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Background: Uteroglobin is a multifunctional protein with anti-inflammatory properties. Studies have revealed the importance of inflammation in type 2 diabetes mellitus (T2D) pathogenesis. Here, we investigated the relationship between uteroglobin and T2D., Methods: We performed diagnostic tests for diabetes in subjects who had not been diagnosed with or treated for T2D. We established three groups, containing those with normal glucose tolerance (NGT), prediabetes and T2D, consisting of 80 people each, and compared their uteroglobin levels. In addition, 28 patients newly diagnosed with T2D were treated with metformin for 12 weeks, and 63 patients newly diagnosed with dyslipidaemia during the treatment for T2D were treated with statin for 12 weeks., Results: This study showed that uteroglobin levels were significantly lower in prediabetes and T2D groups than in the NGT group. Uteroglobin levels were not significantly correlated with other metabolic parameters, except BMI, HOMA-β and eGFR. In the group treated with metformin or statin, uteroglobin levels increased after treatment compared to before treatment., Conclusions: Uteroglobin is a sensitive factor that was decreased even in prediabetes and increased upon treatment with drugs with anti-inflammatory effects. Uteroglobin is a potential early biomarker that reflects a chronic inflammatory condition in T2D., 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 Lim, Ju, Kim, Yi, Lee, Kim, Ku and Joung.)

Objective: The aim of this study was to evaluate the admission indicators and characteristics of individuals diagnosed with type 1 diabetes (T1D) to ascertain potential impact on the choice of glucose control therapy after discharge., Methods: A total of 398 eligible T1D patients were selected. We conducted multivariable logistic regression analysis to determine the independent influence of predictors on the selection of glucose control therapy after discharge. To explore the influencing factors of different subgroups, we additionally performed subgroup analyses based on gender and age., Results: Our study revealed that body mass index (BMI) was noteworthy influence factor for prescription of insulin and non-insulin antidiabetic drug (NIAD prescription) in T1D patients of general population [OR = 1.109 (1.033-1.195), p = 0.006], male [OR = 1.166 (1.040-1.318), p = 0.011] and individuals below the age of 30 years [OR = 1.146 (1.020-1.301), p = 0.028]. Diastolic blood pressure (DBP) was a protective factor for NIAD prescription in the general population [OR = 0.971 (0.949-0.992), p = 0.008] and women [OR = 0.955 (0.923-0.988), p = 0.008]. The other risk factor of NIAD prescription in men was dyslipidemia [OR = 4.824 (1.442-22.246), p = 0.020]. Pulse pressure [OR = 1.036 (1.007-1.068), p = 0.016] constituted an additional risk factor of NIAD prescription among individuals below the age of 30 years. The risk factors of NIAD prescription for people aged 30 to 50 years were length of stay [OR = 1.097 (1.014-1.196), p = 0.026] and initial blood glucose [OR = 1.078 (1.007-1.168), p  = 0.047]. In the case of individuals aged above 50 years, physicians exhibited a higher tendency to prescribe supplementary non-insulin medications to men [OR = 9.385 (1.501-87.789), p = 0.029]., Conclusions: We identified notable factors that influence discharge prescriptions in patients with T1D. In order to enhance the treatment outcome for the patient, clinicians ought to have a special focus on these indicators or factors., 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 handling editor XW declared a past co-authorship with the authors JH & CX., (Copyright © 2024 Cheng, Li, Liu, Jin, Han, Du and Xu.)

Fetal and neonatal development is a critical period for the establishment of the future metabolic health and disease risk of an individual. Both maternal undernutrition and overnutrition can result in abnormal fetal organ development resulting in inappropriate birth size, child and adult obesity, and increased risk of Type 2 diabetes and cardiovascular diseases. Inappropriate adaptive changes to the maternal pancreas, placental function, and the development of the fetal pancreas in response to nutritional stress during pregnancy are major contributors to a risk trajectory in the offspring. This interconnected maternal-placental-fetal metabolic axis is driven by endocrine signals in response to the availability of nutritional metabolites and can result in cellular stress and premature aging in fetal tissues and the inappropriate expression of key genes involved in metabolic control as a result of long-lasting epigenetic changes. Such changes result is insufficient pancreatic beta-cell mass and function, reduced insulin sensitivity in target tissues such as liver and white adipose and altered development of hypothalamic satiety centres and in basal glucocorticoid levels. Whilst interventions in the obese mother such as dieting and increased exercise, or treatment with insulin or metformin in mothers who develop gestational diabetes, can improve metabolic control and reduce the risk of a large-for-gestational age infant, their effectiveness in changing the adverse metabolic trajectory in the child is as yet unclear., 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 Hill and Hill.)

Multiple Endocrine Neoplasia type 1 ( MEN1 ) is a rare genetic disease, characterized by co-occurrence of several lesions of the endocrine system. In MEN1 , the pathogenic MEN1 gene mutations lead to the Abnormal expression of menin, a critical tumor suppressor protein. We here reported a case of a 14-year-old male with insulinoma and primary hyperparathyroidism. Genetic testing demonstrated a novel heterozygote variant c.587delA of MEN1, resulting in the substitution of the 196th amino acid, changing from glutamic acid to glycine, followed by a frameshift translation of 33 amino acids. An identical variant was identified in the proband's father, who was further diagnosed with hyperparathyroidism. To the best of our knowledge, this is the first report of MEN1 syndrome caused by the c.587delA MEN1 variant. Observations indicated that, despite sharing the same MEN1 gene change, family members exhibited diverse clinical phenotypes. This underscored the presence of genetic anticipation within the familial context., 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 Huang, Li, Zhang, Tang, Zhang, Fan, Wang and Liu.)

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.

Thyroid nodules are a prevalent health issue in society. Interventional radiological methods are successfully applied for both the diagnosis and treatment of nodules. Diagnostically, a fine-needle aspiration biopsy and a core needle biopsy can be performed to ascertain the benign or malignant nature of a lesion. In recent years, imaging-guided percutaneous treatment methods have become popular in the treatment of thyroid nodules. Aspiration, ablation, and embolization are techniques employed in the treatment process. In this study, we aimed to discuss the current role of interventional radiology in the diagnosis and treatment of thyroid nodules, which occupy an important place in clinical practice., 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 Taydas, Arik, Sevinc, Kara, Ozdemir, Cengiz, Bayhan and Ozturk.)

Background: Patients with type 2 diabetes mellitus (DM) have a high prevalence of chronic kidney disease (CKD). Energy imbalance and inflammation may be involved in the pathogenesis of CKD. We examined the effects of brain-derived neurotrophic factor (BDNF) and vascular cell adhesion molecule-1 (VCAM-1) on CKD in patients with type 2 DM., Methods: Patients with type 2 DM were enrolled for this cross-sectional study. Fasting serum was prepared to measure the BDNF and VCAM-1 levels. An estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 was used as the criterion for identifying patients with CKD., Results: Of the 548 enrolled participants, 156 had CKD. Patients with CKD exhibited significantly lower BDNF (median of 21.4 ng/mL, interquartile range [IQR]: 17.0-27.0 ng/mL vs. median of 25.9 ng/mL, IQR: 21.0-30.4 ng/mL, P < 0.001) and higher VCAM-1 (median of 917 ng/mL, IQR: 761-1172 ng/mL vs. median of 669 ng/mL, IQR: 552-857 ng/mL, P < 0.001) levels than those without CKD. Serum BDNF levels were inversely correlated with VCAM-1 levels (Spearman's rank correlation coefficient = -0.210, P < 0.001). The patients were divided into four subgroups based on median BDNF and VCAM-1 levels (24.88 ng/mL and 750 ng/mL, respectively). Notably, patients in the high VCAM-1 and low BDNF group had the highest prevalence (50%) of CKD. Multivariate logistic regression revealed a significantly higher odds ratio (OR) of CKD in the high VCAM-1 and low BDNF group (OR = 3.885, 95% CI: 1.766-8.547, P < 0.001), followed by that in the high VCAM-1 and high BDNF group (OR = 3.099, 95% CI: 1.373-6.992, P =0.006) compared with that in the low VCAM-1 and high BDNF group. However, the risk of CKD in the low VCAM-1 and low BDNF group was not significantly different from that in the low VCAM-1 and high BDNF group ( P =0.266)., Conclusion: CKD in patients with type 2 DM is associated with low serum BDNF and high VCAM-1 levels. BDNF and VCAM-1 have a synergistic effect on CKD. Thus, BDNF and VCAM-1 can be potential biomarkers for CKD risk stratification in patients with type 2 DM., 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 Chiang, Li, Chan, Cheng, Wu, Lin, Huang and Lee.)

Objective: Although radiofrequency ablation (RFA) is a safe and effective non-surgical treatment for benign thyroid nodules, injury to the recurrent laryngeal nerve (RLN), is a potential and feared complication. Intermittent voice checks have been proposed to monitor vocal cord (VC) function during RFA, but such assessment is highly subjective and effort-dependent., Methods: We are here reporting the methodological use of flexible laryngoscopy (FL) for VC monitoring during bilateral thyroid RFA treatment. The patient, a 35-year-old woman, was referred to the Endocrinology Unit for subclinical hyperthyroidism due to bilateral autonomously functioning thyroid nodules., Results: At the end of the treatment of the first nodule, the FL performed by an otorhinolaryngologist specialist allowed evaluating VC function and ruling out possible paralysis before proceeding with the contralateral RFA treatment. The patient was awake during the entire procedure and well tolerated the laryngoscopic examination. The TSH serum evaluations performed one month and 9 months after the procedure assessed an euthyroid state (TSH 3.2 mIU/L and 2.8 mIU/L, respectively)., Conclusion: During bilateral thyroid RFA the use of FL for VC monitoring treatment resulted in a safe, easy-to-perform, and effective strategy to minimize and anticipate RLN injury risk in the awake patient. The prevention of RLN damage is advisable in the case of single RFA treatment, while it should be strongly recommended when RFA is performed on bilateral nodules., 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 Teliti, Occhini, Fonte, Croce, Calì, Ripepi, Carbone, Rotondi and Chytiris.)

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.

Background: Cardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD)., Method: We enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m 2 ). Logistic and Cox regression analyses were performed., Results: Patients with elevated uACR (n=107) and reduced eGFR (n=32) had a higher rate of definite CAN. After adjusting for covariates, definite CAN was associated with elevated uACR (OR=2.4, 95% CI 1.07-5.36) but not with reduced eGFR (OR=3.43, 95% CI 0.62-18.90). A total of 94 patients repeated uACR measurements within 2 years (mean follow-up, 586.3 ± 116.8 days). Both definite and early CAN were independent risk factors for elevated uACR (HR=8.61 and 8.35, respectively; both p <0.05). In addition, high-density lipoprotein cholesterol, ACE inhibitors/angiotensin receptor blockers and glucagon-like peptide-1 receptor agonists were independent protective factors for elevated uACR (HR=0.96, 0.25, and 0.07, respectively; all p <0.05)., Conclusion: Cardiovascular autonomic neuropathy is a potential indicator of DKD. Comprehensive management of DKD in the early stages of CAN may prevent microalbuminuria., 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 Cho, Lim, Kwon, Chung, Moon, Yoon and Won.)

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.

Objective: To investigate the molecular mechanisms through which exercise influences metabolic syndrome (MS) and identify key research trends and collaborative networks using bibliometric and visualization techniques., Methods: We conducted a systematic literature search using the Web of Science Core Collection for articles published from 2014 to 2023. Using CiteSpace, we performed a bibliometric analysis of 562 eligible papers, generating visual knowledge maps to identify prevailing patterns, popular subjects, and emerging trends in the literature., Results: The study reveals that exercise mitigates MS by reversing high-fat diet-induced abdominal obesity, reducing lipid accumulation and inflammation, enhancing insulin sensitivity, and improving cardiovascular function. Key molecular pathways include PPAR-γ/CPT-1/MCAD signaling, AMPK activation, and nitric oxide production. The USA leads in research output, with significant contributions from American institutions. Collaboration among researchers is limited, highlighting the need for more extensive and high-quality research initiatives., Conclusions: Regular, moderate-to-high-intensity exercise is crucial for managing MS. Exercise activates beneficial molecular pathways, improving metabolic health and cardiovascular function. Future research should focus on expanding collaborations and exploring novel molecular targets to enhance the therapeutic potential of exercise in metabolic syndrome management., 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 Wan, Jin, Fan, Xu, Li, Yan and Wang.)

Background: To clarify the controversy between inflammatory or autoimmune skin diseases and thyroid diseases, we performed two-sample Mendelian randomization (MR) analyses., Participants: Genetic data on factors associated with atopic dermatitis (AD, n=40,835), seborrheic dermatitis (SD, n=339,277), acne (n=363,927), rosacea (n=299,421), urticaria (n=374,758), psoriasis (n=373,338), psoriasis vulgaris (n=369,830), systemic lupus erythematosus (SLE, n=14,267), vitiligo (n=353,348), alopecia areata (AA, n=361,822), pemphigus (n=375,929), bullous pemphigoid (BP, n=376,274), systemic sclerosis (SSc, n=376,864), localized scleroderma (LS, n=353,449), hypothyroidism (n=314,995 or n=337,159), and hyperthyroidism (n=281,683 or n=337,159) were derived from genome-wide association summary statistics of European ancestry., Main Measures: The inverse variance weighted method was employed to obtain the causal estimates of inflammatory or autoimmune skin diseases on the risk of thyroid diseases, complemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO)., Key Results: AD, SLE, SD, and psoriasis vulgaris were associated with an increased risk of hypothyroidism, whereas BP was associated with a lower risk of hypothyroidism (all with p < 0.05). The multivariable MR analyses showed that AD (OR = 1.053; 95%CI: 1.015-1.092; p = 0.006), SLE (OR = 1.093; 95%CI: 1.059-1.127; p < 0.001), and SD (OR = 1.006; 95%CI: 1.002-1.010; p = 0.006) independently and predominately contributed to the genetic causal effect on hypothyroidism after adjusting for smoking. The results showed no causal effects of inflammatory or autoimmune skin diseases on hyperthyroidism., Conclusion: The findings showed a causal effect of AD, SLE, SD on hypothyroidism, but further investigations should be conducted to explore the pathogenic mechanisms underlying these relationships., 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 You, Duan, Zhou, Yu, Zou, Wei, Chai, Zeng, Xiao, Yuan and Xiao.)

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have cardiovascular (CV) benefits, particularly in reducing the risk of heart failure (HF). Pioglitazone (Pio) has shown potential in decreasing the risks of recurrent stroke, non-fatal myocardial infarction (MI), and all-cause mortality but increasing risks of HF. Our study aimed to examine the synergistic effects on CV outcomes in patients with type 2 diabetes mellitus (T2DM) who received the combined treatment of SGLT2i and Pio., Materials and Methods: A total of 117,850 patients with T2DM and without a history of HF were selected as the observational study cohort from the Chang Gung Research Database (CGRD) in Taiwan between January 1, 2016, and December 31, 2019. The primary composite outcome was 4-point major adverse CV events (4P-MACE), including CV death, non-fatal MI, non-fatal ischemic stroke, and hospitalization for HF. The study was divided into four groups: a combined treatment group in which SGLT2i and Pio were used, two individual groups in which SGLT2i or Pio was used separately, and a reference group (non-study drugs)., Results: Combined treatment of SGLT2i and Pio had the lowest risk of 4P-MACE (adjusted hazard ratio [aHR], 0.66; 95% confidence interval [CI], 0.54-0.80) compared with the reference group after a mean follow-up of 2.2 years. There was no significant difference in risks of hospitalization for HF (adjusted subdistribution hazard ratio, 0.73; 95% CI, 0.49-1.07) compared with the reference group., Conclusions: In T2DM patients without HF, the combined treatment with SGLT2i and Pio may synergistically provide CV benefits without increasing risks of HF., 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 Li, Wang, Liu, Yen, Wu, Huang, Lee and Hsiao.)

Background: Mounting evidence indicates the importance of the interplay between skeletal muscles and lipid metabolism. Remnant cholesterol (remnant-C) is considered one of the principal residual risk factors for cardiovascular disease and metabolic disorders; however, there are limited studies on the impact of remnant-C on sarcopenia., Methods: Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) between 2008 and 2011 were used in this nationwide population-based study. In total, 17,408 participants were enrolled in this study. The subjects were categorized into four groups according to the quartile of remnant-C values. We conducted multivariable logistic regression analysis to evaluate the association between remnant-C and muscle mass measured using dual-energy X-ray absorptiometry., Results: A total of 1,791 participants (10.3%) presented low muscle mass, and there was a sequential increase in the percentage of low muscle mass across remnant-C quartiles (Q1, 5.2%; Q2, 8.7%; Q3, 11.5%; Q4, 15.7%). In the full adjusted model, those in the highest remnant-C quartile group showed significantly increased odds ratio (OR) for low muscle mass compared with those in the lowest remnant-C group after adjusting for various confounding factors (OR = 1.33, 95% confidence interval (CI) = 1.06-1.68, P < 0.05). A wide range of subgroups and sensitivity analyses showed consistent results, supporting the robustness of our findings., Conclusions: Increased remnant-C value was associated with a high risk of low muscle mass in the Korean population. Remnant-C may be a novel marker for the prediction and management of sarcopenia in aging societies., 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 Jang, Hwang, Jang, Kim, Yu, Kim, Yoo, Kim, Baik and Choi.)

Purpose: The natural history in unselected cohorts of patients with pheochromocytoma/ paraganglioma (PPGL) followed for a period >10 years remains limited. We aimed to describe baseline characteristics and outcome of a large cohort and to identify predictors of shorter survival., Methods: This retrospective single-center study included 303 patients with newly diagnosed PPGL from 1968 to December 31, 2023, in 199 prospectively supplemented since July 2020. Mean follow-up was 11.4 (range 0.3-50) years, germline genetic analyses were available in 92.1%. The main outcome measures were overall (OAS), disease-specific (DSS), recurrence-free (RFS) survival and predictors of shorter survival evaluated in patients with metastases at first diagnosis (n=12), metastatic (n=24) and nonmetastatic (n=33) recurrences and without evidence of PPGL after first surgery (n=234)., Results: Age at study begin was 49.4 ± 16.3 years. There were 72 (23.8%) deaths, 15 (5.0%), 29 (9.6%) and 28 (9.2%) due to PPGL, cardiovascular disease (CVD) and malignant or other diseases, respectively. Median OAS, DSS1 (tumor-related) and DSS2 (DSS1 and death caused by CVD) were 4.8, 5.9 and 5.2 years (patients with metastases at first diagnosis), 21.2, 21.2 and 19.9 years, and 38.0, undefined and 38.0 years (patients with metastatic and with nonmetastatic recurrences, respectively). Major adverse cardiovascular events (MACE) preceded the first diagnosis in 15% (n=44). Shorter DSS2 correlated with older age (P ≤ 0.001), male sex (P ≤ 0.02), MACE (P ≤ 0.01) and primary metastases (P<0.0001, also for DSS1)., Conclusion: The clinical course of unselected patients with PPGL is rather benign. Survival rates remain high for decades, unless there are MACE before diagnosis or metastatic disease., 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 Raber, Schendl, Arikan, Scheuba, Mazal, Stadlmann, Lehner, Zeitlhofer, Baumgartner-Parzer, Gabler and Esterbauer.)

Objective: Associations between acromegaly and several respiratory diseases, such as obstructive lung disease or sleep apnea, have been suggested, but the relationship between bronchiectasis and acromegaly is unclear. We investigated whether acromegaly is related to the development of bronchiectasis., Materials and Methods: Using the Korean National Health Insurance System database between 2006 and 2016, we studied the relationship between acromegaly and bronchiectasis in patients with acromegaly (n=2593) and controls (1:5 age- and sex-matched subjects without acromegaly, n=12965) with a mean follow-up period of 8.9 years. Cox proportional hazards regression analysis was used to assess the risk of bronchiectasis in patients with acromegaly compared with controls after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia., Results: The mean age of the participants was 47.65 years, and male subjects comprised 45.62% of the cohort. The incidence rate of bronchiectasis in patients with acromegaly was 3.64 per 1,000 person-years and was significantly higher than that in controls (2.47 per 1,000 person-years) (log-rank test p = 0.002). In multivariable Cox proportional hazards regression modeling, the risk of bronchiectasis was significantly higher in patients with acromegaly than that in controls (HR: 1.49; 95% CI: 1.15-1.94, p = 0.0025) after adjusting for age, sex, household income, place, type 2 diabetes, hypertension, and dyslipidemia., Conclusions: Our results suggest that acromegaly may be associated with bronchiectasis., 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 Gil, Han, Hong and Park.)

Background: Type 2 diabetes mellitus(T2DM) is characterized by hyperglycemia. Gut microbiome adjustment plays a positive part in glucose regulation, which has become a hotspot. Probiotics have been studied for their potential to control the gut flora and to treat T2DM. However, the conclusion of its glucose-lowering effect is inconsistent based on different probiotic intervention times., Objectives: To comprehensively evaluate how various probiotic intervention times affect glycemic control in people with T2DM., Methods: We retrieved PubMed, Embase, Web of Science, and Cochrane Library on randomized controlled trials(RCTs)regarding the impact of probiotics on glycemic control in patients with T2DM from the inception to November 16, 2023. Separately, two researchers conducted a literature analysis, data extraction, and bias risk assessment of the involved studies. We followed the PRISMA guidelines, used RevMan 5.4 software for meta-analysis, and assessed the risk of bias by applying the Cochrane Handbook for Systematic Reviews 5.1.0., Results: We included eight RCTs with 507 patients. Meta-analysis revealed that the use of probiotics might considerably reduce levels of glycosylated hemoglobin (HbA1c) {mean deviation (MD) = -0.33, 95% confidence interval (CI) (-0.59, -0.07), p = 0.01}, Insulin {standard mean deviation (SMD) = -0.48, 95% CI (-0.74, -0.22), p = 0.0003} and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR){SMD = -1.36, 95% CI (-2.30, -0.41), p = 0.005} than placebo group. No statistically significant differences were found regarding fasting blood glucose (FBG) and body mass index (BMI) {SMD = -0.39, 95% CI (-0.83, 0.05), p = 0.08}, {SMD = -0.40, 95% CI (-1.07, 0.27), p = 0.25}, respectively. Subgroup analyses, grouped by intervention times, showed that six to eight weeks of intervention improved HbA1c compared to the control group (p < 0.05), both six to eight weeks and 12-24 weeks had a better intervention effect on Insulin, and HOMA-IR (p < 0.05).In contrast, there was no statistically significant variation in the length between FBG and BMI regarding duration., Conclusion: This meta-analysis found probiotics at different intervention times play a positive role in modulating glucose in T2DM, specifically for HbA1c in six to eight weeks, Insulin and HOMA-IR in six to eight weeks, and 12-24 weeks. To confirm our findings, further excellent large-sample research is still required., Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023483325., 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 Wang, Chen, Zhang, Shi, Zhu, Zhao, Luo and Long.)

Background: Lymph node metastasis is the major cause of increased recurrence and death in patients with papillary thyroid carcinoma (PTC). We evaluate the clinicopathologic factors affecting excellent response (ER) in patients with PTC with lymph node metastasis following operation and 131 I ablation therapy., Methods: A total of 423 patients with PTC with lymph node metastasis who underwent thyroidectomy and postoperative 131 I ablation therapy were enrolled. The relationship between clinicopathological factors affecting ER achievement was analyzed., Results: Multivariate analysis showed that the foci diameter (≤1 cm), unifocal, combination with Hashimoto's thyroiditis (HT), lymph node metastases rate (LR) (≤40%), no postoperative lymph node metastasis, low preablative stimulated thyroglobulin (ps-Tg) level (≤3.87 ng/mL), and the time of 131 I ablation therapy (one time) were positively correlated with the ER achievement [odds ratio (OR): 1.744, 3.114, 3.920, 4.018, 2.074, 9.767, and 49.491, respectively; all p < 0.05]. The receiver operating characteristic (ROC) curves showed that the cutoff values of ps-Tg and LR were 4.625 ng/mL and 50.50%, respectively. The AUC of ROC of ps-Tg and LR for predicting ER achievement was 0.821 and 0.746, respectively. The Tg and the cumulative risk of non-ER elevated with the increase of LR, especially for the high-level ps-Tg (>4.625 ng/mL) group., Conclusion: The foci diameter and number, combination with HT, LR, and ps-Tg level are independent factors for ER. Ps-Tg level and LR are valid predictive factors for the efficacy of 131 I therapy in patients with PTC. The predictive value of the cumulative risk of non-ER can be improved by the combination of ps-Tg and LR., 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 Xu, Li, Yu, Wang, Guo, Ni, Zhao, Wang and Dong.)

Background: Chronic inflammation is implicated in the development of diabetic retinopathy (DR). The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been linked to cardiovascular and diabetic kidney diseases. However, the link between NLR and DR remains unclear. As such, this study investigated the association between NLR and DR in Chinese patients., Method: A total of 857 adults diagnosed with type 2 diabetes mellitus (T2DM) without DR at baseline between 2018 and 2021, from a single center in Ningbo, China, were included. Baseline clinical data, including age, sex, T2DM duration, hypertension, smoking, drinking, glycated hemoglobin level, lipid profile, renal function, and NLR, were recorded and analyzed. Cox proportional hazard regression analysis was used to assess the association between NLR and the risk for incident DR., Results: During a median follow-up of 3.0 years, 140 patients developed DR. The multivariable-adjusted hazard ratio (HR) for incident DR across ascending NLR quartiles (≤1.46 [reference], 1.47-1.90, 1.91-2.45 and > 2.45) were 1.000, 1.327 (95% confidence interval [CI] 0.754-2.334), 1.555 (95% CI 0.913-2.648) and 2.217 (95% CI 1.348-3.649), respectively. For each 1-standard deviation increase in NLR, the risk for DR increased by 29.2% (HR 1.292 [95% CI 1.112-1.501) after adjusting for confounding factors., Conclusion: Results revealed that a higher NLR at baseline was associated with an increased risk for incident DR. NLR has the potential to be an inexpensive, reliable, and valuable clinical measure that merits further exploration in future studies., 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 Tang, Li and Li.)

Background: Metabolic syndrome(MetS) and depression are independently associated with type 2 diabetes (T2DM) risk. However, little is known about the combined effect of MetS and depression on the risk of T2DM. The present study aims to prospectively explore the impact of MetS and depression on T2DM susceptibility among the Chinese general population., Methods: 6489 general population without T2DM adults in Southwest China were recruited from 2010 to 2012. Depression and MetS were prospectively assessed using a 9-item Patient Health Questionnaire(PHQ-9) and Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition) (CDS2020) during 2016-2020, respectively. Modified Poisson regression models were conducted to estimate relative risk(RR) and 95% confidence intervals (95%CI) for independent and combined associations of MetS and depression with an incidence of T2DM., Results: During a median follow-up of 6.6 years, 678 cases of T2DM were documented. Individuals with MetS were 1.33 times more likely to develop T2DM than those without MetS. The corresponding RR(95%CI) for depression with no depression was 1.45(1.22-1.72). Notably, compared with no MetS or depression, the multivariate-adjusted RR for a combined effect of MetS and depression on the risk of T2DM was 2.11(1.39-3.22). Moreover, an increased risk of T2DM was more apparent in those ≥ 60 years, males, and overweight., Conclusions: Individuals with multimorbidity of MetS and depression are at a higher risk of T2DM compared with those with no MetS or depression., 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 Cai, Zhou, Fan, Yang, Tian, Luo, Deng, Dai, Wang, Zhu and Liu.)

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG)., Materials and Methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 ± 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis., Results and Conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D., 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 Pixner, Chaikouskaya, Lauth, Zimmermann, Mörwald, Lischka, Furthner, Awender, Geiersberger, Maruszczak, Forslund, Anderwald, Cadamuro, Weghuber and Bergsten.)

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.

Background: Papillary thyroid microcarcinoma (PTMC) is characterized by its favorable prognosis and potential for active surveillance (AS) as a management option. However, the presence of cervical lymph node (LN) metastasis, especially lateral LN metastasis, significantly impacts management and prognosis. Previous studies have focused on post-surgery risk factors for cervical LN metastasis. This study aims to identify predictors of lateral LN metastasis by analyzing pre-operative ultrasonographic findings alongside clinicopathological factors., Methods: A retrospective review of medical records was conducted for patients with PTMC who underwent surgery at Chonnam National University Hwasun Hospital between 2004 and 2013. This is a case-control study that compares patients with lateral LN metastasis (N1b) to age- and sex-matched patients without LN metastasis (N0). Subgroup analysis was performed to evaluate risk factors of skip metastasis., Results: The study included 90 patients with PTMC with lateral LN metastasis (N1b) and 268 age- and sex-matched patients without LN metastasis (N0). The mean age was 49.3 years, and female patients were dominant in both groups. Structural recurrences of 4.4% (4/90) were observed only in the N1b group. The N1b group exhibited a higher frequency of upper lobe tumor location compared to the N0 group (38.9% vs. 16.0%, p < 0.001). There was no significant difference in the locations with the presence of invasion to adjacent organs. A higher proportion of non-parallel shape was observed in the N1b group than the N0 group (80.0% vs. 66.0%, p = 0.013). There were no differences in echogenicity, sonographic feature, margin, and AP diameter of the thyroid gland between the two groups. In multivariate analysis, independent risk factors for lateral LN metastasis included extrathyroidal extension, multiplicity, upper lobe tumor location, and non-parallel shape. Skip metastasis in patients with PTMC was associated with upper lobe tumor location., Conclusion: Detailed ultrasound examinations, evaluating tumor location, number, orientation, and the presence of ETE, are crucial in accurately predicting lateral LN metastasis especially when primary tumor was in the upper lobe to avoid missing skip metastasis. These evaluations can help guide the decision between AS and immediate surgery in patients with PTMC., 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 Yoon, Park, Hong, Kim and Kang.)

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 author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Background and Aims: The American Heart Association (AHA) recently introduced the Life's Essential 8 (LE8) to improve cardiovascular health (CVH). However, the association between LE8 and the risk of prediabetes or diabetes is not yet fully understood. Consequently, this study aims to assess the association between CVH, as evaluated by LE8, and the risk of prediabetes and diabetes., Methods and Results: This cross-sectional study encompassed 7,739 participants aged ≥20 years from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES). The CVH of participants was evaluated using the LE8, combining four health behaviors and three health factors. Glucose metabolic status categories included normal glucose metabolism, prediabetes including isolated impaired fasting glucose, isolated impaired glucose tolerance, both IFG and IGT, and diabetes. The associations between CVH and prediabetes and diabetes were analyzed using logistic regression, linear regression, restricted cubic splines, and subgroup analyses. Among 7,739 participants, 1,949 had iIFG, 1,165 were diagnosed with iIGT, 799 were IFG+IGT, and 537 were diagnosed with diabetes. After multivariable adjustments, CVH scores were inversely associated with prediabetes and diabetes, with the most robust inverse association observed between IFG+IGT and CVH across all prediabetes subgroups. Of all CVH components not directly in the causal pathway, body mass index (BMI) had the most robust associations with prediabetes and diabetes. Subgroup analyses indicated that the negative correlation between CVH and prediabetes was stronger among those with university or higher education., Conclusion: CVH, as defined by LE8, showed a significant negative association with prediabetes and diabetes., 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 Xu, Feng, Abdullah, Li, Fang, Tang, Yang, Kong, Huang, Wang and Xue.)

Background: Lipodystrophy is a rare disease that is poorly diagnosed due to its low prevalence and frequent phenotypic heterogeneity. The main therapeutic measures for patients with clinical lipodystrophy are aimed at improving general metabolic complications such as diabetes mellitus, insulin resistance, and hypertriglyceridemia. Therefore, there is an urgent need to find new biomarkers to aid in the diagnosis and targeted treatment of patients with congenital generalized lipodystrophy (CGL)., Methods: Dataset GSE159337 was obtained via the Gene Expression Omnibus database. First, differentially expressed genes (DEGs) between CGL and control samples were yielded via differential expression analysis and were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment to explore the functional pathways. Next, protein-protein interaction analysis and the MCC algorithm were implemented to yield candidate genes, which were then subjected to receiver operating characteristic (ROC) analysis to identify biomarkers with an area under the curve value exceeding 0.8. Moreover, random forest (RF), logistic regression, and support vector machine (SVM) analyses were carried out to assess the diagnostic ability of biomarkers for CGL. Finally, the small-molecule drugs targeting biomarkers were predicted, and ibuprofen was further validated in lipodystrophy mice., Results: A total of 71 DEGs in GSE159337 were sifted out and were involved in immune receptor activity, immune response-regulating signaling pathway, and secretory granule membrane. Moreover, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN were considered as biomarkers by performing ROC analysis on 10 candidate genes. Meanwhile, RF, logistic regression, and SVM analyses further described that those biomarkers had an excellent diagnosis capability for CGL. Eventually, the drug-gene network included ibuprofen-CXCR1, ibuprofen-CXCR1, cenicriviroc-CCR2, fenofibrate-JUN, and other relationship pairs. Ibuprofen treatment was also validated to downregulate CXCR1 and CXCR2 in peripheral blood mononuclear cells (PBMCs) and improve glucose tolerance, hypertriglyceridemia, hepatic steatosis, and liver inflammation in lipodystrophy mice., Conclusion: Eight biomarkers, namely, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN, were identified through bioinformatic analyses, and ibuprofen targeting CXCR1 and CXCR2 in PBMCs was shown to improve metabolic disturbance in lipodystrophy, contributing to studies related to the diagnosis and treatment of lipodystrophy., 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 Cao, Zhao, Liu, Yan, Wang and Chen.)

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear., Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference., Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference., Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment., 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 Tang, Meng, Ni, Liu, Wang, Li, Chai, Kou, Zhang and Zhang.)

Background: Patients with Cushing's disease (CD) often experience slow recovery of bone mineral density (BMD), and the effectiveness of anti-osteoporosis drugs in young CD patients who have achieved biochemical remission after surgery is not well understood. Therefore, we aimed to explore whether bisphosphonates could help accelerate the recovery of osteoporosis in young CD patients with remission., Methods: We retrospectively enrolled 34 young patients with CD who achieved postoperative biochemical remission. All patients suffered from osteoporosis before surgery and were divided into postoperative bisphosphonate treatment group (16 cases) and without bisphosphonate treatment group (18 cases). Clinical data, BMD (Z Value), and bone turnover markers were collected at the time of diagnosis and one year after successful tumor resection., Results: The Z values in the lumbar spine showed slight improvement in both groups at follow-up compared to baseline, but this improvement was not statistically significant. There was no significant difference observed between the two groups at follow-up. One year after operation, bone formation markers (OC and P1NP) were significantly higher than those at baseline in both groups. However, OC and P1NP in the bisphosphonate treatment group were lower than those in control group at one year follow-up. In without bisphosphonate treatment group, β-CTX from follow-up visit was higher than that at baseline, while no significant difference was observed in the bisphosphonate treatment group before and after surgery., Conclusion: Young patients with Cushing's disease combined with osteoporosis might not benefit from bisphosphonate therapy for osteoporosis recovery in the first year after achieving biochemical remission., 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 Sun, Sun, Ye and Zhang.)

Background: Oxidative Balance Score (OBS) is a novel indicator of the overall antioxidant/oxidant balance, providing a comprehensive reflection of the body's overall oxidative stress status, with higher OBS suggesting more substantial antioxidant exposures. We aimed to investigate the possible relationship between OBS with serum uric acid (SUA) and hyperuricemia., Methods: Data utilized in this study were sourced from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). Participants under 18 years old, those with ≤16 complete data out of 20 OBS components, incomplete serum uric acid data, and missing covariates were excluded from the analysis. OBS was computed by evaluating 16 nutrients and 4 lifestyle factors, encompassing 5 pro-oxidants and 15 antioxidants, guided by a priori knowledge of their relationship with oxidative stress., Results: A total of 1,5096 individuals were included in our analysis with 49.7% being male, and an average age of 49.05 ± 17.56 years. The mean OBS was 19.76 ± 7.17. Hyperuricemia was present in 19.28% of participants. Due to the right-skewed distribution of the OBS, a natural log transformation was applied to address this issue, and Quartiles of lnOBS 1, 2, 3, and 4 were 1.10-2.56 (N=3526), 2.64-2.94 (N=3748), 3.00-3.22 (N=4026), and 3.26-3.61 (N=3796), respectively. Multivariable logistic regression showed that higher lnOBS quantiles were correlated with lower serum uric acid levels. Compared with the lowest lnOBS quantile, participants in the highest lnOBS quantile had a significant serum uric acid decrease of 16.94 μmol/L for each unit increase in lnOBS (β=-16.94, 95% CI: -20.44, -13.45). Similar negative associations were observed in the second-highest (β=-8.07, 95% CI: -11.45, -4.69) and third-highest (β=-11.69, 95% CI: -15.05, -8.34) lnOBS quantiles. The adjusted odds ratios (ORs) for hyperuricemia in Quartiles 1, 2, 3, and 4 were 1.00, 0.84 (95% CI: 0.75, 0.95), 0.78 (95% CI: 0.69, 0.88), and 0.62 (95% CI: 0.55, 0.71), respectively. Compared to Quartile 1, participants in Quartile 4 had a 38% lower prevalence of hyperuricemia. Subgroup analysis and interaction test showed that there was a significant dependence of sex between OBS and serum uric acid (p for interaction <0.05), but not hyperuricemia (p for interaction >0.05). Subgroup analysis stratified by age, BMI, hypertension, diabetes, and hyperlipidemia showed there is no significant dependence on these negative correlations (all p for interaction >0.05)., Conclusions: The serum uric acid levels and prevalence of hyperuricemia in US adults exhibited a negative association with OBS. By exploring this connection, our research aims to gain a better understanding of how oxidative balance affects the prevalence of hyperuricemia. This could provide valuable insights for developing preventive strategies and interventions for hyperuricemia. Additional large-scale prospective studies are required to explore the role of OBS in hyperuricemia further., 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 Yang, Wu, An and Li.)

The proposed expert opinion aimed to address the current knowledge on conceptual, clinical, and therapeutic aspects of diabetic peripheral neuropathy (DPN) and to provide a guidance document to assist clinicians for the best practice in DPN care. The participating experts consider the suspicion of the disease by clinicians as a key factor in early recognition and diagnosis, emphasizing an improved awareness of the disease by the first-admission or referring physicians. The proposed "screening and diagnostic" algorithm involves the consideration of DPN in a patient with prediabetes or diabetes who presents with neuropathic symptoms and/or signs of neuropathy in the presence of DPN risk factors, with careful consideration of laboratory testing to rule out other causes of distal symmetric peripheral neuropathy and referral for a detailed neurological work-up for a confirmative test of either small or large nerve fiber dysfunction in atypical cases. Although, the first-line interventions for DPN are currently represented by optimized glycemic control (mainly for type 1 diabetes) and multifactorial intervention (mainly for type 2 diabetes), there is a need for individualized pathogenesis-directed treatment approaches for DPN. Alpha-lipoic acid (ALA) seems to be an important first-line pathogenesis-directed agent, given that it is a direct and indirect antioxidant that works with a strategy targeted directly against reactive oxygen species and indirectly in favor of endogenous antioxidant capacity for improving DPN conditions. There is still a gap in existing research in the field, necessitating well-designed, robust, multicenter clinical trials with sensitive endpoints and standardized protocols to facilitate the diagnosis of DPN via a simple and effective algorithm and to track progression of disease and treatment response. Identification of biomarkers/predictors that would allow an individualized approach from a potentially disease-modifying perspective may provide opportunities for novel treatments that would be efficacious in early stages of DPN, and may modify the natural course of the disease. This expert opinion document is expected to increase awareness among physicians about conceptual, clinical, and therapeutic aspects of DPN and to assist them in timely recognition of DPN and translating this information into their clinical practice for best practice in the management of patients with DPN., Competing Interests: Author HS was employed by the company Abdi Ibrahim Turkey. The remaining 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 Atmaca, Ketenci, Sahin, Sengun, Oner, Erdem Tilki, Adas, Soyleli and Demir.)

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.

Objective: Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC) required to achieve proficiency are still lacking., Materials and Methods: The first 179 RFA procedures performed by a single operator in patients with non-functioning BTN were retrospectively analyzed. Six-month nodule volume reduction rate (VRR) ≥ 50% was regarded as reflection of proficiency. Multiple linear regression analysis has been performed to determine the relationship between the VRR and clinical variables. Cumulative sum (CUSUM) charts were plotted to assess LCs for all consecutive procedures and in relation to basal nodule size. In details, Group 1 (G1): 57 patients with small nodules (<10 ml); Group 2 (G2): 87 patients with intermediate nodules (10 - 25 ml); Group 3 (G3): 35 patients with large size (> 25 ml)., Results: LC of all 179 procedures showed 3 phases: initial learning (1-39 procedures); consolidation (40-145 procedures); and experienced period (146-179 procedures). For G1 and G2 proficiency is achieved starting from the 10th procedure within the group (or 37th considering consecutively all procedures) and from the 59th procedure within the group (or 116th considering consecutively all procedures), respectively. LC of G3 did not detect operator proficiency., Conclusion: Specific LCs exist concerning the basal size of the nodule treated with RFA. In nodules with baseline volume > 25 ml suboptimal VRR has to be expected. Previously achieved experience on small-intermediate nodules does not seem to provide advantages in terms of higher VRR in the treatment of large nodules. Other potential and non-modifiable factors likely play a key role in the final volume reduction independently from the increased skill of the operator., 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 Chytiris, Teliti, Croce, Coperchini, Grillini, Cerutti, Fonte, Magri and Rotondi.)

Background: The Oxidative Balance Score (OBS), which quantifies the balance between antioxidants and pro-oxidants influenced by diet and lifestyle, is crucial given oxidative stress's significant role in Chronic Kidney Disease (CKD). This study aims to determine the association between OBS and CKD using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018., Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. OBS was constructed from a detailed array of 20 factors, including dietary nutrients and lifestyle behaviors. The relationship between OBS and CKD risk was evaluated using weighted logistic regression models, adjusted for potential confounders, with a generalized additive model (GAM) examining non-linear associations. Subgroup analyses and interaction effects across diverse demographic and clinical groups, along with sensitivity analyses, were performed to validate the findings., Results: Among 32,120 participants analyzed, 4,786 were identified with CKD. Fully adjusted weighted logistic regression analysis revealed that each unit increase in OBS was associated with a 2% reduction in CKD prevalence [OR: 0.98 (0.98-0.99), P < 0.001]. Higher OBS quartiles were significantly correlated with a decreased CKD risk [Q4 vs . Q1: OR: 0.82 (0.68-0.98), P = 0.03; P for trend = 0.01]. The GAM and smoothed curve fit indicated a linear relationship between OBS and the risk of CKD. Stratified and sensitivity analyses further substantiated the inverse relationship between OBS and CKD prevalence., Conclusions: Our findings from the NHANES data affirm a significant inverse association between OBS and CKD risk in the U.S. population, underscoring the role of optimizing dietary and lifestyle factors in managing CKD risk. These results advocate for incorporating OBS considerations into CKD prevention and treatment strategies., 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 Wen, Li, Chen, Li, Yang and Tan.)

Purpose: This study aimed to investigate the prevalence and co-prevalence of comorbidities among Chinese individuals with type 2 diabetes (T2DM)., Methods: Medical records were retrospectively retrieved from the 3B Study database, which provided a comprehensive assessment of comorbid conditions in Chinese adult outpatients with T2DM. Patient characteristics, laboratory measures, and comorbidities were summarized via descriptive analyses, overall and by subgroups of age (<65, 65-74, 75 years) and gender., Results: Among 25,454 eligible patients, 53% were female, and the median age was 63 years. The median time of diabetes duration was 6.18 years. A total of 20,309 (79.8%) patients had at least one comorbid condition alongside T2DM. The prevalence of patients with one, two, three, and four or more comorbid conditions was 28.0%, 24.6%, 15.6%, and 11.6%, respectively. Comorbidity burden increased with longer T2DM duration. Older age groups also exhibited higher comorbidity burden. Females with T2DM had a higher overall percentage of comorbidities compared to males (42.7% vs. 37.1%). The most common comorbid conditions in T2DM patients were hypertension (HTN) in 59.9%, overweight/obesity in 58.3%, hyperlipidemia in 42.0%, retinopathy in 16.5%, neuropathy in 15.2%, cardiovascular disease (CVD) in 14.9%, and renal disease in 14.4%. The highest co-prevalence was observed for overweight/obesity and HTN (37.6%), followed by HTN and hyperlipidemia (29.8%), overweight/obesity and hyperlipidemia (27.3%), HTN and CVD (12.6%), HTN and retinopathy (12.1%), and HTN and renal disease (11.3%)., Conclusion: The majority of T2DM patients exhibit multiple comorbidities. Considering the presence of multimorbidity is crucial in clinical decision-making., Systematic Review Registration: https://clinicaltrials.gov/, identifier NCT01128205., Competing Interests: SC, RZ, JL, and YZ are employees of MSD China. SR is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. The remaining author declares 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 Ji, Chai, Zhang, Li, Zheng and Rajpathak.)

Background and Objective: Previous research suggested a relationship between the Systemic Immune-Inflammation Index (SII) and multiple adverse health conditions. However, the role of SII in prediabetes and insulin resistance (IR) remains poorly understood. Therefore, this study aims to explore the potential relationship between SII and prediabetes and IR, providing data support for effective diabetes prevention by reducing systemic inflammation., Methods: Linear regression models were used to assess the correlation between continuous SII and risk markers for type 2 diabetes (T2D). Subsequently, multivariate logistic regression models and subgroup analyses were employed to evaluate the association between SII tertiles and prediabetes and IR, controlling for various confounding factors. Finally, restricted cubic spline graphs were used to analyze the nonlinear relationship between SII and IR and prediabetes., Results: After controlling for multiple potential confounders, SII was positively correlated with fasting blood glucose (FBG) (β: 0.100; 95% CI: 0.040 to 0.160), fasting serum insulin (FSI) (β: 1.042; 95% CI: 0.200 to 1.885), and homeostasis model assessment of insulin resistance (HOMA-IR) (β: 0.273; 95% CI: 0.022 to 0.523). Compared to participants with lower SII, those in the highest tertile had increased odds of prediabetes (OR: 1.17; 95% CI: 1.02-1.34; p for trend < 0.05) and IR (OR: 1.35; 95% CI: 1.18 to 1.51; p for trend<0.001)., Conclusions: Our study results demonstrate an elevated association between SII levels and both IR and prediabetes, indicating SII as a straightforward and cost-effective method identifying individuals with IR and prediabetes., 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 Guo, Wan, Zhu, Jiang and Li.)

Cuproptosis, a recently discovered form of cell death, stems from an overabundance of copper ions infiltrating mitochondria. These ions directly engage lipoylated proteins, prompting their oligomerization and subsequent loss of iron-sulfur clusters. This sequence induces proteotoxic stress, ultimately culminating in cell death. Type 2 diabetes, a chronic metabolic disorder resulting from a complex interplay of genetic and environmental factors, has not yet been fully understood in terms of its etiology and pathogenesis. Intricately, it is linked to various modalities of cell death, including mitochondrial autophagy, apoptosis, pyroptosis, and ferroptosis. Studies have discovered impaired copper metabolism in individuals with Type 2 diabetes, hinting at a unique role for copper homeostasis in the progression of the disease. To this end, the present research aims to delineate the potential correlation between cuproptosis and Type 2 diabetes by exhaustively reviewing the existing literature. By synthesizing relevant research on cuproptosis, the paper intends to lay the groundwork for a thorough exploration of the pathogenesis of Type 2 diabetes and the development of targeted therapeutic interventions. The ultimate objective is to facilitate a deeper understanding of Type 2 diabetes and to identify novel therapeutic strategies associated with cuproptosis., 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 Qu, Wang and Wang.)

Background: The current clinical practice lacks sufficient objective indicators for evaluating thyroid-associated ophthalmopathy (TAO). This study aims to quantitatively assess TAO by evaluating levator palpebrae superioris (LPS) using Dixon-T2WI., Methods: The retrospective study included 231 eyes (119 patients) in the TAO group and 78 eyes (39 volunteers) in the normal group. Dixon-T2WI provided data on maximum thickness of LPS (LPS&#95;T) and signal intensity ratio (LPS&#95;SIR) between the muscle and ipsilateral brain white matter. TAO diagnosis and assessment of its activity and severity were quantitatively determined using LPS&#95;T and LPS&#95;SIR., Results: In the TAO group, LPS&#95;T and LPS&#95;SIR were higher than those in the normal group ( p < 2.2e-16). The upper lid retraction (ULR) ≥ 2 mm group exhibited higher LPS&#95;T and LPS&#95;SIR compared to the ULR < 2 mm and normal groups. Optimal diagnostic performance was achieved with an AUC of 0.91 for LPS&#95;T (cutoff: 1.505 mm) and 0.81 for LPS&#95;SIR (cutoff: 1.170). LPS&#95;T ( p = 2.8e-07) and LPS&#95;SIR ( p = 3.9e-12) in the active phase were higher than in the inactive phase. LPS&#95;T and LPS&#95;SIR showed differences among the mild, moderate-to-severe, and sight-threatening groups ( p < 0.05). ROC showed an AUC of 0.70 for LPS&#95;T (cutoff: 2.095 mm) in judging the active phase, and 0.78 for LPS&#95;SIR (cutoff: 1.129). For judging the moderate-to-severe and above, AUC was 0.76 for LPS&#95;T (cutoff: 2.095 mm) and 0.78 for LPS&#95;SIR (cutoff: 1.197)., Conclusion: The maximum thickness and SIR of LPS provide imaging indicators for assisting in the diagnosis and quantitative evaluation of TAO., 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 Liu, Duan, Huang, Song, Ouyang, Lin, Shen and Chen.)

Background: Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences., Methods: We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF., Results: Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What's more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% ( P < 0.001)., Conclusion: In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children., 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 author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zhang, Wang, Gu, Xu, Zhou, Wang, Lau, Wang and Li.)

Objective: This systematic review and meta-analysis was conducted to compare the benefits of adrenalectomy and conservative treatment for comorbidities associated with mild autonomous cortisol secretion (MACS) in patients diagnosed with MACS., Background: MACS is the most common benign hormone-secreting functional adrenal incidentaloma. Overproduction of cortisol is observed in MACS patients, resulting in a variety of long-term health issues, including arterial hypertension (HTN), diabetes mellitus (DM), dyslipidemia, obesity, and osteoporosis; however, the classic clinical manifestations of Cushing's syndrome (CS) are not present., Methods: A systematic search was conducted using MEDLINE, Embase, Web of Sciences, and Scopus databases on December, 2023. Two reviewers independently extracted data and assessed the quality of the included articles. A meta-analysis was performed to compare the beneficial effects of adrenalectomy versus conservative management for MACS-related comorbidities., Results: Fifteen articles were included in this study, which evaluated 933 MACS patients (384 Adrenalectomy and 501 Conservative treatment, and 48 excluded due to incomplete follow-up duration). MACS diagnosis criteria were different among the included articles. All studies, however, stated that there must be no overt CS symptoms. Meta-analysis demonstrates the overall advantage of adrenalectomy over conservative treatment for MACS-related comorbidities (Cohen's d = -0.49, 95% CI [-0.64, -0.34], p = 0.00). Subgroup analysis indicated that the systolic blood pressure (pooled effect size = -0.81, 95% CI [-1.19, -0.42], p = 0.03), diastolic blood pressure (pooled effect size = -0.63, 95% CI [-1.05, -0.21], p = 0.01), and BMD (pooled effect size = -0.40, 95% CI [-0.73, -0.07], p = 0.02) were significantly in favor of adrenalectomy group rather than conservative treatment but no significant differences between the two treatment groups in other MACS-related comorbidities were reported., Conclusion: Despite the limited and diverse data, this study demonstrates the advantage of adrenalectomy over conservative treatment for MACS-related comorbidities., 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 Khadembashiri, Mohseni, Harandi, Pejman Sani, Khadembashiri, Atlasi, SeyedAlinaghi, Mohajeri- Tehrani and Larijani.)

Background: Although the relationship between health literacy and glycemic control has been explored in patients with diabetes, little is known about the relationship between different categories of diabetes health literacy and glycemic control in rural areas. Therefore, this study focused on the relationship between different categories of health literacy and glycemic control among diabetic patients in rural areas of Guangxi, China., Objective: To explore the potential profiles of health literacy among rural diabetes patients in Guangxi and investigate their relationship with blood sugar control., Methods: A health literacy questionnaire was administered to 2280 rural diabetes patients in five cities in the Guangxi Zhuang Autonomous Region. Latent profile analysis was conducted to identify potential health literacy profiles., Results: Health literacy among rural diabetes patients in Guangxi could be categorized into high literacy-high functionality and low literacy-low criticality groups. The latent categories of health literacy were associated with blood sugar control, with diabetes patients in the high literacy-high functionality group demonstrating better blood sugar control than those in the low literacy-low criticality group (P < 0.05)., Conclusion: Health literacy among rural diabetes patients in Guangxi exhibits heterogeneity. Healthcare professionals should pay attention to patients with low literacy and low criticality in rural areas and develop interventions to enhance their health literacy, thereby improving their blood sugar control., 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 Chen, Wen, Fu, Bai, Lei and Zhang.)

Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic β cell destruction and mediated primarily by autoreactive CD8+ T cells. It has been shown that only a small number of stem cell-like β cell-specific CD8+ T cells are needed to convert normal mice into T1D mice; thus, it is likely that T1D can be cured or significantly improved by modulating or altering self-reactive CD8+ T cells. However, stem cell-type, effector and exhausted CD8+ T cells play intricate and important roles in T1D. The highly diverse T-cell receptors (TCRs) also make precise and stable targeted therapy more difficult. Therefore, this review will investigate the mechanisms of autoimmune CD8+ T cells and TCRs in T1D, as well as the related single-cell RNA sequencing (ScRNA-Seq), CRISPR/Cas9, chimeric antigen receptor T-cell (CAR-T) and T-cell receptor-gene engineered T cells (TCR-T), for a detailed and clear overview. This review highlights that targeting CD8+ T cells and their TCRs may be a potential strategy for predicting or treating T1D., 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 Yang, Zhang, Ding, Li, Zhang and Zou.)

Background: Previous studies have revealed the sex-specific features of pituitary-thyroid hormone (TH) actions and the prevalence of thyroid nodules (TNs) in children and adolescents. However, it was unclear in adults. We aimed to investigate the features of pituitary-TH actions in women and men at different ages, and the associations of thyrotropin (TSH), THs, and central sensitivity to THs indices including the thyroid feedback quantile-based index by FT4 (TFQI FT4 ) and the thyroid feedback quantile-based index by FT3(TFQI FT3 ) with of TNs in Chinese euthyroid adults., Methods: 8771 euthyroid adults from the communities in China were involved. Demographic, behavioral, and anthropometric data were gathered through the questionnaires. Ultrasound was performed to evaluate the TNs. TSH and THs levels were measured. The multivariable logistic regression and multivariable ordinal logistic regression were conducted., Results: TFQI FT3 among both genders, except women aged 43 to 59 years, where it increased slightly. Additionally, there was an age-related decline in TFQI FT4 levels in both women and men at ages < 50 and < 53, respectively, but a marked increase after that. Lower TSH levels were significantly associated with a higher prevalence and lower odds of having fewer TNs using multiple nodules as the base category in both men and women (both P for trend < 0.05). Additionally, lower TFQI FT3 and TFQI FT4 levels were significantly associated with a higher prevalence of TNs in women (both P for trend < 0.05), and lower TFQI FT3 levels were significantly associated with a higher prevalence of TNs in men. Both higher TFQI FT3 and TFQI FT4 levels were significantly associated with higher odds of having fewer TNs using multiple nodules as the base category in women. However, the relationships between TFQI FT4 and the prevalence or number of TNs in men were not found., Conclusions: The trends of THs, TSH, TFQI FT4 , and TFQI FT3 at different ages were sex-dependent. Both TFQI FT4 and TFQI FT3 levels were negatively associated with the prevalence and number of TNs in women. The present results may lead to a better understanding of the sex-specific relationships between the development of the pituitary-TH axis and the formation of TNs., 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 Li, Yu, Yao, Liu, Wang, Ma, Liu, Wan and Shen.)

Introduction: The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups., Methods: This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves., Results: Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m 2 and 4.0% decrease in the overall cohort, 0.85 kg/m 2 and 3.9% decrease in males, and 1.2 kg/m 2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m 2 , the cutoff values were 0.75 kg/m 2 and 2.7% BMI reduction., Discussion: Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population., Competing Interests: TY has received honoraria from Kyowa Kirin, MSD, Astra Zeneca, Kissei Pharmaceutical, Novo nordisk pharma, Taisho Pharmaceutical, Sumitomo pharma, and Eli Lilly Japan; research funding from Nippon Boehringer Ingelheim, and Mitsubishi Tanabe Pharma, Suntory; and subsidies or donations from Ono Pharmaceutical, and Nippon Boehringer Ingelheim. The remaining 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 Fukuda, Okamoto, Fukaishi, Kawakami, Tanaka, Yamada and Monzen.)

Background: Thermogenic beige adipocytes, which dissipate energy as heat, are found in neonates and adults. Recent studies show that neonatal beige adipocytes are highly plastic and contribute to >50% of beige adipocytes in adults. Neonatal beige adipocytes are distinct from recruited beige adipocytes in that they develop independently of temperature and sympathetic innervation through poorly defined mechanisms., Methods: We characterized the neonatal beige adipocytes in the inguinal white adipose tissue (iWAT) of C57BL6 postnatal day 3 and 20 mice (P3 and P20) by imaging, genome-wide RNA-seq analysis, ChIP-seq analysis, qRT-PCR validation, and biochemical assays., Results: We found an increase in acetylated histone 3 lysine 27 (H3K27ac) on the promoter and enhancer regions of beige-specific gene UCP1 in iWAT of P20 mice. Furthermore, H3K27ac ChIP-seq analysis in the iWAT of P3 and P20 mice revealed strong H3K27ac signals at beige adipocyte-associated genes in the iWAT of P20 mice. The integration of H3K27ac ChIP-seq and RNA-seq analysis in the iWAT of P20 mice reveal epigenetically active signatures of beige adipocytes, including oxidative phosphorylation and mitochondrial metabolism. We identify the enrichment of GA-binding protein alpha (GABPα) binding regions in the epigenetically active chromatin regions of the P20 iWAT, particularly on beige genes, and demonstrate that GABPα is required for beige adipocyte differentiation. Moreover, transcriptomic analysis and glucose oxidation assays revealed increased glycolytic activity in the neonatal iWAT from P20., Conclusions: Our findings demonstrate that epigenetic mechanisms regulate the development of peri-weaning beige adipocytes via GABPα. Further studies to better understand the upstream mechanisms that regulate epigenetic activation of GABPα and characterization of the metabolic identity of neonatal beige adipocytes will help us harness their therapeutic potential in metabolic diseases., 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 Mooli, Zhu, Khan, Nagati, Michealraj, Jurczak and Ramakrishnan.)

Background: Increasing evidence emphasizes the potential relationship between diabetes and OAB (overactive bladder). However, large population epidemiology is still lacking., Methods: This cross-sectional study included six cycle NHANES surveys, with a total of 23863 participants. Logistic regression models were constructed to analyze the association between diabetes mellitus, diabetes-related markers, and inflammatory biomarkers with OAB. Restricted cubic splines were used to analyze the non-linear associations. Mediating analysis was performed to test the effect of inflammatory biomarkers on the relationship between diabetes-related markers and OAB. Finally, machine learning models were applied to predict the relative importance and construct the best-fit model., Results: Diabetes mellitus participants' OAB prevalence increased by 77% compared with non-diabetes. As the quartiles of diabetes-related markers increased, the odds of OAB monotonically increased in three models (all p for trend < 0.001). Glycohemoglobin exhibited a linear association with OAB (p for nonlinearity > 0.05). White blood cells significantly mediated the associations between diabetes-related markers (glycohemoglobin, fasting glucose, and insulin) with OAB, and the proportions were 7.23%, 8.08%, and 17.74%, respectively (all p < 0.0001). Neutrophils partly mediated the correlation between (glycohemoglobin, fasting glucose, and insulin) and OAB at 6.58%, 9.64%, and 17.93%, respectively (all p < 0.0001). Machine learning of the XGBoost model constructs the best fit model, and XGBoost predicts glycohemoglobin is the most important indicator on OAB., Conclusion: Our research revealed diabetes mellitus and diabetes-related markers were remarkably associated with OAB, and systemic inflammation was an important mediator of this association., 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 He, Wu, Deng, He, Wen, Wei and You.)

Objective: Diabetic peripheral neuropathy frequently occurs and presents severely in individuals suffering from type 2 diabetes mellitus, representing a significant complication. The objective of this research was to develop a risk nomogram for DPN, ensuring its internal validity and evaluating its capacity to predict the condition., Methods: In this retrospective analysis, Suqian First Hospital's cohort from January 2021 to June 2022 encompassed 397 individuals diagnosed with T2DM. A random number table method was utilized to allocate these patients into two groups for training and validation, following a 7:3 ratio. By applying univariate and multivariable logistic regression, predictive factors were refined to construct the nomogram. The model's prediction accuracy was assessed through metrics like the ROC area, HL test, and an analysis of the calibration curve. DCA further appraised the clinical applicability of the model. Emphasis was also placed on internal validation to confirm the model's dependability and consistency., Results: Out of 36 evaluated clinicopathological characteristics, a set of four, duration, TBIL, TG, and DPVD, were identified as key variables for constructing the predictive nomogram. The model exhibited robust discriminatory power, evidenced by an AUC of 0.771 (95% CI: 0.714-0.828) in the training cohort and an AUC of 0.754 (95% CI: 0.663-0.845) in the validation group. The congruence of the model's predictions with actual findings was corroborated by the calibration curve. Furthermore, DCA affirmed the clinical value of the model in predicting DPN., Conclusion: This research introduces an innovative risk nomogram designed for the prediction of diabetic peripheral neuropathy in individuals suffering from type 2 diabetes mellitus. It offers a valuable resource for healthcare professionals to pinpoint those at elevated risk of developing this complication. As a functional instrument, it stands as a viable option for the prognostication of DPN in clinical settings., 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 Luo, Long, Cheng, Xu and Li.)