Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial.

OBJECTIVE: To evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia. DESIGN: Multicentre, open label, randomised trial. SETTING: 15 hospitals in China between December 2017 and December 2020. PARTICIPANTS: 412 patients with newly diagnosed type 2 diabetes and significant hyperglycaemia (HbA1c ≥8.5%). INTERVENTIONS: All randomised participants initially received SIIT for 2-3 weeks, followed by linagliptin 5 mg/day, metformin 1000 mg/day, combination linagliptin plus metformin, or lifestyle modification alone (control) for 48 weeks. MAIN OUTCOME MEASURES: The primary outcome was the percentage of participants achieving HbA1c <7.0% at week 48 after SIIT. Secondary outcomes included glycaemic control, ß cell function, and variations in insulin sensitivity. RESULTS: 412 participants were randomised. At baseline, the mean age was 46.8 (standard deviation 11.2) years, mean body mass index was 25.8 (2.9), and mean HbA1c was 11.0% (1.9%). At week 48, 80% (78/97), 72% (63/88), and 73% (69/95) of patients in the linagliptin plus metformin, linagliptin, and metformin groups, respectively, achieved HbA1c <7.0%, compared with 60% (56/93) in the control group (P=0.02 overall; P=0.003 for linagliptin plus metformin versus control; P=0.12 for linagliptin versus control; P=0.09 for metformin versus control). Additionally, 70% (68/97), 68% (60/88), and 68% (65/95) of patients in the linagliptin plus metformin, linagliptin, and metformin group, respectively, achieved HbA1c <6.5% compared with 48% (45/93) in the control group (P=0.005 overall; P=0.005 for linagliptin plus metformin versus control; P=0.01 for linagliptin versus control; P=0.008 for metformin versus control; all were significant after adjustment for multiple comparisons). Thus, compared with the control group, participants in the linagliptin plus metformin group were more likely to achieve HbA1c <7.0% at week 48 (odds ratio 2.78, 95% confidence interval 1.37 to 5.65; P=0.005). Moreover, the linagliptin plus metformin group showed the most significant improvement in fasting plasma glucose and ß cell function indices. All treatments were well tolerated. CONCLUSIONS: The intense simplified strategy using subsequent oral therapies post-SIIT, especially the linagliptin plus metformin combination, sustainably improved glycaemic control and ß cell function in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia. This approach offers a promising direction for decision making in the clinical management of type 2 diabetes mellitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT03194945.

Long-term outcome of unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia.

PURPOSE: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a form of Cushing's syndrome (CS) characterized by heterogeneous cortisol secretion and clinical comorbidities. Previously, bilateral adrenalectomy was the standard treatment for PBMAH, but this approach carried a high risk of primary adrenocortical insufficiency. In recent decades, unilateral adrenalectomy (U-Adx) has emerged as an effective alternative. However, limited research exists on its postoperative efficacy and prognostic predictors. Therefore, the present study aimed to investigate the long-term effectiveness and prognostic predictors of U-Adx in treating PBMAH. METHODS: A total of 61 patients with PBMAH diagnosis who underwent U-Adx at a single center between 2004 and 2022 were retrospectively evaluated. Patients were categorized into persistent hypercortisolism and remission groups based on postoperative biochemical outcomes at the last follow-up (>12 months after U-Adx). Clinical characteristics, comorbidities, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-h urinary-free cortisol (24-h UFC) levels were analyzed pre- and postoperatively. We further examined whether baseline plasma ACTH, serum cortisol, 24-h UFC levels, and the inhibition of cortisol and 24-h UFC after a low-dose dexamethasone suppression test (LDDST) could predict non-remission following U-Adx. Additionally, we explored the improvements in hypertension, abnormal glucose metabolism, osteoporosis, and other complications in patients with PBMAH post-U-Adx. RESULTS: After U-Adx, 22 of the 45 patients (48.89%) achieved initial remission within 6 months. At the last follow-up, 25 of the 45 patients underwent all required biochemical tests and cortisol assessment tests, among which eight of 25 (32.00%) were in remission and 17 of 25 (68.00%) were experiencing persistent hypercortisolism. Moreover, five of those 25 patients exhibited recurrence after initial remission. Baseline 24-h UFC level > 2 times the upper limit of normal (2ULN) and unsuppressed 24-h UFC after LDDST may predict persistent hypercortisolism postoperatively. Lastly, long-term postoperative follow-up revealed that hypertension decreased with hypercortisolism remission, whereas osteoporosis worsened with persistent hypercortisolism. CONCLUSION: The short-term remission rate of hypercortisolism was 48.89% in patients with PBMAH treated with U-Adx, while a long-term remission rate of 32.00% was achieved after a median follow-up of 38.58 months. Furthermore, this finding suggests that baseline 24-h UFC level > 2ULN and unsuppressed 24-h UFC after LDDST predict persistent hypercortisolism in the long-term post-U-Adx. Finally, U-Adx improved cortisol circadian rhythm alterations and ACTH suppression in the patients in the remission group, thereby substantially alleviating hypertension and delaying the development of osteoporosis linked to PBMAH.

Breaking the chain in organ failure: Role of umbilical cord and bone marrow derived mesenchymal stem cells in treatment of severe acute pancreatitis.

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 × 106 UC-MSCs, and 1 × 106 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-1ß, 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.

Clinical Characteristics and Management of Hypercalcemic Crisis in 155 Patients: A Single Center Retrospective Study.

Objective: This study aimed to analyse the etiology and clinical characteristics of hypercalcemic crisis in a large cohort of Chinese patients and summarised our clinical experience in the management of this serious endocrinological emergency. Methods: This was a retrospective analysis of a cohort of patients with hypercalcemic crisis hospitalized in the First Medical Center of Chinese PLA General Hospital between January 2009 and March 2024. The general data, clinical manifestations, etiology, photographic examination, emergency treatment, etiological treatment, and prognosis were analysed. Results: A total of 155 patients with hypercalcemic crisis (91 males and 64 females) with a mean age of 54.60 ± 16.99 years old were enrolled. The most frequent disease-causing hypercalcemic crisis was hyperparathyroidism (41.94%), followed by solid malignancy (41.29%) and multiple myeloma (9.03%), et al. Patients mainly presented with symptoms of the digestive system (78.10%), nervous system (63.30%), skeletal system (59.60%), urinary system (59.50%), and cardiovascular system (34.90%). These 155 patients with hypercalcemic crisis got effective therapies that included simultaneous administration of intravenous injection (IV) isotonic saline, subcutaneous calcitonin, bisphosphonate, or hemodialysis in serious cases. After emergency treatment, all the symptoms in the patients were relieved obviously. The cure rate of hypercalcemic with etiological treatments was 84.50% (131/155). Conclusion: Hypercalcemic crisis is a serious endocrinological emergency with a variety of etiologies and a high risk of mortality. A prompt diagnosis and the implementation of a comprehensive and effective treatment can efficiently alleviate this endocrinological emergency. Etiological treatment targeting different causes can improve prognosis significantly.

Remnant cholesterol is more positively related to diabetes, prediabetes, and insulin resistance than conventional lipid parameters and lipid ratios: A multicenter, large sample survey.

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.

Clinical characteristics and complication risks in data-driven clusters among Chinese community diabetes populations.

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 ß-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.

M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice.

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-1ß (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.

Gender Disparities in the Association Between Educational Attainment and Cardiovascular-Kidney-Metabolic Syndrome: Cross-Sectional Study.

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.

Association Between Nonalcoholic Fatty Liver Disease and the Risk of Cardiovascular Disease in the Middle-Age and Elderly Population of Northern China: A Cross-Sectional Study.

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.

Prevalence and Risk Factors of Chronic Kidney Disease in Patients With Type 2 Diabetes in China: Cross-Sectional Study.

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 (HbA1c), 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 m2 had proteinuria, whereas 3.4% (234/6909) who had a UACR <30 mg/g presented with an eGFR <60 mL/min/1.73 m2. Compared with patients who were cognizant of CKD, those who were unaware of CKD had increased rates of HbA1c ≥7%, total cholesterol >5.18 µmol/L, LDL cholesterol >3.37 µmol/L, BMI ≥30 kg/m2, 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.

Perceptions, attitudes and barriers to effective obesity care among people living with obesity and healthcare professionals in China: The ACTION-China study.

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.

Development and validation of a machine learning-based model to predict isolated post-challenge hyperglycemia in middle-aged and elder adults: Analysis from a multicentric study.

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.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study.

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.

Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study.

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 (PM2.5) 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.

Exosomes derived from umbilical cord-derived mesenchymal stem cells exposed to diabetic microenvironment enhance M2 macrophage polarization and protect against diabetic nephropathy.

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.

Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study.

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.

The efficacy and safety of iGlarLixi versus IDegAsp in Chinese people with type 2 diabetes suboptimally controlled with oral antidiabetic drugs: The Soli-D randomized controlled trial.

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.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case-control study.

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.