Association of Visceral Obesity Indices With Incident Diabetic Retinopathy in Patients With Diabetes: Prospective Cohort Study.

Visceral adipose tissue plays an active role in the pathogenesis of type 2 diabetes and vascular dysfunction. The lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese VAI (CVAI) have been proposed as simple and validated surrogate indices for measuring visceral adipose tissue. However, the evidence from prospective studies on the associations between these novel indices of visceral obesity and diabetic retinopathy (DR) remains scant. This study aimed to investigate the longitudinal associations of LAP, VAI, and CVAI with incident DR in Chinese patients with diabetes. This was a prospective cohort study conducted in Guangzhou in southern China. We collected baseline data between November 2017 and July 2020, while on-site follow-up visits were conducted annually until January 2022. The study participants consisted of 1403 patients with a clinical diagnosis of diabetes, referred from primary care, who were free of DR at baseline. The LAP, VAI, and CVAI levels were calculated by sex-specific equations based on anthropometric and biochemical parameters. DR was assessed using 7-field color stereoscopic fundus photographs and graded according to the modified Airlie House Classification scheme. Time-dependent Cox proportional hazard models were constructed to estimate the hazard ratios with 95% CIs. Restricted cubic spline curves were fitted to examine the dose-response relationship between the 3 indices of visceral obesity and new-onset DR. Subgroup analyses were performed to investigate the potential effect modifiers. The mean age of study participants was 64.5 (SD 7.6) years, and over half (816/1403, 58.2%) were female. During a median follow-up of 2.13 years, 406 DR events were observed. A 1-SD increment in LAP, VAI, or CVAI was consistently associated with increased risk for new-onset DR, with a multivariable‑adjusted hazard ratio of 1.24 (95% CI 1.09-1.41; P=.001), 1.22 (95% CI 1.09-1.36; P<.001), and 1.48 (95% CI 1.19-1.85; P=.001), respectively. Similar patterns were observed across tertiles in LAP (P for trend=.001), VAI (P for trend<.001), and CVAI (P for trend=.009). Patients in the highest tertile of LAP, VAI, and CVAI had an 84%, 86%, and 82% higher hazard of DR, respectively, compared to those in the lowest tertile. A nonlinear dose-response relationship with incident DR was noted for LAP and VAI (both P for nonlinearity<.05), but not for CVAI (P for nonlinearity=.51). We did not detect the presence of effect modification by age, sex, duration of diabetes, BMI, or comorbidity (all P for interaction>.10). Visceral obesity, as measured by LAP, VAI, or CVAI, is independently associated with increased risk for new-onset DR in Chinese patients with diabetes. Our findings may suggest the necessity of incorporating regular monitoring of visceral obesity indices into routine clinical practice to enhance population-based prevention for DR.

Chen J ，Li YT ，Niu Z ，He Z ，Xie YJ ，Hernandez J ，Huang W ，Wang HHX ，Guangzhou Diabetic Eye Study Group ... -  《JMIR Public Health and Surveillance》

Erratum: Eyestalk Ablation to Increase Ovarian Maturation in Mud Crabs.

《Jove-Journal of Visualized Experiments》

The interaction between triglyceride-glucose index and visceral adiposity in cardiovascular disease risk: findings from a nationwide Chinese cohort.

Globally, cardiovascular disease (CVD) constitutes the primary cause of death, with insulin resistance (IR), measured by the triglyceride-glucose (TyG) index, and visceral obesity, reflected by the Chinese Visceral Adiposity Index (CVAI), as key contributors. However, the relationship between the TyG index and CVAI regarding CVD risk remains insufficiently understood. This research investigates the interactive impact of the TyG index and CVAI on the risk of cardiovascular disease. We analyzed data from 8,358 participants from the China Health and Retirement Longitudinal Study (CHARLS) over a 9-year follow-up period. Participants were classified into four groups based on median TyG index (8.59) and CVAI values (101.26), and baseline characteristics were summarized. Missing data were addressed using multiple imputation by chained equations (MICE). Cox proportional hazards models assessed associations between TyG index, CVAI, CVD, coronary heart disease (CHD), and stroke risks, with Kaplan-Meier analysis used for cumulative hazard. Interaction effects were evaluated using both multiplicative and additive measures. Subgroup analyses by age, gender, and clinical conditions were conducted to explore interaction effects across different populations. Sensitivity analyses re-tested models, excluding the covariates BMI and diabetes, using tertiles for classification, and re-evaluating imputed data. Over the 9-year follow-up, 1,240 participants (14.8%) developed CVD, including 896 cases of CHD and 475 strokes. Kaplan-Meier curves indicated that participants with low TyG index but high CVAI had the highest cumulative hazard of CVD. Cox regression showed that this group had the highest CVD risk (HR = 1.87, 95% CI: 1.57-2.24), followed by those with both high TyG index and high CVAI (HR = 1.75, 95% CI: 1.49-2.06). Interaction analysis revealed a negative interaction effect between high TyG and high CVAI on CVD and CHD risks, with no significant effect on stroke. Subgroup and sensitivity analyses further confirmed these findings, showing consistent results across demographic groups and under various analytical conditions. This study suggests that the interaction between IR (TyG index) and visceral fat accumulation (CVAI) plays a complex role in CVD risk, with a potential antagonistic effect observed between high TyG and high CVAI on CVD events. These findings highlight the importance of considering both IR and visceral adiposity in CVD risk assessments to improve the identification of high-risk individuals.

Yang Y ，Li S ，Ren Q ，Qiu Y ，Pan M ，Liu G ，Zheng R ，An Z ，Li S ... -  《Cardiovascular Diabetology》

Impact of Chinese visceral adiposity index on all-cause mortality risk in community-dwelling older adults: a prospective cohort study.

Whether excess visceral fat tissue increases the risk of death in older individuals remains controversial. To investigate the association between the Chinese Visceral Adiposity Index (CVAI) and all-cause mortality risk in older Chinese individuals. This cohort study utilized data of individuals aged ≥ 65 years in 2014 to 2018 wave from the Chinese Longitudinal Healthy Longevity Survey database. Older individuals in the 2014 wave were included and followed up in 2018. CVAI was calculated based on age, body size, and blood lipid parameters, with higher values indicating increased visceral fat. Survival status was determined from official death certificates, local primary healthcare providers, or the family members of participants. Kaplan-Meier survival curve and log-rank test were employed to analyze cumulative mortality risk through CVAI tertiles (tertile 1: CVAI index < 97.34; tertile 2: 97.43 ≤ CVAI index < 132.21; and tertile 3: CVAI index ≥ 132.21). A Cox proportional hazards regression model was used to assess the relationship between the CVAI groups and all-cause mortality risk. Additionally, a sensitivity analysis was performed by excluding participants who died within the first year of follow-up. A subgroup analysis was performed based on age and sex, and a restricted cubic spline plot was created to analyze the dose-response relationship between CVAI and mortality risk. A total of 1414 individuals were included, and the mean age of the participants was 84.6 (standard deviation: 10.9) years, of which 46.4% were women and 32.8% were died during a median follow-up time of 36.4 months. In the multivariable adjusted Cox regression model, we observed a significantly lower risk of mortality in the CVAI tertile 2 and 3 groups than in the tertile 1 group. The hazard ratios (HR) of the tertile 2 and 3 groups were 0.68 (95% CI, approximately 0.52-0.89) and 0.63 (95% CI, approximately 0.48-0.82), respectively. Subgroup analysis revealed that the protective effect of higher CVAI levels on mortality was more pronounced in participants aged 65-79 years and in women. Our study established a linear relationship between CVAI and mortality risk among community-dwelling older adults, with higher CVAI levels associated with a lower risk of all-cause mortality. These findings highlight the potential importance of visceral adiposity in predicting mortality risk in community-dwelling older adults.

Zhang Y ，Shi M ，Dong Z ，Li T ，Gong Y ，Ge W ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》