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.

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.

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.

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.

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.

Remnant cholesterol, but not other traditional lipids or lipid ratios, is independently and positively related to future diabetes risk in Chinese general population: A 3 year cohort study.

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.

Association of advanced glycation end products with ear lobe crease: A cross-sectional study.

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)-AGEage (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-AGEage 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-AGEage 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-AGEage and ELC. CONCLUSION: ELC is associated with coronary heart disease, and the SAF-AGE has a potential role in ELC development in elder people.

Predictive factors that influence the clinical efficacy of umbilical cord-derived mesenchymal stromal cells in the treatment of type 2 diabetes mellitus.

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.

Association of remnant cholesterol and newly diagnosed early-onset type 2 diabetes mellitus in Chinese population: A retrospective cross-sectional study.

BACKGROUND: With the increasing incidence of diabetes worldwide, patients diagnosed with diabetes has been getting younger. Previous studies have shown that high remnant cholesterol (RC) level leads to an increased risk of cardiovascular disease events. However, the relationship between RC levels and newly diagnosed early-onset type 2 diabetes mellitus (T2DM) is unknown. This study aimed to explore the association between RC and newly diagnosed early-onset T2DM. METHODS: A total of 606 patients newly diagnosed with early-onset T2DM and 619 gender-matched subjects with normal blood glucose levels were retrospectively enrolled in this study. All T2DM patients showed onset age of 18-40 years. Binary logistic regression analysis was performed to analyze independent risk factors and receiver operating characteristic (ROC) analysis was used to explore the predictive value of RC and other unconventional lipids. Moreover, the correlation between RC and insulin resistance in patients with newly diagnosed early-onset T2DM was also examined with binary logistic regression analysis and Spearman correlation analysis. RESULTS: Increased RC level was an independent risk factor for early-onset T2DM (p < .05). The area under the curve on ROC analysis of RC was 0.805, 95% confidence interval (CI) was 0.781 ~ 0.826, sensitivity was 82.18% and specificity was 66.24%, which showed higher predictive value than those of triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and total cholesterol (TC)/HDL-C ratio. Cutoff value of RC was 0.32 mmol/L. Level of RC in early-onset T2DM patients with moderate or severe insulin resistance was significantly higher than that in patients with mild insulin resistance (p < .0001). No difference in RC levels was found between patients with moderate and severe insulin resistance (p > .05). RC was still correlated with insulin resistance after adjusting the conventional lipid parameters (TG, TC, HDL-C, and low-density lipoprotein cholesterol) using partial correlation analysis. CONCLUSION: RC level was higher in patients with early-onset T2DM and was correlated to the degree of insulin resistance as well. Patients aged 18-40 years with RC >0.32 mmol/L showed an increased risk of developing T2DM.

Clinical characteristics of patients with early-onset diabetes mellitus: a single-center retrospective study.

BACKGROUND: The prevalence of diabetes mellitus (DM) is dramatically increasing around the world, and patients are getting younger with changes in living standards and lifestyle. This study summarized and analyzed the clinical characteristics of different types of newly diagnosed diabetes mellitus patients with an onset age between 18 and 40 years to provide clinical evidence for the early diagnosis and treatment of diabetes, reduce short-term and long-term complications and offer scientific and personalized management strategies. METHODS: A total of 655 patients newly diagnosed with early-onset diabetes mellitus in the Department of Endocrinology, the First Medical Center of PLA General Hospital from January 2012 to December 2022 were retrospectively enrolled in this study, with an onset age of 18-40 years. Their clinical data were collected and investigated. All patients were divided into two groups according to whether they presented with diabetic microangiopathy. Similarly, patients with early-onset type-2 diabetes were grouped in accordance with whether they had ketosis at the time of diagnosis. Binary logistic regression analysis was performed to analyze risk factors, and receiver-operating characteristic (ROC) analysis was used to explore the predictive value of significant risk factors. RESULTS: The findings were as follows: (1) Of 655 enrolled patients, 477 (72.8%) were male and 178 (27.1%) were female, with a mean age of onset of was 29.73 years ± 0.24 SD. (2) The prevalence of early-onset diabetes was gradually increasing. Type-2 diabetes was the most common type of early-onset diabetes (491, 75.0%). The ages of onset of early-onset type-1 diabetes, type-2 diabetes and LADA were mainly 18-24 years, 25-40 years and 33-40 years, respectively. (3) Initial clinical manifestations of early-onset diabetes were classic diabetes symptoms (361, 55.1%), followed by elevated blood glucose detected through medical examination (207, 31.6%). (4) Binary logistic regression analysis suggested that high serum uric acid (UA), a high urinary albumin-to-creatinine ratio (UACR) and diabetic peripheral neuropathy (DPN) were risk factors for microangiopathy in early-onset diabetes patients (P < 0.05). The area under the curve (AUC) on ROC analysis of the combination of UA, UACR and DPN was 0.848, 95% CI was 0.818 ~ 0.875, sensitivity was 73.8% and specificity was 85.9%, which had higher predictive value than those of UA, UACR and DPN separately. (5) Weight loss, high glycosylated hemoglobin (HbA1c) and young onset age were risk factors for ketosis in patients with early-onset type-2 diabetes (P < 0.05). CONCLUSION: (1) Men were more likely to have early-onset diabetes than women. (2) Early-onset diabetes patients with high serum uric acid levels, high UACRs and peripheral neuropathy were prone to microangiopathy. Comprehensive evaluation of these risk factors could have higher predictive value in the prediction, diagnosis and treatment of microvascular lesions. (3) Patients with weight loss at onset, high HbA1c and young onset age were more likely to develop ketosis. Attention should be given to the metabolic disorders of these patients.

Efficacy of Umbilical Cord-Derived Mesenchymal Stem Cells in the Treatment of Type 2 Diabetes Assessed by Retrospective Continuous Glucose Monitoring.

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.

Prevalence of obesity and associated complications in China: A cross-sectional, real-world study in 15.8 million adults.

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/m2 ; 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.

The association between brachial-ankle pulse-wave velocity and adverse cardiovascular events in 5719 community participants a prospective cohort study.

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.

Association between hemoglobin glycation index and 5-year major adverse cardiovascular events: the REACTION cohort study.

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.

Analysis of characteristics of four patients with adrenal unicentric Castleman disease.

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.

Association of skin autofluorescence with depressive symptoms and the severity of depressive symptoms: The prospective REACTION study.

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.

Nomogram for Predicting Intraoperative Hemodynamic Instability in Patients With Normotensive Pheochromocytoma.

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.

The first compound heterozygous mutations in SLC12A3 and PDX1 genes: a unique presentation of Gitelman syndrome with distinct insulin resistance and familial diabetes insights.

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.

Parathyroid carcinoma: Report of 10 patients and literature review.

OBJECTIVE: Parathyroid carcinoma (PC) is a rare disease with high rates of misdiagnosis and recurrence. This report summarized the clinical and pathological characteristics of 10 patients with PC at our hospital, to improve the early recognition and prognosis of PC. METHODS: The clinical manifestations, imaging findings, pathological features, treatments, and prognostic data of 10 patients diagnosed with PC at the First Medical Center, Chinese PLA General Hospital from 2003 to 2021 were analyzed. RESULTS: There were 7 male and 3 female patients with PC whose average age was 41.4 ± 9.4 years. All patients had bone involvement (bone pain and/or osteoporosis), meanwhile 6 patients had kidney stones and 7 patients had palpable neck masses. Five patients presented with tumor metastasis, invading lymph nodes, lung, liver, or bone. Laboratory examinations revealed elevated serum total calcium (4.15 ± 0.81 mmol/L), parathyroid hormone (PTH, 1236.1 ± 519.9 pg/mL) and alkaline phosphatase (405.8 ± 219.0 IU/L) levels. Especially, hypercalcemic crisis occurred in 9 patients. The diagnosis of PC depended on histopathological features of the parathyroid tumor, including capsular and/or vascular invasion. All patients underwent at least en bloc resection. In the follow-up, six patients with relatively high preoperative PTH levels (1519.5 ± 436.8 pg/mL) relapsed postoperatively. Two patients with the Ki-67 index ≥ 10% in parathyroid tumor tissue and distant metastasis died within 2 years after the operation. CONCLUSION: Severe bone pain, kidney stones, hypercalcemic crisis, and markedly elevated PTH usually indicate PC. A markedly elevated PTH level, tumor metastasis, and the Ki-67 index ≥ 10% may be indicators of poor prognosis.

Comparison of efficacy and safety of three novel hypoglycemic agents in patients with severe diabetic kidney disease: A systematic review and network meta-analysis of randomized controlled trials.

Objective: To analyze the efficacy and safety of three novel hypoglycemic agents, glucagon-like peptidyl-1 receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter two inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) patients with severe chronic kidney disease (CKD) (defined in this study as CKD stage 3 B or above, eGFR< 45 mL/min/1.73 m²) based on important RCTs to date. Methods: We retrieved studies published before April 15, 2022, from EMBASE, PubMed/MEDLINE, Cochrane Library and included randomized controlled trials in which the participants were patients with T2DM and severe CKD. Frequentist methods were used in the network meta-analysis. Results: Nineteen studies of 17 trials involving 6,607 participants met our inclusion criteria. Compared with placebo and DPP-4i, SGLT2i demonstrated a significantly lower incidence of serious renal-related adverse events or renal death, and the odds ratios (OR) were 0.69 (0.58, 0.81) and 0.63 (0.40, 1.00), respectively. Compared with placebo, SGLT2i significantly reduced the incidence of all-cause death and severe AE; the ORs were 0.72 (0.55, 0.94) and 0.65 (0.47, 0.91), respectively. Compared with placebo, DPP-4i significantly reduced the level of HbA1c, and the difference between mean changes from baseline was -0.36 (-0.63, -0.09). Conclusions: Patients with T2DM complicated by severe CKD may benefit from SGLT2i. SGLT2i can reduce the incidence of serious renal-related AEs or renal death, as well as severe side effects, and has a positive effect on the patient's renal function and survival, even for only CKD patients can also be considered. GLP-1 RAs can be used as a supplement if blood sugar control is poor. For dialysis patients, DPP-4i can assist blood glucose control, reduce insulin dosage, and reduce the risk of hypoglycemia. Systematic review registration: INPLASY https://inplasy.com/inplasy-2021-12-0106/, identifier INPLASY2021120106.