Home Medicine Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018
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Exploration of the association between estimated glucose disposal rate and osteoarthritis in middle-aged and older adults: An analysis of NHANES data from 2011 to 2018

  • XiaoPeng Gu , SongOu Zhang and WeiHu Ma EMAIL logo
Published/Copyright: February 4, 2025
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Open Medicine
From the journal Open Medicine Volume 20 Issue 1

Abstract

Background

It is unclear how the estimated glucose disposal rate (eGDR) index relates to osteoarthritis (OA). The goal of this research is to explore the possible link between the eGDR index and the likelihood of OA development.

Methods

The study encompassed 9,051 individuals from the National Health and Nutrition Examination Survey (2011–2018). Participants were divided into quartiles according to their eGDR, calculated with the equation: eGDR (mg/kg/min) = 21.158 − (0.09 × waist circumference) − (3.407 × hypertension) − (0.551 × glycosylated hemoglobin). We assessed the independent correlation between the eGDR metric and the incidence of OA through weighted multivariate regression, stratified analysis, and threshold effect evaluation.

Results

The study encompassed 9,051 participants, who had an average eGDR of 7.09. Participants with OA had lower eGDR levels compared to those without OA (6.27 ± 0.09 vs 7.31 ± 0.06, P < 0.001). The odds ratios (ORs) for OA associated with the eGDR index in the logistic regression models were 0.87 (95% confidence interval [CI]: 0.84, 0.89) in the unadjusted model I and 0.87 (95% CI: 0.84, 0.91) in model II (adjusted for all covariates). Higher eGDR index was associated with a reduced risk of OA when compared to the lowest quartile (Q1). A restricted cubic spline analysis indicated a linear negative relationship between eGDR and OA risk.

Conclusion

An increased eGDR index is inversely related to the risk of OA. The eGDR may serve as a valuable biomarker for the detection of OA and offers a new perspective for the assessment and management of the condition.

Keywords: NHANES; eGDR; osteoarthritis; diabetes mellitus; insulin resistance

1 Introduction

Osteoarthritis (OA) is a chronic joint disorder characterized by cartilage degradation, bone proliferation adjacent to the joints, and inflammation of the synovial membrane. It ranks among the primary sources of discomfort and impairment among the elderly population. OA represents a significant global public health issue, especially affecting middle-aged and older individuals aged 50 and over. According to statistics, the incidence of OA ranges from 9.29 to 35.1% [1,2,3], and this figure is continuously rising with the aging of the population. The pathogenesis of OA involves multiple aspects, including the degenerative changes of articular cartilage, joint inflammation, and abnormal bone remodeling, leading to symptoms such as joint pain, swelling, and limited mobility. In severe cases, it can result in joint deformity and loss of function. Currently, the treatment for OA primarily includes pharmacological therapy (such as non-steroidal anti-inflammatory drugs and analgesics), physical therapy, and surgical intervention, but no definitive treatment exists that can reverse joint damage. OA not only inflicts physical suffering on patients but also imposes a significant economic burden on society. Medical expenses, loss of labor force, and decreased productivity are socioeconomic issues associated with OA. Regarding the etiology of OA, in addition to age and genetic factors, obesity, excessive joint use, and metabolic abnormalities are also considered important risk factors [4,5,6,7,8].

Diabetes mellitus, a common metabolic disorder, is characterized by persistently elevated blood glucose levels, which are typically the result of insufficient insulin production or inadequate response to insulin by the body [9]. There are two main forms of diabetes mellitus: type 1 and type 2 diabetes. The relationship between diabetes and OA is increasingly being recognized. Obesity is a shared risk factor for both diseases, potentially increasing the risk of developing either condition. However, obesity alone does not solely account for the occurrence of OA. Studies have indicated that even after accounting for obesity, diabetes may still increase the risk of OA [10]. Diabetes mellitus may lead to an elevation in systemic inflammation levels, which could potentially accelerate joint degeneration. The metabolic disturbances associated with diabetes may also affect joint health. Insulin resistance (IR), a precursor to diabetes, is considered a potential risk factor for the onset of OA [11,12,13]. Traditional methods for detecting IR, such as the euglycemic hyperinsulinemic clamp, are accurate but are limited in clinical application due to their high cost and invasiveness [14]. In contrast, the estimated glucose disposal rate (eGDR) is a convenient and non-invasive assessment method that calculates IR based on clinical features such as waist circumference (WC), hypertension, and glycosylated hemoglobin (HbA1c). eGDR has a strong correlation with IR [15]. A lower eGDR value indicates more severe IR [16].

Although eGDR has advantages in assessing IR, its association with OA remains unclear. Recently, a growing body of research has indicated a possible connection between IR and OA. For example, IR might result in metabolic disruptions in articular chondrocytes, which could aggravate joint inflammation and the degeneration of cartilage [17]. Drawing on the findings of these investigations, we propose that eGDR could function as an indicator for OA in middle-aged and older individuals.

The NHANES is a nationwide survey conducted by the National Center for Health Statistics within the Centers for Disease Control and Prevention in the United States, with the objective of assessing the health and nutritional status of the population. Data collected via NHANES are widely utilized in scholarly research, policy formulation, and public health monitoring [18,19,20]. This study leverages data from the US NHANES from 2011 to 2018 to conduct an in-depth analysis of the relationship between the eGDR index and OA in middle-aged and elderly populations. Our findings indicate that the incidence of OA among middle-aged and elderly individuals with lower eGDR values is significantly higher than that among those with higher eGDR values. The results of this study provide new insights into the role of IR in the pathogenesis of OA and offer a theoretical basis for the clinical practice of preventing and managing OA by improving insulin sensitivity. Future research can further explore the role of eGDR in predicting OA risk and treatment response, with the aim of providing more evidence for precise treatment of OA.

2 Methods

2.1 Study population

This study initially included cross-sectional data from 39,156 participants across four consecutive NHANES cycles (2011–2018). The exclusion criteria were as follows: (1) participants under 40 years of age (n = 24,090); (2) participants lacking information on OA (n = 1,590); (3) participants with missing data on WC, HbA1c, and hypertension, which are necessary for the calculation of eGDR (n = 1,831); and (4) participants with missing information on other covariates (n = 2,594). After a manual review of the data, a total of 9,051 subjects were chosen for subsequent analysis. Figure 1 provides a detailed depiction of the participant enrollment flow for the study.

Figure 1 An elaborate diagram of the participant enrollment process.
Figure 1

An elaborate diagram of the participant enrollment process.

2.2 Assessment of eGDR

eGDR stands for the estimated glucose disposal rate, a metric that represents the milligrams of glucose disposed per kilogram of body weight per minute. The calculation of eGDR is based on the following formula, which incorporates WC (in centimeters), the presence of hypertension (yes = 1/no = 0), and the percentage of HbA1c. The calculation of eGDR is based on the following formula: eGDR (mg/kg/min) = 21.158 − (0.09 × WC) − (3.407 × hypertension) − (0.551 × HbA1c).

2.3 Assessment of OA

NHANES’s “Medical Conditions” section provided diagnostic data for OA. Initially, participants were inquired whether a physician had ever informed them of having OA. If they responded affirmatively, they were subsequently prompted to specify the type of OA diagnosed (according to the NHANES questionnaire data, OA is categorized into osteoarthritis, rheumatoid arthritis, and psoriatic arthritis, among others).

2.4 Covariates

In this study, we included several covariates that might affect the risk of OA. Ethnicity was categorized into five groups: White, Black, Hispanic, and other racial/ethnic groups. Education level was divided into less than high school and high school or above. The poverty income ratio (PIR) was used as an indicator of household income, which has been linked to human health in various studies. PIR was classified into three categories: <1.3%, 1.3–3.49%, and ≥3.5%. Participants were classified as drinkers if they reported having consumed a minimum of 12 drinks within the year prior to the survey. No matter whether they smoked at the time of the interview or not, smokers were classified as those who had smoked 100 or more cigarettes in their lifetime. Blood pressure measurements, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), were taken by clinicians following standardized procedures, with three successive readings at 30 s intervals, and the average of these was employed to determine the blood pressure value. Laboratory tests were conducted following standardized procedures to determine serum triglyceride concentration, total cholesterol (TC), and HbA1c. To calculate the estimated glomerular filtration rate (eGFR), the NHANES researchers applied the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, which takes into account age, sex, race/ethnicity, and serum creatinine concentrations to cater to a varied demographic. Hypertension was identified based on either self-reported diagnoses by a physician or readings from a physical examination. Study participants were deemed hypertensive if they fulfilled one or more of the following criteria: (1) an average SBP of at least 140 mmHg; (2) an average DBP of at least 90 mmHg; (3) a self-reported diagnosis of hypertension; and (4) the current use of antihypertensive medications. Participants were considered to have diagnosed diabetes if a medical professional had identified the condition. Individuals who had not been previously diagnosed but exhibited HbA1c levels equal to or greater than 6.5% (47.5 mmol/mol), fasting plasma glucose levels of 126 mg/dL (7.0 mmol/L) or higher, or 2 h post-meal plasma glucose levels of 200 mg/dL (11.1 mmol/L) or higher following an oral glucose tolerance test were classified as having undiagnosed diabetes. Participants with either diagnosed or undiagnosed diabetes were collectively referred to as diabetic.

2.5 Statistical analysis

The method employed facilitated the precise computation of associated statistical data, accounting for the intricate sampling strategy inherent to the NHANES survey. Continuous variables are described by their mean and standard deviation, while nominal variables are depicted by frequency and percentage. Student’s t-tests and chi-square tests were applied to discern baseline differences in characteristics between participants with and without OA. eGDR values were divided into four quartiles, with the first quartile (Q1) serving as the reference category. The analysis comprised an unadjusted model and two adjusted models (model I and model II) to evaluate the relationship between eGDR and OA. Model I included adjustments for years, gender, and race, whereas model II accounted for educational level, poverty–income ratio, smoking habits, alcohol intake, body mass index (BMI), hemoglobin levels, TC, and the presence of diabetes and hypertension.

  1. Informed consent: This is a study based on a public database. Our team did not need to obtain patient informed consent before conducting the study.

  2. Ethical approval: This is a study based on a public database. Our team did not need to obtain additional ethics approval. We put the ethics approval of the NHANES database in the Supplementary Material.

3 Result

3.1 Descriptive statistics of clinical features in the study cohort

A total of 9,051 participants were included in the analysis, with a weighted average age of 57.35 ± 0.22 years. These individuals were divided into OA and non-OA categories, with the prevalence of OA across the entire participant pool standing at 72.81%. Compared to individuals without OA, those with OA were generally older and predominantly Caucasian and exhibited significant differences in BMI, hemoglobin, WC, HbA1c, eGDR, TC, eGFR, and smoking status (all P  <  0.05). Among those with OA, there was a higher proportion of Caucasians (83.70% versus 69.88% in non-OA individuals). They tended to be older (63.23 ± 0.31 years versus 55.77 ± 0.22 years), had higher BMI (31.10 ± 0.26 versus 29.07 ± 0.12), and had larger WCs (105.32 ± 0.54 cm versus 101.07 ± 0.28 cm). They also had a higher incidence of diabetes (24.84% versus 18.62%) and hypertension (63.84% versus 45.78%) and had lower hemoglobin levels (105.32 ± 0.54 g/L versus 101.07 ± 0.28 g/L). The detailed demographic and clinical characteristics of all participants are presented in Table 1. This table shows the demographic and clinical characteristics of the study population grouped by eGDR quartiles. In the OA group, eGDR values were notably lower compared to the entire study cohort. (6.27 ± 0.09 versus 7.31 ± 0.06) (Table 1).

Table 1

Clinical characteristics of the study population

Variables Overall Non-OA OA P value
Age (%) 57.35 ± 0.22 55.77 ± 0.22 63.23 ± 0.31 <0.001***
Race/ethnicity (%) <0.001***
 White 72.81 (64.65, 80.97) 69.88 (66.27, 73.49) 83.70 (81.31, 86.09)
 Black 8.95 (7.67, 10.24) 9.78 (7.95, 11.61) 5.89 (4.52, 7.26)
 Mexican 6.26 (4.85, 7.67) 7.12 (5.44, 8.79) 3.06 (2.01, 4.12)
 Others 11.98 (10.73, 13.23) 13.23 (11.51, 14.95) 7.34 (5.99, 8.69)
Education levels, % 0.01*
 Less than high school 12.72 (11.10, 14.35) 13.37 (11.56, 15.18) 10.32 ( 8.49, 12.15)
 High school or equivalent 22.18 (19.77, 24.59) 22.40 (20.67, 24.13) 21.37 (18.51, 24.22)
 College or above 65.10 (59.45, 70.75) 64.23 (61.50, 66.96) 68.32 (65.34, 71.29)
PIR, % 0.40
 ≤1.30 16.43 (14.40, 18.45) 16.74 (14.65, 18.82) 15.28 (12.78, 17.78)
 1.31–3.49 34.31 (31.39, 37.24) 34.44 (32.35, 36.54) 33.84 (30.98, 36.71)
 ≥3.50 49.26 (44.02, 54.50) 48.82 (45.60, 52.04) 50.88 (46.70, 55.06)
BMI (kg/m2) 29.50 ± 0.12 29.07 ± 0.12 31.10 ± 0.26 <0.001***
Hemoglobin (g/dl) 14.19 ± 0.03 14.23 ± 0.04 14.02 ± 0.04 <0.001***
waist circumference (cm) 101.97 ± 0.28 101.07 ± 0.28 105.32 ± 0.54 <0.001***
HbA1c (%) 5.81 ± 0.02 5.80 ± 0.02 5.86 ± 0.03 0.05
eGDR 7.09 ± 0.05 7.31 ± 0.06 6.27 ± 0.09 <0.001***
TC (mmol/L) 5.15 ± 0.02 5.16 ± 0.02 5.11 ± 0.04 0.25
eGFR (mL/min/1.73 m2) 85.77 ± 0.35 87.24 ± 0.38 80.30 ± 0.60 <0.001***
Smoking (%) 45.78 (41.53, 50.02) 44.52 (42.62, 46.43) 50.43 (46.54, 54.33) 0.004**
Drinking (%) 76.64 (70.83, 82.45) 77.05 (75.18, 78.92) 75.13 (72.04, 78.21) 0.20
Hypertension (%) 49.61 (46.11, 53.11) 45.78 (43.84, 47.72) 63.84 (60.46, 67.22) <0.001***
DM (%) 19.94 (18.24, 21.63) 18.62 (17.32, 19.91) 24.84 (21.94, 27.74) <0.001***

Continuous data were presented as the mean ± SEM, and category data were presented as the proportion and 95% confidence interval. SEM, standard error of the mean; OA, osteoarthritis; PIR, poverty income ratio; BMI, body mass index; HbA1c, glycosylated hemoglobin; eGDR, estimated glucose disposal rate; TC, total cholesterol; eGFR, estimated glomerular filtration rate; DM, diabetes mellitus; ***P value <0.001, **P value <0.01, *P value <0.05.

3.2 Association between eGDR and the incidence of OA

To investigate the potential link between eGDR and the development of OA, we conducted a weighted multivariate analysis, adjusting for variables including age, sex, ethnicity, educational level, BMI, PIR, smoking habits, alcohol consumption, hypertension, and diabetes. A notable correlation between eGDR and the frequency of OA was detected, both in unadjusted and adjusted models for confounders, suggesting that an increased eGDR, when considered a continuous measure, is linked to a lower likelihood of developing OA. The odds ratio (OR) (95% confidence interval [CI]) for the relationship between eGDR and the incidence of OA was 0.87 [0.84–0.89] (P < 0.001) (refer to Table 2). Furthermore, by uniformly dividing all participants into quartiles based on eGDR, we observed that participants with higher eGDR quartiles had a significantly lower prevalence of OA (Table 2). Constrained cubic spline functions were employed to assess the association between eGDR and the occurrence of OA. The results indicate a linear inverse relationship between eGDR and the risk of OA (non-linear P = 0.136) (Figure 2). With increasing eGDR, the incidence of OA decreased more prominently. Constrained cubic spline techniques were utilized to investigate the correlation between eGDR and the frequency of OA among individuals with diabetes and hypertension. The results demonstrate a non-linear inverse relationship between eGDR and OA prevalence in these patient groups (diabetes: non-linear P = 0.005; hypertension: non-linear P = 0.01) (Figure 3). With increasing eGDR, the decrease in the incidence of OA was more pronounced.

Table 2

Weighted logistic regression analysis on the association between eGDR and OA

Non-adjusted model Model I Model II
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Continuous eGDR 0.87 (0.84, 0.89) <0.001*** 0.88 (0.85, 0.91) <0.001*** 0.87 (0.84, 0.91) <0.001***
eGDR-Q1 Reference — Reference — Reference —
eGDR-Q2 0.77 (0.62, 0.94) 0.01* 0.69 (0.55, 0.86) 0.001** 0.68 (0.53, 0.87) 0.003**
eGDR-Q3 0.51 (0.41, 0.63) <0.001*** 0.51 (0.40, 0.64) <0.001*** 0.50 (0.39, 0.64) <0.001***
eGDR-Q4 0.34 (0.26, 0.44) <0.001*** 0.38 (0.29, 0.50) <0.001*** 0.37 (0.27, 0.51) <0.001***

Data are presented as OR (95% CI). Model I adjusted for age, sex, and race/ethnicity. Model II adjusted for age, sex, race/ethnicity, education levels, poverty income ratio, smoking, drinking, DM, hemoglobin, TC, and eGFR. OA, Osteoarthritis; eGDR, estimated glucose disposal rate; TC, total cholesterol; eGFR, estimated glomerular filtration rate; ***P value < 0.001, **P value < 0.01, *P value < 0.05.

Figure 2 The relationship between eGDR and OA as depicted in a constrained cubic spline regression model.
Figure 2

The relationship between eGDR and OA as depicted in a constrained cubic spline regression model.

Figure 3 Restricted cubic spline analyses illustrating the relationship between eGDR and OA within subgroups, stratified by (a) hypertensive status and (b) diabetes mellitus.
Figure 3

Restricted cubic spline analyses illustrating the relationship between eGDR and OA within subgroups, stratified by (a) hypertensive status and (b) diabetes mellitus.

Results are expressed as ORs (95% CIs). Model I included adjustments for age, gender, and ethnicity. Model II was adjusted for age, gender, ethnicity, educational attainment, poverty–income ratio, tobacco use, alcohol consumption, diabetes mellitus, hemoglobin levels, total cholesterol, and estimated glomerular filtration rate. OA: osteoarthritis; eGDR: estimated glucose disposal rate; TC: total cholesterol; eGFR: estimated glomerular filtration rate; *** indicates P-value <0.001, ** indicates P-value <0.01, * indicates P-value <0.05.

3.3 Sensitivity analysis

To ascertain the consistency of our study’s outcomes, we performed a sensitivity analysis with unweighted logistic regression. This sensitivity analysis confirmed a statistically significant relationship between eGDR and the incidence of OA, with higher eGDR scores inversely related to the risk of OA. For each unit increment in eGDR, the OR for OA prevalence was 0.87 (95% CI: 0.85–0.88) (refer to Table 3). The unweighted logistic regression model applied in the sensitivity analysis underscored the reliability of our findings, suggesting that the correlation between eGDR and OA prevalence aligns with the initial analysis.

Table 3

Unweighted logistic regression analysis on the correlation between eGDR and OA in sensitivity analysis

Non-adjusted model Model I Model II
OR (95% CI) P value OR (95% CI) P value OR (95% CI) P value
Continuous eGDR 0.87 (0.85, 0.88) <0.001*** 0.88 (0.86, 0.90) <0.001*** 0.87 (0.85, 0.89) <0.001**
eGDR-Q1 Reference — Reference — Reference —
eGDR-Q2 0.75 (0.65, 0.86) <0.001*** 0.67 (0.57, 0.77) <0.001*** 0.65 (0.56, 0.76) <0.001***
eGDR-Q3 0.50 (0.43, 0.58) <0.001*** 0.50 (0.43, 0.59) <0.001*** 0.49 (0.41, 0.57) <0.001***
eGDR-Q4 0.35 (0.29, 0.41) <0.001*** 0.41 (0.34, 0.49) <0.001*** 0.39 (0.32, 0.47) <0.001***

Data are presented as OR (95% CI). Model I adjusted for age, sex, and race/ethnicity. Model II adjusted for age, sex, race/ethnicity, education levels, poverty income ratio, smoking, drinking, DM, hemoglobin, TC, and eGFR. OA, osteoarthritis; eGDR, estimated glucose disposal rate; TC, total cholesterol; eGFR, estimated glomerular filtration rate; ***P value < 0.001, **P value < 0.01.

3.4 Subgroup analysis across different populations

Stratified analyses were performed to investigate the potential relationships between eGDR and the incidence of OA, classified according to age, sex, ethnicity, BMI, educational status, PIR, smoking habits, alcohol use, hypertension, and diabetes (refer to Table 4). eGDR might interact with the prevalence of OA across various age strata, among smokers, and in individuals with diabetes.

Table 4

Subgroup analysis for the association between the eGDR and OA

Variable name Non-OA OA P value P for interaction
Age 0.001
 40–60 years Ref 0.85 (0.82, 0.89) <0.001
 >60 years Ref 0.94 (0.90, 0.98) 0.01
Sex 0.59
 Male Ref 0.84 (0.81, 0.88) <0.001
 Female Ref 0.85 (0.82, 0.88) <0.001
BMI 0.50
 ≤30 Ref 0.87 (0.83, 0.91) <0.001
 >30 Ref 0.89 (0.85, 0.93) <0.001
Race 0.06
 White Ref 0.87 (0.84, 0.90) <0.001
 Black Ref 0.90 (0.84, 0.95) <0.001
 Mexican American Ref 0.83 (0.78, 0.89) <0.001
 Others Ref 0.81 (0.76, 0.86) <0.001
Education levels 0.23
 Less than high school Ref 0.83 (0.78, 0.88) <0.001
 High school or equivalent Ref 0.84 (0.77, 0.90) <0.001
 College or above Ref 0.88 (0.85, 0.90) <0.001
PIR 0.91
 ≤1.30 Ref 0.87 (0.82, 0.91) <0.001
 1.31–3.49 Ref 0.86 (0.82, 0.89) <0.001
 ≥3.50 Ref 0.87 (0.83, 0.91) <0.001
Smoking 0.03
 No Ref 0.85 (0.81, 0.88) <0.001
 Yes Ref 0.90 (0.87, 0.93) <0.001
Drinking 0.54
 No Ref 0.88 (0.83, 0.93) <0.001
 Yes Ref 0.86 (0.84, 0.89) <0.001
Hypertension 0.21
 No Ref 0.87 (0.81, 0.94) <0.001
 Yes Ref 0.93 (0.88, 0.98) 0.01
DM 0.02
 No Ref 0.85 (0.82, 0.88) <0.001
 Yes Ref 0.92 (0.87, 0.98) 0.01

OA, osteoarthritis; eGDR, estimated glucose disposal rate; BMI, body mass index; PIR, poverty income ratio; DM, diabetes mellitus.

4 Discussion

This cross-sectional investigation leveraged the comprehensive demographic data available through NHANES to explore the association between eGDR and the prevalence of OA. A total of 9,051 individuals from the 2011 to 2018 NHANES surveys were included, of which 1,655 had been diagnosed with OA. Across different adjustment models, we noted that participants with reduced eGDR levels were more likely to have OA. This pattern held true in both continuous and categorical analytical approaches. Furthermore, after controlling for all potential confounders, a significant inverse relationship was identified between eGDR and the prevalence of OA, indicating a linear association. This significant negative relationship was also evident within various demographic subgroups. Additionally, our study revealed that the relationship between eGDR and OA prevalence was independent of gender, race/ethnicity, educational attainment, marital status, PIR, BMI, alcohol use, and hypertension, as demonstrated in the subgroup analyses(all interaction P-values >0.05). This indicates that the inverse relationship may extend to individuals with varying demographic characteristics. As far as we are aware, this is the initial investigation to uncover the connection between eGDR and OA within a substantial cross-sectional cohort of middle-aged and older adults in the United States.

Diabetes mellitus has become a worldwide public health emergency, experiencing marked shifts in its epidemiological profile in recent times. The global prevalence of diabetes is increasing, presenting a significant threat to personal well-being and healthcare infrastructure. Current estimates suggest that around 462 million adults across the globe are affected by diabetes, and projections indicate that this figure could rise to 700 million by the year 2045. Diabetes not only drastically affects the lives of those afflicted but also imposes a heavy financial strain on healthcare systems [21,22,23]. The associated medical costs and treatment expenses for complications of diabetes represent a significant economic burden. OA is considered a complex disease influenced by various factors. These include genetics, age, gender, obesity, joint injury, and metabolic disorders. Among these influencing factors, diabetes is regarded as a crucial causative factor, with a positive correlation observed between OA and type 2 diabetes [24,25]. However, this conclusion is subject to debate, as some studies argue that diabetes is not a risk factor for OA [26]. Within the context of this current research, following the exclusion of the impact of BMI, it was observed that eGDR continued to be inversely associated with the incidence of OA. Consequently, these findings endorse the concept that diabetes serves as a risk factor for the development of OA.

Diabetes mellitus is characterized by insufficient insulin secretion or an inadequate response of the body to insulin. Insulin, a hormone secreted by pancreatic β cells, primarily functions to regulate blood glucose levels by promoting the uptake of glucose by the liver, muscles, and fat tissues, thereby reducing blood glucose levels. IR refers to a decrease in the body’s response to insulin, where insulin cannot effectively promote the uptake and utilization of glucose by cells, leading to elevated blood glucose levels. IR is one of the main mechanisms of disease onset. Under conditions of IR, pancreatic β cells must secrete more insulin to maintain normal blood glucose levels. Prolonged overwork can lead to β-cell dysfunction, gradually reducing insulin secretion and eventually failing to meet the body’s needs, leading to elevated blood glucose levels and eventually developing into type 2 diabetes. There are various methods to assess IR, such as the euglycemic hyperinsulinemic clamp (the gold standard), the intravenous glucose tolerance test, and oral glucose or mixed meal tolerance tests. However, due to the time-consuming and cumbersome nature of these assessment methods, their clinical practicality and feasibility in large-scale epidemiological surveys are limited. The eGDR is a recently introduced index for IR that has gained attention for its simplicity and reliability. Many researchers advocate using eGDR as an indicator of IR. Recent studies have shown a strong correlation between eGDR and cardiovascular diseases [27,28], stroke [29], retinopathy [30], and kidney disease [31].

Recent studies indicate that the development of OA is linked to IR. Prior research has documented a connection between the TyG index and OA, suggesting that higher TyG index values are positively associated with the occurrence of OA [32]. For each unit rise in the TyG index, the likelihood of developing OA amplifies by 634% [32]. In certain instances, the TyG index seems to lack adequate sensitivity and specificity [33]. This research is the pioneering effort to examine the relationship between eGDR and OA. Previous studies have demonstrated that eGDR exhibits superior predictive power compared to the TyG index in the context of cardiovascular diseases. This superiority is likely due to the eGDR’s incorporation of both clinical and laboratory data in its computation, which offers a more nuanced evaluation of IR. Compared to traditional methods for assessing IR status, eGDR is non-invasive and less costly, making it more suitable for large-scale clinical applications. Moreover, eGDR has similar accuracy to the euglycemic hyperinsulinemic clamp in assessing IR status [34]. Our study found a negative correlation between eGDR and OA. Although the exact biological mechanisms by which IR leads to OA are not fully understood, several plausible explanations have been proposed. IR can promote the progression of OA through two important mechanisms: inflammation and metabolism. During the onset of OA, the production of TNF-α increases. Synovial fibroblasts in the joint generate IL-1β, IL-6, MMP1, and MMP13 in response to TNF-α. Hamada et al. [35] reported that insulin can inhibit the generation of inflammatory factors and proteases induced by TNF-α. In patients with IR, the signaling of insulin is impaired, weakening the anti-inflammatory effect of insulin. In patients with IR, due to long-term nutritional excess, including free fatty acids, nutrients can induce tissue inflammation [36]. Free fatty acids can induce TNF-α and TLR activation to promote the progression of OA [37,38,39,40]. Carnitine is a key molecule in mitochondrial energy generation [41]. Under continuous metabolic stress, carnitine deficiency affects the energy metabolism of articular cartilage [42,43]. Supplementation with carnitine can improve the clinical symptoms of patients with OA [44]. Many studies have found that anti-diabetic treatment can improve or delay the progression of OA. In future research, we can investigate whether treatments targeting IR can enhance the effectiveness of arthritis treatment in individuals with diabetes.

5 Limitations

Initially, given the observational design of the research, we are unable to infer causation, and a reciprocal causal link may even be present. Nonetheless, this appears to be improbable. Secondly, although our model made extensive adjustments for a multitude of potential confounders, the complete elimination of residual confounding remains a possibility, an inherent difficulty in the realm of observational studies. Furthermore, the outcome of interest in this study was dependent on self-reported data from participants, which were based on their physicians’ diagnoses. This reliance on self-reporting may introduce recall bias and lead to unavoidable misclassification. Despite this limitation, this approach is frequently used in cohort study methodologies.

6 Conclusion

An increased eGDR index is associated with a decreased risk of OA. The eGDR could potentially act as a significant biomarker for the identification of OA, providing a novel approach for evaluating and managing the disorder.

# Represents co-first authors.

  1. Funding information: This study is supported by the Putuo District Public Welfare Science and Technology Project(2023GY002).

  2. Author contributions: Xiaopeng Gu and Weihu Ma designed this study. SongOu Zhang and Xiaopeng Gu wrote and revised this manuscription.

  3. Conflict of interest: None.

  4. Data availability statement: All raw data are available from the corresponding author upon request.

Appendix

Table A1

Clinical characteristics grouped by eGDR quartiles

Variables Overall eGDR-Q1 eGDR-Q2 eGDR-Q3 eGDR-Q4 P value
Age, % 57.35 ± 0.22 60.19 ± 0.32 60.34 ± 0.32 56.93 ± 0.33 53.05 ± 0.33 <0.001***
Race/ethnicity, % <0.001***
White 72.81(64.65, 80.97) 72.86(68.76, 76.95) 71.33(67.46, 75.21) 72.86(69.09, 76.63) 73.91(70.47, 77.34)
Black 8.95( 7.67, 10.24) 12.46(9.64, 15.28) 9.71(7.87, 11.56) 8.24(6.52, 9.97) 6.14(4.90, 7.38)
Mexican 6.26( 4.85, 7.67) 6.24(4.26, 8.21) 5.45(4.01, 6.89) 7.59(5.44, 9.74) 5.74(4.44, 7.05)
Others 11.98(10.73, 13.23) 8.45( 6.93, 9.96) 13.50(11.24, 15.77) 11.31( 9.54, 13.07) 14.21(12.02, 16.40)
Education levels, % <0.001***
Less than high school 12.72(11.10, 14.35) 13.57(11.46, 15.67) 14.40(12.43, 16.38) 13.55(11.18, 15.93) 9.98(7.92, 12.05)
High school or equivalent 22.18(19.77, 24.59) 27.21(24.35, 30.07) 22.83(19.95, 25.70) 22.69(20.17, 25.22) 17.16(14.94, 19.38)
College or above 65.10(59.45, 70.75) 59.22(56.62, 61.83) 62.77(59.30, 66.25) 63.75(60.02, 67.48) 72.85(69.41, 76.29)
PIR, % <0.001***
≤1.30 16.43(14.40, 18.45) 20.21(17.85, 22.57) 17.16(14.76, 19.56) 17.09(14.17, 20.01) 12.22(10.08, 14.36)
1.31–3.49 34.31(31.39, 37.24) 37.16(34.36, 39.96) 36.06(32.86, 39.26) 36.15(32.65, 39.66) 29.03(25.56, 32.49)
≥3.50 49.26(44.02, 54.50) 42.63(39.09, 46.18) 46.78(42.62, 50.94) 46.76(42.63, 50.88) 58.75(54.21, 63.29)
BMI, kg/m2 29.50 ± 0.12 36.05 ± 0.23 29.07 ± 0.15 29.28 ± 0.17 24.74 ± 0.10 <0.001***
Hemoglobin, g/dl 14.19 ± 0.03 14.30 ± 0.05 14.19 ± 0.05 14.24 ± 0.04 14.04 ± 0.04 <0.001***
waist circumference, cm 101.97 ± 0.28 119.27 ± 0.37 101.53 ± 0.33 101.73 ± 0.37 88.58 ± 0.21 <0.001***
HbA1c, % 5.81 ± 0.02 6.58 ± 0.04 5.75 ± 0.03 5.66 ± 0.02 5.39 ± 0.01 <0.001***
TC, mmol/L 5.15 ± 0.02 4.92 ± 0.04 5.15 ± 0.04 5.21 ± 0.03 5.27 ± 0.03 <0.001***
eGFR, mL/min/1.73 m2 85.77 ± 0.35 82.25 ± 0.61 82.84 ± 0.59 86.28 ± 0.48 90.48 ± 0.62 <0.001***
Smoking, % <0.001***
No 54.22(50.31, 58.14) 47.73(44.43, 51.03) 51.86(48.63, 55.08) 52.45(49.07, 55.83) 62.89(60.23, 65.54)
Yes 45.78(41.53, 50.02) 52.27(48.97, 55.57) 48.14(44.92, 51.37) 47.55(44.17, 50.93) 37.11(34.46, 39.77)
Drinking, % <0.001***
No 23.36(20.82, 25.90) 27.25(24.79, 29.71) 25.90(22.94, 28.85) 23.18(20.81, 25.55) 18.37(15.68, 21.06)
Yes 76.64(70.83, 82.45) 72.75(70.29, 75.21) 74.10(71.15, 77.06) 76.82(74.45, 79.19) 81.63(78.94, 84.32)
DM, % <0.001***
No 80.06(73.81, 86.32) 50.32(47.76, 52.89) 81.20(78.66, 83.74) 86.72(85.00, 88.45) 97.35(96.56, 98.13)
Yes 19.94(18.24, 21.63) 49.68(47.11, 52.24) 18.80(16.26, 21.34) 13.28(11.55, 15.00) 2.65( 1.87, 3.44)
OA <0.001***
No 78.79(72.97, 84.60) 69.41(66.30, 72.53) 74.74(72.34, 77.15) 81.74(79.36, 84.13) 86.98(84.79, 89.17)
Yes 21.21(19.10, 23.33) 30.59(27.47, 33.70) 25.26(22.85, 27.66) 18.26(15.87, 20.64) 13.02(10.83, 15.21)

Continuous data were presented as the mean±SEM, category data were presented as the proportion and 95% confidence interval. SEM, Standard Error of the Mean; eGDR, estimated glucose disposal rate; PIR, poverty income ratio; BMI, body mass index; HbA1c, glycosylated hemoglobin; TC, total cholesterol; eGFR, estimated glomerular filtration rate; DM, diabetes mellitus; OA, Osteoarthritis; *** P value < 0.001, ** P value < 0.01, * P value < 0.05.

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Received: 2024-09-17
Revised: 2024-11-28
Accepted: 2024-12-02
Published Online: 2025-02-04

© 2025 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  111. HALP score in Demodex blepharitis: A case–control study
  112. Assessment of SOX2 performance as a marker for circulating cancer stem-like cells (CCSCs) identification in advanced breast cancer patients using CytoTrack system
  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Review Articles
  158. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  159. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  160. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  161. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  162. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  163. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  164. The application of augmented reality in robotic general surgery: A mini-review
  165. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  166. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  167. Plant polyphenols, terpenes, and terpenoids in oral health
  168. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  169. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  170. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  171. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  172. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  173. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  174. Giant borderline ovarian tumours – review of the literature
  175. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  176. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  177. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  178. Supplement strategies for infertility in overweight women: Evidence and legal insights
  179. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  180. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  181. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  182. Strategies for hyperkalemia management in dialysis patients: A systematic review
  183. C-reactive protein-to-albumin ratio in peripheral artery disease
  184. Case Reports
  185. Delayed graft function after renal transplantation
  186. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  187. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  188. Giant right atrial hemangioma presenting with ascites: A case report
  189. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  190. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  191. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  192. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  193. Rapid Communication
  194. Biological properties of valve materials using RGD and EC
  195. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
  199. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  201. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  210. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  211. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  212. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  213. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  214. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  215. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  217. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  219. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  221. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  222. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  224. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
  230. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
https://doi.org/10.1515/med-2024-1120
Keywords for this article
NHANES; eGDR; osteoarthritis; diabetes mellitus; insulin resistance
Creative Commons
BY 4.0

Articles in the same Issue

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  3. Impact of diabetes on long-term survival in elderly liver cancer patients: A retrospective study
  4. Knockdown of CCNB1 alleviates high glucose-triggered trophoblast dysfunction during gestational diabetes via Wnt/β-catenin signaling pathway
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  9. Predictive value of plasma sB7-H3 and YKL-40 in pediatric refractory Mycoplasma pneumoniae pneumonia
  10. Antiangiogenic potential of Elaeagnus umbellata extracts and molecular docking study by targeting VEGFR-2 pathway
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  12. Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis
  13. Adhered macrophages as an additional marker of cardiomyocyte injury in biopsies of patients with dilated cardiomyopathy
  14. Association between statin administration and outcome in patients with sepsis: A retrospective study
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  16. A comparative analysis of the binary and multiclass classified chest X-ray images of pneumonia and COVID-19 with ML and DL models
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  18. Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma
  19. Serum PM20D1 levels are associated with nutritional status and inflammatory factors in gastric cancer patients undergoing early enteral nutrition
  20. Hydromorphone reduced the incidence of emergence agitation after adenotonsillectomy in children with obstructive sleep apnea: A randomized, double-blind study
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  24. Modulatory effects of Lycium barbarum polysaccharide on bone cell dynamics in osteoporosis
  25. Mechanism research on inhibition of gastric cancer in vitro by the extract of Pinellia ternata based on network pharmacology and cellular metabolomics
  26. Examination of the causal role of immune cells in non-alcoholic fatty liver disease by a bidirectional Mendelian randomization study
  27. Clinical analysis of ten cases of HIV infection combined with acute leukemia
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  37. Commiphora gileadensis ameliorate infertility and erectile dysfunction in diabetic male mice
  38. The correlation between epithelial–mesenchymal transition classification and MMP2 expression of circulating tumor cells and prognosis of advanced or metastatic nasopharyngeal carcinoma
  39. Tetrahydropalmatine improves mitochondrial function in vascular smooth muscle cells of atherosclerosis in vitro by inhibiting Ras homolog gene family A/Rho-associated protein kinase-1 signaling pathway
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  41. A comparative analysis of the impact of repeated administration of flavan 3-ol on brown, subcutaneous, and visceral adipose tissue
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  43. Perform tumor-specific survival analysis for Merkel cell carcinoma patients undergoing surgical resection based on the SEER database by constructing a nomogram chart
  44. Unveiling the role of CXCL10 in pancreatic cancer progression: A novel prognostic indicator
  45. High-dose preoperative intraperitoneal erythropoietin and intravenous methylprednisolone in acute traumatic spinal cord injuries following decompression surgeries
  46. RAB39B: A novel biomarker for acute myeloid leukemia identified via multi-omics and functional validation
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  86. Correlations of health literacy with individuals’ understanding and use of medications in Southern Taiwan
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  109. Hemorrhoids and cardiovascular disease: A bidirectional Mendelian randomization study
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  111. HALP score in Demodex blepharitis: A case–control study
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  113. Risk and prognosis for brain metastasis in primary metastatic cervical cancer patients: A population-based study
  114. Comparison of the two intestinal anastomosis methods in pediatric patients
  115. Factors influencing hematological toxicity and adverse effects of perioperative hyperthermic intraperitoneal vs intraperitoneal chemotherapy in gastrointestinal cancer
  116. Endotoxin tolerance inhibits NLRP3 inflammasome activation in macrophages of septic mice by restoring autophagic flux through TRIM26
  117. Lateral transperitoneal laparoscopic adrenalectomy: A single-centre experience of 21 procedures
  118. Petunidin attenuates lipopolysaccharide-induced retinal microglia inflammatory response in diabetic retinopathy by targeting OGT/NF-κB/LCN2 axis
  119. Procalcitonin and C-reactive protein as biomarkers for diagnosing and assessing the severity of acute cholecystitis
  120. Factors determining the number of sessions in successful extracorporeal shock wave lithotripsy patients
  121. Development of a nomogram for predicting cancer-specific survival in patients with renal pelvic cancer following surgery
  122. Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force
  123. A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer
  124. Glutathione attenuates sepsis-associated encephalopathy via dual modulation of NF-κB and PKA/CREB pathways
  125. FAHD1 prevents neuronal ferroptosis by modulating R-loop and the cGAS–STING pathway
  126. Association of placenta weight and morphology with term low birth weight: A case–control study
  127. Investigation of the pathogenic variants induced Sjogren’s syndrome in Turkish population
  128. Nucleotide metabolic abnormalities in post-COVID-19 condition and type 2 diabetes mellitus patients and their association with endocrine dysfunction
  129. TGF-β–Smad2/3 signaling in high-altitude pulmonary hypertension in rats: Role and mechanisms via macrophage M2 polarization
  130. Ultrasound-guided unilateral versus bilateral erector spinae plane block for postoperative analgesia of patients undergoing laparoscopic cholecystectomy
  131. Profiling gut microbiome dynamics in subacute thyroiditis: Implications for pathogenesis, diagnosis, and treatment
  132. Delta neutrophil index, CRP/albumin ratio, procalcitonin, immature granulocytes, and HALP score in acute appendicitis: Best performing biomarker?
  133. Anticancer activity mechanism of novelly synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative on colon cancer cells
  134. H2valdien3 arrests the cell cycle and induces apoptosis of gastric cancer
  135. Prognostic relevance of PRSS2 and its immune correlates in papillary thyroid carcinoma
  136. Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study
  137. Motivational interviewing for alcohol use reduction in Thai patients
  138. Luteolin alleviates oxygen-glucose deprivation/reoxygenation-induced neuron injury by regulating NLRP3/IL-1β signaling
  139. Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative phosphorylation
  140. Relationship between the expression of copper death promoting factor SLC31A1 in papillary thyroid carcinoma and clinicopathological indicators and prognosis
  141. CSF2 polarized neutrophils and invaded renal cancer cells in vitro influence
  142. Proton pump inhibitors-induced thrombocytopenia: A systematic literature analysis of case reports
  143. The current status and influence factors of research ability among community nurses: A sequential qualitative–quantitative study
  144. OKAIN: A comprehensive oncology knowledge base for the interpretation of clinically actionable alterations
  145. The relationship between serum CA50, CA242, and SAA levels and clinical pathological characteristics and prognosis in patients with pancreatic cancer
  146. Identification and external validation of a prognostic signature based on hypoxia–glycolysis-related genes for kidney renal clear cell carcinoma
  147. Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer targeting efficiency and biocompatibility
  148. Relationship of resting echocardiography combined with serum micronutrients to the severity of low-gradient severe aortic stenosis
  149. Effect of vibration on pain during subcutaneous heparin injection: A randomized, single-blind, placebo-controlled trial
  150. The diagnostic performance of machine learning-based FFRCT for coronary artery disease: A meta-analysis
  151. Comparing biofeedback device vs diaphragmatic breathing for bloating relief: A randomized controlled trial
  152. Serum uric acid to albumin ratio and C-reactive protein as predictive biomarkers for chronic total occlusion and coronary collateral circulation quality
  153. Multiple organ scoring systems for predicting in-hospital mortality of sepsis patients in the intensive care unit
  154. Single-cell RNA sequencing data analysis of the inner ear in gentamicin-treated mice via intraperitoneal injection
  155. Suppression of cathepsin B attenuates myocardial injury via limiting cardiomyocyte apoptosis
  156. Influence of sevoflurane combined with propofol anesthesia on the anesthesia effect and adverse reactions in children with acute appendicitis
  157. Review Articles
  158. The effects of enhanced external counter-pulsation on post-acute sequelae of COVID-19: A narrative review
  159. Diabetes-related cognitive impairment: Mechanisms, symptoms, and treatments
  160. Microscopic changes and gross morphology of placenta in women affected by gestational diabetes mellitus in dietary treatment: A systematic review
  161. Review of mechanisms and frontier applications in IL-17A-induced hypertension
  162. Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus
  163. The safety and efficacy of BCG combined with mitomycin C compared with BCG monotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis
  164. The application of augmented reality in robotic general surgery: A mini-review
  165. The effect of Greek mountain tea extract and wheat germ extract on peripheral blood flow and eicosanoid metabolism in mammals
  166. Neurogasobiology of migraine: Carbon monoxide, hydrogen sulfide, and nitric oxide as emerging pathophysiological trinacrium relevant to nociception regulation
  167. Plant polyphenols, terpenes, and terpenoids in oral health
  168. Laboratory medicine between technological innovation, rights safeguarding, and patient safety: A bioethical perspective
  169. End-of-life in cancer patients: Medicolegal implications and ethical challenges in Europe
  170. The maternal factors during pregnancy for intrauterine growth retardation: An umbrella review
  171. Intra-abdominal hypertension/abdominal compartment syndrome of pediatric patients in critical care settings
  172. PI3K/Akt pathway and neuroinflammation in sepsis-associated encephalopathy
  173. Screening of Group B Streptococcus in pregnancy: A systematic review for the laboratory detection
  174. Giant borderline ovarian tumours – review of the literature
  175. Leveraging artificial intelligence for collaborative care planning: Innovations and impacts in shared decision-making – A systematic review
  176. Cholera epidemiology analysis through the experience of the 1973 Naples epidemic
  177. Risk factors of frailty/sarcopenia in community older adults: Meta-analysis
  178. Supplement strategies for infertility in overweight women: Evidence and legal insights
  179. Scurvy, a not obsolete disorder: Clinical report in eight young children and literature review
  180. A meta-analysis of the effects of DBS on cognitive function in patients with advanced PD
  181. Protective role of selenium in sepsis: Mechanisms and potential therapeutic strategies
  182. Strategies for hyperkalemia management in dialysis patients: A systematic review
  183. C-reactive protein-to-albumin ratio in peripheral artery disease
  184. Case Reports
  185. Delayed graft function after renal transplantation
  186. Semaglutide treatment for type 2 diabetes in a patient with chronic myeloid leukemia: A case report and review of the literature
  187. Diverse electrophysiological demyelinating features in a late-onset glycogen storage disease type IIIa case
  188. Giant right atrial hemangioma presenting with ascites: A case report
  189. Laser excision of a large granular cell tumor of the vocal cord with subglottic extension: A case report
  190. EsoFLIP-assisted dilation for dysphagia in systemic sclerosis: Highlighting the role of multimodal esophageal evaluation
  191. Molecular hydrogen-rhodiola as an adjuvant therapy for ischemic stroke in internal carotid artery occlusion: A case report
  192. Coronary artery anomalies: A case of the “malignant” left coronary artery and its surgical management
  193. Rapid Communication
  194. Biological properties of valve materials using RGD and EC
  195. A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor
  196. Letter to the Editor
  197. Role of enhanced external counterpulsation in long COVID
  198. Expression of Concern
  199. Expression of concern “A ceRNA network mediated by LINC00475 in papillary thyroid carcinoma”
  200. Expression of concern “Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway”
  201. Expression of concern “circ_0020123 promotes cell proliferation and migration in lung adenocarcinoma via PDZD8”
  202. Corrigendum
  203. Corrigendum to “Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism”
  204. Corrigendum to “Comparing the therapeutic efficacy of endoscopic minimally invasive surgery and traditional surgery for early-stage breast cancer: A meta-analysis”
  205. Corrigendum to “The progress of autoimmune hepatitis research and future challenges”
  206. Retraction
  207. Retraction of “miR-654-5p promotes gastric cancer progression via the GPRIN1/NF-κB pathway”
  208. Retraction of: “LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through downregulating SP-A by sponging to miR-424”
  209. Retraction of: “SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways”
  210. Special Issue Advancements in oncology: bridging clinical and experimental research - Part II
  211. Unveiling novel biomarkers for platinum chemoresistance in ovarian cancer
  212. Lathyrol affects the expression of AR and PSA and inhibits the malignant behavior of RCC cells
  213. The era of increasing cancer survivorship: Trends in fertility preservation, medico-legal implications, and ethical challenges
  214. Bone scintigraphy and positron emission tomography in the early diagnosis of MRONJ
  215. Meta-analysis of clinical efficacy and safety of immunotherapy combined with chemotherapy in non-small cell lung cancer
  216. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part IV
  217. Exploration of mRNA-modifying METTL3 oncogene as momentous prognostic biomarker responsible for colorectal cancer development
  218. Special Issue The evolving saga of RNAs from bench to bedside - Part III
  219. Interaction and verification of ferroptosis-related RNAs Rela and Stat3 in promoting sepsis-associated acute kidney injury
  220. The mRNA MOXD1: Link to oxidative stress and prognostic significance in gastric cancer
  221. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part II
  222. Dynamic changes in lactate-related genes in microglia and their role in immune cell interactions after ischemic stroke
  223. A prognostic model correlated with fatty acid metabolism in Ewing’s sarcoma based on bioinformatics analysis
  224. Red cell distribution width predicts early kidney injury: A NHANES cross-sectional study
  225. Special Issue Diabetes mellitus: pathophysiology, complications & treatment
  226. Nutritional risk assessment and nutritional support in children with congenital diabetes during surgery
  227. Correlation of the differential expressions of RANK, RANKL, and OPG with obesity in the elderly population in Xinjiang
  228. A discussion on the application of fluorescence micro-optical sectioning tomography in the research of cognitive dysfunction in diabetes
  229. A review of brain research on T2DM-related cognitive dysfunction
  230. Metformin and estrogen modulation in LABC with T2DM: A 36-month randomized trial
  231. Special Issue Innovative Biomarker Discovery and Precision Medicine in Cancer Diagnostics
  232. CircASH1L-mediated tumor progression in triple-negative breast cancer: PI3K/AKT pathway mechanisms
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