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.

An increasing evidence suggested that chronic kidney disease (CKD) is closely related to oxidative stress, and dietary antioxidant intake can serve as a primary preventive measure for CKD. However, the relationship between composite dietary antioxidant index (CDAI) and renal anemia is not well understood. We postulated that elevated CDAI levels would be inversely related to a higher likelihood of renal anemia. The standardized calculation of CDAI was performed to investigate the relationship between them by a binary regression model. A non-linear relationship was examined through restricted cubic spline curves, and then pinpointed the inflection point. Subgroup analysis was then used to assess the robustness of the model. Finally 5880 participants were included in the study and a notable correlation between CDAI and renal anemia was found (P < 0.0001). In the multivariate linear regression model with adjustment for all confounding variables, the odds ratio (OR) and 95% confidence interval (CI) was 0.96 (0.94, 0.98; P < 0.0001), A non-linear relationship between CDAI and renal anemia was explored through restricted cubic splines, with a inflection at 6.005. Before the inflection point, for each unit rise in CDAI, the prevalence of renal anemia decreased by 5.7%. Subgroup analysis showed no statistically significant differences in interactions between any subgroups (P > 0.05). Our findings indicated a non-linear negative correlation between CDAI and renal anemia. The causal relationship still needs to be further clarified through large-scale prospective studies.

BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA.
METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA.
RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (β = 0.107, β = 0.102, β = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women.
CONCLUSIONS: This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

UNASSIGNED: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated.
UNASSIGNED: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin.
UNASSIGNED: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521±22.960 g/L. The median follow-up time was 21.103±18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males.
UNASSIGNED: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.

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.

BACKGROUND: Most studies had shown a linear relationship between serum albumin (sALB) and the prevalence of diabetic retinopathy (DR). Thus, the purpose of this study is to investigate whether their relationship is non-linear.
METHODS: We included 426 patients with type 2 diabetes who were hospitalized in Guangdong Provincial People\'s Hospital from December 2017 to November 2018. The outcome was the prevalence of DR. A two-piecewise logistics regression model was performed to identify the non-linear relationship between sALB and the prevalence of DR. The inflection point was calculated to determine the saturation effect through the maximum likelihood ratio and a recursive algorithm.
RESULTS: DR was diagnosed in 167 of 426 type 2 diabetic patients. The relationship between sALB and DR was nonlinear. When sALB was less than 38.10 g/L, a significant negative association was observed (OR = 0.82; 95% CI, 0.72-0.94; P = 0.0037), while no significant association was observed when sALB was greater than 38.10 g/L (OR = 1.12; 95% CI, 0.92-1.35; P = 0.2637).
CONCLUSIONS: The relationship between sALB and the prevalence of DR is non-linear. sALB is negatively associated with the prevalence of DR when sALB is less than 38.10 g/L. Our findings need to be confirmed by further prospective research.

This study aimed to investigate the relationship between platelet count (PC) and mortality in patients with hemorrhagic stroke (HS). The research reviewed data from 10,466 patients hospitalized in 208 hospitals in the United States from January 1, 2014, to December 31, 2015. Of these, 3262 HS patients were included in the primary analysis for those admitted to the intensive care unit (ICU). The average age of these patients was 67.05 years, with 52.79% being male. The median PC was (221.67 ± 73.78) × 109/L. Multivariate logistic regression analysis revealed that PC was a protective factor for mortality in HS patients (OR = 0.98, 95% CI 0.97-1.00, P < 0.05). Additionally, a non-linear association between PC and mortality in HS patients was found using a generalized additive model (GAM) and smooth curve fitting (penalty spline method). For the first time, a recursive algorithm identified the inflection point of platelet count as 194 × 109/L. On the left side of the inflection point, for every increase of 10 units in platelet count, the mortality rate of HS patients decreases by 10%. The study demonstrates a non-linear relationship between PC and the risk of mortality in HS patients. A platelet counts higher than the inflection point (194 × 109/L) may be a significant intervention to reduce mortality in HS patients.

The Triglyceride-glucose (TyG) index has been acknowledged as a convenient, cost-effective, and relatively simple marker for insulin resistance (IR). Meanwhile, prediabetes, described as an asymptomatic, moderately hyperglycemic state, tends to be more prevalent than diabetes. Thus, the objective of this study was to explore the relationship between the TyG index and the prevalence of both prediabetes and diabetes within the U.S. population.
This study utilized a cross-sectional dataset derived from the National Health and Nutrition Survey (NHANES) spanning 1999 to 2018. The subjects were individuals aged 18 years and above, who had available fasting glucose and fasting triglyceride information, permitting a diagnosis of prediabetes or diabetes. The TyG index was computed using laboratory data, and participants were subsequently categorized into quartiles based on this information. The relationship between the TyG index and the prevalence of prediabetes and diabetes was investigated using logistic regression analysis.
Out of the 25,159 participants, 23.88% were found to have prediabetes, while 16.22% were diagnosed with diabetes. After adjusting for confounding factors, a linear increase in relative odds was observed in Q2 (OR: 1.69; 95% CI: 1.52, 1.89), Q3 (OR: 2.57; 95% CI: 2.30, 2.88), and Q4 (OR: 4.88; 95% CI: 4.33, 5.49) groups in comparison to the reference group, Q1. In addition, a non-linear relationship was observed between the TyG index and the prevalence of prediabetes and diabetes. Specifically, patients with a TyG index greater than 8.00 overall exhibited a significantly higher risk of prediabetes and diabetes, confirming that an increase in the TyG index is associated with a corresponding increase in risk. However, this shift showed gender-specific variations; the threshold was observed at 8.00 in males but shifted to 9.00 in females.
The TyG index demonstrated a non-linear positive correlation with both prediabetes and diabetes. This suggests that maintaining the TyG index at a certain, reduced level could potentially aid in preventing the onset of prediabetes and diabetes.

Migraine is a common clinical neurological disorder that adversely affects humans and society. The relationship between copper intake and migraine has been less studied and controversial. The purpose of this study was to determine the relationship between copper intake and migraine and to guide dietary interventions. The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2004, involving a total of 12,724 participants. The relationship between copper intake and migraine was examined using weighted multivariate logistic regression models, and smooth-fit curves were plotted to explore the relationship. After non-linear relationships were found, recursive algorithms and two-stage linear regression models were used to calculate inflection points. Stratified analyses were also performed to explore population differences. In the model corrected for all covariates, the OR (95% CI) of copper intake with migraine was 1.19 (0.97, 1.46), which was not statistically significant. However, the results of the linear trend test suggested that their relationship might be non-linear. Smooth-fit curves confirmed the non-linear relationship between copper intake and migraine, and an inflection point (0.98 mg/day) was identified. There was no statistical significance before the inflection point, but after the inflection point, copper intake was positively associated with migraine attacks. Stratified analyses showed that this non-linear relationship persisted in females, people under 45 years old, and people with BMI less than 30. In this large cross-sectional study, we found a non-linear correlation between copper intake and migraine.

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.
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.
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.
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.