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Aim: To compare the efficacy and safety of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs)., Methods: In Soli-D, a 24-week, multicentre, open-label, study, insulin-naïve adults were randomized 1:1 to once-daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium-glucose co-transporter-2 inhibitors. The primary endpoint was non-inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed., Results: At week 24, iGlarLixi showed non-inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: -0.20 [95% confidence interval {CI}: -0.33, -0.07]; P < .001 for non-inferiority; [97.5% CI: -0.35, -0.05]; P = .003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of -1.49 kg in favour of iGlarLixi (97.5% CI: -2.32, -0.66; P < .001). Event rates (per person-year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported., Conclusions: In Chinese people with T2D suboptimally controlled with OADs, once-daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Chronic kidney disease (CKD) is a significant long-term complication of diabetes and is a primary contributor to end-stage kidney disease., Objective: This study aimed to report comprehensive nationwide data on the prevalence, screening, and awareness rates of CKD in Chinese patients with type 2 diabetes, along with associated risk factors., Methods: Baseline data analysis of the ongoing prospective, observational IMPROVE study was conducted. The study cohort comprised patients who had been diagnosed with type 2 diabetes more than 12 months prior, received at least 1 hypoglycemic medication, and were aged ≥18 years. The participants completed questionnaires and underwent laboratory assessments, including blood and urine samples. The data encompassed patient demographics, medical history, concurrent medications, and comorbidities. Comprehensive evaluations involved physical examinations, urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA 1c ), fasting blood glucose, 2-hour postprandial blood glucose, fasting blood lipid profile, and urinalysis. Descriptive statistics were applied for data interpretation, and logistic regression analyses were used to identify the CKD-associated risk factors in patients with type 2 diabetes., Results: A national study from December 2021 to September 2022 enlisted 9672 participants with type 2 diabetes from 45 hospitals that had endocrinology departments. The enrollees were from diverse regions in China, as follows: central (n=1221), east (n=3269), south (n=1474), north (n=2219), and west (n=1489). The prevalence, screening, and awareness rates of CKD among patients with type 2 diabetes were 31% (2997/9672), 27% (810/2997), and 54.8% (5295/9672), respectively. Multivariate binary regression analysis revealed that the CKD risk factors were screening, awareness, smoking, age, diabetes duration, concurrent antihypertensive and microcirculation medications, diabetic complications (foot, retinopathy, and neuropathy), hypertension, elevated low-density lipoprotein (LDL) cholesterol, and suboptimal glycemic control. Subgroup analysis highlighted an increased CKD prevalence among older individuals, those with prolonged diabetes durations, and residents of fourth-tier cities. Residents of urban areas that had robust educational and economic development exhibited relatively high awareness and screening rates. Notably, 24.2% (1717/7107) of patients with an eGFR ≥90 mL/min/1.73 m 2 had proteinuria, whereas 3.4% (234/6909) who had a UACR <30 mg/g presented with an eGFR <60 mL/min/1.73 m 2 . Compared with patients who were cognizant of CKD, those who were unaware of CKD had increased rates of HbA 1c ≥7%, total cholesterol >5.18 μmol/L, LDL cholesterol >3.37 μmol/L, BMI ≥30 kg/m 2 , and hypertension., Conclusions: In a Chinese population of adults with type 2 diabetes, the CKD prevalence was notable, at 31%, coupled with low screening and awareness rates. Multiple risk factors for CKD have been identified., Trial Registration: ClinicalTrials.gov NCT05047471; https://clinicaltrials.gov/study/NCT05047471., (©Lixin Shi, Yaoming Xue, Xuefeng Yu, Yangang Wang, Tianpei Hong, Xiaoying Li, Jianhua Ma, Dalong Zhu, Yiming Mu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 30.08.2024.)

Background: Cardiovascular-kidney-metabolic (CKM) health is affected by social determinants of health, especially education. CKM syndrome has not been evaluated in Chinese population, and the association of education with CKM syndrome in different sexes and its intertwined relation with lifestyles have not been explored., Objective: We aimed to explore the association between educational attainment and the prevalence of CKM syndrome stages in middle-aged and older Chinese men and women as well as the potential role of health behavior based on Life's Essential 8 construct., Methods: This study used data from the nationwide, community-based REACTION (Risk Evaluation of Cancers in Chinese diabetic individuals: a longitudinal study). A total of 132,085 participants with complete information to determine CKM syndrome stage and education level were included. Educational attainment was assessed by the self-reported highest educational level achieved by the participants and recategorized as low (elementary school or no formal education) or high (middle school, high school, technical school/college, or above). CKM syndrome was ascertained and classified into 5 stages according to the American Heart Association presidential advisory released in 2023., Results: Among 132,085 participants (mean age 56.95, SD 9.19 years; n=86,675, 65.62% women) included, most had moderate-risk CKM syndrome (stages 1 and 2), and a lower proportion were at higher risk of CKM (stages 3 and 4). Along the CKM continuum, low education was associated with 34% increased odds of moderate-risk CKM syndrome for women (odds ratio 1.36, 95% CI 1.23-1.49) with a significant sex disparity, but was positively correlated with high-risk CKM for both sexes. The association between low education and high-risk CKM was more evident in women with poor health behavior but not in men, which was also interactive with and partly mediated by behavior., Conclusions: Low education was associated with adverse CKM health for both sexes but was especially detrimental to women. Such sex-specific educational disparity was closely correlated with health behavior but could not be completely attenuated by behavior modification. These findings highlight the disadvantage faced by women in CKM health ascribed to low education, underscoring the need for public health support to address this inequality., (© Yi Ding, Xianglin Wu, Qiuyu Cao, Jiaojiao Huang, Xiaoli Xu, Youjin Jiang, Yanan Huo, Qin Wan, Yingfen Qin, Ruying Hu, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Guijun Qin, Xulei Tang, Gang Chen, Min Xu, Tiange Wang, Zhiyun Zhao, Zhengnan Gao, Guixia Wang, Feixia Shen, Zuojie Luo, Li Chen, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Tao Yang, Huacong Deng, Lulu Chen, Tianshu Zeng, Jiajun Zhao, Yiming Mu, Shengli Wu, Yuhong Chen, Jieli Lu, Weiqing Wang, Guang Ning, Yu Xu, Yufang Bi, Mian Li. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

Background: Nonalcoholic fatty liver disease (NAFLD) has become a major global health burden, which increases the risk of extra-hepatic complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, NAFLD remains underappreciated and underdiagnosed. Our study aimed to explore the prevalence of NAFLD and the association between NAFLD and CVD events among adults aged 40 and older in Northern China., Methods: This study was conducted in the Shijingshan district of Beijing, China from November 2011 to August 2012. A total of 18891 subjects were recruited in the study. The information including demographical information, lifestyle, previous history of diabetes, hypertension, dyslipidemia, CVD, and liver disease were gathered. Data on physical examination, blood lipid profile, fasting blood glucose, and 2-hour blood glucose were recorded. Determination of MetS was according to T2DM guideline of Chinese Diabetes Society (2020 edition). The association between CVD and NAFLD was evaluated by multivariate logistic regression., Results: The prevalence of NAFLD was 15.2%. After adjustment for age, smoking status, alcohol intake, WC, hypertension, dyslipidemia and hyperglycemia, the odds ratios (ORs) of CVD in men were 1.622 (95%CI: 1.345-1.957) and 1.990 (95%CI: 1.709-2.316) in women with NAFLD, compared with the subjects without NAFLD., Conclusions: NAFLD is independently associated with increased risk of CVD development., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Zhang et al.)

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 μm (PM 2 .5 ) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To identify perceptions, attitudes, behaviours and barriers to effective obesity care among people living with obesity (PLwO) and healthcare professionals (HCPs) across mainland China., Materials and Methods: ACTION-China (ClinicalTrials.gov: NCT05428501) was a cross-sectional, observational, descriptive, online survey-based study of 7000 PLwO and 1000 HCPs (conducted between August and November 2022)., Results: The majority of PLwO (76.8% [5374/7000]) and HCPs (94.6% [946/1000]) agreed that obesity is a chronic disease. Only 40.8% of PLwO (2853/7000) had discussed their weight or talked about losing weight with an HCP in the past 5 years. The most frequent reason given by PLwO for not discussing weight management with an HCP was believing it was their responsibility to manage their weight (34.7% [2430/7000]), whereas the most frequent reason HCPs gave for not discussing obesity with their patients with obesity was having more important health issues to discuss (72.1% [721/1000]). A smaller proportion of PLwO (19.1%) than HCPs (53.6%) felt that weight management discussions with an HCP would be very or extremely helpful for the patient, and 30.7% of PLwO experienced negative feelings after their most recent discussion. Overall, 34.8% (2438/7000) of PLwO had been diagnosed with obesity by an HCP, while 30.0% (2101/7000) of PLwO did not recognize that they had obesity., Conclusions: This large, national survey conducted among PLwO and HCPs highlights key barriers to effective obesity care in China, including underestimation of weight status by PLwO and the need for increased communication between HCPs and PLwO regarding weight management., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Previous studies showed that MSCs could mitigate damage in the pancreas during acute pancreatitis (AP). However, acute mortality associated with AP was more often a result of persistent failure of remote organs, rather than local damage, especially in severe acute pancreatitis (SAP), and the effect of MSCs may vary depending on their origin., Methods: An SAP model was induced in 8-week C57BL/6 J male mice by retrograde injection of 5 % sodium taurocholate solution through the bile duct. SAP mice were divided into the SAP group, UC-MSCs group, and BMSCs group, which were treated with saline, 1 × 10 6 UC-MSCs, and 1 × 10 6 BMSCs respectively, through the tail vein. After treatment, serum markers, inflammation, and morphology were assessed in the pancreas, kidneys, lungs, and hearts., Results: MSCs infusion ameliorated the systemic inflammatory response in SAP mice. In the MSCs-treated SAP mice, local tissue injury and inflammation response in the pancreas were alleviated. But more importantly, the renal and lung injury were all significantly and drastically mitigated, and the levels of pro-inflammatory factors such as IL-6, MCP-1, IL-1β, and TNF-α in the kidney, lung and heart were sharply decreased. In terms of origin, UC-MSCs exhibited superior efficacy compared with BMSCs. Furthermore, compared to the normal control mice, UC-MSCs showed an earlier appearance, higher distribution densities, and longer duration of presence in the injured tissue., Conclusions: This study provides compelling evidence supporting the therapeutic potential of MSCs in SAP treatment and particularly their ability to mitigate multi-organ failure. Our results also suggested that UC-MSCs may offer greater advantages over BMSCs in SAP therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Not many large-sample investigations are available that compare the potency of the relationship of remnant cholesterol (RC) and other lipid parameters with diabetes and prediabetes. The goals of our study are to discover the relationship between RC and prediabetes, diabetes, and insulin resistance (IR) and to investigate RC, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C, which are the lipid parameters that are most positively related to diabetes, prediabetes, and IR., Methods: This research enrolled 36 684 subjects from China's eight provinces. We employed multiple logistic regression analysis for testing the relationship between lipid parameters and diabetes, prediabetes, and IR., Results: After adjusting for potential confounders, and comparing the results with other lipid parameters, the positive relationship between RC and diabetes (odds ratio [OR] 1.417, 95% confidence interval [CI]: 1.345-1.492), prediabetes (OR 1.555, 95% CI: 1.438-1.628), and IR (OR 1.488, 95% CI: 1.404-1.577) was highest. RC was still related to diabetes, prediabetes, and IR even when TG <2.3 mmol/L (diabetes: OR 1.256, 95% CI: 1.135-1.390; prediabetes: OR 1.503, 95% CI: 1.342-1.684; and IR: OR 1.278, 95% CI: 1.140-1.433), LDL-C <2.6 mmol/L (diabetes: OR 1.306, 95% CI: 1.203-1.418; prediabetes: OR 1.597, 95% CI: 1.418-1.798; and IR: OR 1.552, 95% CI: 1.416-1.701), or HDL-C ≥1 mmol/L (diabetes: OR 1.456, 95% CI: 1.366-1.550; prediabetes: OR 1.553, 95% CI: 1.421-1.697; and IR: OR 1.490, 95% CI: 1.389-1.598)., Conclusion: RC is more positively related to diabetes, prediabetes, and IR than conventional lipids and lipid ratios in the general population, the relationships between RC and diabetes, prediabetes, and IR are stable, even if HDL-C, LDL-C, or TG are at appropriate levels., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Novel diabetes phenotypes were proposed by the Europeans through cluster analysis, but Chinese community diabetes populations might exhibit different characteristics. This study aims to explore the clinical characteristics of novel diabetes subgroups under data-driven analysis in Chinese community diabetes populations., Methods: We used K-means cluster analysis in 6369 newly diagnosed diabetic patients from eight centers of the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. The cluster analysis was performed based on age, body mass index, glycosylated hemoglobin, homeostatic modeled insulin resistance index, and homeostatic modeled pancreatic β-cell functionality index. The clinical features were evaluated with the analysis of variance (ANOVA) and chi-square test. Logistic regression analysis was done to compare chronic kidney disease and cardiovascular disease risks between subgroups., Results: Overall, 2063 (32.39%), 658 (10.33%), 1769 (27.78%), and 1879 (29.50%) populations were assigned to severe obesity-related and insulin-resistant diabetes (SOIRD), severe insulin-deficient diabetes (SIDD), mild age-associated diabetes mellitus (MARD), and mild insulin-deficient diabetes (MIDD) subgroups, respectively. Individuals in the MIDD subgroup had a low risk burden equivalent to prediabetes, but with reduced insulin secretion. Individuals in the SOIRD subgroup were obese, had insulin resistance, and a high prevalence of fatty liver, tumors, family history of diabetes, and tumors. Individuals in the SIDD subgroup had severe insulin deficiency, the poorest glycemic control, and the highest prevalence of dyslipidemia and diabetic nephropathy. Individuals in MARD subgroup were the oldest, had moderate metabolic dysregulation and the highest risk of cardiovascular disease., Conclusion: The data-driven approach to differentiating the status of new-onset diabetes in the Chinese community was feasible. Patients in different clusters presented different characteristics and risks of complications., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking., Objectives: Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults., Methods: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes., Results: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset., Conclusions: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Aims: Very few cohort studies are available about the relation between remnant cholesterol (RC) and diabetes. Based on a prospective cohort survey, this research aimed at investigating if high RC was related to a future diabetes risk in the Chinese population, as well as to compare the association between RC, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), TG/HDL-C, LDL-C/HDL-C, TC/HDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C), and future diabetes risk., Materials and Methods: 6,700 baseline normoglycemic participants of the REACTION study's Beijing center were recruited in 2011-2012 and followed up in 2015. Multivariate Cox regression analyses were performed to explore the relationship of RC, HDL-C, LDL-C, TC, TG, LDL-C/HDL-C, TG/HDL-C, TC/HDL-C, and non-HDL-C and a future diabetes risk., Results: After potential confounders were adjusted for, only RC (HR 1.134, 95% CI 1.016-1.267, P = 0.025) was positively related to a future diabetes risk, and only HDL-C (HR 0.728, 95% CI 0.578-0.918, P = 0.007) was negatively related to a future diabetes risk. The rest of the lipid parameters were not related to a future risk of diabetes. Sensitivity and stratification analyses revealed that the relation between RC and future diabetes risk was stable. RC and future diabetes risk were still positively correlated even when the HDL-C was ≥1.04 mmol/L (HR 1.167, 95% CI 1.050-1.297, P = 0.004)., Conclusions: It was RC, but not other lipid parameters, that was independently and positively related to a future risk of diabetes among the Chinese general population. Moreover, the relationship between RC and diabetes risk was stable, even with appropriate levels of HDL-C., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The role of mesenchymal-stem-cell-derived exosomes (MSCs-Exo) in the regulation of macrophage polarization has been recognized in several diseases. There is emerging evidence that MSCs-Exo partially prevent the progression of diabetic nephropathy (DN). This study aimed to investigate whether exosomes secreted by MSCs pre-treated with a diabetic environment (Exo-pre) have a more pronounced protective effect against DN by regulating the balance of macrophages. Exo-pre and Exo-Con were isolated from the culture medium of UC-MSCs pre-treated with a diabetic mimic environment and natural UC-MSCs, respectively. Exo-pre and Exo-Con were injected into the tail veins of db/db mice three times a week for 6 weeks. Serum creatinine and serum urea nitrogen levels, the urinary protein/creatinine ratio, and histological staining were used to determine renal function and morphology. Macrophage phenotypes were analyzed by immunofluorescence, western blotting, and quantitative reverse transcription polymerase chain reaction. In vitro, lipopolysaccharide-induced M1 macrophages were incubated separately with Exo-Con and Exo-pre. We performed microRNA (miRNA) sequencing to identify candidate miRNAs and predict their target genes. An miRNA inhibitor was used to confirm the role of miRNAs in macrophage modulation. Exo-pre were more potent than Exo-Con at alleviating DN. Exo-pre administration significantly reduced the number of M1 macrophages and increased the number of M2 macrophages in the kidney compared to Exo-Con administration. Parallel outcomes were observed in the co-culture experiments. Moreover, miR-486-5p was distinctly expressed in Exo-Con and Exo-pre groups, and it played an important role in macrophage polarization by targeting PIK3R1 through the PI3K/Akt pathway. Reducing miR-486-5p levels in Exo-pre abolished macrophage polarization modulation. Exo-pre administration exhibited a superior effect on DN by remodeling the macrophage balance by shuttling miR-486-5p, which targets PIK3R1., (© 2024 Federation of American Societies for Experimental Biology.)

Context: Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies., Objective: To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk., Methods: We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants., Results: In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003)., Conclusions: These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background/aims: : Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China., Methods: : A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators., Results: : Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders., Conclusions: : In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Introduction: Due to the high cost and complexity, the oral glucose tolerance test is not adopted as the screening method for identifying diabetes patients, which leads to the misdiagnosis of patients with isolated post-challenge hyperglycemia (IPH), that is., patients with normal fasting plasma glucose (<7.0 mmoL/L) and abnormal 2-h postprandial blood glucose (≥11.1 mmoL/L). We aimed to develop a model to differentiate individuals with IPH from the normal population., Methods: Data from 54301 eligible participants were obtained from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study in China. Data from 37740 participants were used to develop the diagnostic system. External validation was performed among 16561 participants. Three machine learning algorithms were used to create the predictive models, which were further evaluated by various classification algorithms to establish the best predictive model., Results: Ten features were selected to develop an IPH diagnosis system (IPHDS) based on an artificial neural network. In external validation, the AUC of the IPHDS was 0.823 (95% CI 0.811-0.836), which was significantly higher than the AUC of the Taiwan model [0.799 (0.786-0.813)] and that of the Chinese Diabetes Risk Score model [0.648 (0.635-0.662)]. The IPHDS model had a sensitivity of 75.6% and a specificity of 74.6%. This model outperformed the Taiwan and CDRS models in subgroup analyses. An online site with instant predictions was deployed at https://app-iphds-e1fc405c8a69.herokuapp.com/., Conclusions: The proposed IPHDS could be a convenient and user-friendly screening tool for diabetes during health examinations in a large general population., (© 2024 John Wiley & Sons Ltd.)

Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism. Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism. Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1β (DN group was 34%, M2 group was 13%, p  < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p  < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group ( p  < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells. Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment.

Background: The triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women., Methods: This cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer., Results: Multivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19-2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13-17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09-1.68), 1.27 (1.05-1.54), 1.26 (1.05-1.52), and 1.32 (1.08-1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44-3.87)., Conclusion: The TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewers YM and PB declared a shared parent affiliation with the authors JL, XW, SW, LL, XJ, CH, HQ, HL, RZ, ML, YX, MX, TW, ZZ, JZ, MD, GN, WW, YB, YC, YZ, and QS and the reviewer JY declared a shared parent affiliation with the author LY to the handling editor at the time of review., (Copyright © 2024 Wu, Wang, Lin, Jia, Hu, Qi, Lin, Zheng, Li, Xu, Xu, Chen, Zeng, Hu, Ye, Shi, Su, Yu, Yan, Wang, Zhao, Zheng, Qin, Wan, Chen, Dai, Tang, Gao, Shen, Gu, Luo, Qin, Chen, Hou, Huo, Li, Wang, Zhang, Liu, Wang, Wu, Yang, Deng, Zhao, Mu, Ning, Wang, Bi, Chen and Lu.)

Aims: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk., Materials and Methods: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death., Results: During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity., Conclusions: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: Studies on the relationship between remnant cholesterol (RC) and arterial stiffness (AS) are limited. This study aims to investigate the relationship between RC and AS and to explore RC, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), non-HDL-C, LDL-C/HDL-C, TG/HDL-C, lipoprotein combine index (LCI), and TC/HDL-C, which are lipid parameters most strongly associated with AS., Methods: A total of 4653 participants from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals) study were recruited. AS was defined as a brachial-ankle pulse wave velocity of ≥ 1400 cm/s. Multiple logistic regression analyses were performed to detect its association with lipid parameters (RC, TG, TC, HDL-C, LDL-C, non-HDL-C, LDL-C/HDL-C, TG/HDL-C, LCI, and TC/HDL-C)., Results: Logistic regression analysis showed that compared with other traditional or non-traditional lipid parameters, the association between RC and AS was the strongest (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.30-1.95, P＜0.001). In the stratified analysis, RC was significantly associated with AS in both sexes and at any age, as well as blood glucose, blood pressure, and body mass index levels. Besides, RC and AS were still significantly associated when TG＜1.7 mmol/L (OR:1.58, 95% CI: 1.02-2.45, P=0.04), LDL-C ＜3.4 mmol/L (OR:1.32, 95% CI: 1.01-1.73, P=0.041), HDL-C ≥ 1.0 mmol/L (OR:1.67, 95% CI: 1.34-2.08, P＜0.001), or non-HDL-C＜4.1 mmol/L (OR: 1.42, 95% CI: 1.10-1.82, P=0.007) are controlled within the appropriate range., Conclusion: In conclusion, compared with traditional lipids and lipid ratios, RC is more strongly associated with AS. The association between RC and AS remains significant even when TG, LDL-C, HDL-C, or non-HDL-C levels are controlled within the appropriate range.

Objective: Several studies have demonstrated a significant association between the presence of the ear lobe crease (ELC) and cardiovascular disease. Advanced glycation end-products (AGEs) can affect the structures and functions of proteins and contribute to the development of diabetic complications. However, few studies have reported the relationship between AGEs and ELC. The purpose of this study was to investigate the correlation of skin autofluorescence (SAF)-AGE age (SAF-AGEs × age/100) with ELC., Methods: This cross-sectional study enrolled 6500 eligible participants from two communities in Beijing. Skin autofluorescence (SAF) was used to measure skin AGEs (SAF-AGEs). SAF-AGE age was defined as AGEs × age/100. Binary logistic regression analysis and linear regression analysis nested in logistic models were applied to test outcomes., Results: The overall prevalence of ELC with an average age of 62.7 years participants was 57.1% (n = 3714). Age, fasting blood glucose, systolic blood pressure, and lipoprotein cholesterol were all greater in participants with ELC. ELC-positive participants had higher prevalence of coronary heart disease. Logistic analysis showed a significantly positive relationship between quartiles of SAF-AGE age and ELC (odds ratio [OR] 1.526, 95% CI 1.324-1.759; OR 2.072, CI 1.791-2.396; and OR 2.983, CI 2.551-3.489) for the multivariate-adjusted models, respectively. Stratified research revealed that those with a history of diabetes, hypertension, or coronary heart disease experienced the connection between SAF-AGE age and ELC., Conclusion: ELC is associated with coronary heart disease, and the SAF-AGE has a potential role in ELC development in elder people., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease (CKD) risk, but limited research evaluated the association of reallocating excessive sleep to other behavior with CKD. We included 104 538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study, with self-reported time of daily-life behavior. Using isotemporal substitution models, we found that substituting 1 h of sleeping with sitting, walking, or moderate-to-vigorous physical activity was associated with a lower CKD prevalence. Leisure-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working population. In stratified analysis, a lower CKD prevalence related to substitution toward physical activity was found in long sleepers. More pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes, and they benefited from other behavior substitutions toward a more active way. The U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys, in which the pernicious link with oversleep could be reversed by time reallocation to physical activity. The divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition., (© 2023. Higher Education Press.)

Background: Data on the benefits of the once weekly GLP-1 receptor agonist semaglutide 2·4 mg for weight management in people from east Asia are insufficient. The objective of this study was to determine the efficacy and safety of once weekly semaglutide 2·4 mg versus placebo for weight management in a predominantly east Asian adult population., Methods: This randomised phase 3a, double-blind multicentre controlled trial (STEP 7) recruited participants from 23 hospitals and trial centres in China, Hong Kong, Brazil, and South Korea. Adults with overweight or obesity, with or without type 2 diabetes, were randomly assigned (2:1) to receive a subcutaneous injection of either semaglutide 2·4 mg or placebo once a week for 44 weeks, plus a diet and physical activity intervention. Randomisation was done in blocks of six with an interactive web response system and was stratified by diagnosis of type 2 diabetes. Participants, investigators, and the trial sponsor were masked to treatment allocation until after database lock. Primary endpoints were percentage change in mean bodyweight and proportion of participants having reached a weight reduction of at least 5% of bodyweight from baseline to week 44. Safety was assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04251156, and is now complete., Findings: From Dec 8, 2020, to Aug 23, 2022, 448 participants were screened, of whom 375 were randomly assigned to either the semaglutide 2·4 mg group (n=249) or the placebo group (n=126). Estimated mean percentage change in bodyweight from baseline to week 44 was -12·1% (SE 0·5) with semaglutide 2·4 mg versus -3·6% (0·7) with placebo (estimated treatment difference -8·5 percentage points [95% CI -10·2 to -6·8]; p<0·0001). At week 44, the proportion of participants who lost 5% or more of their bodyweight was higher in the semaglutide 2·4 mg group than in the placebo group (203/238 [85%] vs 36/116 [31%]); odds ratio 13·1 (95% CI 7·4-23·1; p<0·0001). Adverse events were reported by 231 (93%) of 249 participants in the semaglutide 2·4 mg group and 108 (86%) of 126 participants in the placebo group, the most common of which were gastrointestinal disorders (168/249, 67% vs 45/126, 36%)., Interpretation: The results of this study support the use of semaglutide 2·4 mg for weight management in people of east Asian ethnicity with overweight or obesity and with or without type 2 diabetes., Funding: Novo Nordisk., Translations: For the Mandarin, Portuguese and South Korean translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests YM reports having received honoraria and personal fees from Eli Lilly Diabetes, Novo Nordisk, and Sanofi outside the submitted work. XB is a full-time employee of Novo Nordisk (China) Pharmaceuticals, Beijing, China, and is a shareholder in Novo Nordisk. FGE has received clinical research grants from Novo Nordisk, Eli Lilly, AstraZeneca, Novartis, Eurofarma, and Kowa; is on advisory boards for Novo Nordisk, Eli Lilly, AstraZeneca, and Pfizer; and has given lectures for AstraZeneca, Bayer, Novo Nordisk, Eli Lilly, Sanofi, Abbot, Merck, and Novartis. MRH is a full-time employee of Novo Nordisk and shareholder in Novo Nordisk and Eli Lilly; before his current employment MRH received speaking fees from Novartis outside the submitted work. BTK has received research funding from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk for carrying out clinical trials or studies; speaker honoraria from Alvogen Korea and Novo Nordisk; all proceeds have been donated to the Ajou University Hospital to support obesity research. AK is an employee of and shareholder in Novo Nordisk. RCWM has received research funding from AstraZeneca, Bayer, Novo Nordisk, Pfizer, Roche Diagnostics Hong Kong and Tricida for carrying out clinical trials, and has received speaker honorarium or consultancy in advisory boards from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Merck, and Kyowa Kirin; all proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. NZ is an employee of and shareholder in Novo Nordisk. ML has received consulting fees from Novo Nordisk and Sanofi, and honoraria from Novo Nordisk, Sanofi, and Bayer, and is a committee member of the Chinese Society of Endocrinology. TY declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Infusion of mesenchymal stem cells (MSCs) induces polarization of M2 macrophages in adipose tissue of type 2 diabetes (T2D) mice. Studies have shown that M2 macrophages were divided into four sub-phenotypes (M2a, M2b, M2c and M2d) with different functions, and manuscripts have also confirmed that macrophages co-cultured with MSCs were not matched with known four phenotype macrophages. Therefore, our study explored the phenotype and related gene expressions of macrophages in the adipose tissue of T2D mice with/without MSCs infusion., Methods: We induced a T2D mouse model by using high-fat diets and streptozotocin (STZ) injection. The mice were divided into three groups: the control group, the T2D group, and the MSCs group. MSCs were systemically injected once a week for 6 weeks. The phenotype of macrophages in adipose tissue was detected via flow cytometric analysis. We also investigated the gene expression of macrophages in different groups via SMART-RNA-sequencing and quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR)., Results: The present study found that the macrophages of adipose tissue in the MSCs group were polarized to the M2 phenotype mixed with four sub-phenotypes. Besides, M2a and M2c held a dominant position, while M2b and M2d (tumor-associated macrophages, TAMs) exhibited a decreasing trend after infusion of MSCs. Moreover, the MSCs group did not appear to express higher levels of tumor-associated, inflammation-associated, or fibrosis-associated genes in comparison to the T2D group., Conclusion: The present results unveiled that the macrophage phenotype was inclined to be present in a hybridity state of four M2 sub-phenotypes and the genes related to tumor-promoting, pro-inflammation and pro-fibrosis were not increased after MSCs injection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint., Methods: In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed., Results: At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels., Conclusions: Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the effect of noiiglutide as an adjunct to lifestyle intervention on the reduction in body weight and tolerability in obese Chinese adults without diabetes., Materials and Methods: In this 24-week, randomized, double-blind, placebo-controlled phase 2 trial, 254 obese adults with a body mass index of 28.0-40.0 kg/m 2 and without diabetes were enrolled. Participants were initially randomized in a 1:1:1 ratio to one of three dose levels: 0.12, 0.24, or 0.36 mg of the study treatment. Within each dose level, participants were further randomized in a 3:1 ratio to receive either subcutaneous injection of noiiglutide or a matching placebo. The primary endpoint was the change in body weight from baseline to week 24., Results: Across all noiiglutide dosage levels, least squares mean reductions in body weight from baseline to week 24 ranged from 8.03 to 8.50 kg, compared with 3.65 kg in the placebo group (all p-values <.0001). In the noiiglutide groups (0.12, 0.24, 0.36 mg/day), a significantly higher proportion of participants achieved a weight loss ≥5% (68.8%, 60.0%, 73.0%) and ≥10% (37.5%, 36.9%, 39.7%), compared with the pooled placebo group (≥5%: 29.0%; ≥10%: 8.1%). Gastrointestinal adverse events, such as nausea, diarrhoea and vomiting, were more common in all noiiglutide groups (15.4%-30.2%, 18.8%-22.2%, 15.6%-18.5%) than in the pooled placebo group (8.1%, 6.5%, 0%)., Conclusions: In obese Chinese adults without diabetes, once-daily subcutaneous noiiglutide significantly reduced body week at week 24 compared with placebo, and had a manageable safety profile, primarily involving gastrointestinal disorders., (© 2023 John Wiley & Sons Ltd.)

Objective: The sneaky onset and dismal prognosis of chronic kidney disease (CKD) make it an important public health issue. Obesity-related kidney illness has garnered more attention in recent times. Establishing and validating a risk prediction model for chronic renal illness in overweight or obese adults was the goal of this investigation., Methods: Data from the China Health and Retirement Longitudinal Study were used for analysis. The definition of CKD was reduced renal function (eGFR < 60 mL/min/1.73 m²), while overweight and obesity were characterized through a body mass index exceeding 24 kg/m². The dataset was divided into derivation and validation cohorts using a 7:3 ratio. With respect to the derivation cohort, we constructed a prediction model using LASSO analysis and multivariate logistic regression. The model's performance was evaluated using Hosmer-Lemeshow tests, calibration curves, decision curve analysis, and receiver operating characteristic (ROC) curves. The validation cohort's model was subjected to additional assessment., Results: The study was based on survey data from 2011 to 2015 and comprised 3246 individuals who were overweight or obese, with 2274 being part of the derivation cohort and 972 being part of the validation cohort. The research constructed a prediction model that included age, sex, fasting blood glucose, glycated hemoglobin, triglyceride, hypertension, and BMI. The validation cohort's area under the ROC curve was 0.812 (95% CI = 0.763, 0.859) while the derivation cohort's was 0.789 (95% CI = 0.754, 0.831). Hosmer-Lemeshow tests were utilized to evaluate the model's accuracy in the validation and derivation cohorts (P = 0.681 and 0.547, respectively). The calibration curve showed a high level of consistency between the actual observations and the projected outcomes. According to decision curve analysis, the model offered significant net advantages., Conclusions: The forecasting model established in this research has predictive value for CKD in patients with overweight or obesity. These findings could help doctors conduct early detection and intervention in clinical practice and further improve patient prognosis., (© 2024. The Author(s).)

Aim: To investigate the efficacy and safety of beinaglutide as an adjunct to lifestyle intervention among non-diabetic Chinese individuals with overweight or obesity., Methods: This multicentre, randomized, double-blind, placebo-controlled trial (ChiCTR1900023428) included 427 Chinese adults with a body mass index of 28 kg/m 2 or higher (obesity) or 24-27.9 kg/m 2 (overweight) with weight-related complications. Patients were randomized in a 2:1 ratio to receive 0.2 mg of beinaglutide (subcutaneous) thrice daily or placebo for 16 weeks. Co-primary endpoints were body weight change and the proportion of patients with a weight reduction of 5% or more., Results: Mean body weight change from baseline to week 16 was -6.0% and -2.4% in the beinaglutide (n = 282) and placebo (n = 138) groups, respectively; the mixed model repeated measures difference was -3.6% (95% confidence interval: -4.6% to -2.6%; P < .0001). At week 16, more beinaglutide-treated patients achieved a weight reduction of 5% or more (58.2% vs. 25.4% [placebo], odds ratio: 4.4; P < .0001) and of 10% or more (21.3% vs. 5.1% [placebo], odds ratio: 5.5; P < .0001). Beinaglutide also resulted in greater waist circumference reduction (difference: -1.81 cm; P < .01). The weight regain rate 12 weeks after beinaglutide treatment was 0.78%. Nausea (transient and mild-to-moderate) was the most common adverse event in the beinaglutide group (49.3% vs. 7.1% [placebo]). More patients receiving beinaglutide discontinued treatment because of adverse events (5.9% vs. 0.7% [placebo]). Pancreatitis or an increased resting heart rate was not observed in the beinaglutide group., Conclusion: Beinaglutide combined with lifestyle intervention resulted in significant and clinically meaningful weight reduction with good tolerance in non-diabetic Chinese individuals with overweight or obesity., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Triglyceride glucose index (TyG index) was related with both type 2 diabetes (T2DM) and hypertension (HTN). Prospective studies linking the TyG index to the incidence of T2DM and HTN comorbidity remain unclear. This study aimed to to explore the longitudinal association between TyG and new-onset T2DM with HTN., Methods: 4,434 subjects (1249 males and 3185 females) without initial T2DM and HTN were followed up for 7 years. This study was conducted from November 2011 to August 2018 in the Gucheng, Laoshan and Jinding communities of Beijing. The incidence of T2DM with HTN during the 7-year follow-up was identified as the endpoint. The TyG index was divided into four quartiles: the < 25% level, the 25-50% level, the 50-75% level and the ≥ 75% level. The relationships between the TyG index and T2DM with HTN were evaluated by Cox proportional hazards regression models., Results: During 7 years, the augmented trend of T2DM with HTN was observed in the participants. After adjusting for all confounding factors, compared with those in the lowest quartile of TyG index, the population in the highest quartile of TyG index had a higher risk of T2DM with HTN (hazard ratio (HR), 2.878; 95% confidence intervals (95% CI), 1.230-6.731, P = 0.015), however, the association remained significant only in the female population (HR 2.753, 95% CI, 1.061-7.139, p = 0.037). The TyG had superior predictive ability of increased risk of T2DM with HTN for the populations of older age (≥ 65 years) (HR 2.694, 95% CI 1.212-5.989, p = 0.015), higher eGFR (≥ 90 mL/(min·1.73 m 2 )) (HR 2.603, 95% CI 1.164-5.818, p = 0.020) or obesity (BMI ≥ 28 kg/m 2 ) (HR 2.547, 95% CI 1.001-6.478, p = 0.020)., Conclusion: A population with a higher TyG index level was more likely to have an enhanced incidence of T2DM and HTN comorbidity. TyG index could have the significance of clinical in early protection against T2DM with HTN., (© 2024. The Author(s).)

Background: Gitelman Syndrome (GS) patients frequently exhibit disrupted glucose metabolism, attributed to hypokalemia, hypomagnesemia and heightened aldosterone. This study delved into the genetic underpinnings linked to insulin resistance and diabetes in a GS patient, contextualized within his family history., Methods: The hydrochlorothiazide and furosemide loading test were performed to ascertain the presence of GS. Oral glucose tolerance test (OGTT) evaluated glucose metabolism and insulin sensitivity. Whole-exome sequencing, validated by Sanger sequencing, was employed to confirm gene mutations, which were then tracked among the patient's relatives., Results: Symptoms and laboratory examination confirmed the clinical diagnosis of GS. Comprehensive whole-exome sequencing, augmented by Sanger sequencing validation, revealed a compound heterozygous mutation within the SLC12A3 gene (c.1108G>C in exon 9, c.676G>A in exon 5 and c.2398G>A in exon 20) in the patient. The OGTT affirmed diabetes and heightened insulin resistance, distinct from previous patients with GS we evaluated. Further genetic analysis identified a missense heterozygous mutation (c.97C>G in exon 1) within the PDX1 gene, inherited from the patient's diabetic mother without GS. Furthermore, the patient's brother, with impaired glucose tolerance but regular potassium levels, also bore this mutation, hinting at additional impacts of the PDX1 gene mutation on glucose metabolism regulation beyond the known impacts of GS., Conclusion: This study unveils unprecedented compound heterozygous mutations in the SLC12A3 and PDX1 genes in a GS patient. These findings illuminate the potential complex genetic factors influencing glucose metabolism disruptions in GS., Take-Home Message: This research uncovers a novel combination of SLC12A3 and PDX1 gene mutations in a Gitelman Syndrome patient, revealing intricate genetic factors that potentially disrupt glucose metabolism and shedding light on familial diabetes links., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yin, Li, Yu, Xin, Zhu, Hu, Chen, Gu, Mu, Zang and Lyu.)

Objective: To compare the diagnostic value of adrenocorticotropic hormone (ACTH) stimulation test (AST) with different doses of ACTH combined with midnight administration of 1 mg dexamethasone for the determination of the subtypes of primary hyperaldosteronism (PA)., Methods: This is a prospective observational study. Patients diagnosed with PA in the Department of Endocrinology, the First Medical Center of of Chinese PLA General Hospital from January 1, 2020 to September 30, 2022 underwent AST with different doses of ACTH. All patients received 1 mg dexamethasone at midnight for inhibition. Then, the patients were randomly assigned to 25-unit and 50-unit ACTH treatment groups by a ratio of 1:2. Subtype classification and diagnosis of aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) was made on the basis of adrenal venous blood samples and/or postoperative pathology and clinical follow-up findings. Receiver operating characteristics (ROC) curves were plotted to examine the diagnostic efficacy and the difference of AST by varying doses of ACTH in distinguishing APA and IHA., Results: A total of 82 patients, including 49 patients with APA (59.8%) and 33 patients with IHA (40.2%), were enrolled. There were 29 patients in the 25-unit ACTH group (35.4%) and 53 patients in the 50-unit ACTH group (64.6%). There were no significant differences in age, sex, blood pressure, minimum serum potassium, and biochemical parameters between the 25-unit and 50-unit groups. After ACTH stimulation, plasma aldosterone concentration (PAC), cortisol (F), and PAC/F at different points of time showed no statistical difference between the two groups ( P >0.05). The area under the curve ( AUC ) of PAC in the 25-unit group was higher than that of PAC/F. The AUC of PAC reached the maximum at 90 minutes (0.948, 95% confidence interval [ CI ]: 0870-1.000) and the optimal cutoff was 38.0 ng/dL, which had a sensitivity of 92.9% and a specificity of 86.7% for differentiating APA and IHA. Similar to the 25-unit group, the maximum AUC of PAC in the 50-unit group was greater than that of PAC/F. The AUC of PAC reached the maximum 90 minutes (0.930, 95% CI : 0.840-0.994) and the optimal cutoff was 39.6 ng/dL, which had a sensitivity of 91.2% and a specificity of 83.3%. The AUC of PAC at different points of time in the 25-unit ACTH group (0.862-0.948) was greater than that of 50-unit ACTH group (0.823-0.930), but the difference was not statistical significance., Conclusion: AST with 25-unit or 50-unit ACTH combined with small-dose dexamethasone can be used in PA subtype determination, ie, differentiation between APA and IHA. The optimal PAC cut-off values for 25-unit or 50-unit ACTH are similar, being 38.0 ng/dL and 39.6 ng/dL, respectively, and both cutoff values show higher sensitivity and specificity at 90 min. The AST with 25-unit ACTH has the smaller dose and the better safety. Therefore, it is recommended for the diagnosis of PA subtypes., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been proved a promising clinical strategy for the treatment of diabetes, and time in range (TIR) has been demonstrated a new metric of glycemic control links to diabetes complications. To further assess the therapeutic effect of UC-MSCs on TIR, a phase II study investigating the efficacy of UC-MSCs in Chinese adults with type 2 diabetes (T2D) assessed by retrospective continuous glucose monitoring (CGM) was conducted. In this randomized and placebo-controlled trial, a total of 73 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 37) or placebo (n = 36) 3 times at 4-week intervals and followed up for 48 weeks. The primary endpoint was the changes in TIR and glycosylated hemoglobin (HbA1c). TIR and HbA1c were both significantly improved in UC-MSCs and placebo groups after 48 weeks of therapy compared with baseline. Compared with placebo group, UC-MSCs group exhibited more pronounced changes at 9 and 48 weeks from baseline in TIR (26.54 vs. 15.84 and 21.36 vs. 6.32) and HbA1c (-1.79 vs. -0.96 and -1.36 vs. -0.51). More patients in UC-MSCs group achieved the glycemic control target of TIR ≥ 70% and HbA1c < 7% at 9 and 48 weeks than in placebo group (59.5% vs. 27.8% and 43.2% vs. 11.1%). The C-peptide area under the curve (AUCC-pep) was an independent risk factor associated with efficacy in T2D undergoing UC-MSCs intervention. These results illustrate that UC-MSCs administration via intravenous infusion is an effective approach for ameliorating TIR., (© The Author(s) 2023. Published by Oxford University Press.)

Background: The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by "Life's Essential 8" has not been characterized. We aim to examine the associations of early adulthood weight change and midlife "Life's Essential 8" CVH status with cardiometabolic outcomes in a Chinese cohort., Methods: The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in "Life's Essential 8" was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria., Results: 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04-1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25-1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01-2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90-2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife., Conclusions: Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population., (© 2023. The Author(s).)

Aim: To evaluate the prevalence of overweight/obesity and associated complications from a large, cross-sectional, nationwide database in China., Materials and Methods: Data were obtained from 519 Meinian health check-up centres across 243 cities. Eligible participants were aged ≥18 years, with a routine check-up in 2019 (N = 21 771 683) and complete height, weight, sex and region data. The unadjusted prevalence rates of overweight/obesity were calculated by age, sex and region. In addition, the nationwide prevalence rates of overweight and obesity were standardized according to the 2010 China census by age group and sex. The prevalence of obesity-related complications by body mass index (BMI) groups was calculated using logistic regression., Results: There were 15 770 094 eligible participants (median age 40 years; mean BMI 24.1 kg/m 2 ; 52.8% male). By Chinese BMI classification, 34.8% were overweight and 14.1% were obese. Overweight and obesity were more prevalent in male than female participants (standardized: overweight 40.2% vs. 27.4%; obesity 17.6% vs. 9.6%, respectively). The prevalence of assessed complications was higher in participants with overweight/obesity versus those with normal BMI (P < 0.001 for trends). The most prevalent complications in participants with overweight/obesity were fatty liver disease, prediabetes, dyslipidaemia and hypertension. The number of complications increased with higher BMI., Conclusions: Overweight/obesity and related complications are highly prevalent in this population. These data may better inform management and prevention public health strategies in China., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China., Methods: A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups., Results: The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders., Conclusions: We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: While evidence supports glycemic control benefits for individuals with type 1 diabetes mellitus (T1DM) using hybrid closed-loop (HCL) systems, HCL automated insulin delivery therapy in China has not been assessed. This study evaluated safety events and effectiveness during HCL system use by Chinese adolescents and adults with T1DM. Methods: Sixty-two participants ( n  = 12 adolescents with a mean ± standard deviation [SD] of 15.5 ± 1.1 years and n  = 50 adults [mean ± SD of 37.6 ± 11.1 years]) with T1DM and baseline A1C of 7.1% ± 1.0% underwent a run-in period (∼2 weeks) using open-loop Manual Mode (sensor-augmented pump) insulin delivery with the MiniMed™ 770G system with the Guardian™ Sensor (3) glucose sensor, followed by a study period (4 weeks) with HCL Auto Mode enabled. Analyses compared continuous glucose monitoring data and insulin delivered during the run-in versus study period (Wilcoxon signed-rank test or t -test). Safety events included rates of severe hypoglycemia and diabetic ketoacidosis (DKA). Results: Compared to baseline run-in, overall Auto Mode use increased time in range (TIR, 70-180 mg/dL) from 75.3% to 80.9% ( P  < 0.001) and reduced time below range (TBR, <70 mg/dL) from 4.7% to 2.2% ( P  < 0.001). Subgroup analysis demonstrated that participants ( n  = 29) with baseline A1C <7.0% had TBR that reduced from 5.6% to 2.0%, while participants ( n  = 21) with baseline A1C ≥7.5% had time above range (TAR, >180 mg/dL) that reduced from 31.6% to 20.8%. Auto Mode use also increased the percentage achieving combined recommendations for time at sensor glucose ranges (i.e., TIR of >70%, TBR of <4% and TAR of <25%) from 24.2% at baseline to 77.4% at study end. Total daily insulin dose reduced from 42.8 ± 19.8 to 40.7 ± 18.9 U ( P  = 0.013). There were no severe hypoglycemic, DKA, or serious adverse events. Conclusions: Chinese adolescents and adults, some of whom met target A1C at baseline, safely achieved significantly improved glycemia with 1 month of MiniMed 770G system use when compared to open-loop insulin delivery. ClinicalTrials.gov ID: NCT04663295.

Background: The brachial-ankle pulse-wave velocity (baPWV) is regarded as the gold standard in the evaluation of arterial stiffness. Its prognostic significance for major adverse cardiovascular events (MACE) has been demonstrated. However, the factors influencing the association between baPWV and MACE risk have not been determined. In this study, we investigated the association of baPWV and MACE risk and whether it is affected by the risk factors for different cardiovascular diseases (CVDs)., Methods: This was a prospective cohort study that initially enrolled 6850 participants from 12 communities in Beijing. The participants were divided into three subgroups according to their baPWV values. The primary outcome was the first occurrence of MACE, defined as hospitalization from cardiovascular diseases, first occurrence of a nonfatal myocardial infarction, or nonfatal stroke. Cox proportional hazards regression and restricted cubic spline analyses were used to examine the association between baPWV and MACE. The effect of CVD risk factors on the relationship between baPWV and MACE was explored in subgroup analyses., Results: The final study population consisted of 5719 participants. During a median follow-up of 34.73 months, MACE occurred in 169 participants. The restricted cubic spline analysis indicated a positive linear relationship between baPWV and MACE risk. After adjustment for cardiovascular risk factors, the hazard ratio (HR) for MACE risk per SD increase in baPWV was 1.272 [95% confidence interval (CI): 1.149-1.407, P  < 0.001], and the HR for MACE in the high-baPWV vs. the low-baPWV group was 1.965 (95% CI: 1.296-2.979, P  = 0.001). Adding baPWV to the conventional cardiovascular risk factors significantly improved the model's prediction performance and the net reclassification (NRI) [NRI: 0.379 (95% CI: 0.072-0.710), P  = 0.025] in MACE discrimination. However, in the subgroup analysis, two CVD risk factors, stable coronary heart disease and hypertension, showed significant interaction effects ( Pinteraction both < 0.05). This result indicated that the effect of CVD risk factors must be taken into account when assessing the relationship between baPWV and MACE., Conclusion: baPWV is a potential marker to improve the identification of MACE risk in the general population. A positive linear correlation was firstly determined between baPWV and MACE risk, but it may not be valid in participants with stable coronary heart disease and hypertension., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Millions of people are afflicted by depression, a highly prevalent mental illness with increased morbidity and mortality. Advanced glycation end-products (AGEs) are potential risk factors for depression. We aimed to investigate the correlation of AGEs with depressive symptoms and the severity of depressive symptoms., Methods: This study was nested in the prospective REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study and included 4420 eligible participants. skin autofluorescence (SAF) was used to measure skin AGEs. Depressive symptoms were evaluated by the Self-Rating Depression Scale (SDS). Multiple logistic regression analysis was used to assess the association of AGEs with depressive symptoms and the severity of depressive symptoms., Results: Logistic analysis showed a significantly positive relationship between quartiles of SAF-AGEs and the risk of depressive symptoms with the OR [95% confidence interval (CI), p value] of 1.24 (95% CI: 1.03-1.50, p = 0.022), 1.39 (95% CI: 1.15-1.68, p = 0.001) and 1.57 (95% CI: 1.28-1.91, p < 0.001) for multivariable-adjusted model respectively. And SAF-AGEs were associated with the severity of depressive symptoms with the multivariable-adjusted OR (95% CI, p value) of 1.06 (95% CI:0.79-1.43, p = 0.681), 1.47 (95% CI: 1.08-1.99, p = 0.014), and 1.54 (95% CI: 1.12-2.11, p = 0.008) respectively. Stratified analyses showed that SAF-AGEs were significantly associated with the severity of depressive symptoms only in females, overweight people, individuals with hypertension, and those without diabetes and insomnia., Conclusions: The present study showed that a higher SAF-AGEs level was associated with depressive symptoms and the severity of depressive symptoms., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes., Objective: To evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes., Design, Setting, and Participants: Randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol)., Interventions: Participants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294)., Main Outcomes and Measures: The primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes., Results: Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], -0.2 [95% CI, -0.3 to -0.1] percentage points), confirming noninferiority (P < .001) and superiority (P = .002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, -6 to 5] mg/dL; P = .90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, -0.19 to 1.10] kg; P = .17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P = .01)., Conclusions and Relevance: Among people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups., Trial Registration: ClinicalTrials.gov Identifier: NCT04795531.

Context: Intraoperative hemodynamic instability (HI) deteriorates surgical outcomes of patients with normotensive pheochromocytoma (NP)., Objective: To characterize the hemodynamics of NP and develop and externally validate a prediction model for intraoperative HI., Methods: Data on 117 patients with NP (derivation cohort) and 40 patients with normotensive adrenal myelolipoma (NAM) who underwent laparoscopic adrenalectomy from January 2011 to November 2021 were retrospectively collected. Data on 22 patients with NP (independent validation cohort) were collected from another hospital during the same period. The hemodynamic characteristics of patients with NP and NAM were compared. Machine learning models were used to identify risk factors associated with HI. The final model was visualized via a nomogram., Results: Forty-eight (41%) out of 117 patients experienced HI, which was significantly more than that for NAM. A multivariate logistic regression including age, tumor size, fasting plasma glucose, and preoperative systolic blood pressure showed good discrimination measured by area under curve (0.8286; 95% CI 0.6875-0.9696 and 0.7667; 95% CI 0.5386-0.9947) for predicting HI in internal and independent validation cohorts, respectively. The sensitivities and positive predictive values were 0.6667 and 0.7692 for the internal and 0.9167 and 0.6111 for the independent validations, respectively. The final model was visualized via a nomogram and yielded net benefits across a wide range of risk thresholds in decision curve analysis., Conclusion: Patients with NP experienced HI during laparoscopic adrenalectomy. The nomogram can be used for individualized prediction of intraoperative HI in patients with NP., Competing Interests: Conflict of Interest The authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Spouses share common socioeconomic, environmental, and lifestyle factors, and multiple studies have found that spousal diabetes status was associated with diabetes prevalence. But the association of spousal diabetes status and ideal cardiovascular health metrics (ICVHMs) assessed by the American Heart Association's Life's Essential 8 measures with incident diabetes has not been comprehensively characterized, especially in large-scale cohort studies., Objective: To explore the association of spousal diabetes status and cardiovascular health metrics with risk of incident diabetes in Chinese adults., Design, Setting, and Participants: This cohort study included individuals in the China Cardiovascular Disease and Cancer Cohort without diabetes who underwent baseline and follow-up glucose measurements and had spouses with baseline glucose measurements. The data were collected in January 2011 to December 2012 and March 2014 to December 2016. The spousal study had a mean (SD) follow-up of 3.6 (0.9) years (median [IQR], 3.2 [2.9-4.5] years). Statistical analysis was performed from July to November 2022., Exposure: Spousal diabetes status was diagnosed according to the 2010 American Diabetes Association (ADA) criteria. All participants provided detailed clinical, sociodemographic, and lifestyle information included in cardiovascular health metrics., Main Outcomes and Measures: Incident diabetes, diagnosed according to 2010 ADA criteria., Results: Overall, 34 821 individuals were included, with a mean (SD) age of 56.4 (8.3) years and 16 699 (48.0%) male participants. Spousal diabetes diagnosis was associated with an increased risk of incident diabetes (hazard ratio [HR], 1.15; 95% CI, 1.03-1.30). Furthermore, participants whose spouses had uncontrolled glycated hemoglobin (HbA1c) had a higher risk of diabetes (HR, 1.20; 95% CI, 1.04-1.39) but the risk of diabetes in participants whose spouses had controlled HbA1c did not increase significantly (HR, 1.10; 95% CI, 0.92-1.30). Moreover, this association varied with composite cardiovascular health status. Diabetes risk in individuals who had poor cardiovascular health status (<4 ICVHMs) was associated with spousal diabetes status (3 ICVHMs: HR, 1.50; 95% CI, 1.15-1.97), while diabetes risk in individuals who had intermediate to ideal cardiovascular health status (≥4 ICVHMs) was not associated with it (4 ICVHMs: HR, 1.01; 95% CI, 0.69-1.50)., Conclusions and Relevance: In this study, spousal diabetes diagnosis with uncontrolled HbA1c level was associated with increased risk of incident diabetes, but strict management of spousal HbA1c level and improving ICVHM profiles may attenuate the association of spousal diabetes status with diabetes risk. These findings suggest the potential benefit of couple-based lifestyle or pharmaceutical interventions for diabetes.

Background: Castleman Disease (CD) is a group of diseases with characteristic lymph node histopathology, characterized by marked enlargement of deep or superficial lymph nodes. Adrenal CD is rarely reported, and an accurate preoperative diagnosis of adrenal CD is difficult., Method: We report four cases of CD in the adrenal gland confirmed by pathology and review the characteristics of this rare disease, highlighting the necessity of diagnostic evaluation and follow-up of the patients., Results: All of the patients sought medical advice because of adrenal incidentalomas. No significant abnormalities were presented in the biochemistry or endocrine systems. The imaging suggested a moderate-to-large mass with uneven moderate contrast enhancement of the adrenal region, similar to a pheochromocytoma. All cases were misdiagnosed as pheochromocytomas before operation and finally confirmed by histopathology. Three cases were pathologically diagnosed as hyaline vascular CD, and one case was diagnosed as plasma cell CD. All the patients are alive without recurrence after a median follow-up of 8 years., Conclusion: The adrenal CD should be considered after excluding pheochromocytoma and malignancy in the adrenal region. The long-term prognosis of patients with complete resection of the mass is excellent., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Wang, Li, Du, Guo, Gu, Lyu, Dou, Mu and Zang.)

Aims: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method., Materials and Methods: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets., Results: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia., Conclusions: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Kidney disease is related to visceral obesity. As a new indicator of obesity, body roundness index (BRI) has not been fully revealed with kidney disease. This study's objective is to assess the relationship between estimated glomerular filtration rate (eGFR) and BRI among the Chinese population., Methods: This study enrolled 36,784 members over the age of 40, they were from 7 centers in China by using a random sampling method. BRI was computed using height and waist circumference, eGFR ≤ 90 mL/min/1.73 m 2 was considered to indicate low eGFR. To lessen bias, propensity score matching was employed, multiple logistic regression models were utilized to examine the connection between low eGFR and BRI., Results: The age, diabetes and coronary heart disease rates, fasting blood glucose, and triglycerides were all greater in participants with low eGFR. The BRI quartile was still positively connected with low eGFR after controlling for confounding variables, according to multivariate logistic regression analysis. (OR [95%CI] Q2:1.052 [1.021-1.091], OR [95%CI] Q3:1.189 [1.062-1.284], OR [95%CI] Q4:1.283 [1.181-1.394], P trend < 0.001). Stratified research revealed that the elders, women, habitual smokers, and those with a history of diabetes or hypertension experienced the connection between BRI level and low eGFR. According to ROC, BRI was able to detect low eGFR more accurately., Conclusion: Low eGFR in the Chinese community is positively connected with BRI, which has the potential to be used as an effective indicator for screening kidney disease to identify high-risk groups and take appropriate measures to prevent subsequent complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Gao, Ren, Liu, Li, Wang, Tang, Yan, Luo, Qin, Chen, Wan, Gao, Wang, Ning and Mu.)

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic β cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: High blood pressure (BP) is highly prevalent in patients with chronic kidney disease. However, the thresholds to initiate BP-lowering treatment in this population are unclear. We aimed to examine the associations between BP levels and clinical outcomes and provide evidence on potential thresholds to initiate BP-lowering therapy in people with chronic kidney disease., Methods: This nationwide, multicenter, prospective cohort study included 12 523 chronic kidney disease participants without antihypertensive therapy in mainland China. Participants were followed up during 2011 to 2016 for cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, hospitalized or treated heart failure, and cardiovascular death) and renal events (≥20% decline in the estimated glomerular filtration rate, end-stage kidney disease, and renal death)., Results: Overall, 652 cardiovascular events and 1268 renal events occurred during 43 970 person-years of follow-up. We observed a positive and linear relationship between systolic BP and risks of cardiovascular and renal events down to 90 mm Hg, as well as between diastolic BP and risks of renal events down to 50 mm Hg. A J-shaped trend was noted between diastolic BP and risks of cardiovascular events, but a linear relationship was revealed in participants <60 years ( P for interaction <0.001). A significant increase in the risk of cardiovascular and renal outcomes was observed at systolic BP ≥130 mm Hg (versus 90-119 mm Hg) and at diastolic BP ≥90 mm Hg (versus 50-69 mm Hg)., Conclusions: In people with chronic kidney disease, a higher systolic BP/diastolic BP level (≥130/90 mm Hg) is significantly associated with a greater risk of cardiovascular and renal events, indicating potential thresholds to initiate BP-lowering treatment.

Islet β-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment of islet β-cell function is beneficial to better management of T2DM. Protecting islet β-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet β-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet β-cell function in type 2 diabetes mellitus." This consensus suggests that β-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet β-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet β-cell function, independent of glycemic control., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prediabetes with hypertension or prehypertension increases the risk of cardiovascular events. Lipid accumulation product (LAP) is a powerful marker of visceral obesity. The current study aimed to explore the relationship between LAP and hypertension and prehypertension among prediabetic individuals. A total of 12,388 prediabetic participants from the REACTION study were recruited. LAP was calculated from waist circumference and fasting triglyceride levels. Multiple logistic regression models were conducted to assess the relationship between LAP and hypertension and prehypertension. Multiple logistic regression analysis showed that elevated LAP was associated with hypertension (Q2: odds ratio (OR): 1.263, P < 0.001; Q3: OR: 1.613, P < 0.001; Q4: OR: 1.754, P < 0.001) and prehypertension (Q2: OR: 1.255, P = 0.005; Q3: OR: 1.340, P = 0.002; Q4: OR: 1.765, P < 0.001). The results of the stratified analysis showed that prediabetic people with higher LAP levels and characterized by overweight, normal weight and a high waist-to-hip ratio (WHR) were more likely to have hypertension, and prediabetic people with higher LAP levels and characterized by overweight, normal weight, a high WHR, age <65, and low and high levels of physical activity were more likely to have prehypertension. In conclusion, visceral obesity assessed by LAP is significantly associated with hypertension and prehypertension in the Chinese prediabetic population., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)