear association between the non-HDL-c/HDL-c ratio and reversion to normoglycemia using a Cox proportional hazards regression model with cubical spline smoothing. We also performed several sensitivity and subgroup analyses. A competing risk multivariate Cox regression was utilized as well to examine the development to diabetes as a competing risk for the reversal of normoglycemic events. Results In our study, a total of 15,524 individuals participated, with a mean age of 50.9 ± 13.5 years, and 64.7% were male. The average baseline non-HDL-c/HDL-c ratio was 2.9 ± 0.9. Over a median follow-up period of 2.9 years, we observed a reversion rate to normoglycemia of 41.8%. After adjusting for covariates, our findings revealed a negative association between the non-HDL-c/HDL-c ratio and the likelihood of reverting to normoglycemia (HR = 0.71, 95% CI 0.69–0.74). Notably, we identified a non-linear relationship between the non-HDL-c/HDL-c ratio and the probability of transitioning from IFG to normoglycemia. We found an inflection point at a non-HDL-c/HDL-c ratio of 3.1, with HRs of 0.63 (95% CI 0.69, 0.74) on the left side and 0.78 (95% CI 0.74, 0.83) on the right side of the point. Competing risks multivariate Cox's regression, sensitivity analysis, and subgroup analysis consistently supported our robust results. Conclusion Our study has revealed a negative and non-linear relationship between the non-HDL-c/HDL-c ratio and reversion to normoglycemia in Chinese people with IFG. Specifically, when the non-HDL-c/HDL-c ratio was below 3.1, a significant and negative association with reversion to normoglycemia was observed. Furthermore, keeping the non-HDL-c/HDL-c ratio below 3.1 significantly elevated the probability of returning to normoglycemia.

Abstract Objective Evidence on the association between the creatinine to body weight (Cre/BW) ratio and the risk of pre-diabetes to diabetes development remains limited. Our study aimed to examine the association between the Cre/BW ratio and incident diabetes in pre-diabetic patients. Methods This retrospective cohort study included 24,506 pre-diabetic participants who underwent health checks from 2010 to 2016 in China. We used the Cox proportional-hazards regression model to explore the relationship between baseline Cre/BW ratio and diabetes risk in pre-diabetes patients. Using a Cox proportional hazards regression with cubic spline function and smooth curve fitting (cubical spline smoothing), we were able to determine the non-linear relationship between them. We also carried out a number of subgroup and sensitivity analyses. Results The age range of the participants included in this study was 20–99 years, with a majority of 16,232 individuals (66.24%) being men. The mean baseline Cre/BW ratio was 1.06 (SD 0.22) umol/L/kg. 2512 (10.25%) participants received a diabetes final diagnosis over a median follow-up period of 2.89 years. After adjusting for covariates, the Cre/BW ratio had a negative association with incident diabetes in participants with pre-diabetes, per umol/L/kg increase in Cre/BM ratio was accompanied by a 55.5% decrease in diabetes risk (HR = 0.445, 95%CI 0.361 to 0.548). The Cre/BW ratio and risk of diabetes had a non-linear connection, with 1.072 umol/L/kg serving as the ratio's inflection point. The HR were 0.294 (95%CI:0.208–0.414) and 0.712 (95%CI:0.492–1.029), respectively, on the left and right sides of the inflection point. The sensitivity analysis demonstrated the robustness of these results. Subgroup analyses indicated that the Cre/BW ratio was strongly associated with the risk of diabetes among participants who were younger than 50 years, as well as among those with diastolic blood pressure (DBP)

Objective Previous research has shown that pulse pressure (PP) has a significant role in the start and development of type 2 diabetes mellitus. However, there is little proof that PP and pre-diabetes mellitus (Pre-DM) are related. Our study aimed to investigate the relationship between PP and incident pre-DM in a substantial cohort of Chinese participants.Design The ‘DATADRYAD’ database (www.Datadryad.org) was used to retrieve the data for this secondary retrospective cohort analysis.Participants Data from 182 672 Chinese individuals who participated in the medical examination programme were recorded in this retrospective cohort study between 2010 and 2016 across 32 sites and 11 cities in China.Setting PP assessed at baseline and incident pre-DM during follow-up were the target-independent and dependent variables. The association between PP and pre-DM was investigated using Cox proportional hazards regression.Primary outcome measures The outcome was incident pre-DM. Impaired fasting glucose levels (fasting blood glucose between 5.6 and 6.9 mmol/L) were used to define pre-DM.Results After controlling for confounding variables, PP was positively correlated with incident pre-DM among Chinese adults (HR 1.009, 95% CI 1.007 to 1.010). Additionally, at a PP inflection point of 29 mm Hg, a non-linear connection between the PP and incident pre-DM was discovered. Increased PP was an independent risk factor for developing pre-DM when PP was greater than 29 mm Hg. However, their association was not significant when PP was less than 29 mm Hg. According to subgroup analyses, females, never-smokers and non-obesity correlated more significantly with PP and pre-DM.Conclusion We discovered that higher PP independently correlated with pre-DM risk in this study of Chinese participants. The connection between PP and incident pre-DM was also non-linear. High PP levels were related to a higher risk of pre-DM when PP was above 29 mm Hg.Article focus Our study investigated the relationship between PP and incident pre-DM in a secondary retrospective cohort of Chinese participants.

Abstract Objective The current body of evidence on the association between the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-c) and the reversal of prediabetes to normoglycemia remains limited. The aim of this study is to investigate the association between TG/HDL-c and the reversion to normoglycemia in patients with prediabetes. Methods This retrospective cohort study included 15,107 individuals with prediabetes from 32 Chinese districts and 11 cities who completed health checks from 2010 to 2016. The Cox proportional-hazards regression model examined baseline TG/HDL-c and reversion to normoglycemia from prediabetes. Cox proportional hazards regression with cubic spline functions and smooth curve fitting determined the non-linear connection between TG/HDL-c and reversion to normoglycemia. We also ran sensitivity and subgroup analysis. By characterizing progression to diabetes as a competing risk for the reversal of prediabetes to normoglycemic event, a multivariate Cox proportional hazards regression model with competing risks was created. Results Upon adjusting for covariates, the findings indicate a negative association between TG/HDL-c and the likelihood of returning to normoglycemia (HR = 0.869, 95%CI:0.842–0.897). Additionally, a non-linear relationship between TG/HDL-c and the probability of reversion to normoglycemia was observed, with an inflection point of 1.675. The HR on the left side of the inflection point was 0.748 (95%CI:0.699, 0.801). The robustness of our results was confirmed through competing risks multivariate Cox's regression and a series of sensitivity analyses. Conclusion The present study reveals a negative and non-linear correlation between TG/HDL-c and the reversion to normoglycemia among Chinese individuals with prediabetes. The findings of this study are anticipated to serve as a valuable resource for clinicians in managing dyslipidemia in prediabetic patients. Interventions aimed at reducing the TG/HDL-c ratio through the reduction of TG or elevation of HDL-c levels may substantially enhance the likelihood of achieving normoglycemia in individuals with prediabetes.

Abstract Objective The evidence on the relationship between remnant cholesterol (RC) and stroke remains controversial. Therefore, this study aimed to explore the relationship between RC and stroke risk in a Chinese population of middle-aged and elderly individuals. Methods The present study included 10067 Chinese subjects of middle-aged and elderly individuals. The connection between RC and incident stroke was investigated using the multivariate Cox proportional hazards regression model, several sensitivity analyses, generalized additive models, and smoothed curve fitting. Results A total of 1180 participants with stroke were recorded during the follow-up period. The multivariate Cox proportional hazards regression model identified a positive connection between RC and stroke risk (hazard ratio (HR) = 1.087, 95% confidence interval (CI): 1.001–1.180). In addition, the current study discovered a nonlinear connection between RC and incident stroke, and the point of inflection for RC was 1.78 mmol/L. The risk of stroke increased by 25.1% with each unit increase in RC level when RC was

Abstract Background The atherogenic index of plasma (AIP) can reflect the burden of atherosclerosis. Hyperglycemia is one of the leading causes of atherosclerosis. However, the relationship between AIP and prediabetes is rarely studied. Therefore, we aimed to explore the relationship between AIP and prediabetes. Methods This retrospective cohort study recruited 100,069 Chinese adults at the Rich Healthcare Group from 2010 to 2016. AIP was calculated according to Log10 (triglyceride/high-density lipoprotein cholesterol) formula. Cox regression method, sensitivity analyses and subgroup analyses were used to examine the relationship between AIP and prediabetes. Cox proportional hazards regression with cubic spline functions and smooth curve fitting was performed to explore the non-linearity between AIP and prediabetes. The two-piece Cox proportional hazards regression model was used to determine the inflection point of AIP on the risk of prediabetes. Results After adjusting for confounding covariates, AIP was positively associated with prediabetes (HR: 1.41, 95%CI: 1.31–1.52, P 0.03, their association was not significant (HR: 1.04, 95%CI: 0.91–1.19, P = 0.5528). Conclusion This study shows that AIP was positively and non-linearly associated with the risk of prediabetes after adjusting for other confounding factors. When AIP ≤ 0.03, AIP was positively associated with the risk of prediabetes.

Abstract Background In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. Methods 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. Results In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777–0.853)) and external validation (AUC: 0.816 (95% CI 0.770–0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783–0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755–0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688–0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. Conclusion We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

ObjectiveDespite the clear association of TyG-BMI with prediabetes and the progression of diabetes, no study to date has examined the relationship between TyG-BMI and the reversal of prediabetes to normoglycemia.Methods25,279 participants with prediabetes who had physical examinations between 2010 and 2016 were enrolled in this retrospective cohort study. The relationship between baseline TyG-BMI and regression to normoglycemia from prediabetes was examined using the Cox proportional hazards regression model in this study. Additionally, the nonlinear association between TyG-BMI and the likelihood of regression to normoglycemia was investigated using the Cox proportional hazards regression with cubic spline function. Competing risk multivariate Cox regression analysis was conducted, with progression to diabetes as a competing risk for prediabetes reversal to normoglycemia. Furthermore, subgroup analyses and a series of sensitivity analyses were performed.ResultsAfter adjusting for covariates, the results showed that TyG-BMI was negatively associated with the probability of returning to normoglycemia (per 10 units, HR=0.970, 95% CI: 0.965, 0.976). They were also nonlinearly related, with an inflection point for TyG-BMI of 196.46. The effect size (HR) for TyG-BMI to the right of the inflection point (TyG-BMI ≥ 196.46) and the probability of return of normoglycemia was 0.962 (95% CI: 0.954, 0.970, per 10 units). In addition, the competing risks model found a negative correlation between TyG-BMI and return to normoglycemia (SHR=0.97, 95% CI: 0.96-0.98). Sensitivity analyses demonstrated the robustness of our results.ConclusionThis study demonstrated a negative and nonlinear relationship between TyG-BMI and return to normoglycemia in Chinese adults with prediabetes. Through active intervention, the combined reduction of BMI and TG levels to bring TyG-BMI down to 196.46 could significantly increase the probability of returning to normoglycemia.

BackgroundThe connection between the triglyceride-glucose index (TyG index) and gestational diabetes mellitus (GDM) is currently debated. Our study aimed to investigate the connection between the TyG index and GDM within the Korean population.MethodsUsing publically accessible data in Korea, we performed a secondary study on a sample of 589 pregnant women who were carrying a single fetus. The analysis employed a binary logistic regression model, some sensitivity analyses, and subgroup analysis to investigate the association between the TyG index and the occurrence of GDM. To assess the TyG index’s potential to predict GDM, a receiver operating characteristic (ROC) study was also carried out.ResultsThe mean age of the pregnant women was 32.065 ± 3.798 years old, while the mean TyG index was 8.352 ± 0.400. The prevalence rate of GDM was found to be 6.112%. Upon adjusting for potential confounding variables, a positive association was detected between the TyG index and incident GDM (OR = 12.923, 95%CI: 3.581–46.632, p = 0.00009). The validity of this connection was further confirmed by subgroup analysis and sensitivity analyses. With an area under the ROC curve of 0.807 (95%CI: 0.734–0.879), the TyG index showed strong predictive power for GDM. The TyG index’s ideal cutoff value for detecting GDM was found to be 8.632, with a sensitivity of 78.7% and a specificity of 72.2%.ConclusionThe findings of our study provide evidence that an increased TyG index is significantly associated with the occurrence of GDM. Utilizing the TyG index during the 10–14 week gestational period may be a valuable tool in identifying pregnant individuals at a heightened risk for developing GDM. Early detection enables timely and efficacious interventions, thereby enhancing the prognosis of affected individuals.

ObjectiveThis study aims to assess the association between the non-HDL-c/HDL-c ratio and stroke risk among middle-aged and older adults participating in the China Health and Retirement Longitudinal Study (CHARLS).MethodsThis study conducted a prospective cohort analysis, enrolling a total of 10,183 participants who met the designated criteria from CHARLS between 2011 and 2012. We then used the Cox proportional-hazards regression model to explore the relationship between baseline non-HDL-c/HDL-c ratio and stroke risk. Using a Cox proportional hazards regression with cubic spline function, we were able to identify the non-linear relationship between the non-HDL-c/HDL-c ratio and stroke occurrence. A series of sensitivity analyses were also carried out.ResultsThe average age of the participants included in this study was 59.16 ± 9.35 years, and 4,735 individuals (46.68%) were male. Over a median follow-up period of 7.0 years, a total of 1,191 people (11.70%) experienced a stroke. Using a Cox proportional hazards regression model that was fully adjusted, we found no statistically significant correlation between the non-HDL-c/HDL-c ratio and the risk of stroke (HR=1.022; 95% CI 0.964, 1.083). Nevertheless, we did observe a non-linear relationship and saturation effect between the non-HDL-c/HDL-c ratio and stroke. Employing a two-piece Cox proportional hazards regression model and a recursive algorithm, we determined an inflection point of 2.685 for the non-HDL-c/HDL-c ratio. In instances where the non-HDL-c/HDL-c ratio fell below 2.685, for every 1-unit decrease in the non-HDL-c/HDL-c ratio, the likelihood of stroke decreased by 21.4% (HR=1.214, 95% CI: 1.039-1.418). In contrast, when the non-HDL-c/HDL-c ratio exceeded 2.685, there was no statistically significant change in the risk of stroke for each unit decrease in the non-HDL-c/HDL-c ratio (HR: 0.967, 95% CI: 0.897-1.042). The consistency of these findings across multiple sensitivity analyses suggests their robustness.ConclusionThis study unveils a non-linear relationship between the non-HDL-c/HDL-c ratio and stroke risk in middle-aged and older adults in China. Specifically, when the non-HDL-c/HDL-c ratio was below 2.685, a significant and clearly positive association with stroke risk was observed. Additionally, maintaining the non-HDL-c/HDL-c ratio below 2.685 could potentially lead to a substantial reduction in the risk of stroke.

AbstractBackground Renal dysfunction and disruption of renal endothelial glycocalyx are two important events during septic acute kidney injury (AKI). Here, the role and mechanism of hyaluronidase 1 (HYAL1) in regulating renal injury and renal endothelial glycocalyx breakdown in septic AKI were explored for the first time.Methods BALB/c mice were injected with lipopolysaccharide (LPS, 10 mg/kg) to induce AKI. HYAL1 was blocked in vivo using lentivirus-mediated short hairpin RNA targeting HYAL1 (LV-sh-HYAL1). Biochemical assays were performed to measure the levels and concentrations of biochemical parameters associated with AKI as well as levels of inflammatory cytokines. Renal pathological lesions were determined by hematoxylin-eosin (HE) staining. Cell apoptosis in the kidney was detected using terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) assay. Immunofluorescence and immunohistochemical (IHC) staining assays were used to examine the levels of hyaluronic acid in the kidney. The protein levels of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, endothelial glycocalyx, and autophagy-associated indicators were assessed by western blotting.Results The knockdown of HYAL1 in LPS-subjected mice by LV-sh-HYAL1 significantly reduced renal inflammation, oxidative stress, apoptosis and kidney dysfunction in AKI, as well as alleviated renal endothelial glycocalyx disruption by preventing the release of hyaluronic acid to the bloodstream. Additionally, autophagy-related protein analysis indicated that knockdown of HYAL1 significantly enhanced autophagy in LPS mice. Furthermore, the beneficial actions of HYAL1 blockade were closely associated with the AMPK/mTOR signaling.Conclusion HYAL1 deficiency attenuates LPS-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice.

Abstract Background Low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of alanine aminotransferase (ALT) are related to insulin resistance, metabolic syndrome, and diabetes mellitus (DM). However, evidence on the connection between the alanine aminotransferase to high-density lipoprotein cholesterol (ALT/HDL-C) ratio and diabetes mellitus (DM) risk was limited. The study aimed to investigate the relationship between baseline ALT/HDL-C ratio and DM among Japanese individuals. Methods This second analysis was based on a cohort study using open-source data. Data from 15,342 individuals who participated in the medical examination program were recorded at Murakami Memorial Hospital in Japan between 2004 and 2015. Smooth curve fitting, subgroup analysis, Cox proportional-hazards regression, and a series of sensitivity analyses were conducted to examine the relationship between ALT/HDL-C ratio and incident diabetes. The ability of the ALT/HDL-C ratio to predict diabetes was evaluated using a receiver operating characteristic curve analysis. Results After controlling for confounding covariates, the ALT/HDL-C ratio was found to be positively correlated to the DM risk in Japanese adults (HR: 1.01, 95%CI: 1.00–1.02, P = 0.049). This study also found a stable relationship between ALT/HDL-C ratio and diabetes after employing a series of sensitivity analyses. Additionally, there was a non-linear association between the ALT/HDL-C ratio and incident diabetes, and the ALT/HDL-C ratio inflection point was 30.12. When the ALT/HDL-C ratio was below 30.12, the present study discovered a significant positive association between the ALT/HDL-C ratio and incident diabetes (HR: 1.04, 95%CI: 1.02–1.06, P = 0.001). Furthermore, among liver enzymes, blood lipids, and anthropometric indicators, the ALT/HDL-C ratio best predicts DM (AUC = 0.75, 95%CI: 0.73–0.78). Conclusion Increased ALT/HDL-C ratio levels at baseline correlated to incident DM. The relationship between ALT/HDL-C ratio and incident DM was also non-linear. When the ALT/HDL-C ratio is below 30.12, there is a statistically significant positive correlation between the ALT/HDL-C ratio and incident DM.

Abstract Background By identifying individuals at high risk for non-alcoholic fatty liver disease (NAFLD), interventional programs could be targeted more effectively. Some studies have demonstrated that triglyceride glucose-body mass index (TyG-BMI) showed an independent positive association with NAFLD. However, research on its diagnostic value in patients with suspected NAFLD is limited. In this study, we aimed to evaluate whether TyG-BMI was accurate in detecting NAFLD in the general Japanese population. Methods A cross-sectional study of 14,280 individuals who underwent a comprehensive health examination was conducted. Standard protocols were followed to collect anthropometric measurements, lab data, and ultrasonography features. All participants were randomly stratified into the development group (n = 7118) and validation group (n = 7162). The TyG-BMI was calculated. Following this, the diagnostic value of the TyG-BMI was evaluated based on the area under the receiver-operating characteristic curve (AUROC). Two cutoff points were selected and used to rule out or rule in the NALFD, and the specificity, sensitivity, negative predictive value, and positive predictive value were explored, respectively. In order to verify the stability of the results, external verification was performed. Results There were 1272 and 1243 NAFLD participants in the development and validation groups, respectively. The area under the ROC curve (AUC) of TyG-BMI was 0.888 (95% CI 0.876–0.896) and 0.884 (95% CI 0.875–0.894) for the training and validation group, respectively. Using the low TyG-BMI (182.2) cutoff, NAFLD could be excluded with high accuracy (negative predictive value: 96.9% in estimation and 96.9% in validation). The presence of NAFLD could effectively be determined by applying the high cutoff of TyG-BMI (224.0), as the positive predictive value of the estimation and validation groups is 70.7% and 70.1%, respectively. As a result of applying this model, 9996 (70%) of the 14,280 participants would not have undergone ultrasonography, with an accurate prediction of 9308 (93.1%). AUC was 0.874 for external validation using 183,730 Chinese non-obese participants. TyG-BMI was demonstrated to be an excellent diagnostic tool by both internal and external validation. Conclusions In conclusion, the present study developed and validated a simple, non-invasive, and cost-effective tool to accurately separate participants with and without NAFLD in the Japanese population, rendering ultrasonography for identifying NAFLD unnecessary in a substantial proportion of people.

BackgroundAlthough there is strong evidence linking triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to insulin resistance and diabetes mellitus, its clinical importance in pregnant women has not been well determined. This study sought to determine the connection between the TG/HDL-C ratio in the first trimester and the eventual onset of gestational diabetes mellitus (GDM).MethodsWe performed a secondary analysis of open-access data from a prospective cohort study. This present study included 590 singleton pregnant women at 10-14 weeks who visited the outpatient clinics for prenatal checks and were recorded at Incheon Seoul Women’s Hospital and Seoul Metropolitan Government Seoul National University Boramae Medical Center in Korea. A binary logistic regression model, a series of sensitivity analyses, and subgroup analysis were used to examine the relationship between TG/HDL-C ratio and incident GDM. A receiver operating characteristic (ROC) analysis was also conducted to assess the ability of the TG/HDL-C ratio to predict GDM.ResultsThe mean age of the included individuals was 32.06 ± 3.80 years old. The mean TG/HDL-C ratio was 1.96 ± 1.09. The incidence rate of GDM was 6.27%. After adjustment for potentially confounding variables, TG/HDL-C ratio was positively associated with incident GDM (OR=1.77, 95%CI: 1.32-2.38, P=0.0001). Sensitivity analyses and subgroup analysis demonstrated the validity of the relationship between the TG/HDL-C ratio and GDM. The TG/HDL-C ratio was a good predictor of GDM, with an area under the ROC curve of 0.7863 (95% CI: 0.7090-0.8637). The optimal TG/HDL-C ratio cut-off value for detecting GDM was 2.2684, with a sensitivity of 72.97% and specificity of 75.05%.ConclusionOur results demonstrate that the elevated TG/HDL-C ratio is related to incident GDM. The TG/HDL-C ratio at 10-14 weeks could help identify pregnant women at risk for GDM and may make it possible for them to receive early and effective treatment to improve their prognosis.

ObjectiveBody mass index (BMI) and stroke risk have been linked, but these findings are still debated. This study investigated the relationship between BMI and stroke risk in a middle-aged and elderly Chinese population.MethodsThis study used four waves of CHARLS data (2011, 2013, 2015, and 2018), including 12,161 participants. The CHARLS sample was obtained by multi-stage probability sampling and all participants were assessed by one-to-one interviews using a standardized questionnaire. We used a Cox proportional-hazards regression model to examine the relationship between BMI and stroke risk. We used Cox proportional hazards regression with cubic spline functions and smooth curve fitting to identify the non-linear relationship between them. A series of sensitivity analyses were also conducted.ResultsThe multivariate Cox proportional hazards regression model identified a positive association between BMI and stroke risk (HR=1.025, 95% CI: 1.010-1.040). We also found a non-linear relationship between BMI and stroke incidence, with an inflection point at 26.63 kg/m2 for BMI. Each 1 kg/m2 increase in BMI to the left of the inflection point was related to a 4.4% increase in stroke risk (HR=1.044, 95% CI: 1.019-1.069). We stratified individuals by gender to further investigate their association and found a particular non-linear relationship and saturation effect between BMI and stroke risk in men, with the inflection point at 25.94 kg/m2. Each 1 kg/m2 increase in BMI to the left of the inflection point was related to a 7.6% increase in stroke risk (HR=1.076, 95% CI 1.034-1.119). The association was linear in women, with each 1 kg/m2 increase in BMI associated with a 2.1% increase in stroke risk (HR=1.021, 95% CI 1.002, 1.040).ConclusionIn men, there was a specific non-linear association and saturation effect of BMI with stroke (inflection point of 25.94 kg/m2), while in women, there was none. When males had a BMI below 25.94 kg/m2, the risk of stroke was significantly and positively associated with BMI. By controlling BMI below 25.94 kg/m2 in men, a further decrease in BMI may promote a significant reduction in stroke risk.

Abstract Previous evidence revealed that central obesity played a vital role in the development of diabetes mellitus (DM). However, because of imbalanced confounding variables, some studies have not wholly established the association between central obesity and diabetes. Propensity score matching (PSM) analysis can minimize the impact of potential confounding variables. Therefore, the aim of the present study was to explore the relationship between central obesity and diabetes in the Japanese population by using PSM analysis. This retrospective cohort study included 15,453 Japanese adults who were free of diabetes at baseline between 2004 and 2015, which provided all medical records for individuals participating in the physical exam. Central obesity at baseline was an independent variable, and incident diabetes during follow-up was an outcome variable. Using a 1:1 PSM analysis, the present retrospective cohort study included 1639 adults with and without central obesity. Additionally, we employed a doubly robust estimation method to identify the association between central obesity and diabetes. Subjects with central obesity were 92% more likely to develop DM (HR = 1.65, 95%CI 1.12, 2.41). After adjusting for covariates, subjects with central obesity had a 72% increased risk of developing DM compared with subjects with non-central obesity in the PSM cohort (HR = 1.72, 95% CI 1.16, 2.56). Central obesity individuals had a 91% higher risk of DM than non-central obesity individuals, after adjustment for propensity score (HR = 1.91, 95% CI 1.29, 2.81). In sensitivity analysis, the central obesity group had a 44% (HR = 1.44, 95% CI 1.09, 1.90) and 59% (HR = 1.59, 95% CI1.35, 1.88) higher risk of DM than the non-central obesity group in the original and weighted cohorts after adjusting for confounding variables, respectively. Central obesity was independently associated with an increased risk of developing diabetes. After adjustment for confounding covariates, central obesity participants had a 72% higher risk of development of diabetes than non-central obesity individuals in the PSM cohort.

Abstract Background and objective High-density lipoprotein cholesterol (HDL-C) may be directly involved in glucose metabolism by enhancing insulin sensitivity and insulin secretion. This current study aimed to explore the association between HDL-C and the risk of diabetes mellitus (DM) in Japanese population. Methods This retrospective cohort study was based on a publicly available DRYAD dataset. We enrolled 15,388 Japanese participants who received medical examinations from 2004 to 2015 at Murakami Memorial Hospital. Our study selected HDL-C at baseline and incident DM during follow-up as the target independent variable and the dependent variable, respectively. Cox proportional-hazards regression was used to investigate the association between HDL-C and DM, generalized additive models to identify non-linear relationships. Results After adjusting for the demographic and clinical covariates, the result showed low HDL-C levels were associated with increased risk for diabetes (HR = 0.54, 95%CI (0.35, 0.82)). The results remained robust in a series of sensitive analysis. A non-linear relationship was detected between HDL-C and incident DM with an inflection point of HDL-C at 1.72 mmol/L (Log-likelihood ratio test P = 0.005). Subgroup analysis showed that a stronger association could be found in ex-smokers and current-smokers. The same trend was also seen in the community with hypertension (P for interaction = 0.010, HR = 1.324). Conclusion This study demonstrates a negative and non-linear relationship between HDL-C and diabetes in the Japanese population. There is a threshold effect between HDL-C and diabetes. When HDL-C is lower than 1.72 mmol/L, the decreased HDL-C levels were associated with an increased risk for diabetes.

Abstract Background Research on the relationship between creatinine to body weight ratios (Cre/BW ratios) and the prevalence of diabetes is still lacking. The intention of this research was to explore the potential relationship between Cre/BW ratio and diabetes prevalence in Chinese adults. Methods This retrospective study was conducted on 199 526 patients in the Chinese Rich Healthcare Group from 2010 to 2016. The participants were divided into four groups on the basis of the quartiles of the Cre/BW ratios. Multivariate multiple imputation and dummy variables were used to handle missing values. Multivariate regression analysis was applied to detect the relationship between Cre/BW and diabetes. A smoothing plot was also used to identify whether there were nonlinear relationships. Results After handling missing values and adjusting for potential confounders, the multivariate Cox regression analysis results showed that Cre/BW was inversely correlated with diabetes risk (hazard ratio [HR]: 0.268; 95% confidence interval [CI]: 0.229–0.314, p

BackgroundThe cardiometabolic index (CMI) has been proposed as a novel indicator of cardiometabolic status. However, evidence on the relationship between CMI and diabetes mellitus (DM) risk was limited. Our study aimed to explore the relationship between CMI and DM risk among a large cohort of Japanese adults.MethodsThis retrospective cohort study recruited 15453 Japanese adults without diabetes at baseline who underwent physical examinations at the Murakami Memorial Hospital between 2004 and 2015. Cox proportional-hazards regression was applied to evaluate the independent relationship between CMI and diabetes. Our study performed a generalized smooth curve fitting (penalized spline technique) and an additive model (GAM) to determine the non-linear relationship between CMI and DM risk. In addition, a set of sensitivity analyses and subgroup analyses were employed to evaluate the relationship between CMI and incident DM.ResultsAfter adjusting for confounding covariates, CMI was positively related to the DM risk in Japanese adults (HR: 1.65, 95%CI: 1.43-1.90, P

ObjectiveDespite reports of a connection between body mass index (BMI) and stroke outcome, the findings remain debatable. In this investigation, we sought to determine whether BMI was associated with the probability of 3-month unfavorable outcomes in patients with acute ischemic stroke (AIS).MethodsThis is a second analysis based on a cohort study. 1,897 people with AIS who were treated at a hospital in South Korea from January 2010 to December 2016 were included in the study. The linear relationship between BMI and unfavorable outcomes for AIS patients was evaluated using a binary logistic regression model. The generalized additive model (GAM) and smoothed curve fitting (penalized spline approach) were employed to see if there was a non-linear association between BMI and unfavorable outcomes in patients with AIS.ResultsThe binary logistic regression model did not detect any statistically significant correlation between BMI and unfavorable outcomes in AIS patients after controlling for variables. The association between them, however, was non-linear, with the BMI inflection point occurring at 23.07 kg/m2. Each 1 kg/m2 rise in BMI on the left side of the inflection point was linked to a 12% lower risk of unfavorable outcomes (OR= 0.88, 95% CI: 0.82 to 0.96, p = 0.003). We stratified the AIS patients by gender to further explore their relationship. The results showed a specific non-linear relationship and saturation effect of BMI (kg/m2) with 3-month unfavorable outcomes in male patients but not in female patients. The inflection point for BMI was 23.35 kg/m2. When BMI was below 23.35 kg/m2 in men with AIS, BMI was inversely associated with unfavorable outcomes (OR=0.89,95% CI:0.80-0.98).ConclusionA particular non-linear connection and saturation effect between BMI (kg/m2) and 3-month unfavorable outcomes were present in male patients with AIS but not in females. 23.35 kg/m2 was the BMI’s inflection point. The probability of unfavorable outcomes was substantially and inversely associated with BMI in men with AIS when it was less than 23.35 kg/m2. Men with AIS should have a BMI of no less than 23.35 kg/m2 to reduce the probability of unfavorable outcomes following AIS.

ObjectiveRecent evidence has revealed that the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio) may be closely associated with metabolic syndrome and insulin resistance. However, it is unclear whether the AST/ALT ratio correlates with prediabetes risk. The aim of our study was to examine the association between AST/ALT ratios and the risk of prediabetes among a large cohort of Chinese subjects.MethodsThis retrospective cohort study recruited 75204 Chinese adults with normoglycemia at baseline who underwent physical examinations at the Rich Healthcare Group from 2010 to 2016. The AST/ALT ratio at baseline was the target independent variable, and the risk of developing prediabetes during follow-up was the dependent variable. Cox proportional-hazards regression was used to evaluate the independent association between the AST/ALT ratio and prediabetes. This study identified nonlinear relationships by applying a generalized additive model (GAM) and smooth curve fitting. In order to assess the robustness of this study, we performed a series of sensitivity analyses. Moreover, we performed a subgroup analysis to evaluate the consistency of the association in different subgroups. Data from this study have been updated on the DATADRYAD website.ResultsThe AST/ALT ratio was negatively and independently related to the prediabetes risk among Chinese adults (HR: 0.76, 95% CI: 0.75-0.84, P

ObjectiveThe role of triglyceride (TG) and estimated glomerular filtration rate (eGFR) effect modifiers on the risk of non-alcoholic fatty liver disease (NAFLD) is unknown. This study examined whether TG modifies the relationship between eGFR and incident NAFLD.MethodsIn a Chinese hospital from January 2010 to December 2014, 15,555 non-obese subjects were collected systematically for this retrospective cohort study. The target-independent and dependent variables were eGFR measured at baseline and NAFLD appearing during follow-up. The modified variable was TG measured at baseline. The multivariate Cox proportional hazards model was used to explore eGFR and TG’s association with NAFLD risk. We explored a priori interaction between eGFR and TG, and performed subgroup analyses to further assess whether the relationship between eGFR and incident NAFLD was modified by TG. We also explored the effect of TG and eGFR interaction on the risk of NAFLD.ResultsThe mean age was 43.09 ± 14.92 years, and 8,131 (52.27%) were males. During a median follow-up time of 35.8 months, 2,077 (13.35%) individuals developed NAFLD. In the adjusted model, eGFR was negatively associated with incident NAFLD (HR = 0.984, 95% CI: 0.982, 0.987), while TG was positively related to NAFLD (HR = 1.582, 95% CI: 1.490, 1.681). TG could modify the relationship between eGFR and incident NAFLD. A stronger association between eGFR and NAFLD could be found in the participants without hypertriglyceridemia (HTG) (HR = 0.981, 95% CI: 0.978–0.984, P for interaction = 0.0139). In contrast, the weaker association was probed in the population with HTG (HR = 0.986, 95% CI: 0.983–0.989). At the same time, we also found an interaction between eGFR and TG in influencing NAFLD risk. In participants with decreased eGFR and HTG, the risk of NAFLD was significantly increased. Further, compared to non-HTG subjects with eGFR ≥ 116.56 ml/min/1.73 m2, participants with HTG and eGFR < 82.88 ml/min/1.73 m2 had about a fourfold increase in the risk (HR = 4.852 95% CI: 3.943–5.970) of NAFLD.ConclusioneGFR and TG is independently associated with NAFLD risk. The association of eGFR with incident NAFLD is likely to be modified by TG in the Chinese non-obese population. There was an interactive effect between eGFR and TG in affecting NAFLD risk. In participants with decreased eGFR and hypertriglyceridemia, the risk of NAFLD is significantly increased.

Abstract Background Previous studies have demonstrated that nonalcoholic fatty liver disease (NAFLD) is a significant risk factor for diabetes mellitus (DM). However, these studies did not completely determine the relationship between NAFLD and DM due to unbalanced confounding factors. The propensity score (PS) is the conditional probability of having a particular exposure, given a set of baseline measured covariates. Propensity score matching (PSM) analysis could minimise the effects of potential confounders. Thus, this study aimed to use PSM analysis to explore the association between NAFLD and DM in a large Japanese cohort. Methods This retrospective PSM cohort study was performed on 14,280 Japanese participants without DM at baseline in Murakami Memorial Hospital between 2004 and 2015. The independent variable was NAFLD at baseline, and the outcome was the incidence of DM during follow-up. One-to-one PSM revealed 1671 participants with and without NAFLD. A doubly robust estimation method was applied to verify the correlation between NAFLD and DM. Results The risk of developing DM in participants with NAFLD increased by 98% according to the PSM analysis (HR = 1.98, 95% confidence interval [CI]: 1.41–2.80, P

Abstract Background Acute kidney injury (AKI) is a frequent complication of community acquired pneumonia (CAP). However, the impact of AKI on in-hospital outcomes of patients with CAP in the Chinese population remains unclear. Methods Patients diagnosed with CAP were evaluated in this retrospective observational study. Multiple Cox regression models were employed to identify the association between AKI and in-hospital mortality and 30-day mortality, respectively. Results A total of 4213 patients were recruited; 950 (22.5%) patients were diagnosed with AKI. Independent risk factors for AKI were age, male gender, hypertension, cardiac dysfunction, diabetes, chronic kidney disease, acute respiratory failure, use of diuretics, use of vasoactive drugs, and CURB-65. Cox proportional hazards regression revealed AKI, use of angiotensin receptor blocker, hypertension, CURB-65, acute respiratory failure, and use of vasoactive drugs to be independent risk factors for both in-hospital and 30-day mortality. Compared to patients without AKI, those suffering AKI were found to have 1.31-fold (HR 1.31, 95% CI, 1.04–1.66; P = 0.023) and 1.29-fold (HR 1.29, 95% CI, 1.02–1.62; P = 0.033) increased in-hospital and 30-day mortality risks, respectively. In addition, patients with AKI were likely to require admission to intensive care unit (ICU) (42.9% versus 11.4%; P

Abstract Renal fibrosis arises by the generation of matrix-producing fibroblasts and myofibroblasts through the epithelial–mesenchymal transition (EMT), a process in which epithelial cells undergo a transition into a fibroblast phenotype. A key feature of the EMT is the reorganization of the cytoskeletons, which may involve the Ca2+-binding protein S100A16, a newly reported member of the S100 protein family. However, very few studies have examined the role of S100A16 in renal tubulointerstitial fibrosis. In this study, S100A16 expression was examined by immunohistochemical staining of kidney biopsy specimens from patients with various nephropathies and kidney tissues from a unilateral ureteral obstruction (UUO) mouse model. Renal histological changes were investigated in S100A16Tg, S100A16+/−, and WT mouse kidneys after UUO. The expression of epithelia marker E-cadherin, mesenchymal markers N-cadherin, and vimentin, extracellular matrix protein, and S100A16, as well as the organization of F-actin, were investigated in S100A16 overexpression or knockdown HK-2 cells. Mass spectrometry was employed to screen for S100A16 binding proteins in HK-2 cells. The results indicated that S100A16 is high expressed and associated with renal tubulointerstitial fibrosis in patient kidney biopsies and in those from UUO mice. S100A16 promotes renal interstitial fibrosis in UUO mice. S100A16 expression responded to increasing Ca2+ and interacted with myosin-9 during kidney injury or TGF-β stimulation to promote cytoskeleton reorganization and EMT progression in renal tubulointerstitial fibrosis. Therefore, S100A16 is a critical regulator of renal tubulointerstitial fibroblast activation and is therefore a potential therapeutic target for the treatment of renal fibrosis.

Context: Evidences have suggested complement C3 is a biomarker for nonalcoholic fatty liver disease (NAFLD) in the general population. Objective: The present study was conducted to explore the predictive function of C3 for NAFLD in chronic kidney disease (CKD) patients. Design, Setting, and Participants: CKD patients were recruited for evaluation of their liver function, kidney function, serum lipids, glycated hemoglobin, blood, and immune function. The glomerular filtration rate was calculated using the CKD-EPI equation. NAFLD was diagnosed according to predefined ultrasonographic criteria. Results: A total of 648 consecutive CKD patients were included, with 216 (33.3%) patients diagnosed with NAFLD. The NAFLD group had significant higher levels of serum protein, serum albumin, triglycerides, glycated hemoglobin, complement C3, hemoglobin (p = 0.001), alanine aminotransferase (p = 0.002), estimated glomerular filtration rate (p = 0.007), and C4 (p = 0.043) and lower levels of cystatin C, β2-microglobulin, proteinuria (p = 0.001), and high-density lipoprotein cholesterol (p = 0.008). In a logistic regression model, only complement C3 (OR = 1.003; 95% CI 1.002–1.004, p = 0.001) was associated with a higher likelihood of being diagnosed with NAFLD. Finally, we constructed ROC curves for complement C3 for prediction of having NAFLD. The best cut-off for complement C3 was 993.5 mg/L and it yielded a sensitivity of 63.9% and a specificity of 70.1%. Conclusion: Our study revealed that complement C3 can be used as a surrogate biomarker of NAFLD in CKD patients.

Nephrogenic proteins are re-expressed after ischemia/reperfusion (I/R) injury; however, the role of these proteins is still unknown. We found that sine oculis homeobox 1 (SIX1), a developmentally regulated homeoprotein, is reactivated in tubular epithelial cells after I/R injury associated with cell proliferation/migration and anti-inflammation. We demonstrated that SIX1 promoted cell proliferation by upregulating cyclin and glycolytic genes, and might increase cell migration by upregulating the expression of matrix metalloproteinase 9 (MMP9) directly or indirectly in the cell model. Notably, SIX1 targeted the promoters of the amino-terminal enhancer of split (AES) and fused in sarcoma (FUS), which are cofactors of nuclear factor-κB (NF-κB) subunit RELA, and then inhibited the transactivation function of RELA. The expression of monocyte chemotactic protein-1 (MCP-1) was decreased by the SIX1-mediated NF-κB pathway. Our results showed that the expression of cyclin, glycolytic genes, and MMP9 were significantly increased, and the infiltration of monocytes/macrophages (Mophs) was suppressed in SIX1 overexpression kidney at 1, 2, and 3 days after reperfusion. The overexpression of SIX1 resulted in reducing kidney damage from I/R injury in mice by promoting cell proliferation and migration and by inhibiting inflammation. Our study provides evidence that SIX1 involved in cell proliferation, migration, and anti-inflammation in the I/R model, which might be a potential therapeutic target that could be used to ameliorate kidney damage.

Context: Patients with chronic kidney disease (CKD) usually manifest with disorder of thyroid hormone; however, the correlation is unknown. Objective: The study was designed to explore the relationships between CKD and thyroid dysfunction. Design, Setting, and Participants: A total number of 905 non-dialysis participants were collected at Nanjing First Hospital from August 2009 to October 2012 according to the case records system. Patients were grouped via the estimated glomerular filtration rate (eGFR) according to the KDIGO guideline. Levels of thyroid hormone and biomarkers in different CKD groups were compared by ANOVA. Prevalence of different thyroid diseases was calculated by χ2 test. Results: We found that FT3 or T3 became more prevalent with increasing eGFR with the lowest level in CKD5 (p < 0.01). No significant differences were found between groups in FT4, T4, or TSH (p > 0.05). Frequency of euthyroid sick syndrome (ESS) in CKD groups was high, especially in CKD stage 5 (69.1%, p < 0.01). eGFR had positive correlation with T3 and FT3 (r = 0.239, p = 0.0001; r = 0.292, p = 0.0001). ESS had correlations with prealbumin, β2-microglobin, eGFR, and C-reactive protein (r = 0.095, p = 0.004; r = –0.12, p = 0.001; r = 0.091, p = 0.007; r = –0.096, p = 0.008; r = 0.154, p = 0.001). After adjustment for prealbumin, uric acid, HbA1c, age, gender, eGFR, and β2-microglobin, binary regression revealed that hemoglobin, C-reactive protein, and albumin were independent influence factors of ESS (p = 0.016, r = 1.014; p = 0.023, r = 1.007; p = 0.029, r = 0.996). Conclusion: CKD patients have a high morbidity of ESS, mainly low T3 syndrome. Anemia, inflammation, and malnutrition may contribute to ESS in CKD.

Objective. To explore the correlation of indoleamine-2,3-dioxygenase (IDO) and chronic kidney disease (CKD). Methods. A total of 154 CKD patients and 42 non-CKD patients were recruited. Patients were grouped into ACR1~ACR3 (300 mg/g). Biomarkers in different groups were compared by ANOVA. Correlation was calculated by Pearson or Spearman analysis and binary logistic regression. The ROC curve was also performed. Results. The levels of albumin, serum creatinine (sCr), and IDO in non-CKD patients were significantly different from those in CKD3-CKD5 stages (p

Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA’s effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5flox/flox:Cagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA’s effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice. In vitro, RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis. In vivo, RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI in vivo and in vitro.Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy.

BackgroundPapillary renal cell carcinoma (pRCC) is a heterogeneous multifocal or isolated tumor with an invasive phenotype. Previous studies presented that alternative splicing, as a crucial posttranscriptional regulator in gene expression, is associated with tumorigenesis. However, the association between alternative splicing and pRCC has not been clarifiedMethodsThe RNA sequencing data and clinical information were downloaded from The Cancer Genome Atlas database and mRNA splicing profiles from TCGASpliceSeq. The percent spliced in data of alternative splicing merged with survival information was firstly calculated by univariate Cox regression analysis to screen for survival‐associated alternative splicing events, and survival‐associated alternative splicing events were then analyzed by Gene Ontology categories using Kyoto Encyclopedia of Genes and Genomes. Meanwhile, the least absolute shrinkage and selection operator Cox analysis and multivariate Cox analysis were performed to calculate the prognostic index for each alternative splicing type. In addition, clinical factors were introduced to assess the performance of prognostic index.ResultsA total of 4,084 candidate survival-associated alternative splicing events in 2,558 genes were screened out. Patients were divided into the low-risk group and the high-risk group based on the median prognostic index value. The Kaplan-Meier survival analysis (p < 0.05) and receiver operating characteristics curves (AUC>0.9) indicated that prognostic index was effective and stable for predicting the prognosis of pRCC patients. Furthermore, a regulatory network was constructed incorporating alternative splicing events and survival-associated splicing factors.ConclusionOur study provides new insights into the mechanism of alternative splicing events in tumorigenesis and their clinical potential for pRCC.

Clear cell renal cell carcinoma (ccRCC), the most common histological subtype of kidney cancer, shows poor prognosis, and non-sensitivity to radiotherapy or chemotherapy. The lncRNA small nucleolar RNA host gene 12 (SNHG12) has been revealed to play a carcinogenic role in various neoplasms, but the underlying mechanism in ccRCC is still unclear. To explore the potential role of SNHG12 in ccRCC, the data downloaded from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) Data Portal was used to compare the expression of SNHG12 in tumors and adjacent normal tissues. MRNA microarray and quantitative real-time PCR revealed that SNHG12 was overexpressed in the ccRCC tissues and cell lines. Functional inhibition of SNHG12 suppressed the viability and mobility of ccRCC cells. Mechanistically, dual luciferase assay and RNA immunoprecipitation (RIP) assay showed that miR-129-5p could bind to SNHG12 directly. There was a negative relationship between SNHG12 and miR-129-5p. What's more, we used bioinformatics-based prediction software to predict the target genes of miR-129-5p. Through data analysis and experimental verification, we found MDM4, a regulatory factor in p53 pathway, was involved in this ceRNA network. Our findings demonstrated that SNHG12 served as a sponge for miR-129-5p to regulate the expression of MDM4 and p53 pathway in the development of ccRCC.

Stromal cell-derived factor-1(SDF-1) is a chemotactic and angiogenic factor that mediates the repair of various tissues. As macrophages are important contributors to ischemic kidney injury, we examine the role of SDF-1 in a rodent model of ischemia-reperfusion (I/R) injury.Male wild-type (WT) (C57BL/6) mice were subjected to bilateral I/R injury or sham operation in the presence or absence of macrophage depletion (liposomal clodronate [0.2 ml/20-25 g body weight i.p.]). Macrophage accumulation was assessed by immunohistochemistry. Tissue levels of SDF-1 (ELISA) and SDF-1 mRNA expression (real-time PCR) were measured. The cellular location of SDF-1 was assessed using immunohistochemical staining.Immunofluorescence staining of renal tissue sections confirmed macrophage depletion by liposomal clodronate. SDF-1 production was elevated in response to I/R injury and was significantly increased upon macrophage depletion. SDF-1 positive cells initially appeared initially in the cortex, and subsequently diffused to the outer medulla after I/R injury.Our study demonstrates that SDF-1 is significantly upregulated during renal I/R. We hypothesize that SDF-1 upregulation may be an important macrophage effector mechanism during I/R injury.

AIMS: Atherosclerosis is a public health concern affecting many worldwide, but its pathogenesis remains unclear. In this study we investigated the role of IKKε during the formation of atherosclerosis and its molecular mechanism in the mouse aortic vessel wall. METHODS AND RESULTS: C57BL/6 wild-type or IKKε knockout mice bred into the ApoE knockout genetic background were divided into 4 groups: (1) wild-type (WT), (2) ApoE knockout (AK), (3) IKKε knockout (IK), (4) or both ApoE and IKKε knockout (DK). Each group of mice were fed with a high fat diet (HFD) for 12 weeks from 8 weeks of age. Immunohistochemistry and Western blotting analysis demonstrated obvious increases in the expression of IKKε in the AK group compared with the WT group, especially in the intima. Serum lipid levels were significantly higher in the AK and DK groups than in the other two groups. Staining with hematoxylin-eosin and Oil Red, as well as scanning electron microscopy revealed less severe atherosclerotic lesions in the DK group than in the AK group. Immunofluorescence and Western blot analysis demonstrated obvious increases in the expression of NF-κB pathway components and downstream factors in the AK group, especially in the intima, while these increases were blocked in the DK group. CONCLUSION: The knockout of IKKε prevented significant atherosclerosis lesions in the mouse aorta from in both wild-type and ApoE knockout mice fed a HFD, suggesting that IKKε may play a vital role in HFD-induced atherosclerosis and would be an important target for the treatment of atherosclerosis.

Objective: Despite the clear association of TyG-BMI with prediabetes and the progression of diabetes, no study to date has examined the relationship between TyG-BMI and the reversal of prediabetes to normoglycemia. Methods: 25,279 participants with prediabetes who had physical examinations between 2010 and 2016 were enrolled in this retrospective cohort study. The relationship between baseline TyG-BMI and regression to normoglycemia from prediabetes was examined using the Cox proportional hazards regression model in this study. Additionally, the nonlinear association between TyG-BMI and the likelihood of regression to normoglycemia was investigated using the Cox proportional hazards regression with cubic spline function. Competing risk multivariate Cox regression analysis was conducted, with progression to diabetes as a competing risk for prediabetes reversal to normoglycemia. Furthermore, subgroup analyses and a series of sensitivity analyses were performed. Results: After adjusting for covariates, the results showed that TyG-BMI was negatively associated with the probability of returning to normoglycemia (per 10 units, HR=0.970, 95% CI: 0.965, 0.976). They were also nonlinearly related, with an inflection point for TyG-BMI of 196.46. The effect size (HR) for TyG-BMI to the right of the inflection point (TyG-BMI = 196.46) and the probability of return of normoglycemia was 0.962 (95% CI: 0.954, 0.970, per 10 units). In addition, the competing risks model found a negative correlation between TyG-BMI and return to normoglycemia (SHR=0.97, 95% CI: 0.96-0.98). Sensitivity analyses demonstrated the robustness of our results. Conclusion: This study demonstrated a negative and nonlinear relationship between TyG-BMI and return to normoglycemia in Chinese adults with prediabetes. Through active intervention, the combined reduction of BMI and TG levels to bring TyG-BMI down to 196.46 could significantly increase the probability of returning to normoglycemia. [ABSTRACT FROM AUTHOR]