Link between remnant cholesterol and the reversion to normoglycemia in Chinese adults with prediabetes: a 5-year cohort study.

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 < 50.08 mg/dL), the HR for the probability of returning to normoglycemia was 0.907 (95% CI 0.897-0.917 per 5 mg/dL). Additionally, the competing risks model demonstrated a negative relationship between RC and the reversal of prediabetes to normoglycemia (SHR = 0.92, 95% CI 0.91-0.93). Sensitivity analyses confirmed the robustness and stability of these results. This study demonstrated a negative and non-linear association between RC and the probability of reversion to normoglycemia in Chinese adults with prediabetes. By actively intervening to reduce RC levels, at least to below 51.08 mg/dL, further reduction of RC may significantly increase the probability of returning to normoglycemia from prediabetes.

Association between excessive alcohol consumption and incident diabetes mellitus among Japanese based on propensity score matching.

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.

Inflammation-Derived and Clinical Indicator-Based Predictive Model for Ischemic Stroke Recovery.

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.

Protection of blood-brain barrier by endothelial DAPK1 deletion after stroke.

Death-associated protein kinase (DAPK) 1 is a critical mediator for neuronal cell death in cerebral ischemia, but its role in blood-brain barrier (BBB) disruption is incompletely understood. Here, we found that endothelial-specific deletion of Dapk1 using Tie2 Cre protected the brain of Dapk1fl/fl mice against middle cerebral artery occlusion (MCAO), characterized by mitigated Evans blue dye (EBD) extravasation, reduced infarct size and improved behavior. In vitro experiments also indicated that DAPK1 deletion inhibited oxygen-glucose deprivation (OGD)-induced tight junction alteration between cerebral endothelial cells (CECs). Mechanistically, we revealed that DAPK1-DAPK3 interaction activated cytosolic phospholipase A2 (cPLA2) in OGD-stimulated CECs. Our results thus suggest that inhibition of endothelial DAPK1 specifically prevents BBB damage after stroke.

Fluorescent identification of immunomagnetically captured CTCs using triplex-aptamer-targeted dendritic SiO2@Fe3O4 nanocomposite.

The enumeration of circulating tumor cells (CTCs) in peripheral blood plays a crucial role in the early diagnosis, recurrence monitoring, and prognosis assessment of cancer patients. There is a compelling need to develop an efficient technique for the capture and identification of these rare CTCs. However, the exclusive reliance on a single criterion, such as the epithelial cell adhesion molecule (EpCAM) antibody or aptamer, for the specific recognition of epithelial CTCs is not universally suitable for clinical applications, as it usually falls short in identifying EpCAM-negative CTCs. To address this limitation, we propose a straightforward and cost-effective method involving triplex fluorescently labelled aptamers (FAM-EpCAM, Cy5-PTK7, and Texas Red-CSV) to modify Fe3O4-loaded dendritic SiO2 nanocomposite (dmSiO2@Fe3O4/Apt). This multi-recognition-based strategy not only enhanced the efficiency in capturing heterogeneous CTCs, but also facilitated the rapid and accurate identification of CTCs. The capture efficiency of heterogenous CTCs reached up to 93.33%, with a detection limit as low as 5 cells/mL. Notably, the developed dmSiO2@Fe3O4/Apt nanoprobe enabled the swift identification of captured cells in just 30 min, relying solely on the fluorescently modified aptamers, which reduced the identification time by approximately 90% compared with the conventional immunocytochemistry (ICC) technique. Finally, these nanoprobe characteristics were validated using blood samples from patients with various types of cancers.

Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway.

Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to ß-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.

A nonlinear relationship between the triglycerides to high-density lipoprotein cholesterol ratio and stroke risk: an analysis based on data from the China Health and Retirement Longitudinal Study.

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.

Non-linear relationship between pulse pressure and the risk of pre-diabetes: a secondary retrospective Chinese cohort study.

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.

Association between alanine aminotransferase to high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: a retrospective cohort study in lean Chinese individuals.

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 < 24 kg/m2 and DBP < 90 mmHg had a stronger correlation between the ALT/HDL-C ratio and NAFLD risk. The current study shows a positive and non-linear connection between the ALT/HDL-C ratio and NAFLD risk in lean Chinese individuals. When the ALT/HDL-C ratio is less than 12.963, it is significantly linked to NAFLD. Therefore, from a therapy standpoint, it is advised to keep the ALT/HDL-C ratio less than the inflection point.

A non-linear connection between the total cholesterol to high-density lipoprotein cholesterol ratio and stroke risk: a retrospective cohort study from the China Health and Retirement Longitudinal Study.

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.

Relationship between glycated hemoglobin levels and three-month outcomes in acute ischemic stroke patients with or without diabetes: a prospective Korean cohort study.

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.

Nrf2 activation by neferine mitigates microglial neuroinflammation after subarachnoid hemorrhage through inhibiting TAK1-NF-κB signaling.

Oxidative stress and neuroinflammation are two major causes leading to early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor E2-related factor 2 (Nrf2) is a critical transcription factor that contributes to antioxidant responses. Additionally, Nrf2 could inhibit transforming growth factor beta-activated kinase 1 (TAK1), which plays a vital role in microglial activation-mediated neuroinflammation. Neferine (NE) exhibits considerable protective effects in diverse disease models. However, the detailed effect and mechanism of NE on SAH remain unknown. Our data showed that NE treatment significantly reduced behavior and cognitive impairment, and brain edema in the early period after SAH. In addition, NE mitigated SAH-induced oxidative damage, neuroinflammation, and neural death. Moreover, NE inhibited M1 microglial polarization and enhanced M2 phenotype microglia both in vivo and in vitro. Further investigations revealed that NE enhanced the Nrf2-antioxidant response element (ARE) signaling pathway and suppressed TAK1-NF-κB signaling. In contrast, depletion of Nrf2 by ML385 suppressed Nrf2-ARE signaling, induced TAK1-NF-κB activation, and further promoted M1 microglial polarization. Additionally, ML385 abated the neuroprotective effects of NE against SAH. Notably, LPS also aggravated TAK1-NF-κB activation and reversed the beneficial effects of NE after SAH. In summary, NE provides protection after SAH by inhibiting oxidative stress and modulating microglial polarization through Nrf2 activation and TAK1-NF-κB suppression.

Relationships between triglyceride-glucose index and incident gestational diabetes mellitus: a prospective cohort study of a Korean population using publicly available data.

Background: The 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. Methods: Using 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. Results: The 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%. Conclusion: The 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.

Link between triglyceride-glucose-body mass index and future stroke risk in middle-aged and elderly chinese: a nationwide prospective cohort study.

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.

Elevated triglyceride-glucose-body mass index associated with lower probability of future regression to normoglycemia in Chinese adults with prediabetes: a 5-year cohort study.

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.

Association between high-density lipoprotein cholesterol and reversion to normoglycemia from prediabetes: an analysis based on data from a retrospective cohort study.

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 < 0.001). Furthermore, there was a non-linear relationship between HDL-C and the reversion from Pre-DM to normoglycemia in both genders, and the inflection point of HDL-C was 1.540 mmol/L in males and 1.620 mmol/L in females. We found a strong positive correlation between HDL-C and the reversion from Pre-DM to normoglycemia on the left of the inflection point (Male: HR 2.783, 95% CI 2.373-3.263; Female: HR 2.217, 95% CI 1.802-2.727). Our sensitivity analysis confirmed the robustness of these findings. Subgroup analyses indicated that patients with SBP < 140 mmHg and ever smoker exhibited a more pronounced correlation between HDL-C levels and the reversion from Pre-DM to normoglycemia. In contrast, a less robust correlation was observed among patients with SBP ≥ 140 mmHg, current and never smokers. This study provides evidence of a positive and nonlinear association between HDL-C levels and the reversion from Pre-DM to normoglycemia in Chinese patients. Implementing intensified intervention measures to control the HDL-C levels of patients with Pre-DM around the inflection point may substantially enhance the likelihood of regression to normoglycemia.

The association between creatinine to body weight ratio and the risk of progression to diabetes from pre-diabetes: a 5-year cohort study in Chinese adults.

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) < 90 mmHg and triglyceride (TG) < 1.7 mmol/L. In contrast, among participants 50 years of age or older, those with DBP ≥ 90 mmHg, and those with TG ≥ 1.7 mmol/L, the relationship between the Cre/BW ratio and the risk of diabetes was attenuated. CONCLUSION: This study demonstrates a negative, non-linear relationship between the Cre/BW ratio and the risk of diabetes among the Chinese population with pre-diabetes. From a therapeutic standpoint, it is clinically meaningful to maintain the Cre/BW ratio levels above the inflection point of 1.072 umol/L/kg.

Triglyceride to high-density lipoprotein cholesterol ratio is associated with regression to normoglycemia from prediabetes in adults: a 5-year cohort study in China.

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.

A nomogram model for predicting 5-year risk of prediabetes in Chinese adults.

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.