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Objective: This study aimed to investigate the relationship between bone metabolism markers, including serum klotho, fibroblast growth factor 23 (FGF23), 25(OH)D3, iPTH, calcium (Ca), and PHOS and the progression of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Additionally, the predictive value of these markers for DKD progression was evaluated., Methods: This study involved 126 patients with T2DM between May 2021 and March 2023. DKD staging was assessed based on urinary protein excretion rates and estimated glomerular filtration rate (eGFR). The study evaluated serum concentrations of klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS across various stages and examined their relationships with clinical parameters. Receiver operating characteristic (ROC) curve analysis was utilized to determine the predictive accuracy of these bone metabolism markers for DKD. Multivariate linear and logistic regression analyses identified risk factors linked to DKD severity., Results: Among the 126 participants, 30 had non-DKD with normal proteinuria, while 96 had DKD, categorized as 31 with stage III DKD (microproteinuria), 34 with stage IV DKD, and 31 with stage V DKD (massive proteinuria). With advancing DKD from stage III to V, levels of klotho, 25(OH)D3, and Ca decreased significantly, whereas FGF23, iPTH and PHOS levels increased markedly. Klotho is significantly positively correlated with eGFR ( r = 0.285, P = 0.001.) and negative correlations with serum creatinine (Scr) and UACR ( r = -0.255, P = 0.004; r = -0.260, P = 0.011). FGF23 was positively related to systolic blood pressure (SBP) ( r = 0.224, P = 0.012), but negatively with eGFR ( r = -0.294, P = 0.001). Additionally, 25(OH)D3 exhibited significant negative correlations with several adverse clinical biomarkers, and both iPTH, Ca and PHOS were strongly associated with DKD progression ( P <0.05). ROC analysis showed high predictive accuracy for DKD using these bone metabolism markers, with a combined area under the curve (AUC) of 0.846. Multivariate logistic regression analysis reinforced the significance of these markers in DKD progression., Conclusion: Bone metabolism markers, such as klotho, FGF23, 25(OH)D3, iPTH, Ca and PHOS are intricately linked to DKD progression and may function as valuable predictive biomarkers., 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 Kang, Jin, Zhou, Li, Zheng, Li, Liu, Wang and Lv.)

Background: Periodontitis is a common complication of type II diabetes (T2D). However, the existing research cannot fully elucidate the association between them, let alone identify therapeutic targets for precise treatment of diabetic periodontitis. Therefore, we employed integrated genetic approaches such as single-cell analysis, Mendelian randomization (MR) analysis and colocalization analysis to uncover novel therapeutic targets for T2D and periodontitis., Methods: This study integrated single-cell analysis, MR analysis, colocalization analysis, phenotype scanning, cell-cell communication analysis and metabolic pathway activity analysis to unveil novel therapeutic targets for periodontitis and T2D. We firstly identified core cell clusters of T2D and periodontitis, and important marker genes were selected. The causal associations between these genes and the two diseases were evaluated through MR analysis. Reverse MR analysis, colocalization analysis, additional validation and phenotype scanning further supported our findings. Finally, cell-cell communication analysis and metabolic pathway activity analysis were employed to preliminarily investigate the mechanisms of the observed causal associations., Results: Through analysis of scRNA-seq data, we identified classical monocytes and intermediate monocytes as core cell subclusters. Differential analysis identified 221 differentially expressed genes (DEGs). MR analysis identified 13 genes exhibiting causal associations with T2D, and 11 causal genes with periodontitis. Colocalization analysis, reverse MR analysis, additional validation and phenotype scanning further enhanced the robustness of our results. Finally, we identified NCF1 as the core therapeutic target for T2D (OR = 1.09, 95% CI: 1.03-1.14, p = 1.85   × 10 - 3 ) and LRRC25 for T2D (OR = 0.96, 95% CI: 0.93-0.99, p = 3.44   × 10 - 2 ) and periodontitis (OR = 0.92, 95% CI: 0.84-0.99, p = 4.45   × 10 - 2 ). At last, cell-cell communication analysis indicated significant differences in functions and metabolic pathway activity between monocytes expressing or not expressing the core causal genes, which preliminarily interpreted the observed causal associations., Conclusion: This study integrated single-cell analysis, MR analysis and colocalization analysis to identified novel therapeutic targets for T2D and periodontitis. 13 causal genes were identified for T2D, and 11 for periodontitis. Among them, NCF1 and LRRC25 were regarded as core therapeutic targets. Our findings bridge the gap in the understanding of the association between T2D and periodontitis, and pave the way for targeted therapy of the two 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 Zou and Yang.)

Objective: To evaluate the prevalence and risk factors of painful diabetic peripheral neuropathy (PDPN) in patients with type 2 diabetic peripheral neuropathy (DPN) in Hunan Province, and establish and verify the prediction model., Methods: This was a retrospective study involving 4908 patients, all patients were randomly divided into the training dataset(3436 cases)and the validation dataset (1472 cases) in a ratio of 7:3. Electroneurogram, clinical signs,and symptoms were used to evaluate neuropathy. Least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal factors, and multifactorial logistic regression analysis was used to build a clinical prediction model. Calibration plots, decision curve analysis (DCA), and subject work characteristic curves (ROC) were used to assess the predictive effects., Result: The prevalence of PDPN was 33.2%, and the multivariate logistic regression model showed that peripheral artery disease, duration of diabetes, smoking, and HBA1c were independent risk factors for PDPN in patients with type 2 diabetes. ROC analysis results showed that the AUC of the established prediction model was 0.872 in the training dataset and 0.843 in the validation dataset. The calibration curve and decision curve show that the model has good consistency and significant net benefit., Conclusion: 33.2% of DPN patients had PDPN in Hunan Province, China. Peripheral artery disease, duration of diabetes, smoking, and HBA1c are risk factors for PDPN in patients with type 2 diabetes. The prediction model is based on the above factors, which can well predict the probability of PDPN., 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 Yu, Zhao, Cao and Xie.)

Background: Type 2 diabetes mellitus (T2DM) is linked to a heightened likelihood of experiencing fractures. It is crucial to ascertain whether medications used to lower blood sugar levels can elevate the risk of fractures. We aimed to investigate and compare the effects of glucagon-like peptide 1 receptor agonists (GLP-1RA), Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) on the fracture risk in patients with T2D in the real world., Methods: A network meta-analysis conducted an inclusive literature search in PubMed, Scopus, Web of Science, and Cochrane Library to select appropriate population-based cohort studies that investigated the risk of bone fractures of (GLP-1RA), (DPP-4i) or (SGLT-2i) in the real world. A network meta-analysis (NMA) was performed using R software to investigate the risk of total fractures as a primary outcome among patients who used (GLP-1RAs), (SGLT-2i) or (DPP-4i) versus each other or other glucose-lowering medications (GLMs). The odds ratio (OR) and 95% confidence interval (CI) were summarized overall network and for each pairwise direct and indirect comparison. The surface under the cumulative ranking curve (SUCRA) with the P-scores was calculated for each treatment in the network meta-analysis to detect their cumulative ranking probabilities in lowering the risk of total fractures., Results: In our NMA, we identified a set of 13 population-based cohort studies comprising a total of 1,064,952 patients. The risk of fracture was identified with the follow-up duration for each class. We found a significant decrease in the fracture risk by about 87% associated with patients who used SGLT2 inhibitors in combination with other glucose-lowering medications, followed by SGLT2 inhibitors alone by about 67%, then GLP-1 receptor agonists by about 60%, and at last DPP-4 inhibitors by about 55%., Conclusion: Our study's collective findings suggest a significant association of the low risk of fracture with the use of SGLT2i with other GLMs combination, SGLT2i alone, GLP-1RA, and DPP-4i, respectively. This population-based analysis offers the best available evidence and might be helpful for clinicians in the decision of the most suitable T2DM treatment strategies, especially for elderly type 2 diabetic patients, as they may be safe in terms of fracture., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023448720., 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 Mostafa and Alrasheed.)

Aims: To explore the predictive value of the IGF-1/IGFBP-3 ratio for the presence of thyroid nodules in patients with type 2 diabetes mellitus (T2DM)., Methods: This observational study prospectively enrolled patients with T2DM at the Second Hospital of Jilin University between May 2021 and January 2022. Thyroid nodule (TN) status was determined by ultrasonography. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of the serum IGF-1/IGFBP-3 molar ratio for TNs. Multivariable logistic regression analysis was conducted to identify risk factors for thyroid nodules in patients with T2DM., Results: A total of 122 patients (mean age ± standard deviation: 52.57 ± 11.71 years; 74 males) were enrolled. 37.7% (n=46) of patients did not have TNs, while 62.3% (n=76) had TNs. The duration of diabetes, age, and HDL-C level were significantly higher in the T2DM group with TNs compared to the group without TNs (all P < 0.05). The area under the ROC curve (AUC) for the combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio in predicting TNs in T2DM patients was 0.619 (P < 0.001). Additionally, multivariable logistic regression analysis revealed that the duration of diabetes, age, fasting plasma glucose (FPG), fasting insulin (FINS), thyroid-stimulating hormone (TSH), IGF-1, and IGFBP-3 levels were independent risk factors for thyroid nodules, while the serum IGF-1/IGFBP-3 molar ratio level was an independent protective factor for thyroid nodules in patients with T2DM (all P < 0.05)., Conclusion: The combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio may have a better predictive value for TNs in T2DM patients than using any single marker alone. The duration of diabetes, age, FPG, FINS, TSH, IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio levels were independently associated with thyroid nodules in patients with T2DM., 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 and Wang.)

Polycystic ovary syndrome (PCOS) is a disease affecting as many as about 10% of women of reproductive age, also 3-11% of teenage patients, and can lead to numerous complications and coexists with many diseases. Research is ongoing to establish an appropriate diagnostic and therapeutic path for adolescent girls with PCOS. It is also important to implement appropriate check-ups among teenagers with PCOS in order to prevent PCOS complications and initiate appropriate treatment as soon as possible and prevent the long-term consequences of these complications. The relationship between the co-occurrence of PCOS and diseases such as metabolic syndrome, hypertension, obesity, insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) is increasingly being investigated. A great attention is also being paid to the problem of mental health in this group of patients. In our study, we will review the latest reports on the treatment of PCOS and look at the complications that this syndrome can cause., 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 Jakubowska-Kowal, Skrzyńska and Gawlik-Starzyk.)

Introduction: The aim of this study was to investigate the effects of blood flow-restrictive resistance training (BFR-RT) on improving metabolic abnormalities, blood pressure (BP), obesity, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk in middle-aged patients with type 2 diabetes mellitus (T2DM)., Method: We conducted a parallel-group, single blind randomized controlled trial. Participants who met the inclusion criteria were randomly divided into control group, BFR-RT group and aerobic exercise (AE) group. Control group received health education and follow-up; Two exercise groups received supervised collective training for a period of six months, three times per week. AE group trained at moderate-intensity for 60 minutes each time, while BFR-RT group trained at low-intensity for 40 minutes each time. The primary outcomes were change in 10-year ASCVD risk index and level, and the secondary outcomes included changes in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), blood lipids, BP, and obesity level within and across the three groups at baseline, the third and sixth months of intervention., Result: Among 93 individuals (control group, n=31; AE, n=30; BFR-RT, n=32) were analyzed. At baseline, there were no significant differences in various indicators among the three groups (p>0.05). After intervention, the 10-year ASCVD risk index and risk level of both exercise groups significantly decreased compared to the control group and baseline (p<0.05), and the risk reduction became more pronounced over time. In the sixth month of intervention, the 10-year ASCVD risk index in the AE group decreased by 27.40%, and that in the BFR-RT group decreased by 26.78%. Meanwhile, apart from lipoprotein (a) and diastolic blood pressure, both exercise groups showed significant improvements in FPG, HbA1c, dyslipidemia, systolic blood pressure, and obesity indicators compared to the control group and baseline (p<0.05). There was no significant difference in various indicators between the two exercise groups (p>0.05)., Conclusion: BFR-RT could reduce the 10-year ASCVD risk in middle-aged T2DM patients for by improving metabolic abnormalities, BP and obesity, and its effect was similar to that of moderate-intensity AE., Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357., 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 Ma, Lin, Zhou, Li, Yi, Lei, Tang, Ai, Zhan, Luo, Wang, Lei, He, Yang and Ruan.)

Background: Secondary osteoporosis is associated with type 2 diabetes mellitus (T2DM), and there is conflicting evidence regarding the relationship between insulin-like growth factor-1 (IGF-1) and bone mineral density (BMD) in different populations. The objective of this study was to investigate the relationship between serum IGF-1 levels and BMD in patients with T2DM., Method: A retrospective cross-sectional study was performed on a cohort of 363 patients with T2DM, comprising men aged over 50 and women who are postmenopausal. Those with no significant medical history or medication affecting BMD or IGF-1 were considered. Data analyzed included IGF-1 levels, markers of bone metabolism, and measurements of BMD. To account for age and gender variations, we calculated IGF-1 standard deviation scores (IGF-1 SDS) for further investigation., Results: A significant increase in BMD at lumbar spine (LS), femoral neck (FN), and total hip (TH) was observed as IGF-1 SDS tertiles rose. We revealed a nonlinear correlation between IGF-1 SDS and BMD at these sites, with a common inflection point identified at an IGF-1 SDS level of -1.68. Additionally, our multivariate piecewise linear regression analysis highlighted a positive association between IGF-1 SDS and BMD at LS, FN, and TH when IGF-1 SDS exceeded the inflection point (β 0.02, 95% CI 0.01, 0.04 for LS; β 0.02, 95% CI 0.01, 0.03 for FN; β 0.02, 95% CI 0.01, 0.03 for TH). Conversely, below the inflection point, this association was not significant (β -0.04, 95% CI -0.10, 0.01 for LS; β -0.04, 95% CI -0.08, 0.01 for FN; β -0.03, 95% CI -0.08, 0.01 for TH)., Conclusion: These findings reveal a nonlinear relationship between IGF-1 SDS and BMD in T2DM patients. Higher serum IGF-1 levels were connected to increased bone density only after surpassing a certain threshold., 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 Zhao, Li, Zhang, Zhang and Ban.)

Aims: This study aimed to assess the effects of Low-to-Moderate Intensity Continuous Training (LMICT), Moderate-Intensity Interval Training (MIIT), and Reduced-Exertion High-Intensity Training (REHIT) on blood glucose regulation, functional recovery, and lipid levels in individuals who have experienced a stroke and are diagnosed with Type 2 Diabetes Mellitus (T2DM)., Methods: Forty-two T2DM stroke patients were randomly allocated to four groups: LMICT, MIIT, REHIT, and a control group (CON). Participants continuously monitored their blood glucose levels throughout the intervention using continuous glucose monitoring (CGM) devices. The study comprised two exercise intervention cycles: the first lasting from Day 3 to Day 14 and the second from Day 15 to Day 28, with the initial two days serving as contrasting periods. Primary outcomes encompassed CGM-derived blood glucose measurements, the Barthel Index (BI), Fugl-Meyer Assessment lower-extremity subscale (FMA-LE), and alterations in triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c)., Results: Compared with the CON, the MIIT group showed significant improvements in mean glucose (MG), glucose standard deviation (SD), time above range (TAR), and time in range (TIR). The REHIT group exhibited significantly reduced time below range (TBR), glucose SD, and coefficient of variation (CV). Regarding lipid levels, although the REHIT group achieved a significant reduction in TG levels compared with the CON, the overall effects of LMICT, MIIT, and REHIT on lipid profiles were relatively modest. Concerning functional recovery, the REHIT group significantly improved the BI and FMA-LE., Conclusion: Although the short-term quantitative impact of exercise on lipid levels may be limited, both REHIT and MIIT significantly improved glycemic management and reduced glucose variability in post-stroke patients with Type 2 Diabetes Mellitus. Additionally, REHIT notably enhanced functional recovery., 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, Wang, Li, Li, Huang, Huang and Ma.)

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.)

Background: Past studies have demonstrated that diabetic neuropathy is related to sarcopenia, but the further causal relation is still unclear. We sought to investigate the causal relationship by combining data from cross-sectional and Mendelian randomization (MR) studies., Methods: The genome-wide association studies data were collected from the UK Biobank and the European Working Group on Sarcopenia to conduct a bi-directional two-sample MR study to explore the causality between diabetic neuropathy and relevant clinical traits of sarcopenia, including appendicular lean mass (ALM), walking speed and low hand grip strength. The inverse-variance weighted and various sensitivity analyses were used to obtain MR estimates. We also enrolled a total of 196 Type 2 diabetes patients from April 2021 to April 2024 and divided them into the Distal peripheral neuropathy (DPN) group (n=51) and non-DPN group (n=145) via vibration perception threshold (VPT) and neuropathy deficit score. Logistic regression and ROC curve analysis were used to investigate the relationship between DPN and relevant sarcopenia clinical features., Results: According to a forward MR analysis, decreased walking speed (OR: 0.04, 95% confidence interval (CI): 0.01-0.16; P<0.001) and increased ALM (1.25 [1.05-1.50], P=0.012) had a causal effect on developing diabetic neuropathy. According to reverse MR results, developing diabetic neuropathy had a causal effect on decreased walking speed (0.99 [0.99-1.00], P=0.007) and low grip strength (1.05 [1.02-1.08], P<0.001). The cross-sectional study showed that 5-time stand time (P=0.002) and 6-meter walking speed (P=0.009) had an inverse association with DPN. Additionally, we discovered that ASMI (P=0.030) and 5-time stand time (P=0.013) were separate risk factors for DPN.ConclusionThe MR study suggested that diabetic neuropathy may have a causality with relevant clinical traits of sarcopenia, and our cross-sectional study further proved that sarcopenia indexes are predictors of diabetic neuropathy., 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 Fang, Yuan, Zhang, Liu, Yao and Ye.)

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.)

Introduction: Alpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of non-functional ACH with glucagon-producing NET is herein presented., Case Report: A 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient's past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg/ml (<209), and 68 Ga-SSTR PET/CT positive uptake was only found at the pancreatic tail (SUVmax 11.45). The patient underwent a caudal pancreatectomy and the post-operative 68 Ga-SSTR PET/CT was negative. A multifocal well-differentiated NET G1, pT1N0M0R0 (mf) strongly staining for glucagon on a background neuroendocrine alpha-cell hyperplasia with some degree of acinar fibrosis was identified on pathology analysis., Discussion and Conclusion: This case reports the incidental finding of a clinically non-functioning pNET in a patient with T2D and elevated glucagon levels, unexpectedly diagnosed as glucagon-producing NET and ACH. A high level of suspicion was required to conduct the glucagon immunostaining, which is not part of the pathology routine for a clinically non-functioning pNET, and was key for the diagnosis that otherwise would have been missed. This case highlights the need to consider the diagnosis of glucagon-producing pNET on an ACH background even in the absence of glucagonoma syndrome., 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 Cidade-Rodrigues, Santos, Calheiros, Santos, Matos, Moreira, Inácio, Souteiro, Oliveira, Jácome, Pereira, Henrique, Torres and Monteiro.)

Objective: Whether the role of post-traumatic stress disorder (PTSD) on type 2 diabetes (T2D) is mediated by obesity or other mediating factors is controversial. This study was designed to assess the impact of PTSD on genetic susceptibility to T2D and mediating factors., Methods: The datasets for PTSD, T2D, obesity, hypertension, hyperlipidemia, smoking status, and alcohol consumption were obtained from genome-wide association studies. Mendelian randomization (MR) was used to assess exposure-outcome causality, and inverse variance weighted was used as the primary tool for MR analysis. MR-Egger intercept, Cochran's Q, and leave-one-out sensitivity analysis were employed to assess horizontal pleiotropy, heterogeneity, and robustness, respectively., Results: The MR analysis showed that PTSD was associated with increased genetic susceptibility to T2D (OR, 1.036; 95% CI, 1.008-1.064; p = 0.011), obesity (OR, 1.033; 95% CI, 1.016-1.050; p < 0.001), and hypertension (OR, 1.002; 95% CI, 1.000-1.003; p = 0.015), but not not with genetic susceptibility to hyperlipidemia, alcohol consumption, and smoking status ( p ≥ 0.05). Mediated effect analysis showed that PTSD increased genetic susceptibility to T2D by increasing genetic susceptibility to obesity and hypertension, with obesity accounting for 9.51% and hypertension accounting for 2.09%. MR-Egger intercept showed no horizontal pleiotropy ( p ≥ 0.05). Cochran's Q showed no heterogeneity ( p ≥ 0.05). Leave-one-out sensitivity analysis showed that the results were robust., Conclusion: This MR analysis suggests that PTSD increases the risk of T2D and that this effect is partially mediated by obesity and hypertension. Active prevention and treatment of PTSD can help reduce the risk 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 Yu, Hu, Yang, Bai, Wu, Tong and Yu.)

Background: The association between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) has been explored in various studies, revealing inconsistent correlations that impact therapeutic effectiveness. This heterogeneity in findings requires further exploration to understand what may be driving this. Therefore, this study focuses on systematically reviewing the data, classification of variables, and analytical approach to understand if and how this may be contributing to the mixed findings. This review aims to provide insights that can enhance the generalisability of future research findings., Methods: A comprehensive electronic search was conducted, including EMBASE, MEDLINE, PsycINFO, CINAHL, Web of Science Core Collection, Scopus and specialised sleep journals. The included studies were observational studies published in English from 2011 onwards, involving adults above 18 years with OSA and T2DM or prediabetes, and included a control group. Exclusions were pregnant women, interventional studies, randomised trials, systematic reviews, conference abstracts, case studies and studies without a control group or only with descriptive analysis., Results: We reviewed 23 studies that met the inclusion criteria. Among cohort studies, 54% did not report attrition rates, and 52% did not detail methods for handling missing data in all studies. Nine studies (39%) predominantly included male participants. Objective measures were prevalent in assessing OSA, with 11 using home portable sleep monitors and four employing clinic polysomnography, though only three validated home sleep monitors. The apnea-hypopnea index was commonly used to define OSA severity, with six studies adapting the American Academy of Sleep Medicine criteria. Two studies utilised validated self-report questionnaires for OSA symptoms. T2DM diagnosis methods varied, with 17 studies using blood samples, two relying only on self-reporting, and four confirmed diagnosis via medical records., Conclusions: The variability in sample characteristics, data quality, and variable coding may contribute to the mixed finding. This review identifies gaps in using the standardised measures, reporting attrition rates, handling missing data, and including both sexes. Addressing these issues is crucial to enhancing future research generalisability. Standardising diagnostic criteria, considering clinical and sociodemographic factors, and ensuring inclusivity in study populations are essential for advancing understanding and treatment strategies for OSA and T2DM., Protocol Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023397547., 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 Taimah, Juber, Holland and Brown.)

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting people worldwide. It is characterized by several key features, including hyperinsulinemia, hyperglycemia, hyperlipidemia, and dysbiosis. Epidemiologic studies have shown that T2DM is closely associated with the development and progression of cancer. T2DM-related hyperinsulinemia, hyperglycemia, and hyperlipidemia contribute to cancer progression through complex signaling pathways. These factors increase drug resistance, apoptosis resistance, and the migration, invasion, and proliferation of cancer cells. Here, we will focus on the role of hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with T2DM in cancer development. Additionally, we will elucidate the potential molecular mechanisms underlying their effects on cancer progression. We aim to identify potential therapeutic targets for T2DM-related malignancies and explore relevant directions for future investigation., 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 Zhang, Li, Xue, Li, Gao and Qin.)

Objective: The purpose of this study was to compare different intensities of aerobic exercise for patients with knee osteoarthritis (KOA) and type 2 diabetes mellitus (T2DM) in terms of glycemic control, pain relief, and functional outcomes., Methods: A prospective randomized open-label parallel multicenter clinical trial conducted at two hospitals in Shanghai and Sichuan that included 228 patients with type 2 diabetes mellitus (T2DM) and knee osteoarthritis (KOA). Enrollment occurred between January 2021 and February 2023, and follow-up was completed in September 2023. Participants were randomized to threshold training/high-intensive stationary cycling training (n=76), intensive endurance/moderate-intensive stationary cycling training (n=77), and regular rehabilitation programs (n=75). The primary outcome at the 6-month follow-up was the HbA1c level. Key secondary outcomes included the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale of pain and quality of life., Results: Of 228 patients, 212 (93%) completed the trial. The mean adjusted (sex, baseline BMI, and baseline outcome measures) HbA1c level at the 6-month follow-up decreased significantly in the high-intensive training group compared with other groups (high-intensity group vs. control group; difference, 0.51%, 95% confidence interval, 0.05% to 1.15%). Mean KOOS subscales of pain and quality of life were statistically significantly different between the control group and moderate-intensity or high-intensity groups, but no statistical differences were noted between the different intensities of aerobic exercise. Patients in all groups achieved a greater reduction in BMI but no significant differences were observed between groups., Conclusion: In KOA and T2DM patients, high-intensity stationary cycling can significantly improve glycemic control compared with moderate-intensity and regular rehabilitation programs. However, high-intensity stationary cycling does not exert a superior effect on pain relief and functional improvement for KOA compared with moderate-intensity and regular rehabilitation programs., 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 Su, Huang, Tu and Lu.)

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: Mitochondrial dysfunction plays a crucial role in Type 2 Diabetes Mellitus (T2DM) and its complications. However, the genetic pathophysiology remains under investigation. Through multi-omics Mendelian Randomization (MR) and colocalization analyses, we identified mitochondrial-related genes causally linked with T2DM and its complications., Methods: Summary-level quantitative trait loci data at methylation, RNA, and protein levels were retrieved from European cohort studies. GWAS summary statistics for T2DM and its complications were collected from the DIAGRAM and FinnGen consortiums, respectively. Summary-data-based MR was utilized to estimate the causal effects. The heterogeneity in dependent instrument test assessed horizontal pleiotropy, while colocalization analysis determined whether genes and diseases share the same causal variant. Enrichment analysis, drug target analysis, and phenome-wide MR were conducted to further explore the biological functions, potential drugs, and causal associations with other diseases., Results: Integrating evidence from multi-omics, we identified 18 causal mitochondrial-related genes. Enrichment analysis revealed they were not only related to nutrient metabolisms but also to the processes like mitophagy, autophagy, and apoptosis. Among these genes, Tu translation elongation factor mitochondrial ( TUFM ), 3-hydroxyisobutyryl-CoA hydrolase ( HIBCH ), and iron-sulfur cluster assembly 2 ( ISCA2 ) were identified as Tier 1 genes, showing causal links with T2DM and strong colocalization evidence. TUFM and ISCA2 were causally associated with an increased risk of T2DM, while HIBCH showed an inverse causal relationship. The causal associations and colocalization effects for TUFM and HIBCH were validated in specific tissues. TUFM was also found to be a risk factor for microvascular complications in T2DM patients including retinopathy, nephropathy, and neuropathy. Furthermore, drug target analysis and phenome-wide MR underscored their significance as potential therapeutic targets., Conclusions: This study identified 18 mitochondrial-related genes causally associated with T2DM at multi-omics levels, enhancing the understanding of mitochondrial dysfunction in T2DM and its complications. TUFM , HIBCH , and ISCA2 emerge as potential therapeutic targets for T2DM and its complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Miao, Feng, Zhu, Chen, Kang, Wang, Lu and Zhang.)

Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder strongly linked to type 2 diabetes mellitus (T2DM). Understanding the predictive value of lipid parameters in identifying abnormal glucose metabolism in NAFLD patients is crucial for early intervention., Methods: This study analyzed data from the National Health and Nutrition Examination Survey(NHANES) database (2017-2020) involving 1066 NAFLD patients. Participants were categorized into three groups: T2DM (n=414), prediabetes mellitus (pre-DM) (n=507), and normoglycemia (NG) (n=145). Traditional lipid parameters [triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)] and nontraditional lipid parameters [atherogenic index of plasma (AIP), residual cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C)] were evaluated for their association with T2DM and pre-DM., Results: Elevated TG levels were significantly associated with an increased risk of T2DM and pre-DM, whereas high HDL-C demonstrated a protective effect. Among nontraditional lipid parameters, increased AIP and RC were most strongly associated with T2DM risk, while high non-HDL-C was best associated with the development of pre-DM. Stratified analyses revealed that these associations were stronger in younger, non-obese, smoking, and female NAFLD patients., Conclusion: Nontraditional lipid parameters, particularly AIP and RC, show superior predictive value over traditional lipid parameters in identifying abnormal glucose metabolism in NAFLD patients. Incorporating these novel biomarkers into clinical practice could enhance early detection and prevention strategies for T2DM and pre-DM in this high-risk population., 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, Fu, Su, Liu, Wu, Li, Wu and Zhang.)

Objective: This study explored the utility of NLR (neutrophil-to-lymphocyte ratio) as a marker to predict Lower Extremity Peripheral Artery Disease (PAD) in the Chinese population, as well as to assess its consistency and diagnostic value with digital subtraction angiography., Methods: Patients were distributed into three groups according to the angiography in lower limb arterial: group L1, plaque with no stenosis; group L2, plaque with luminal stenosis and group L3, total vascular occlusion. Changes in the neutrophil-to-lymphocyte ratio were documented and compared among groups., Results: Compared to group L1, NLR was significantly increased in L2 (1.76 vs 2.35, p =0.037) and L3 (1.76 vs 3.60, p< 0.001), with a gradual decrease in ABI (Ankle-Brachial Index, 1.11 vs 1.02 vs 0.94, p< 0.001). Those older patients with higher prevalence of hypertension ( p =0.002), obesity ( p =0.032), or reduced high-density lipoprotein cholesterol ( p =0.020) were more likely to develop PAD; higher glycosylated hemoglobin ( p =0.045), low-density lipoprotein cholesterol ( p =0.006), and systolic blood pressure ( p< 0.001) levels led to a greater tendency to suffer stenosis or even occlusion; the probability of severe stenosis (>70%) increased to 2.075 times for every 1 increase in NLR, while it was 46.8% for every 0.1 increase in ABI. The optimal NLR cut-off value to predict severe stenosis in PAD was 2.73. Receiver operating characteristic curve analysis of the inflammatory biomarkers and severe stenosis prediction displayed an area under the curve of 0.81., Conclusion: NLR could serve as a new noninvasive and accurate marker in predicting PAD., 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, Jia, Jiang, Yang, Wang and Zhang.)

Introduction: Depression can exacerbate diabetes by impairing self-care behaviors and increasing the risk of complication; however, the underlying mechanism is still unclear. Given the suggested associations between walking activity, depression status, and blood glucose levels this study explores the intricate relationship between depression and blood glucose (BG) control, with a focus on walking activity as a behavioral mediator. The purpose of this study is to examine walking activity's mediating role in depression's impact on BG levels, investigating and validating the non-linear association between BG levels and walking activity. This retrospective real-world study demonstrates the potential of regular walking activity as a simple and accessible intervention to mitigate the negative effects of depression on BG levels in T2D and prediabetes., Methods: A cohort of 989 users with T2D and prediabetes, who regularly tracked their steps levels and BG levels for 12 months using the Dario digital health platform was evaluated. The mediating role of the monthly average number of steps on the relationship between the self-reported depression status and lagged monthly average BG was assessed. Additionally, the association between monthly walking activity and monthly average BG was tested using a piecewise linear mixed effects model., Results: Users with self-reported depression demonstrated increased BG levels compared to users without depression (B=8.00, P=.01). The association between depression and monthly average number of steps was significant (B=-.27, P<.005) and monthly average number of steps significantly predicted the following months' average BG (B=-.81, P=.001), adjusting for depression. The monthly average number of steps significantly mediated the effect of self-reported depression on the following month's average BG (M=.22, P<.005). Further sensitivity analysis demonstrated model robustness over various periods. Finally, non-linear dynamics of walking activity over time was validated using unseen data showing a decrease in monthly average BG for users with over an average of 400 steps per day (B=-1.87, P<.01)., Discussion: This study shows how regular walking may reduce the negative impact of depression on BG levels in people with T2D. Our findings advocate for the integration of walking activity into treatment protocols as a cost-effective, accessible intervention strategy to improve glycemic management and depressive symptoms in this population., Competing Interests: YF-H, IB, and OM are employees at Dario Health. MR and DH serve as Dario Health scientific advisory board members. PG has received a consulting fee to assist with analyses but otherwise has no conflict of interest. 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 Fundoiano-Hershcovitz, Breuer Asher, Kantor, Rahmon, Ritholz, Horwitz, Manejwala and Goldstein.)

Objective: Evaluate the effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiovascular and cerebrovascular diseases., Methods: Articles of SGLT2i on cardiovascular and cerebrovascular diseases were searched. Two authors independently screened the literature, extracted the data, assessed the quality of the study and performed statistical analyses using Review Manager 5.4., Results: Random-effect model was used to merge the OR values, and the pooled effect showed that SGLT2i had significant preventive effects on cardiovascular death (OR=0.76, 95%CI 0.64 to 0.89), myocardial infarction (OR=0.90, 95%CI 0.84 to 0.96), heart failure (OR=0.69, 95%CI 0.64 to 0.74) and all-cause mortality (OR=0.65, 95%CI 0.58 to 0.73). Empagliflozin, dapagliflozin and canagliflozin all reduced the incidence of heart failure (OR=0.72, 95%CI 0.64 to 0.82; OR=0.56, 95%CI 0.39 to 0.80; OR=0.62, 95%CI 0.53 to 0.73), but only dapagliflozin displayed a favorable effect on inhibiting stroke (OR=0.78, 95%CI 0.63 to 0.98). SGLT2i could prevent stroke (OR=0.86, 95%CI 0.75 to 0.99), heart failure (OR=0.63, 95%CI 0.56 to 0.70) and all-cause mortality (OR=0.64, 95%CI 0.57 to 0.72) compared to DPP-4i. Furthermore, SGLT2i could reduce the incidence of heart failure (OR=0.72, 95%CI 0.67 to 0.77) and cardiovascular death (OR=0.72, 95%CI 0.54 to 0.95) in patients with high-risk factors., Conclusions: SGLT2i affects cardiovascular death, myocardial infarction, heart failure and all-cause mortality. Only dapagliflozin displayed a favorable effect on inhibiting stroke. SGLT2i could prevent stroke, heart failure and all-cause mortality compared to DPP-4i. In addition, SGLT2i significantly reduced the development of heart failure and cardiovascular death in patients with high-risk factors., Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024532783., 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, Li, Cui, Gu, Zhao and Wang.)

Background: To investigate the association between oxidative balance score (OBS), cardiovascular mortality (CVM), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients., Methods: We included 6,119 participants with T2DM from the 2005-2020 National Health and Nutrition Examination Surveys (NHANES). The status of CVM and ACM of participants was followed through December 31, 2019. Multivariable Cox regression models, Kaplan-Meier curves, log-rank test, restricted cubic spline regression, and subgroup analysis, were used to evaluate the relationship between OBS, CVM, and ACM., Results: During a median of 100.9 months follow-up, 1,790 ACM cases had occurred, 508 of which were due to cardiovascular disease. The T2DM participants were divided into four groups based on the quartiles of OBS. Participants with Q4 tended to be younger, financially better-off, married, highly educated, had lower alcohol consumption rates, were non-smokers, and exhibited a lower likelihood of ACM and CVM. In multivariate Cox regression models, compared with the patients with Q4, those with Q1 had a 30% increased risk for ACM (Q1, reference; Q4, HR: 0.70, 95%CI: 0.58-0.86) and a 43% increased risk for CVM (Q1, reference; Q4, HR: 0.57, 95%CI: 0.36-0.88). The restricted cubic spline regression models have no nonlinear relationship between OBS, CVM, and ACM. Kaplan-Meier survival curves showed that patients with Q4 had a lower risk of ACM and CVM (log-rank P < 0.05)., Conclusions: We find that ACM and CVM increase with higher OBS in T2DM patients. Moreover, there are linear relationships between OBS, ACM, and CVM., 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 Ni, Wang, Zhou, Wang, Cai, Wang, Chen, Liu and Sun.)

Aim: The aim of this research was to ascertain the correlations between alexithymia, social support, depression, and glycemic control in patients diagnosed with type 2 diabetes mellitus. Additionally, this study sought to delve into the potential mediating effects of social support and depression in the relationship between alexithymia and glycemic control., Method: A purposive sampling methodology was employed to select a cohort of 318 patients afflicted with type 2 diabetes mellitus, hailing from a care establishment situated in Chengdu City. This investigation embraced a cross-sectional framework, wherein instruments such as the General Information Questionnaire, the Toronto Alexithymia Scale 20, the Social Support Rating Scale, and the Hamilton Depression Scale were judiciously administered. The primary objective of this endeavor was to unravel the interplay that exists amongst alexithymia, social support, depression, and glycemic control. The inquiry discerned these interrelationships through both univariate and correlational analyses, subsequently delving into a comprehensive exploration of the mediating ramifications engendered by social support and depression in the nexus between alexithymia and glycemic control., Results: The HbA 1c level of patients diagnosed with type 2 diabetes mellitus was recorded as (8.85 ± 2.107), and their current status with regards to alexithymia, social support, and depression were measured as (58.05 ± 4.382), (34.29 ± 4.420), and (7.17 ± 3.367), respectively. Significant correlations were found between HbA 1c and alexithymia (R=0.392, P <0.01), social support (R=-0.338, P <0.01), and depression (R=0.509, P <0.01). Moreover, alexithymia correlation with social support (R=-0.357, P <0.01) and with depression (R=0.345, P <0.01). Regarding the mediation analysis, the direct effect of alexithymia on HbA 1c was calculated to be 0.158, while the indirect effect through social support and depression were 0.086 and 0.149, respectively. The total effect value was determined to be 0.382, with the mediating effect accounting for 59.95%, and the direct effect accounting for 40.31%., Conclusion: Alexithymia exerts both direct and indirect adverse effects on glycemic control, thereby exacerbating disease outcomes. Hence, it is imperative to prioritize the mental health status of individuals with type 2 diabetes to enhance overall well-being, ameliorate diabetes-related outcomes, elevate patients' quality of life, and alleviate the psychological distress and financial burden associated with the condition., 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 Gan, Tian, Fan, Wang, Zhou, Yang and Qi.)

Background: Periodontitis is a chronic inflammatory disease potentially associated with obesity and type 2 diabetes (T2D). Sleeve gastrectomy (SG) has shown substantial effect on weight loss and treatment of T2D. However, there is no direct evidence comparing the impact of SG on the periodontal status of patients with and without T2D., Objectives: To determine the impact of SG on the periodontal status of patients with and without T2D in a real-world setting., Methods: In a prospective and two-armed cohort design, participants who were scheduled for SG at an affiliated hospital between April 2022 and December 2022 were approached for eligibility. After a clinical evaluation and oral examination, those with periodontitis were included and further divided into the DM group (diabetic) and the Control group (non-diabetic) with a 1-year follow-up after surgery. The primary outcome was the periodontal status of patients at 12 months after SG. The secondary outcomes included weight loss, diabetes remission, and alterations in inflammatory markers for up to 1 year after SG., Results: Fifty-seven and 49 patients were included in the DM and the Control group, respectively. Before surgery, patients in the DM group had further worsened periodontal condition compared with those in the Control group. Accompanied by weight loss and glucose reduction, patients in both groups demonstrated significant decreases in plaque index (PLI) and bleeding index (BI) with no alterations in probing depth or clinical attachment loss for up to 1 year after SG. Even patients in the DM group achieved less TWL% (32.79 ± 6.20% vs. 37.95 ± 8.34, P <0.01), their periodontal condition had more substantial improvement with no significant difference in PLI and BI between groups at 1 year after SG. We also observed a significant reduction in the levels of high sensitive C-reactive protein and interleukin-6 in both groups at 1 year after SG., Conclusion: Both patients with and without T2D demonstrated improved periodontal status for up to 1 year after SG. Patients with T2D achieved less weight loss but a more substantial improvement in periodontal condition. The significant reduction in inflammatory biomarkers contributed to the improvement of periodontal status after SG., 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 Bi, Zhao, Liu, Zhu, Li, Xiong, Liu, Hu and Huang.)

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: Central retinal artery occlusion (CRAO) is a medical condition characterized by sudden blockage of the central retinal artery, which leads to a significant and often irreversible loss of vision. Observational studies have indicated that diabetes mellitus is a risk factor for CRAO; however, there is no research on the causal relationship between diabetes mellitus, particularly type 2 diabetes, and CRAO. This study aimed to perform Mendelian randomization (MR) analysis to clarify the causal relationship between type 2 diabetes and CRAO., Methods: Genetic variants associated with type 2 diabetes were selected from two different datasets. A recent genome-wide association study of CRAO conducted using the FinnGen database was used as the outcome data. A two-sample MR was performed to evaluate the causal relationship between type 2 diabetes and CRAO. Inverse variance weighting was the primary method, and MR-Egger, maximum likelihood, and median weighting were used as complementary methods. A multivariate MR (MVMR) analysis was performed to further evaluate the robustness of the results. Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test were used for the sensitivity analyses., Results: Genetically predicted type 2 diabetes was causally associated with CRAO(odds ratio [OR] =2.108, 95% confidence interval [CI]: 1.221-3.638, P=7.423×10 -3 ), which was consistent with the results from the validation dataset (OR=1.398, 95%CI: 1.015-1.925, P=0.040). The MVMR analysis suggested that type 2 diabetes may be an independent risk factor for CRAO (adjusted OR=1.696; 95%CI=1.150-2.500; P=7.655×10 -3 ), which was assumed by the validation dataset (adjusted OR=1.356; 95%CI=1.015-1.812; P=0.039)., Conclusion: Our results show that genetically predicted type 2 diabetes may be causally associated with CRAO in European populations. This suggests that preventing and controlling type 2 diabetes may reduce the risk of CRAO., 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, Lu, Liu, Lin, Peng, Lu, Guo, Liu, Zhang and Wu.)

Background: Large-scale prospective cohort studies on diabetic foot ulcers risk factor screening in China are limited. Therefore, this prospective cohort study aimed to explore the predictive risk factors for diabetic foot ulcers to provide clinicians with concise and effective clinical indicators for identifying a high-risk diabetic foot and guiding the prevention of diabetic foot ulcers., Methods: Patients with diabetes who visited the Department of Endocrinology of Peking University First Hospital from October 2017 to December 2018 were selected as research participants by convenience sampling. A total of 968 patients were included. After enrollment, a dedicated person collected and recorded all baseline data. A dedicated telephone follow-up was conducted every 12-24 months to evaluate whether the endpoint event had occurred. All patients were followed up for an average of 61 (57-71) months, with 95% of them followed up for more than 60 months. According to the occurrence of endpoint events, they were divided into the DFU and non-DFU groups. The data between the two groups were analyzed using independent-sample t-test, Wilcoxon rank sum test, and chi square test. We used univariate and multivariate logistic regression analysis to analyze the factors that affected the occurrence of diabetic foot ulcers., Results and Conclusions: After the 5-year follow-up, the incidence of diabetic foot was 25.83%. Multivariate logistic regression analysis revealed that body mass index (odds ratio: 1.046; 95% confidence interval: 1.001-1.093), abnormal pinprick sensation (odds ratio: 4.138; 95% confidence interval: 1.292-13.255), history of fungal foot infection (odds ratio: 2.287; 95% confidence interval: 1.517-3.448), abnormal 128-Hz tuning fork test (odds ratio: 2.628; 95% confidence interval: 1.098-6.294), and HbA1c≥ 8% (odds ratio: 1.522; 95% confidence interval: 1.014-2.284) were independent predictors of diabetic foot. Our study highlights clinically relevant indicators that may help to prevent the occurrence of diabetic foot and guide timely interventions., 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 Su, Yuan, Yuan, Sun, Zhang, Liu, Zhang and Guo.)

Background: Observational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications., Methods: We identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications., Results: The study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47-0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62-0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed., Conclusions: Our MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Liu, Gu, Shen, Zhou and Luo.)

Objective: To investigate the factors influencing accelerated aging in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD)., Methods: A total of 216 patients diagnosed with T2DM and CHD between August 2019 and August 2023 at Xuzhou Central Hospital were selected. Patients were divided into an aging group and a non-aging group, based on the positive or negative values of phenotypic age acceleration (PhenoAgeAccel). Logistic regression analysis was conducted. Variables that had a univariate analysis P < 0.05 were included in the multivariate analysis to identify factors influencing aging in patients with T2DM and CHD, and the area under the curve of the model was reported., Results: This study included 216 patients, with 89 in the accelerated aging group, and 127 in the non-accelerated aging group. The average age of patients was 70.40 (95% CI: 69.10-71.69) years, with 137 males (63.4%). Compared with the non-accelerated aging group, patients in the accelerated aging group were older, with a higher proportion of males, and a higher prevalence of hypertension, stable angina pectoris, and unstable angina pectoris. Multivariate Logistic regression analysis indicated that the absolute value of neutrophils (NEUT#), urea (UREA), adenosine deaminase (ADA), and the triglyceride-glucose index (TyG) were risk factors for accelerated aging, while cholinesterase (CHE) was a protective factor. For each unit increase in NEUT#, UREA, ADA, and TyG, the risk of aging increased by 64%, 48%, 10%, and 789%, respectively. The overall area under the receiver operating characteristic (ROC) curve of the model in the training set was 0.894, with a 95% confidence interval (CI) of 0.851-0.938., Conclusion: NEUT#, CHE, UREA, ADA, and TyG are predictors of accelerated aging in patients with T2DM and CHD, with the model showing favorable overall predictive performance., 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, Liu, Chen, Chen and Wang.)

Objective: The oxidative balance score (OBS) is a comprehensive concept that includes 20 oxidative stressors and can be used to assess individual pro-oxidant versus antioxidant exposure, and the aim of the present study was to investigate the association between OBS and the risk of diabetic kidney disease (DKD), low estimated glomerular filtration rate (low-eGFR) and albuminuria in patients with diabetes mellitus (DM)., Methods: This cross-sectional study included nationally representative consecutive National Health and Nutrition Examination Survey DM patients aged 18 years and older from 2003-2018. The continuous variable OBS was converted into categorical variables by quartiles, and weighted multiple logistic regression analyses and restricted triple spline models were used to explore the relationships. We also performed subgroup analyses and interaction tests to verify the stability of the results., Results: A total of 5389 participants were included, representing 23.6 million non-institutionalized US residents. The results from both multivariate logistic regression analysis and restricted cubic spline models indicated that OBS and dietary OBS levels were negatively associated with the risk of DKD, low-eGFR, and albuminuria, without finding a significant correlation between lifestyle OBS and these clinical outcomes. Compared to the lowest OBS quartile group, the prevalence risk of DKD (OR = 0.61, 95% CI: 0.46-0.80), low-eGFR (OR = 0.46, 95% CI: 0.33-0.64) and albuminuria (OR = 0.68, 95% CI: 0.51-0.92) decreased by 39%, 54% and 32%, respectively, in the highest OBS quartile group. The results remained stable in subgroup analyses and no interaction between subgroups was found., Conclusion: Higher levels of OBS and dietary OBS were associated with a lower risk of DKD, low-eGFR, and albuminuria. These findings provided preliminary evidence for the importance of adhering to an antioxidant-rich diet and lifestyle among individuals with 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 Liu, Yang, Li, Deng, He, Zhang and Zhang.)

Diabetic cardiomyopathy (DCM) is a severe secondary complication of type 2 diabetes mellitus (T2DM) that is diagnosed as a heart disease occurring in the absence of any previous cardiovascular pathology in diabetic patients. Although it is still lacking an exact definition as it combines aspects of both pathologies - T2DM and heart failure, more evidence comes forward that declares DCM as one complex disease that should be treated separately. It is the ambiguous pathological phenotype, symptoms or biomarkers that makes DCM hard to diagnose and screen for its early onset. This re-view provides an updated look on the novel advances in DCM diagnosis and treatment in the experimental and clinical settings. Management of patients with DCM proposes a challenge by itself and we aim to help navigate and advice clinicians with early screening and pharmacotherapy of DCM., 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 Galis, Bartosova, Farkasova, Bartekova, Ferenczyova and Rajtik.)

Objectives: This study aimed to explore the synergistic interaction effect between hyperuricemia and hypertension towards chronic kidney disease in patients with type 2 diabetes., Methods: This research originates from a cross-sectional study performed in Zhejiang Province, Eastern China, between March and November 2018. The correlation between serum uric acid levels and the risk of chronic kidney disease was assessed using a restricted cubic spline model. An unconditional multivariable logistic regression model, along with an interaction table, was utilized to explore the potential interaction effect of hyperuricemia and hypertension towards chronic kidney disease., Results: 1,756 patients with type 2 diabetes were included in this study, the prevalence of chronic kidney disease (CKD) was 27.62% in this population. A U-shaped non-linear pattern emerged correlating serum uric acid (SUA) levels and CKD risk, indicating that both low and high SUA levels were linked to an increased CKD risk. This risk achieved its lowest point (nadir) at SUA approximately equals to 285μmol/L (p for trend <0.05). Once adjustments for age, gender, education level, abnormal fasting plasma glucose (FPG), abnormal hemoglobin A1c (HbA1c), abnormal total cholesterol (TC), abnormal high-density lipoprotein cholesterol (HDL-C), alcohol consumption and duration of diabetes were factored in, it was found that patients with both hyperuricemia and hypertension demonstrated a 5.42-fold (95% CI: 3.72-7.90) increased CKD risk compared to the reference group. The additive interaction between hyperuricemia and hypertension was statistically significant, as manifested by the following values: a relative excess risk due to interaction (RERI) of 2.57 (95% CI: 0.71-4.71), an attributable proportion due to interaction (AP) of 0.47 (95% CI: 0.14-0.64), and a synergy index (SI) of 2.39 (95% CI: 1.24-4.58). In contrast, there was no significant interaction effect in multiplicative scale., Conclusion: Hyperuricemia and hypertension may contribute additively to CKD, beyond their isolated impacts. Evaluating the risk of CKD in type 2 diabetes patients necessitates considering this potential interaction., 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, Lu, Zhang, Xu, Du, Liang, Chen and Zhong.)

Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role., Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship., Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio ( OR ) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship., Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis., 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, Wang, Liu, Liu and Zhu.)

Objective: To observe the clinical efficacy and safety of the Qingre Lishi decoction in treating of newly diagnosed overweight and obese patients with type 2 diabetes mellitus (T2DM) from an evidence-based medical perspective., Methods: 70 cases of overweight and obese patients with newly diagnosed T2DM treated in the outpatient clinic of the Department of Endocrinology of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from December 2021 to November 2022 were selected, of which 35 cases were in the observation group and 35 cases were in the control group. The observation group was treated with the Qingre Lishi decoction add lifestyle intervention, and the control group was treated with lifestyle intervention only. We compared and analyzed the fasting blood glucose (FPG), 2-hour postprandial glucose (2hPG), the occurrence of adverse reactions, and the related indexes provided by wearing the CGM device during the observation period of the patients in the two groups., Results: 53 participants completed the clinical trial. In relation of glycemic control, a decreasing trend has shown in both groups, with the decreases in FPG, 2hPG, eHbA1c, and MG in the observation group being higher than those in the control group ( P <0.05). In regard to blood glucose attainment, at the 28d, the attainment rate of patients in the observation group with TIR>80% was 87.10%, and the magnitude of changes in the rise of TIR and the fall of TAR was significantly better than that in the control group ( P <0.01). In terms of blood glucose fluctuation, CV and SD of the patients in the observation group decreased compared with the 0d; the magnitude of daytime blood glucose fluctuation was significantly alleviated compared with that of the control group. The degree of decrease in LAGE, MAGE, and MODD was significantly lower than that of the control group ( P <0.01)., Conclusion: The Qingre Lishi decoction can effectively improve the hyperglycemic condition of overweight and obese patients with newly diagnosed T2DM. It can reduce blood glucose, alleviate blood glucose fluctuations, reduce the incidence of hypoglycemia, and improve patients' adherence and self-confidence in controlling blood glucose., Clinical Trial Registration: https://itmctr.ccebtcm.org.cn/, identifier ITMCTR2024000006., 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 Wei, Gao, Li, Tian and Wang.)

Objective: This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management., Methods: This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks., Results: Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups ( p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group ( p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group ( p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group., Conclusions: PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options., Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2300070919., 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, Cao, Zhao, Zhao, Zhao and Liu.)

Objective: This study aims to conduct a comprehensive investigation of the serum amino acid profiles of individuals with type 2 diabetes (T2D) and its related complications., Methods: Patients with T2D were enrolled in this study. Sixteen kinds of common amino acids in the fasting circulating were assessed through liquid chromatography-mass spectrometry (LC-MS). Subsequently, correlation, regression analyses, and receiver operating characteristic (ROC) curves were conducted to assess the associations between amino acids and clinical indicators., Results: Thirteen different kinds of amino acids were identified in diabetic patients, as compared with normal controls. The Glutamine/Glutamate (Gln/Glu) ratio was negatively correlated with BMI, HbA1c, serum uric acid, and the triglyceride-glucose (TyG) index, while it was positively correlated with HDL-C. Logistic regression analyses indicated that Gln/Glu was a consistent protective factor for both T2D (OR = 0.65, 95% CI 0.50-0.86) and obesity (OR = 0.79, 95% CI 0.66-0.96). The ROC curves demonstrated that Gln/Glu, proline, valine, and leucine provided effective predictions for diabetes risk, with Gln/Glu exhibiting the highest AUC [0.767 (0.678-0.856)]. In patients with T2D, Gln was the only amino acid that displayed a negative correlation with HbA1c ( r = -0.228, p = 0.017). Furthermore, HOMA-β exhibited a negative correlation with Glu ( r = -0.301, p = 0.003) but a positive correlation with Gln/Glu ( r = 0.245, p = 0.017). Notably, logistic regression analyses revealed an inverse correlation of Gln/Glu with the risk of diabetic kidney disease (OR = 0.74, 95% CI 0.55-0.98) and a positive association with the risk of diabetic retinopathy (OR = 1.53, 95% CI 1.08-2.15)., Conclusion: The Gln/Glu ratio exhibited a significant association with diabetes, common metabolic parameters, and diabetic complications. These findings shed light on the pivotal role of Gln metabolism in T2D and its associated complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Xu, Hangfu, Liu, Zhang, Sun and Chen.)

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: Inappropriate management of blood sugar in patients with diabetes mellitus leads to micro-vascular and macro-vascular complications, subsequently leading to high morbidity and mortality rates. In addition, diabetes independently increases the occurrence of cognitive impairment complicated by dementia. Scientific evidence on the magnitude of cognitive impairment will provide a sound basis for the determination of healthcare needs and the planning of effective healthcare services. Despite this, there are no comprehensive data on the prevalence and associated factors of cognitive impairment among patients with diabetes in Africa., Methods: To identify relevant articles for this review, we searched PubMed, Cochrane Library, Science Direct, African Journals Online, and Google Scholar. After extraction, the data were imported into Stata software version 11 (Stata Corp., TX, USA) for further analysis. The random-effects model, specifically the DerSimonian and Laird (D+L) pooled estimation method, was used due to the high heterogeneity between the included articles. Begg's and Egger's regression tests were used to determine the evidence of publication bias. Sub-group analyses and sensitivity analyses were also conducted to handle heterogeneity., Results: The pooled prevalence of cognitive impairment among patients with diabetes in Africa is found to be 43.99% (95% CI: 30.15-57.83, p < 0.001). According to our analysis, primary level of education [pooled odds ratio (POR) = 6.08, 95% CI: 3.57-10.36, I 2 = 40.7%], poorly controlled diabetes mellitus (POR = 5.85, 95% CI: 1.64-20.92, I 2 = 87.8%), age above 60 years old (POR = 3.83, 95% 95% CI: 1.36-10.79, I 2 = 63.7%), and diabetes duration greater than 10 years (POR = 1.13; 95% CI: 1.07-1.19, I 2 = 0.0%) were factors associated with cognitive impairment among patients with diabetes., Conclusion: Based on our systematic review, individuals with diabetes mellitus exhibit a substantial prevalence rate (43.99%) of cognitive impairment. Cognitive impairment was found to be associated with factors such as primary level of education, poorly controlled diabetes mellitus, age above 60 years, and diabetes duration greater than 10 years. Developing suitable risk assessment tools is crucial to address uncontrolled hyperglycemia effectively., Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42024561484., 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 Chekol Tassew, Ferede and Zeleke.)

Introduction: Obstructive sleep apnea (OSA) can have negative impacts on the health outcomes of individuals with type 2 diabetes. However, in the United Arab Emirates (UAE), there is a lack of understanding regarding the relationship between OSA and type 2 diabetes despite the significant implications it has on health. The primary objective of this study is to investigate the association between OSA risk and type 2 diabetes, associated risk factors, and gender differences in OSA symptoms among Emirati adults., Methods: We conducted a cross-sectional analysis of the baseline data from the UAE Healthy Future Study (UAEHFS) collected between February 2016 and March 2023. Our sample consisted of 4578 participants aged 18-71 who completed the STOP-BANG survey, provided body measurements and blood samples. We stratified the patients according to their OSA risk and diabetes. We used univariate and multivariate logistic regression models to analyze the relationship between OSA risk and type 2 diabetes and to identify factors associated with risk for OSA and type 2 diabetes. We estimated odds ratios (ORs) with corresponding 95% confidence intervals (95% CI)., Results: The mean age was 27.5 years (± 8.35), and 55.81% (n=2555) were men. The overall prevalence of high risk for OSA was 16.58% and was higher in men compared to women (26.46% vs 4.10%). Women reported feeling tired more often than men (68.02% vs 48.96%). Both genders have similar rates of stop breathing and BMI ≥ 35. There was a significant association between the OSA risk and type 2 diabetes in the unadjusted model (OR=2.44; 95% CI: 1.78-3.35; p-value <0.0001) and (OR=6.44; 95% CI: 4.32-9.59; p-value < 0.0001) among those who reported intermediate and high OSA risk, respectively. After adjusting the model for education attainment, marital status, waist circumference, and smoking, the association remained significant between diabetes and OSA risk, with an OR of 1.65 (95%CI: 1.18-2.32; p-value =0.004) for intermediate OSA risk and 3.44 (95%CI: 2.23-5.33; p-value <0.0001) for high OSA risk., Conclusions: This study conducted in the UAE found a significant correlation between OSA risk and type 2 diabetes. We suggest introducing routine screening of OSA for individuals with 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 Taimah, Ahmad, Al-Houqani, Al Junaibi, Idaghdour, Abdulle and Ali.)

Background: Small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have emerged as a promising therapy for treating type II diabetic cutaneous wounds. Currently, the evidence supporting the use of MSC-sEVs for treating diabetic skin wounds remains inconclusive and is limited to preclinical studies. To facilitate the clinical translation of cell-free therapy, conducting a comprehensive systematic review of preclinical studies assessing the efficacy of MSC-sEVs is imperative., Methods: A systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library databases until June 14, 2023, to identify studies that met our pre-established inclusion criteria. The outcome indicators comprised wound closure rate (primary outcome), neovascular density, re-epithelialization rate, collagen deposition, and inflammatory factors (secondary Outcomes). A fixed-effects model was employed in instances of low heterogeneity (I 2 <50%), while a random-effects model was utilized for high heterogeneity (I 2 ≥50%). The risk of bias in animal studies was assessed using the SYRCLE tool., Results: Twenty-one studies were included in this meta-analysis. Compared with the control group, MSC-sEVs were found to significantly facilitate the healing of cutaneous wounds in type II diabetic patients (standardized mean difference [SMD]=3.16, 95% confidence interval [CI]: 2.65 to 3.66, P<0.00001, I 2 = 39%)., Conclusions: According to the meta-analysis of preclinical studies, MSC-sEVs show promising applications in promoting type II diabetic wound healing. As a result, translating these findings into clinical applications appears warranted., Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023375467., 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 Yue, Li, Liu, Yu, Cao and Wang.)

Objective: The relationship between diabetes mellitus (DM) and autism spectrum disorder (ASD) remains controversial. This study aimed to analyze the causal relationship between different types of DM and ASD by bidirectional Mendelian randomization (MR)., Methods: Single nucleotide polymorphisms for type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and ASD were obtained from genome-wide association studies. Subsequently, inverse variance weighted, MR-Egger, and weighted median were used to test the exposure-outcome causality. Finally, MR-Egger's intercept, Cochran's Q, and leave-one-out method were used to assess horizontal pleiotropy, heterogeneity, and sensitivity of the results, respectively., Results: The positive analysis showed that T2DM was associated with an increased risk of ASD, whereas neither T1DM nor GDM was associated with the risk of ASD. The reverse analysis showed that ASD was associated with an increased risk of T2DM, while it was not associated with the risk of either T1DM or GDM. MR-Egger intercept showed no horizontal pleiotropy ( p > 0.05) for these results. Cochran's Q showed no heterogeneity expect for the results of T1DM on the risk of ASD, and leave-one-out sensitivity analysis showed these results were robust., Conclusion: This MR analysis suggests that T2DM and ASD are reciprocal risk factors and that they may create an intergenerational risk cycling in female patients. Aggressive prevention and treatment of T2DM and ASD help to break the trap of this risk cycling. Additionally, this study does not support a causal relationship between T1DM and ASD, as well as GDM and ASD. And more studies are needed in the future to continue to explore the interactions and underlying mechanisms between different types of DM and ASD., 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 Yu, Yang, Hu, Tong, Wu and Yu.)

Background: The evidence supporting a connection between elevated serum uric acid (SUA) levels and diabetic peripheral neuropathy (DPN) is controversial. The present study performed a comprehensive evaluation of this correlation by conducting a systematic review and meta-analysis of relevant research., Method: PubMed, Web of Science (WOS), Embase, and the Cochrane Library were searched for published literature from the establishment of each database to January 8, 2024. In total, 5 cohort studies and 15 cross-sectional studies were included, and 2 researchers independently screened and extracted relevant data. R 4.3.0 was used to evaluate the included literature. The present meta-analysis evaluated the relationship between SUA levels and the risk of DPN in type 2 diabetes (T2DM) by calculating the ratio of means (RoM) and 95% confidence intervals (CIs) using the method reported by JO Friedrich, and it also analyzed continuous outcome measures using standardized mean differences (SMDs) and 95% CIs to compare SUA levels between DPN and non-DPN groups. Funnel plot and Egger's test were used to assess publication bias. Sensitivity analysis was conducted by sequentially removing each study one-by-one., Results: The meta-analysis included 20 studies, with 12,952 T2DM patients with DPN and 16,246 T2DM patients without DPN. There was a significant correlation between SUA levels and the risk of developing DPN [odds ratio (OR) = 1.23; 95% CI: 1.07-1.41; p = 0.001]. Additionally, individuals with DPN had higher levels of SUA compared to those without DPN (SMD = 0.4; 95% CI: -0.11-0.91; p < 0.01)., Conclusion: T2DM patients with DPN have significantly elevated SUA levels, which correlate with a heightened risk of peripheral neuropathy. Hyperuricemia (HUA) may be a risk indicator for assessing the risk of developing DPN in T2DM patients., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024500373., Competing Interests: Author JG was employed by the company Amazon. 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 Zhang, Zhang, Li, Zhao, Wei, Shi, Yang, Fan, Zhao, Zhu, Du, Guo and Cao.)

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.)

The increasing prevalence of type 2 diabetes mellitus (T2DM) is a significant worldwide health concern caused by sedentary lifestyles and unhealthy diets. Beyond glycemic control, T2DM impacts multiple organ systems, leading to various complications. While traditionally associated with cardiovascular and microvascular complications, emerging evidence indicates significant effects on pulmonary health. Pulmonary vascular dysfunction and fibrosis, characterized by alterations in vascular tone and excessive extracellular matrix deposition, are increasingly recognized in individuals with T2DM. The onset of T2DM is often preceded by prediabetes, an intermediate hyperglycemic state that is associated with increased diabetes and cardiovascular disease risk. This review explores the relationship between T2DM, pulmonary vascular dysfunction and pulmonary fibrosis, with a focus on potential links with prediabetes. Pulmonary vascular function, including the roles of nitric oxide (NO), prostacyclin (PGI2), endothelin-1 (ET-1), thromboxane A2 (TxA2) and thrombospondin-1 (THBS1), is discussed in the context of T2DM and prediabetes. Mechanisms linking T2DM to pulmonary fibrosis, such as oxidative stress, dysregulated fibrotic signaling, and chronic inflammation, are explained. The impact of prediabetes on pulmonary health, including endothelial dysfunction, oxidative stress, and dysregulated vasoactive mediators, is highlighted. Early detection and intervention during the prediabetic stage may reduce respiratory complications associated with T2DM, emphasizing the importance of management strategies targeting blood glucose regulation and vascular health. More research that looks into the mechanisms underlying pulmonary complications in T2DM and prediabetes is needed., 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 Mzimela, Dimba, Sosibo and Khathi.)

Objective: Perirenal adipose tissue (PAT) has emerged as a potential therapeutic target for cardiovascular disease (CVD). However, the relationship between increased perirenal fat thickness (PrFT) and CVD risks in individuals with type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to evaluate the association between PrFT and the estimated 10-year risk of CVD and atherosclerotic cardiovascular disease (ASCVD) in T2DM., Method: The final analysis included 704 participants. PrFT was quantified using non-enhanced computed tomography scans, while the estimated 10-year CVD and ASCVD risk assessments were based on the Framingham and China-PAR equation risk scores, respectively. Multiple regression analysis was employed to analyze the correlation between PrFT and these risk scores., Results: Higher quartiles of PrFT displayed elevated Framingham and China-PAR equation risk scores ( P <0.001). After adjusting for cardiometabolic risk factors and visceral fat area, PrFT remained significantly correlated with Framingham equation risk scores in men ( β =0.098, P =0.036) and women ( β =0.099, P =0.032). Similar correlations were observed between PrFT and China-PAR equation risk scores in men ( β =0.106, P =0.009) and women ( β =0.108, P =0.007). Moreover, PrFT emerged as an independent variable associated with a high estimated 10-year risk of CVD and ASCVD, with odds ratios (ORs) of 1.14 (95% CI: 1.04-1.25, P =0.016) in men and 1.20 (95% CI: 1.11-1.31, P <0.001) in women for high estimated CVD risk, and ORs of 1.22 (95% CI: 1.08-1.41, P =0.009) in men and 1.34 (95% CI: 1.12-1.60, P <0.001) in women for high estimated 10-year ASCVD risk. Furthermore, restricted cubic spline analyses confirmed a nonlinear relationship between PrFT and high estimated CVD and ASCVD risk in both genders ( P for nonlinearity and overall < 0.05)., Conclusions: PrFT contributed as an independent variable to the estimated 10-year risk of CVD and ASCVD in T2DM., 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, Lv, Tu and Guo.)

Background: Diabetes mellitus (DM) is a global public health problem characterized by an elevated blood glucose level. Monitoring blood sugar levels is vital for effective diabetes management and preventing complications. However, the association between longitudinal biomarkers and the incidence of diabetic complications is often overlooked. Therefore, this study aimed to assess the incidence of diabetic retinopathy, predictors, and association with longitudinal fasting blood sugar level changes among diabetes mellitus patients in Ethiopia., Methods: A multicenter retrospective follow-up study was carried out in referral hospitals in Amhara region, Ethiopia. A random sample of 462 newly diagnosed DM patients was selected. The proportional hazard assumption was checked for the survival sub-model, and for the longitudinal sub-model, the normality assumption was checked. Then the joint modeling with time-dependent lagged parameterizations was fitted. Model assumptions and comparisons were checked. Finally, the hazard ratio with a 95% confidence interval (CI) with a corresponding P-value<0.05 was used to identify predictors., Results: In this study, Overall, 54 patients developed DR, and the incidence rate was 2.33 per 1000 person-months over the follow-up period, with a 95% CI of [1.78, 3.05]. Rural residence (AHR = 2.21, 95% CI: [1.21, 4.05]), hypertension co-morbidity (AHR = 3.01, 95% CI: [1.85, 6.53]), and longer duration of DM (>5 years) (AHR = 2.28, 95% CI: [1.91, 5.15]) were important predictors for the incidence of DR. In addition, the incidence of DR was substantially correlated with the time-dependent lagged value of FBS change (AHR = 4.20, 95% CI [1.62, 10.85])., Conclusions: In this study, the incidence of diabetic retinopathy was somewhat high when compared to prior similar studies in Ethiopia. A joint model of longitudinal fasting blood sugar level changes was significantly associated with an increased risk of DR. Besides, being rural residence, hypertension co-morbidity, and a longer duration of DM were significant predictors for the incidence of DR. Therefore, public awareness, an integrated care approach, and prioritizing glycemic control are highly recommended., 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 Abuhay, Lakew, Wolde, Mengistu, Legesse and Yenit.)

Background: Diabetes ranks among the most widespread diseases globally, with the kidneys being particularly susceptible to its vascular complications. The identification of proteins for pathogenesis and novel drug targets remains imperative. This study aims to investigate roles of circulating inflammatory proteins in diabetic renal complications., Methods: Data on the proteins were derived from a genome-wide protein quantitative trait locus (pQTL) study, while data on diabetic renal complications came from the FinnGen study. In this study, proteome-wide Mendelian randomization (MR) and colocalization analyses were used to assess the relationship between circulating inflammatory proteins and diabetic renal complications., Results: MR approach indicated that elevated levels of interleukin 12B (IL-12B) (OR 1.691, 95%CI 1.179-2.427, P=4.34×10 -3 ) and LIF interleukin 6 family cytokine (LIF) (OR 1.349, 95%CI 1.010-1.801, P=4.23×10 -2 ) increased the risk of type 1 diabetes (T1D) with renal complications, while higher levels of fibroblast growth factor 19 (FGF19) (OR 1.202, 95%CI 1.009-1.432, P=3.93×10 -2 ), fibroblast growth factor 23 (FGF23) (OR 1.379, 95%CI 1.035-1.837, P=2.82×10 -2 ), C-C motif chemokine ligand 7 (CCL7) (OR 1.385, 95%CI 1.111-1.725, P=3.76×10 -3 ), and TNF superfamily member 14 (TNFSF14) (OR 1.244, 95%CI 1.066-1.451, P=5.63×10 -3 ) indicated potential risk factors for type 2 diabetes (T2D) with renal complications. Colocalization analysis supported these findings, revealing that most identified proteins, except for DNER, likely share causal variants with diabetic renal complications., Conclusion: Our study established associations between specific circulating inflammatory proteins and the risk of diabetic renal complications, suggesting these proteins as targets for further investigation into the pathogenesis and potential therapeutic interventions for T1D and T2D with renal complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhang, Zhang and Zhang.)

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.)