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Objective: To assess the mechanism of supraspinatus tendinopathy induced by type 2 diabetes mellitus (T2DM) in rats using untargeted metabolomics analysis., Methods: The liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics approach was used to screen tendon biomarkers of supraspinatus tendinopathy in rats with T2DM. Seventy-eight Sprague-Dawley rats were divided into normal group (NG) and T2DM groups. Rats in T2DM groups were divided into 12-week (T2DM-12w), and 24-week (T2DM-24w) subgroups according to the time point of the establishment of the T2DM rat model. Histological evaluation (modified Bonar score) and biomechanical testing were used to analyze the adverse effects of type 2 diabetes on the tendon of the supraspinatus muscle in rats.Three comparable groups were set up, including T2DM-12w group vs. NG, T2DM-24w group vs. NG, and T2DM-24w group vs. T2DM-12w group. Differentially expressed metabolites (DEMs) in the supraspinatus tendons in the three groups of rats were analyzed using LC-MS, and data were analyzed using multivariate statistical methods to screen potential biomarkers. The DEMs included in the intersection of the three groups were identified as those associated with the development of diabetic supraspinatus tendinopathy, and trend analysis and pathway topology analysis were performed., Results: With the progression of diabetes, the tendinopathy of the supracinatus muscle of diabetic rats gradually intensified, mainly manifested as inflammatory reactions, disordered collagen fibers, fat infiltration, and increased modified Bonar score. The intersection of DEMs among the three comparable groups was resulted in the identification of 10 key DEMs, in which melezitose and raffinose showed a continuous increasing trend with the prolongation of disease course. By pathway topology analysis, 10 DEMs (P < 0.01) were mainly associated with the pathways of galactose metabolism, which could be involved in the development of diabetes-induced supraspinatus tendinopathy., Conclusion: T2DM causes tendinopathy of the supraspinatus muscle in rats. 10 key DEMs obtained by untargeted metabolomics assay suggested that the development of diabetes-induced supraspinatus tendinopathy was associated with changes in metabolic pathways, such as galactose metabolism. melezitose and raffinose hold promise as a biomarker for disease discrimination and/or disease indication in diabetic supraspinatus tendinopathy., Competing Interests: Declarations Ethics approval and consent to participate This study was carried out in accordance with NIH guidelines for the care and use of laboratory animals (8th edition, NIH). The study protocol was approved by the Ethics Committee of Experimental Animals of the Affiliated Hospital of Qingdao University (Approval No. 20220505SD8020221210126). All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The methods are reported in accordance with ARRIVE guidelines (https://arriveguidelines.org) for the reporting of animal experiments. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, with increased prevalence in individuals with chronic liver conditions and type 2 diabetes mellitus (T2DM). Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) have shown promise in diabetes management and may influence liver disease progression. This systematic review and meta-analysis aimed to assess the efficacy of GLP-1 RAs in reducing the risk of HCC in patients with T2DM., Methods: We conducted a literature search of PubMed, EMBASE, and Web of Science up to August 1, 2024. Studies that evaluated the incidence of HCC in T2DM patients treated with GLP-1 RAs compared to other therapies were included. Meta-analyses were performed using a random-effects model to compute pooled hazard ratios (HRs) and 95% confidence intervals (CIs), and heterogeneity was assessed using the I² statistic. All statistical analyses were performed in R software version 4.3., Results: Eight studies met the inclusion criteria. The pooled analysis demonstrated that GLP-1 RA treatment was associated with a significant reduction in HCC risk compared to insulin or no GLP-1 RA treatment (pooled HR = 0.41, 95% CI: 0.28 to 0.55), with considerable heterogeneity (I² = 74%). Compared to metformin and DPP-4 inhibitors, GLP-1 RAs did not significantly alter HCC risk (HR = 0.99, 95% CI: 0.79 to 1.27 for metformin; HR = 1.05, 95% CI: 0.80 to 1.39 for DPP-4 inhibitors). However, GLP-1 RAs were associated with a reduced risk compared to sulfonylureas (HR = 0.78, 95% CI: 0.65 to 0.93)., Conclusion: GLP-1 RAs may offer protective benefits against HCC in T2DM patients compared to insulin or no GLP-1 RAs, but not significantly over other antidiabetic medications. This review indicates the need for further randomized controlled trials to clarify the role of GLP-1 RAs in HCC risk mitigation and to explore their mechanistic pathways in liver disease management., Competing Interests: Declarations Ethical approval Not required. Consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: There are large disparities in the impact of diabetes on cardiovascular disease (CVD) risk and outcomes by sex and gender. Achieving health equity requires understanding risks and medication efficacy in female patients, especially now, as novel pharmacologic treatments are transforming the diabetes and CVD treatment landscape. This review examines 2 bodies of research that can inform sex differences in CVD in patients with diabetes: female-specific risk factors for CVD and sex-related limitations of clinical trial research in evaluating novel diabetes and CVD treatments., Methods: Two literature searches were performed using Ovid Medline(R) All. The first retrieved manuscripts covering sex and gender differences related to CVD risk and therapies and diabetes. The second focused on randomized controlled trial data on sex/gender differences and GLP-1/SGLT-2/DPP-4 drugs., Results: Female-specific risk factors for CVD include early menarche, premature or early menopause, irregular cycles and polycystic ovary syndrome; pregnancy; adverse pregnancy outcomes; history of breast cancer; and autoimmune diseases. Clinical trials of novel pharmacological treatments for diabetes and CVD have undersampled female populations, and clinical characteristics of male and female participants have differed significantly. Thus, evidence to evaluate potential sex differences in treatment efficacy and side effects has been lacking., Conclusion: To improve health of female patients with diabetes, sex-specific cardiovascular risk factors should be taken into account in screening and treatment decisions. Further, studies of cardiovascular and diabetes medications must ensure adequate representation by sex and report participant characteristics and outcomes by sex., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Context: Type 2 diabetes mellitus is associated with more rapid bone loss in women, but less evidence is available for men or those with prediabetes., Objective: To determine whether bone loss rate is affected by diabetes status in older men, we analyzed data from the Osteoporotic Fractures in Men (MrOS) study., Methods: The multisite MrOS study enrolled 5994 men aged ≥ 65 years. Diabetes status was defined by self-report, diabetes medication use, or elevated fasting serum glucose at baseline. Hip bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA) at baseline and a follow-up visit after 4.6 ± 0.4 years. This analysis included 4095 men, excluding those without follow-up DXA or with unknown diabetes status. Changes in hip BMD in participants with normoglycemia (NG), prediabetes, or type 2 diabetes, excluding thiazolidinedione (TZD) users, were evaluated using generalized linear models (GLM). Diabetes medication use and BMD loss among those with type 2 diabetes were also evaluated with GLM., Results: In adjusted models, hip BMD loss was greater in men with type 2 diabetes (- 2.23%; 95% CI: -2.54 to -1.91; P < .001) but not in men with prediabetes (-1.45%; 95% CI -1.63 to -1.26; P = .33) compared with NG (-1.57%; 95% CI -1.73 to -1.41). Among men with type 2 diabetes, TZD, insulin, and sulfonylurea use were associated with greater hip BMD loss., Conclusion: Men with type 2 diabetes, but not prediabetes, experienced accelerated bone loss compared to participants with normoglycemia. More rapid bone loss predicts increased risk of fractures and mortality in broader populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate the association of diabetes duration with cardiovascular disease (CVD) risk and to examine the relationship between lipid levels and CVD risk over the duration., Methods: Using the Korean National Health Insurance Service Cohort database, we identified 2 359 243 subjects with type 2 diabetes aged ≥ 20 years in 2015 to 2016. Baseline lipid levels and diabetes duration were evaluated and followed up until December 2020 (mean follow-up, 3.9 years). Subjects were categorized according to diabetes duration (new-onset, < 5 years, 5-9 years, or ≥ 10 years). We analyzed the new-onset diabetes group with low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL as the reference group. The hazard ratios (HRs) and 95% CIs of myocardial infarction (MI) and ischemic stroke (IS) were estimated using a Cox proportional hazards model adjusted for potential confounders., Results: During follow-up, 45 883 cases of MI and 53 538 cases of IS were identified. The risk of MI or IS began to increase at LDL-C ≥ 160 mg/dL in the new-onset diabetes group, and at LDL-C ≥ 130 mg/dL in the group with diabetes duration < 5 years. Among subjects with diabetes duration of 5 to 9 years, LDL-C levels of 100-129 mg/dL, 130-159 mg/dL, and ≥ 160 mg/dL were significantly associated with the risk of MI (HR [95% CI] 1.13 [1.04-1.22], 1.28 [1.17-1.39], and 1.58 [1.42-1.76], respectively). MI risk in the diabetes duration ≥ 10 years group was increased by 16%, even in the LDL-C 70-99 mg/dL population (HR [95% CI] 1.16 [1.08-1.25])., Conclusion: This population-based longitudinal study revealed that the LDL-C cutoff level for increasing the risk of CVD varied with diabetes duration and that the target LDL-C level should depend on the duration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Diabetic foot ulcers are characterized by disturbances in the epidermis and/or a portion of the dermis in patients with the disease. With over a million amputations performed annually, it has also emerged as one of the primary causes of lower limb amputation globally. To better understand the severity and anatomical distribution of ulcerated areas in patients with type II diabetes mellitus, this study aimed to identify the factors associated with diabetic foot ulcers (DFUs). This descriptive cross-sectional study was conducted at M Abdur Rahim Medical College Hospital in Dinajpur, Bangladesh, from July to September 2023. The study population was selected using a purposive sampling technique based on the patients' availability during their usual and regular treatment at MARMCH. Using a Bangla questionnaire data was obtained to evaluate the DFUs, in addition to measuring blood pressure and assessing the affected area's neurological function. The severity of the ulcer is calculated by using the Wagner grading system. Data was analyzed by using STATS v15 and chi-square was applied. A total of 113 DFU patients took part in this study. The mean age in years was 56 ± 12 (SD + mean) and the male proportion was greater (61.9%). Most of them (93.91%) were negligent about foot care and suffered from severe DFU (86.37%). The majority of respondents (57.94%) had a right foot ulcer, of which 94.50% had severe ulcers. Almost all ulcers were severe (86.14%) and measured <5 cm in diameter (69.71%). The results highlight the tremendous burden of DFUs, which can have serious consequences and substantial mental and economic effects on patients' healthcare systems., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

While there is ample evidence indicating an increased occurrence of general neurological conditions among individuals with diabetes, there has been limited exploration into the cause-and-effect connection between type 2 diabetes (T2D) and specific neurological disorders, including conditions like carpal tunnel syndrome and Bell's palsy. We used Mendelian randomization (MR) approach to investigate the causal effects of T2D on 67 neurological diseases. We primarily utilized the inverse-variance weighted method for the analysis, and also employed the weighted median and MR-Egger methods in our study. To detect and correct potential outliers, MR-PRESSO analysis was used. Heterogeneity was assessed using Cochrane Q-values. The MR analyses found a possible relationship between T2D and a risk increase of 8 diseases at suggestive level of evidence (P < .05). Notably, among the positive findings that met the false discovery rate threshold, nerve, nerve root, and plexus disorders (odds ratio [OR] = 1.11; 95% confidence interval [CI] = 1.08-1.15); neurological diseases (OR = 1.05; 95% CI = 1.03-1.07) and carpal tunnel syndrome (OR = 1.10; 95% CI = 1.05-1.16) were identified. Our findings affirm a cause-and-effect association between T2D and certain neurological disorders., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Metabolic syndrome is a major public health problem worldwide and an independent predictor of cardiovascular disease in patients with type 2 diabetes (T2DM). This study aimed to determine the prevalence of metabolic syndrome and its individual components among Jordanian patients with T2DM. A cross-sectional design was conducted among T2DM patients at the National Center for Diabetes, Endocrinology and Genetics in Jordan. Data were collected using a structured questionnaire and clinical data extracted from medical records. The National Cholesterol Education Program-Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) diagnostic criteria were used to define metabolic syndrome. Among 1017 participants aged between 22 and 90 years, the overall prevalence of IDF defined metabolic syndrome was 84.2% (72.5% and 96.2% among males and females, respectively). Using ATP III criteria, overall prevalence was 79.1% (77.4% and 80.8% among males and females, respectively). Advancing age, female gender, nonadherence to a diet regimen, sedentary lifestyle or insufficient physical activity, and duration of diabetes ≥10 years were significantly associated with increased odds of metabolic syndrome, regardless of the definition used. Current smoking status and family history of cardiovascular diseases were significantly associated with increased likelihood of ATP III defined metabolic syndrome. The prevalence of metabolic syndrome among Jordanian patients with T2DM is extremely high. The main modifiable risk factors of metabolic syndrome among these patients include nonadherence to a diet regimen, insufficient physical activity, being overweight/obese and smoking. It is recommended that healthcare providers counsel patients on the importance of maintaining physical activity, smoking cessation, and adherence to a diet regimen., Competing Interests: The authors have no funding and conflict of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Diverticular disease is a common condition that has numerous complications. Understanding the impact of diabetes mellitus (DM) on these complications, especially diverticulitis, is crucial for optimizing patient care. This study aimed to determine the relationship between type II DM and the complications of colonic diverticulitis. A retrospective cohort study was conducted on 158 patients complaining of diverticulitis at Asir Central Hospital, Abha, Saudi Arabia, between January 2013 and December 2023. Data on gender, age, and chronic diseases, especially DM, were collected. Data retrieved regarding diverticulitis included the involved segment, complications, Hinchey classification, and management. We classified the patients into groups A for nondiabetics and B for diabetics. We analyzed the data using descriptive statistics, chi-square tests, t tests, and analysis of variance. Diabetic patients were significantly older than their nondiabetic counterparts. Diabetic patients showed a significantly higher complication rate (62.5%) and a higher degree of Hinchey classification compared to nondiabetic patients (43.7%). Furthermore, in comparison to individuals without diabetes, they were hospitalized for a considerably extended period (8.06 ± 7.38 days vs 5.26 ± 5.90 days, respectively). In addition, surgical intervention was observed to be considerably more common in patients with diabetes (46.9%) than in those without diabetes (16.5%). The study showed that DM adversely affected patients with diverticulitis. A greater incidence of complications and a higher category of Hinchey classification were associated with DM compared to nondiabetics. Additionally, diabetics underwent more surgical interventions and had longer hospital stays. Diabetics with diverticulitis require particular care to prevent severe complications., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Little is known about the mechanisms underlying the association of the serum phospholipid lipophilic index (LI) with atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes (T2D). Therefore, we investigated whether the LI is associated with glucometabolic control, meta-inflammation, thrombin generation, fibrin clot properties, endothelial function and platelet activation in T2D patients with angiographically documented ASCVD., Methods: We studied 74 T2D patients with ASCVD, aged 65.6 ± 6.8 years, with a median diabetes duration of 10 years and median HbA1c of 7.0%. Serum phospholipid fatty acids (FAs) were measured by gas chromatography. The serum phospholipid LI was calculated as the sum of the products of the proportion (% of total FAs) with the melting points (°C) of each individual FA, divided by the sum of the proportions of all FAs. Levels of HbA1c, insulin, leptin, adiponectin, lipid profiles, inflammatory markers (hsCRP, interleukin-6, TNF-α), Lp-PLA 2 (a biomarker of vascular inflammation), endothelial function (sICAM-1, sVCAM-1, FMD, NMD), thrombin generation, fibrin clot properties and platelet activation, measured by light transmission aggregometry with arachidonic acid [AA] and adenosine diphosphate [ADP], were assessed., Results: Patients with LI > 16.9 °C (median) had higher HbA1c concentrations by 5.9% compared to the remaining subjects (p = 0.035). In this group, HbA1c levels ≥ 7.0% were found more often than in individuals with LI ≤ 16.9 °C (62.2 vs. 35.1%; p = 0.020). Subjects with LI > 16.9 °C had higher levels of TCh by 17.1% (p = 0.012), LDL-Ch by 29.4% (p = 0.003), interleukin-6 by 22.2% (p = 0.031) and Lp-PLA 2 by 32.4% (p = 0.040), compared to the remaining patients. Moreover, they had increased maximal platelet aggregation induced by AA (p = 0.045), but not by ADP. Serum phospholipid LI correlated with HbA1c (r = 0.24; p = 0.037), TCh (r = 0.36; p = 0.002), LDL-Ch (r = 0.38; p < 0.001), interleukin-6 (r = 0.27; p = 0.020) and Lp-PLA 2 (r = 0.26; p = 0.026). There were no intergroup differences in endothelial function, thrombin generation and fibrin clot properties. Regression analysis showed that HbA1c ≥ 7.0% and serum levels of LDL-Ch, interleukin-6 and Lp-PLA 2 were predictors of LI > 16.9 °C in adjusted models., Conclusions: In well-controlled T2D patients with ASCVD, the higher serum phospholipid LI is associated with worse glucometabolic control, enhanced vascular inflammation and higher platelet reactivity during aspirin treatment at cyclooxygenase-1-selective doses., Competing Interests: Abbreviations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Jagiellonian University Medical College Ethics Committee (approval number KBET/190/B/2012). All patients provided written informed consent prior to enrollment. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

We evaluated the impact of hepatic steatosis-insulin resistance (HS-IR) and liver fibrosis (LF) on type 2 diabetes mellitus (DM2) using triglyceride-glucose (TyG) and Fibrosis-4 (FIB-4). The incidence of DM2 was 12.9 [95% confidence interval (CI), 16.9-9.7] and 9.8 (95% CI, 6.9-13.6) per 1000 person-years in HS-IR and LF. The prevalence of HS-IR was significantly lower at 12 and 24 months with TDF + (3TC or FTC) + RPV [hazard ratio (HR) 0.5 [95% CI, 0.3-0.8], P < 0.01 at 12 months; 0.6 [0.4-0.9], P = 0.01 at 24 months]., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In recent years, with the decline in HBV and HCV infections, there has been a corresponding reduction in both the morbidity and mortality of virus-associated HCC. Nevertheless, rising living standards, coupled with the increasing prevalence of metabolic disorders like diabetes and obesity, have led to a rapid surge in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) incidence. The mechanisms underlying the progression from NAFLD to NAFLD-HCC are multifaceted and remain incompletely understood. Current research suggests that genetic predisposition, metabolic dysregulation, lipotoxicity, oxidative stress, and inflammation are key contributing factors. Given the complexity of these mechanisms and the frequent occurrence of metabolic comorbidities like type 2 diabetes mellitus (T2DM) and cardiovascular disease in NAFLD-HCC patients, there is a pressing need for tailored therapeutic strategies, along with novel prevention, monitoring, and treatment approaches that are personalized to the patient's pathophysiology. Due to the limited depth of research, incomplete understanding of pathogenesis, and insufficient clinical data on NAFLD-HCC treatment, current therapeutic approaches largely rely on tumor staging. In this review, we synthesize current research on the pathogenesis, surveillance, diagnosis, treatment, and prevention of NAFLD-HCC, and offer perspectives for future studies, particularly regarding its underlying mechanisms.

The inhibition of dipeptidyl- peptidase 4 (DPP-4) is an essential therapy for controlling hyperglycemia in patients with type 2 diabetes (T2DM). However, the role of DPP-4 in cancer is not yet clear, with some studies suggesting that it may either promote or suppress tumors. This makes it crucial to have personalized treatment for diabetic women with cancer to effectively manage their diabetes whilst and preventing cancer mortality. To address this issue, we conducted an integrative in-silico analysis and systematic review of the literature to comprehensively examine the relationship between DPP-4 expression and the effects of its inhibitors on prevalent female malignancies. We specifically chose studies that examined the effects of DPP-4 expression and DPP-4 inhibition (DPP-4i) on prevalent cancers in women, such as breast cancer (BC), ovarian cancer (OV), cervical cancer (CC), and endometrial cancer (EC). These studies comprised those conducted both in vivo and in vitro. The review of the literature indicated that DPP-4i may worsen aggressive traits such as metastasis, Epithelial-to-mesenchymal transition (EMT), and chemotherapy resistance in BC cells. However, cohort studies on diabetic and BC patients did not confirm these findings. In vitro studies indicate that on OV, DPP-4 upregulation has been shown to prevent metastasis, while CCappears to be influenced by DPP-4 expression in terms of cell migration. sitagliptin, a pharmaceutical inhibitor of DPP-4, had a significant impact on reducing adhesion in CC cells in vitro. Overexpression of DPP-4 increased cell migration and proliferation in CC and EC cells, and hence the application of sitagliptin is expected to prevent this effect. On the other hand, the result of in-silico data confirmed that a significant correlation exists between DPP-4 expression and immune cell infiltration in breast, ovarian, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) as well as downregulated in these cancers compared to their normal tissue samples. Furthermore, a significant (p < 0.05) effect on OS of BC and CESC patients has been reported due to the elevation of DPP-4 methylation on a specific CPG Island. These findings could aid in creating specialized treatments for diabetic women with specific malignancies, but caution should be exercised when considering the patient's medical history and cancer type., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study aimed at understanding the predictive potential of genetic risk scores (GRS) for diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM) and Major Cardiovascular Events (MCVE) and All-Cause Mortality (ACM) as secondary outcomes. We evaluated 30 T2DM and CKD GWAS-derived single nucleotide polymorphisms (SNPs) and their association with clinical outcomes in a central European cohort (n = 400 patients). Our univariate Cox analysis revealed significant associations of age, duration of diabetes, diastolic blood pressure, total cholesterol and eGFR with progression of DKD (all P < 0.05). However, no single SNP was conclusively associated with progression to DKD, with only CERS2 and SHROOM3 approaching statistical significance. While a single SNP was associated with MCVE - WSF1 (P = 0.029), several variants were associated with ACM - specifically CANCAS1, CERS2 and C9 (all P < 0.02). Our GRS did not outperform classical clinical factors in predicting progression to DKD, MCVE or ACM. More precisely, we observed an increase only in the area under the curve (AUC) in the model combining genetic and clinical factors compared to the clinical model alone, with values of 0.582 (95 % CI 0.487-0.676) and 0.645 (95 % CI 0.556-0.735), respectively. However, this difference did not reach statistical significance (P = 0.06). This study highlights the complexity of genetic predictors and their interplay with clinical factors in DKD progression. Despite the promise of personalised medicine through genetic markers, our findings suggest that current clinical factors remain paramount in the prediction of DKD. In conclusion, our results indicate that GWAS-derived GRSs for T2DM and CKD do not offer improved predictive ability over traditional clinical factors in the studied Czech T2DM population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Metformin is a medication that is widely used for lowering blood sugar in patients with type 2 diabetes. Metformin was shown to have significant antidepressant effects; however, it is not clear whether metformin treatment improves outcomes in patients with type 2 diabetes who have concomitant depressive symptoms., Methods: A total of 475 patients with type 2 diabetes mellitus with depressive symptoms were included in this study and divided into metformin and nonmetformin groups according to whether they were taking metformin. The DASS-21 was used to assess patients' depression and anxiety scores before and after a 24-week intervention. In addition, general information about whether the patients had developed complications from diabetes and whether they had been diagnosed with other diseases was assessed., Results: (1) After 24 weeks, anxiety and depression scores were significantly lower in the metformin group than in the nonmetformin group. (2) The prevalence of depressive symptoms was significantly greater in female type 2 diabetic patients than in male patients (OR = 2.039, 95 % CI = 1.160-3.568). (3) People with type 2 diabetes who develop complications from diabetes (OR = 1.794, 95 % CI = 1.015-3.171) and those diagnosed with other conditions are more likely to experience depressive symptoms., Conclusion: Metformin has an ameliorative effect on type 2 diabetes. However, women, those with diabetes complications, and those with type 2 diabetes who are also diagnosed with other conditions are more likely to experience depressive symptoms., Competing Interests: Declaration of competing interest There were no conflicts of interest from the beginning to the end of this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The adenosine triphosphate-binding cassette transporter A1 (ABCA1) is closely linked to various aspects of the regulation of whole-body cholesterol metabolism and atherosclerosis formation. The object of the study was to investigate the association between rs1800977 and rs2230806 polymorphisms in the ABCA1 gene and myocardial infarction (MI) in Slovenian subjects with type 2 diabetes mellitus (T2DM)., Methods: 1590 T2DM patients (484 subjects with MI and 1106 controls) were included in this retrospective cross-sectional case-control study. After genotyping, Pearson χ2 test was used to compare the distribution of genotypes and alleles among the two groups. Logistic regression analysis adjusted for several risk factors for MI was performed., Results: Genotype distribution showed significant association with MI in T2DM subjects for both selected polymorphisms in ABCA1 gene (p = 0.009 for rs2230806 and p = 0.042 for rs1800977). After applying corrections for confounding variables like age, waist circumference, diastolic blood pressure, serum high-density lipoprotein levels, gender and smoking several genetic models still showed significant associations with MI (dominant model for rs2230806 and dominant, overdominant and co-dominant for rs1800977)., Conclusion: Our study showed that presence of the T allele of the rs2230806 ABCA1 gene is associated with higher risk of MI, while the A allele of the rs1800977 conferred protection against MI in Slovenian T2DM subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Shift work, particularly night shifts, disrupts circadian rhythms and increases stroke risk. This manuscript explores the mechanisms connecting shift work with stroke, focusing on circadian rhythms, hypertension, and diabetes. The circadian system, controlled by different mechanisms including central and peripheral clock genes, suprachiasmatic nuclei (SCN), and pineal gland (through melatonin production), regulates body functions and responds to environmental signals. Disruptions in this system affect endothelial cells, leading to blood pressure issues. Type 2 diabetes mellitus (T2DM) is significantly associated with night shifts, with circadian disturbances affecting glucose metabolism, insulin sensitivity, and hormone regulation. The manuscript examines the relationship between melatonin, insulin, and glucose balance, highlighting pathways that link T2DM to stroke risk. Additionally, dyslipidemia, particularly reduced HDL-c levels, results from shift work and contributes to stroke development. High lipid levels cause oxidative stress, inflammation, and endothelial dysfunction, increasing cerebrovascular risks. The manuscript details the effects of dyslipidemia on brain functions, including disruptions in blood flow, blood-brain barrier integrity, and neural cell death. This comprehensive analysis emphasizes the complex interplay of circadian disruption, hypertension, diabetes, and dyslipidemia in increasing stroke risk among shift workers. Understanding these mechanisms is essential for developing targeted interventions to reduce stroke susceptibility and improve cerebrovascular health in this vulnerable population., Competing Interests: Declarations Conflict of interest The authors declare no conflict of interest. Consent to participate Not applicable. Consent for publication Not applicable. Ethical approval Not applicable., (© 2024. The Author(s).)

Background: Diabetes-associated cognitive dysfunction, characterized by hippocampal synaptic loss as an early pathological feature, seriously threatens patients' quality of life. Synapses are dynamic structures, and hormones play important roles in modulating the formation and elimination of synapses. The pituitary, the master gland of the body, releases several hormones with multiple roles in hippocampal synaptic regulation. In this study, we aimed to explore the relationship between pituitary hormones and cognitive decline in diabetes., Methods: A total of 744 patients with type 2 diabetes (T2DM) (445 men and 299 postmenopausal women) who underwent serum pituitary hormone level assessments, comprehensive cognitive evaluations and MRI scans were enrolled. Dynamic diet interventions were applied in both chow diet-fed mice and high-fat diet (HFD)-fed diabetic mice. The cognitive performance and hippocampal pathology of prolactin (PRL)-knockout mice, neuronal prolactin receptor (PRLR)-specific knockout mice and microglial PRLR-specific knockout mice were assessed. Microglial PRLR-specific knockout mice were fed an HFD to model diabetes. Diabetic mice received an intracerebroventricular infusion of recombinant PRL protein or vehicle., Results: This clinical study revealed that decreased PRL levels were associated with cognitive impairment and hippocampal damage in T2DM patients. In diabetic mice, PRL levels diminished before hippocampal synaptic loss and cognitive decline occurred. PRL loss could directly cause cognitive dysfunction and decreased hippocampal synaptic density. Knockout of PRLR in microglia, rather than neurons, induced hippocampal synaptic loss and cognitive impairment. Furthermore, blockade of PRL/PRLR signaling in microglia exacerbated abnormal microglial phagocytosis of synapses, further aggravating hippocampal synaptic loss and cognitive impairment in diabetic mice. Moreover, PRL infusion reduced microglia-mediated synaptic loss, thereby alleviating cognitive impairment in diabetic mice., Conclusion: PRL is associated with cognitive dysfunction and hippocampal damage in T2DM patients. In diabetes, a decrease in PRL level drives hippocampal synaptic loss and cognitive impairment by increasing microglia-mediated synapse engulfment. Restoration of PRL levels ameliorates cognitive dysfunction and hippocampal synaptic loss in diabetic mice., Competing Interests: Declaration Ethics approval and consent to participate The study protocols of participants was approved by the ethics committee of Nanjing Drum Tower Hospital by the Ethics Review Committee of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School (Approval number: 2017-017-01). All animal experimental procedures were conducted under the Institutional Animal Care and Use Committee-approved protocols (2005010) at Nanjing University according to Laboratory Animal Care Guidelines. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: The prevalence of type 2 diabetes mellitus (T2DM) in cancer patients is high. During the medication review process, clinical pharmacists could detect and manage drug-related problems (DRP) to optimize pharmacotherapy but there is a need to standardize pharmacists' interventions (PI) especially for T2DM-related DRP. The present study aims to describe DRP in cancer patients with T2DM undergoing anticancer treatment (AT) and to propose related preliminary guidelines to manage T2DM-related DRP., Methods: The study was conducted in one oncology outpatient hospital where a clinical pharmacy team performs medication reviews to detect and manage DRP by performing PI in cancer patients undergoing AT. All the data from November 23rd, 2015 to November 23rd, 2019 were extracted and demographic, clinical, oncological, and biological data were collected and analyzed. Based on these results and a literature review, a working group (2 pharmacists and one diabetologist) was constituted to propose a first set of preliminary guidelines clinical pharmacists that were then reviewed using the Delphi method by an expert panel of oncologists and pharmacists., Results: A total of 161 T2DM cancer patients were included in the study (19.7% of all cancer patients screened). Overall, 152 DRP (mean 1.67/patient) were detected (49.3% drug interaction) and 152 PI were performed by clinical pharmacists, mainly drug monitoring (48.0) and drug discontinuation (25.7%). Specifically, there was 24 T2DM-related DRP (including 29.2% drug interactions). Twenty-four DRPs were directly related to T2DM status. The five proposed guidelines reached a consensus after revisions and a sixth has been added., Conclusion: DRPs were frequent among cancer patients with T2DM and we hypothesize that the preliminary guidelines should improve the detection of DRPs directly related to T2DM. The implementation of the preliminary guidelines should now be assessed in clinical practice., Competing Interests: Declarations Ethics approval The study was conducted in accordance with the Helsinki declaration. Patients’ records were anonymized prior to analysis. A database from ONCOPTIMAL (F20220817142044) was created in accordance with the reference methodology MR004 of the National Commission of Liberties and Informatics (no. MR00414012022). As per French regulations about retrospective study, no informed consent and additional ethical committee review were required. Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Diabetic peripheral neuropathy (DPN), a prevalent complication among individuals diagnosed with type 2 diabetes, has a significant impact on both the well-being of patients and their financial situation. Acupuncture has been employed for thousands of years within China and is regarded as one of the primary characteristic therapies of traditional Chinese medicine. Research has indicated that acupuncture has the potential to enhance microcirculation, decrease the generation of free radicals, and augment nerve conduction velocity. There had been several meta-analyses of acupuncture on DPN. Nevertheless, there has been inadequate attention given to the assessment of blood glucose control, and scores related to quality of life. Hence, we get additional evidence by enhancing the quantity and quality of studies to draw more distinct findings., Methods: We will conduct a comprehensive search for reports published from the beginning until June 2023 using various databases including Web of Science, Embase, Cochrane Library, PubMed, AMED, Wanfang database, VIP database, China National Knowledge Infrastructure, and Chinese Biomedical Literature database. Only randomized controlled trials will be considered, with no exclusion of quasi-randomized control trials. Articles in both English and Chinese will be taken into account without any limitations on publication dates. The data will be extracted, managed, and analyzed by two researchers working independently. The primary outcomes will include improvement of symptom scores, change of nerve conduction velocity, and quality of life scores. Additional outcomes will encompass blood glucose levels after fasting and 2 hours after eating, levels of glycosylated hemoglobin, and any adverse events associated with acupuncture. We plan to use the RevMan V.5.4 application and the random-effects model for conducting the meta-analysis. The assessment of potential prejudice can be conducted by Cochrane's 'risk of bias' 2 (RoB 2) tool. Registration: PROSPERO (registration number: CRD42023425203)., Discussion: Our goal is to perform a meta-analysis that offers an unbiased approach to treating individuals with type 2 DPN. At the same time, it also provides doctors with more choices in the treatment of diabetes peripheral neuropathy., Competing Interests: The researchers affirm that the study was carried out without any business or financial affiliations that can be interpreted as a possible clash of interests., (Copyright: © 2024 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: Anemia and chronic kidney disease (CKD) are common findings in diabetic patients. Lack of glycemic control is associated with increased risk of diabetic complications. This study aimed to determine the effect of poor glycemic control on the prevalence and determinants of anemia and CKD among type 2 diabetes mellitus (T2DM) patients in Jordan., Methods: A cross-sectional study design was used in this research. T2DM patients with controlled diabetes (HbA1c ≤7.0%, n = 120) and age-, gender- and body mass index-matched uncontrolled diabetic patients (HbA1c >7.0%, n = 120) were recruited. Blood sample for HbA1c and serum insulin measurement were obtained. Complete blood count and kidney function test results were obtained from the patient's medical records. Anemia was determined according to World Health Organization criteria. A binomial logistic regression was performed to ascertain the effects of age, gender, CKD and glycemic control on the likelihood that participants have anemia., Results: The prevalence of anemia was significantly higher in the uncontrolled T2DM compared to controlled T2DM patients (40% vs 27.5%, OR: 2.14, 95% CI: 1.23, 3.71, P = 0.006). Female patients with uncontrolled T2DM had significantly greater prevalence of anemia compared to male patients with uncontrolled T2DM. The binomial logistic regression analysis showed that age, female gender, and CKD were positively associated with anemia in the multivariate model, while in the univariate model, lack of glycemic control increases the odds of anemia by 1.74 (95% CI: 1.01, 2.99, P = 0.046)., Conclusion: Anemia is commonly present among T2DM patients in Jordan and is associated with poor glycemic control especially in females. These results emphasize the necessity of including anemia screening in standard diabetes care to enable early detection and treatment of anemia and to enhance the overall care of diabetic patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Al-Dwairi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: While Type 2 Diabetes Mellitus (T2DM) prevalence is increasing among younger individuals, few studies have examined how age at T2DM diagnosis relates to dementia risk in diabetic populations. We aimed to investigate the association between age at T2DM diagnosis and subsequent dementia risk, and to determine whether obesity moderates this relationship., Methods: We conducted a prospective cohort study using data from the Health and Retirement Study (2002-2016) matched with its 2003 Diabetes Mail-Out Survey. The study included 1,213 dementia-free adults aged ≥50 with diagnosed T2DM. Primary exposures were age at T2DM diagnosis (categorized as <50, 50-59, 60-69, and ≥70 years) and obesity status (BMI ≥30 kg/m2). The outcome was incident dementia, assessed using the Telephone Interview for Cognitive Status. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sociodemographic factors, health behaviors, health status, and diabetes medication use., Results: Over a median follow-up of 10 (interquartile range, 6-14) years, 216 (17.8%) participants developed dementia. Compared to participants diagnosed with T2DM at age ≥70 years, those diagnosed at younger ages had increased dementia risk: HR 1.70 (95% CI, 1.03-2.80) for 60-69 years, 1.72 (95% CI, 1.06-2.79) for 50-59 years, and 1.90 (95% CI, 1.14-3.18) for <50 years. Obesity significantly moderated this relationship, with obese individuals diagnosed with T2DM before age 50 showing the highest dementia risk (HR 3.05; 95% CI 1.23-7.56) compared to non-obese individuals diagnosed at ≥50 years., Conclusions: Younger age at diagnosis of T2DM was significantly associated with a higher risk of dementia, particularly among individuals with obesity. Interventions specifically targeting obesity may be more effective in preventing dementia for adults with a younger onset of T2DM., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright: © 2024 Qi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aims to explore the correlation between renal blood perfusion (RBP) and diabetic nephropathy (DN)., Methods: A total of 72 mice included db/db and db/m mice at the ages of 6, 14, and 22 weeks, forming six groups. RBP was assessed using Laser Speckle Contrast Imaging (LSCI). Kidney function markers and the extent of pathological damage were evaluated. Pearson correlation analysis was employed to predict the relationship between RBP and various indicators of kidney damage., Results: Compared to db/m mice of all ages, 6-week-old db/db mice showed no significant difference in kidney function markers and had no apparent pathological damage. However, db/db mice at other ages showed deteriorating kidney functions and evident pathological damage, which worsened with age. The RBP in db/m mice of all ages and 6-week-old db/db mice showed no significant difference; however, RBP in db/db mice demonstrated a significant declining trend with age. The correlation between RBP and kidney damage indicators was as follows: 24 h urinary microalbumin (r=-0.728), urinary transferrin (r=-0.834), urinary beta2-microglobulin (r=-0.755), urinary monocyte chemoattractant protein-1 (r=-0.786), Masson's trichrome staining (r=-0.872), and Periodic Acid-Schiff staining (r=-0.908)., Conclusion: RBP is strongly correlated with the extent of diabetic kidney damage.

Despite public health measures, type 2 diabetes (T2D) is still a significant concern worldwide, given its associated complications, including hepatic alterations. The role of epithelial-to-mesenchymal transition (EMT) in liver fibrosis is well established. However, its effects on the progression of diabetic liver diseases are not well understood. Therefore, this study aims to investigate the mRNA/miRNA axes involved in this process. Bioinformatic analysis revealed new EMT-associated genes (CDH2, ITGB1, COL4A1, COL1A1, TNC, CCN2, and JUN), which showed higher expression in obese T2D and hepatocellular carcinoma (HCC) patients. In addition, six miRNAs (miR-21-5p, miR-26a-5p, miR-34a-5p, miR-106a-5p, miR-320a-3p and miR-424-5p) have been found as potential targets. Among them, miR-26a-5p and miR-424-5p were significantly downregulated in nonalcoholic steatohepatitis (NASH) and HCC (p < 0.05), being considered potential negative regulators of the EMT process. In our hepatic mesenchymal culture model, miR-26a-5p negatively regulated cadherin 2 (also known as N-cadherin, CDH2) and promoted the cadherin 1 (also known as E-cadherin, CDH1) expression. Our results reveal potential molecules involved in liver tumor development. Moreover, we observe that miR-26a-5p impairs EMT in the initial stages of diabetic liver disease by inhibiting CDH2 and could be a valuable target in this pathology., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval All research was conducted in accordance with the Declarations of Helsinki. The research experimental procedure was approved by the Ethics Committee of the Fundeni Clinical Institute (51715/27.09.2022). Informed consent All enrolled patients gave written informed consent., (© 2024. The Author(s).)

Mendelian Randomization studies indicate that BMI contributes to various diseases, but it's unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement. Similar attenuation was observed for chronic kidney disease and stroke, though results varied. Findings were consistent across sexes, except for myocardial infarction. Residual effects may result from temporal BMI changes, pleiotropy, measurement error, non-linear relationships, non-collapsibility, or confounding. The attenuation extent of BMI genetic risk score on disease associations suggests the potential impact of reducing BMI on disease risk., Competing Interests: Competing interests G.E., G.T., V.S., F.Z., H.Helgason, T.O., S.R., V.T., M.O.U., G.S., A.S.S., H.E., H.M.A., G.A.J., A.H., S.G., U.S., H.K.A., D.O.A., G.B., H.S., T.T., P.S., U.T., H.Holm, D.F.G. and K.S. are employees of deCODE Genetics/Amgen Inc. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Background: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2D). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2D with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2D and HFpEF remain unknown., Methods: A total of 24 patients with T2D and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period., Results: During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P <0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise ( P <0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs., Conclusions: In patients with T2D and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2D and HFpEF., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335., Competing Interests: H.W. has served as the principal or a subinvestigator in studies involving the following pharmaceutical companies: MSD, Bayer, Daiichi-Sankyo, Novartis, Novo Nordisk, Sanofi-Aventis, and Pfizer. R.N. was the principal investigator or a subinvestigator in studies involving the following pharmaceutical companies: Imbria, Medtrace, and Janssen. B.B. receives research support from the National Institutes of Health and the United States Department of Defense, as well as research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics. B.B. has served as a consultant for Actelion, Amgen, Aria, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Janssen, Merck, and Novo Nordisk. B.B. is a named inventor (US Patent No. 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat HF. The other authors report no conflicts.

Background: Diabetic peripheral neuropathy (DPN) impacts approximately 50% of individuals with Type 2 diabetes mellitus (T2DM), leading to severe complications such as foot ulcers and amputations. Notably, visceral adiposity is increasingly recognized as a pivotal factor in augmenting the risk of DPN. We aim to evaluate the correlation between obesity-related body composition, particularly visceral fat, and DPN to facilitate early identification of high-risk patients with T2DM. Methods: This cross-sectional analysis encompassed 113 T2DM patients from the Department of Endocrinology and Metabolism at the Second Affiliated Hospital of Fujian Medical University, conducted between September 2020 and January 2021. Patients were categorized into two cohorts: those with DPN (DPN group) and those without (NDPN group). We utilized bioelectrical impedance analysis (BIA) to determine body measurements, such as weight and visceral fat area, in addition to collecting clinical and biochemical data. Logistic regression was employed to analyze the data. Results: The study uncovered a statistically significant difference in the visceral fat area between the DPN and NDPN groups ( p = 0.048). Through multivariate logistic regression analysis, the visceral fat area was identified as an independent risk factor for DPN among T2DM patients (OR 1.027; 95% CI 1.004-1.051, p = 0.022). Other significant risk factors included the duration of diabetes and the presence of diabetic retinopathy. Conclusion: The visceral fat area serves as an independent risk factor for DPN in individuals with T2DM. Implementing measures to assess and manage visceral obesity could be vital in the prevention and management of DPN. This underscores the value of technologies such as BIA in clinical and community settings for early intervention., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Rui-Ling Wu et al.)

Type 2 diabetes mellitus (T2DM) seriously threatens human health and the quality of life, cognitive impairment is considered as a common complication of T2DM. Neuroimaging meta-analysis found brain functional and structural abnormality in patients with T2DM. Therefore, the purpose of the meta-analysis was to identify brain regions of patients with T2DM-related cognitive impairment (T2DM-CI) where functional and structural indicators changed together or could not synchronize. A literature screening of neuroimaging studies on cognitive impairment in T2DM was conducted from 1 January 2007 to 26 May 2023 in PubMed, Web of Science, Cochrane Library, and Medline databases. The functional indicators we studied were amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and degree centrality (DC), while the structural indicator was gray matter (GM), which included gray matter volume (GMV) and cerebral cortical thickness. Studies reporting ALFF, ReHo, DC and GM abnormalities between T2DM-CI and healthy controls (HCs) were selected and their significant peak coordinates (x, y, z) and effect size (t-value) were extracted to perform a meta-analysis using anisotropic effect size sign differential mapping (AES-SDM) 5.15 software. Moreover, the brain regions with significant differences obtained from meta-analysis were saved as masks and then validated in our data. Total 19 studies and 20 datasets were involved in this study. Compared to HCs, combining ALFF, ReHo, and DC measurements, the brain activity of the left anterior cingulate/paracingulate gyri (ACC.L, BA24) in T2DM-CI patients increased significantly, while the brain activity of the left lingual gyrus (LING.L, BA18) in T2DM-CI patients decreased significantly. The GM indicator of the right superior temporal gyrus (STG.R, BA42) and left inferior occipital gyrus (IOG.L, BA19) in T2DM-CI patients decreased significantly. Meta-regression analysis showed the negative relationship between the brain activity reduction in LING.L and the percentage of female patients, as well as the negative relationship between GM reduction in IOG.L and T2DM duration. Furthermore, we validated a decrease in brain activity in the LING.L of T2DM-CI patients in our independent dataset. The decrease of brain activity in LING.L and the decrease of GM in IOG.L were closely related to visual impairment in T2DM-CI patients. These abnormal brain regions may be the main targets for future research, early intervention can delay the further development of cognitive impairment in T2DM patients and improve their quality of life, which also provided early biomarkers for clarifying the mechanism of cognitive impairment in T2DM., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate All methods used in this article complied with relevant regulations and rules, and the protocol of meta-analysis was registered on PROSPERO(CRD42023448917). This validation study was approved by the Hospital Medical Ethics Committee (NCT02420470), and all study subjects signed a written informed consent form., (© 2024. The Author(s).)

Given the limited head-to-head comparison of cardiovascular and renal outcomes between liraglutide and dulaglutide, our study aimed to investigate the clinical outcomes between dulaglutide and liraglutide in a real-world setting. In this new-user design, comparative and retrospective cohort study, patients with type 2 diabetes mellitus with prescription for GLP-1RAs from January 1, 2016 to December 31, 2022 (n = 8,278) were included. Primary outcome was composite cardiovascular outcomes which was composed of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke. The composite renal outcome was also interested, including new macroalbuminuria, doubling of serum creatinine, worsening of estimated glomerular filtration rate (eGFR), and progression to dialysis. A total of 3,210 subjects receiving liraglutide and 5,068 subjects receiving dulaglutide were identified. In the adjusted cohort by applying inverse probability of treatment weighting, the incidence of composite cardiovascular outcomes was 18.4 and 18.7 events per 1000 person-years in the liraglutide and dulaglutide groups, respectively. The risk of cardiovascular outcomes did not significantly differ between groups (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.85-1.15). Moreover, the risk of composite renal outcomes was also comparable between groups (subdistribution HR 1.07, 95% CI 0.995-1.16). Liraglutide and dulaglutide demonstrated comparable cardiovascular and renal outcomes in a real-world setting., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (diabetic MASLD) frequently coexist and worsen liver and non-liver outcomes, but effective pharmacological therapies are limited. We aimed to evaluate the long-term effect of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on liver and non-liver outcomes among patients with diabetic MASLD., Design: This population-based cohort study retrieved patients with diabetic MASLD from Merative Marketscan Research Databases (April 2013 and December 2021). The active comparator was other glucose-lowering drugs (oGLDs). Primary outcomes were liver complications including hepatocellular carcinoma (HCC) and liver cirrhosis, as well as non-liver complications including cardiovascular disease (CVD), chronic kidney disease (CKD) and non-liver cancer. Propensity score matching was applied and Cox regression models were conducted., Results: Compared with oGLD, SGLT-2i users had significantly lower risk of HCC (HR 0.76, 95% CI 0.62 to 0.93), liver cirrhosis (HR 0.80, 95% CI 0.76 to 0.84), CVD (HR 0.82, 95% CI 0.79 to 0.85) and CKD (HR 0.66, 95% CI 0.62 to 0.70), non-liver cancer (HR 0.81, 95% CI 0.76 to 0.86). Compared with patients without metformin and SGLT-2i, a stepwise decreasing risk was observed in users of either metformin or SGLT-2i (HRs 0.76-0.97) and in users of both medications (HRs 0.58-0.79). The lower risk also was shown in liver decompensation, compensated cirrhosis, major CVD, end-stage renal disease and specific common cancers (HRs 0.61-0.84)., Conclusion: In a nationwide cohort, SGLT-2i users were associated with a substantially lower risk of liver and non-liver complications than oGLD users among patients with diabetic MASLD. The risk was further reduced with concomitant metformin use., Competing Interests: Competing interests: MHN received research grants via Stanford University from Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Cancer Institute, Glycotest and personal fees from consulting/advisory board from Intercept, Exact Science, Gilead, GSK. MFY received research funding from Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation, Roche and is an advisory board member and/or received research funding from AbbVie, Aligos therarpeutics, Arbutus Biopharma, Bristol Myer Squibb, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals, Roche. W-KS received speaker’s fees and is an advisory board member of Abbott, received research funding from Alexion Pharmaceuticals, Boehringer Ingelheim, Pfizer and Ribo Life Science, received speaker’s fees and received research funding from AstraZeneca, and is an advisory board member, received speaker’s fees and researching funding from Gilead Sciences. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Cardiac rehabilitation is crucial in managing coronary disease, particularly in type 2 diabetes, yet it remains almost non-existent in West Africa., Objectives: This study aimed to compare the profiles of diabetic and non-diabetic coronary patients undergoing cardiac rehabilitation at the Principal Hospital of Dakar, Senegal., Methodology: A comparative, descriptive, and analytical study was conducted from January 2019 to December 2022 involving two groups of coronary patients (diabetic and nondiabetic) at the rehabilitation centre. Patients who completed at least 10 sessions were included. We analysed sociodemographic, clinical, and paraclinical data before and after rehabilitation, as well as therapeutic adherence. Data analysis was performed using SPSS version 18, with a significance level set at 0.05., Results: A total of 199 coronary patients participated, including 75 diabetics and 124 non-diabetics. The average age was 61.6 ± 8.3 years for diabetics and 59.8 ± 12.4 years for non-diabetics, with a male predominance (sex ratio: 2 for diabetics and 3.9 for non-diabetics). In diabetics, the main cardiovascular risk factors were age (80%), hypertension (62.7%), physical inactivity (57.3%), dyslipidaemia (40%), and smoking (33.3%). Cardiac rehabilitation significantly improved clinical symptoms and parameters such as systolic blood pressure, heart rate, and abdominal obesity in diabetic patients. Glycated haemoglobin levels were balanced in 70.4%, an improvement of 40.8%. Rehabilitation had a greater impact on METS improvement and adherence in diabetic patients, along with reduced depression., Conclusion: Cardiac rehabilitation improves control of cardiovascular risk factors, but its availability and accessibility need improvement., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background: The global increase in diabetes, especially in developing nations, has escalated complications like diabetic foot ulcers. Hypovitaminosis D is considerably prevalent among individuals with Type 2 Diabetes Mellitus (T2DM), especially among those with chronic vascular complications., Objectives: To determine the association between vitamin D levels and foot ulcers among patients with T2DM., Methods: The study population comprised of 176 individuals (88 individuals with diabetic foot ulcers (DFUs) and 88 individuals with T2DM without DFU). Vitamin D levels were assessed using blood samples according to standard methods., Results: The majority of participants in the DFU group presented with Grade 2 and Grade 3 ulcers. There was a significant difference in serum vitamin D levels, indicating lower levels among cases (mean of 19.6 ng/ml ± 13.6) compared to controls (mean of 36.2 ng/ml ± 11.4) with a p-value of 0.014. Data shows 84.1% of persons with foot ulcers had deficient/insufficient vitamin D, while only 29.5% of persons without DFU had deficient/insufficient vitamin D levels. Regression analysis shows that persons with DFU were 12.6 (6.0 - 26.2) times likely to have deficient/insufficient vitamin D levels. Chi-square analysis shows that the distribution of the DFU severity was significantly higher among persons with deficient Vitamin D levels, compared to persons with sufficient Vitamin D levels (p = 0.0001)., Conclusion: Lower serum vitamin D levels are significantly associated with diabetic foot ulcers (DFUs), potentially hindering healing and immune function. Screening for and correcting vitamin D deficiency may potentially improve the outcome in patients with diabetic foot ulcers., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background and Aims: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 195 T2DM patients were defined as Control or DPN group. Clinical parameters were compared, and the association between HbA1c (or UACR) and DPN was analyzed. Risk factors for DPN were observed, and the diagnostic values of HbA1c and UACR were assessed., Results: Compared with 104 participants without DPN, 91 individuals with DPN exhibited higher HbA1c and UACR levels. In all patients, increased HbA1c and UACR were identified as risk factors for DPN in individuals with T2DM. Moreover, increased HbA1c was a risk factor for DPN in volunteers without DN, whereas elevated UACR was determined as a risk factor for DPN in participants with DN. The cut-off point for HbA1c (7.65%) in patients without DN had a sensitivity of 86.0% and specificity of 44.6%, while the cut-off point for UACR (196.081 mg/g) in patients with DN had a sensitivity of 52.9% and specificity of 76.2%., Conclusion: Elevated HbA1c and UACR levels are risk factors for DPN and may serve as potential biomarkers for DPN in T2DM patients., (© 2024. The Author(s).)

Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with liver inflammation, fibrosis, and cirrhosis and is associated with a greater risk of hepatocarcinoma. Nonalcoholic steatohepatitis (NASH) is a persistent and progressive form of NAFLD. Recent evidence suggested that ertugliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2), suppresses NAFLD development in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to determine the impact of ertugliflozin on improving NAFLD in patients with T2DM and the function of liver enzymes., Methods: This prospective, randomized, double-blind, placebo-controlled, interventional study aimed to determine the effectiveness of 15 mg of ertugliflozin versus 30 mg of the standard therapy pioglitazone versus placebo in NAFLD patients with T2DM. The study was established based on patient randomization in three groups: ertugliflozin, pioglitazone, and a placebo. This study was registered under the Australian New Zealand Clinical Trial Registry (Trial ID: ACTRN12624000032550)., Results: The impact of therapy was determined in the treatment groups by utilizing liver ultrasonography and biochemical parameters. After 24 weeks of clinical study, the results revealed significant improvement in the grades of fatty liver, especially in the ertugliflozin group. The number of patients with hepatic steatosis significantly decreased among the respective groups classified according to fatty liver grade. Among patients in the ertugliflozin and pioglitazone groups, 45% to 23.4% and 41.7% to 26.6%, respectively, decreased in the Grade 2 group. The aspartate aminotransferase and alanine aminotransferase levels were significantly lower in all the study groups, especially in the ertugliflozin group (P ≤ .001)., Conclusion: The present study revealed that the concomitant use of ertugliflozin has favorable effects on liver enzymes, as it decreases liver fat intake and reduces complications in patients with NAFLD-associated T2DM. However, more in-depth studies will be required to observe every aspect of ertugliflozin., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Coronary artery calcification is commonly found in patients with type 2 diabetes mellitus (T2DM), which may compromise the diagnostic accuracy of coronary computed tomography angiography (CTA). Computed tomography-derived fractional flow reserve (CT-FFR), which integrates coronary anatomy with functional assessment, holds the potential to become a powerful diagnostic tool for evaluating calcified lesions., Objective: We aim to assess the prognostic value of CT-FFR for calcific lesions in patients with T2DM and unstable angina (UA)., Methods: We conducted a retrospective study involving 3,392 patients who were diagnosed with T2DM and UA who underwent coronary CTA, with at least one visible calcification site. Of those, 1,091 patients and 1,372 vessels were recommended by cardiovascular specialists and completed invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR) measurements. Simultaneously, those patients also underwent CT-FFR measurements and were divided into two groups based on CT-FFR values: one group with CT-FFR > 0.80 and the other with CT-FFR ≤ 0.80. Demographics, clinical data, the diagnostic performance of CT-FFR, analysis of calcified lesions on CTA, and major adverse events during follow-up were recorded., Results: The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of CT-FFR were 84.8%, 84.6%, 85.1%, 84.7%, 85.0%, and 84.8%, respectively, per patient, and 82.2%, 80.3.2%, 81.8%, 79.7%, 81.1%, and 82.9% respectively, per vessel. For lesion and calcification characteristics, the degree of stenosis, lesion length, rate of bifurcation lesions, diffusive lesions, occlusion, calcium volume, and coronary artery calcification score (CACS) were significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. In contrast, the minimum cross-sectional area was smaller in the CT-FFR ≤ 0.8 group than in the CT-FFR > 0.8 group. Major adverse cardiovascular and cerebrovascular events (MACCE) at the 3-year follow-up was significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. The CT-FFR value is an independent predictor of MACCE at the 3-year follow-up., Conclusion: CT-FFR demonstrated significant diagnostic performance using invasive FFR as the reference standard and proved to be an important predictive tool for assessing prognosis not only in calcified lesions but also in lesions with a CACS score of zero in patients with T2DM and UA. CT-FFR may serve as a valuable tool for guiding treatment decisions in these patients., (© 2024. The Author(s).)

Objective: This study investigated the association of Time In Range (TIR) obtained from Blood Glucose Monitoring (BGM) with Cognitive Impairment (CI) inpatients with middle-aged Type 2 Diabetes Mellitus (T2DM) and further explored whether a TIR goal for T2DM in adults with > 70% possess a protective effect on cognitive function., Research Design and Methods: A total of 274 inpatients with T2DM aged 40-64 years, who underwent seven-point BGM ( pre meals and 120 min post meals and at bedtime) were recruited in this cross-sectional study. TIR was defined as the percentage of blood glucose within the target range of 3.9-10.0mmol/L. Subjects were divided into Normal Cognitive Function (NCF) (n = 160) and CI (n = 114) groups according to the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The association of TIR and other glycemic metrics, calculated from seven-point BGM data, with cognitive dysfunction was analyzed., Results: The prevalence of CI was 41.6% in patients with middle-aged T2DM (median age 58 years). TIR was lower in CI group than in NCF group (28.6% vs. 42.9%, P = 0.004). The prevalence of CI decreased with ascending tertiles of TIR (p for trend < 0.05). Binary logistic regression analysis showed a significant association between TIR and CI (odds ratio [OR] = 0.84, p < 0.001) after adjusting for confounders (age, education, marital status, age at Diabetes Mellitus (DM) onset, cerebrovascular disease). Further adjustment of Standard Deviation (SD)(OR = 0.84, p = 0.001) or Coefficient of Variation (CV)(OR = 0.83, p < 0.001), TIR was still associated with CI. While a TIR goal of > 70% probably possessed independent protective effect on cognitive function (OR = 0.25, p = 0.001) after controlling for confounders above., Conclusions: TIR obtained from BGM was related to CI in middle-aged T2DM individuals and a TIR goal of > 70% probably possessed a protective effect on cognitive function for middle-aged T2DM ., (© 2024. The Author(s).)

Metformin is an antihyperglycemic used to treat type 2 diabetes mellitus (T2DM). Patients with T2DM are at increased risk of cardiovascular disease. We explored the association between metformin use and cardiovascular magnetic resonance (CMR) derived stress myocardial blood flow (MBF), myocardial perfusion reserve (MPR) and major adverse cardiovascular events (MACE; all cause death, MI, stroke, heart failure hospitalisation and coronary revascularisation) in patients with T2DM. Multi-centre study of patients with T2DM, and healthy controls, underwent quantitative myocardial perfusion CMR using an artificial intelligence supported process. Multivariable regression analysis, and cox proportional hazard models of propensity score weighted patients quantified associations between metformin use, MBF, MPR, all cause death and MACE. Analysis included 572 patients with T2DM (68% prescribed metformin) with median follow-up 851 days (IQR 935 - 765). Metformin use was associated with an increase of MPR of 0.12 [0.08-0.40], p = 0.004. There were 82 MACE events (14.3%) including 25 (4.4%) deaths of which 16 were in those not prescribed metformin (8.7%), compared to 9 in patients prescribed metformin (2.3%): adjusted hazard ratio 0.24 (95% CI 0.08-0.70, p = 0.009). MACE events were similar between groups. This multicentre, inverse probability weighting propensity score analysis study showed that in patients with T2DM, metformin use is associated with higher MPR and improved all cause survival., (© 2024. The Author(s).)

An increasing body of evidence suggests that diabetes mellitus (DM) plays a role in sensorineural hearing loss (SNHL). However, the specific causal relationship between DM and SNHL remains partially uncertain. This study aimed to investigate the causal relationship between DM and the risk of SNHL using a Mendelian randomization (MR) study. Single nucleotide polymorphisms closely related to DM were selected as instrumental variables using open genome-wide association study datasets. Three methods based on inverse variance weighted were utilized to investigate the causal relationship between DM and SNHL. Subsequently, multivariable MR (MVMR) was executed to adjust for confounding genetic associations. In addition, a range of sensitivity analyses were performed to assess the stability and reliability of the MR results. The inverse variance weighted analysis indicated a potential genetic causality between DM and SNHL (odds ratio [OR]: 2.179; 95% confidence interval [CI]: 1.123-4.231; P = .021). The sensitivity analyses showed that the included single nucleotide polymorphisms had no heterogeneity, horizontal pleiotropy, and outliers (P > .05). Moreover, the leave-one-out method further verified the robustness of the MR analysis results. Finally, the results of the MVMR study predicted that there was a genetic causal relationship between type 1 DM and SNHL (OR: 1.032; 95%CI: 1.018-1.047; P = 5.45 × 10-6), while there was no causality between type 2 DM and SNHL (OR: 1.000; 95%CI: 0.958-1.036; P = .853). Our study suggested that DM and type 1 DM may be genetically responsible for SNHL. Although our study did not detect a genetic causal relationship between type 2 DM and SNHL, this does not rule out a relationship between them at other mechanistic levels. Further studies are required to confirm the findings and look into the physiological and pathological mechanism underlying these relationships., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Type 2 diabetes (T2D), a widespread chronic metabolic disorder, presents frequently in clinical settings. The relationship between T2D and bone mineral density (BMD) has been subject to ongoing investigation, yielding inconclusive results., Methods: A systematic literature search was conducted across several databases, including CNKI, VIP, CBM, Wanfang, PubMed, Cochrane Library, and Embase, targeting observational studies that explored the impact of microangiopathy associated with T2D on BMD or bone metabolism. The search spanned from the inception of each database to July 1, 2023. The Newcastle-Ottawa Scale was employed for quality assessment, and RevMan 5.3 software was utilized for data analysis. Stata 14.0 was used for the quantitative evaluation of publication bias regarding outcome measures., Results: The inclusion criteria were met by 30 observational studies, comprising 6470 participants-3121 with diabetes and 3349 without. The meta-analysis revealed no significant difference in overall BMD between the nondiabetic and T2D groups (mean difference [MD] = -0.07, 95% confidence interval [CI] [-0.17, 0.03], Z = 1.45, P = .15). However, BMD at the lumbar vertebrae was significantly higher in nondiabetic individuals compared with those with T2D (MD = -0.14, 95% CI [-0.22, -0.06], Z = 3.32, P = 0.0009), as was the case with femoral neck BMD (MD = -0.11, 95% CI [-0.18, -0.04], Z = 3.08, P = .002). A difference in femoral neck BMD between nondiabetics and individuals with T2D approached but did not reach statistical significance (MD = -0.14, 95% CI [-0.27, 0.00], Z = 1.94, P = .05). An inverted funnel plot analysis suggested possible publication bias, as evidenced by an asymmetrical distribution of studies around the axis of symmetry, with overlap observed in several cases., Conclusion: The findings indicate a significant association between T2D and reduced BMD at critical sites such as the lumbar vertebrae and femoral neck, highlighting an increased risk of osteoporosis or osteoporotic fractures in these regions., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This systematic review and meta-analysis aimed to quantify differences in type 2 diabetes (T2D) complications between ethnic minority populations and European host populations, in both cross-sectional and prospective studies. Following Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, we searched multiple databases for studies (until July 1, 2024) with T2D complications as outcome. Studies were included if they compared ethnic minority populations to the host population and were conducted in Europe. T2D complications included mortality, macrovascular and microvascular complications and mental disorders. Risk of bias was assessed with the assessment tool for observational cohort and cross-sectional studies. Risk estimates were pooled using random effects models. From a total of 2901 references, 58 studies were included, comprising 805 to 1 230 410 individuals for the meta-analyzed complications. Compared with the host population, ethnic minority populations generally had a lower risk of all-cause mortality (RR 0.70 (95% CI 0.63; 0.77); I 2 =87%)) and macrovascular complications (RR 0.72 (95% CI 0.58; 0.88); I 2 =88%). South Asians, however, showed comparable risks for most macrovascular complications and a slighthly higher risk of major adverse cardiovascular events. Increased risks for microvascular complications, nephropathy and retinopathy were observed (eg, in prospective studies RR 1.50 (95% CI 1.14; 1.96); I 2 =86% for nephropathy). No ethnic differences were observed for mental disorders. Ethnic minority populations with T2D in Europe are generally at reduced risk of all-cause mortality and macrovascular complications, but at higher risk of nephropathy and retinopathy. Our findings may help to further identify high-risk populations and to develop guidelines and future interventions. PROSPERO registration number:PROSPERO 2022 CRD42022366854., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Low back pain (LBP) and insomnia are common global health issues, but their relationship and potential mediators remain unclear. This study aimed to explore the impact of insomnia on LBP using mendelian randomization (MR) methods and analyze the mediating role of modifiable factors., Methods: Univariable MR (UVMR) analysis was employed to examine the causal relationship between insomnia and LBP, as well as the association between modifiable factors [smoking, alcohol consumption, body mass index (BMI), and type 2 diabetes (T2DM)] and LBP. Subsequently, multivariable MR (MVMR) analysis was conducted to explore the impact of insomnia on the mediation of LBP risk by modifiable factors., Results: In the UVMR analysis, insomnia [odds ratio (OR) = 2.95, 95%CI: 2.33-3.72)] and BMI (OR = 1.18, 95%CI: 1.02-1.37) were positively associated with the prevalence of LBP. The effects of smoking, alcohol consumption, and T2DM on LBP were not significant (P > 0.05). In the MVMR analysis, the proportion of mediation of BMI on the relationship between insomnia and LBP was 7.12%., Conclusion: This study revealed the causal relationship between insomnia and LBP using MR methods for the first time, and identified the mediating role of BMI. These findings offer new insights into understanding the relationship between insomnia and LBP, informing the prevention and treatment of these two health issues., (© 2024. The Author(s).)

Background: Although the exact role of mitophagy in the pathogenesis of diabetic cardiomyopathy (DCM) caused by type 2 diabetes mellitus (T2DM) remains controversial, recent studies revealed inhibition of mitophagy exacerbates cardiac injury in DCM. The zinc transporter ZIP7 has been reported to be upregulated by high glucose in cardiomyocytes and ZIP7 upregulation leads to inhibition of mitophagy in mouse hearts in the setting of ischemia/reperfusion. Nevertheless, little is known about the role of ZIP7 and its relationship with mitophagy in DCM caused by T2DM., Methods: T2DM was induced with high-fat diet (HFD) and streptozotocin. The cardiac-specific ZIP7 conditional knockout (ZIP7 cKO) mice were generated by adopting CRISPR/Cas9 system. Cardiac function was evaluated with echocardiography. Mitophagy was assessed by detecting mito-LC3II, mitoKeima, and mitoQC. Reactive oxygen species (ROS) were detected with DHE and mitoB., Results: ZIP7 was upregulated by T2DM in mouse hearts and ZIP7 cKO reduced mitochondrial ROS generation in mouse hearts with T2DM. Mitophagy was suppressed by T2DM in mouse hearts, which was prevented by ZIP7 cKO. T2DM inhibited PINK1 and Parkin accumulation in cardiac mitochondria, an effect that was prevented by ZIP7 cKO, pointing to that ZIP7 upregulation mediates T2DM-induced suppression of mitophagy by inhibiting the PINK1/Parkin pathway. T2DM induced mitochondrial hyperpolarization and decrease of mitochondrial Zn 2+ and this was blocked by ZIP7 cKO, indicating that upregulation of ZIP7 leads to mitochondrial hyperpolarization by reducing Zn 2+ within mitochondria. Finally, ZIP7 cKO prevented cardiac dysfunction and fibrosis caused by T2DM., Conclusions: ZIP7 upregulation mediates the inhibition of mitophagy by T2DM in mouse hearts by suppressing the PINK1/Parkin pathway. Reduction of mitochondrial Zn 2+ due to upregulation of ZIP7 accounts for the inhibition of the PINK1/Parkin pathway. Prevention of ZIP7 upregulation is essential for the treatment of T2DM-induced cardiomyopathy., (© 2024. The Author(s).)

Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction., (© 2024. The Author(s).)

Objective: To investigate the association between sodium-glucose cotransporter-2 (SGLT-2) inhibitor use and risk of all cause mortality among patients with heart failure with reduced ejection fraction., Design: Linked database study., Setting: National registers in Denmark, July 2020 to June 2023., Participants: Patients with heart failure, aged ≥45 years, with left ventricular ejection fraction ≤40%., Main Outcome Measures: The primary outcome was all cause mortality comparing initiation and continued treatment with SGLT-2 inhibitors versus continued treatment with other standard-of-care heart failure drugs and non-use of SGLT-2 inhibitors; secondary outcomes were the composite of cardiovascular mortality or admission to hospital with heart failure and its individual components. Hazard ratios were estimated using Cox regression adjusted using inverse probability of treatment weighting based on propensity scores., Results: The study included 6776 patients who started SGLT-2 inhibitors (79% dapagliflozin; 21% empagliflozin) and 14 686 patients who remained on other standard-of-care heart failure drugs and did not use SGLT-2 inhibitors. Most SGLT-2 inhibitor users were male (70%), the mean age was 71.2 (standard deviation 10.6) years, and 20% had type 2 diabetes. During follow-up, 374 deaths occurred among SGLT-2 inhibitor users (incidence rate 5.8 per 100 person years) and 1602 among non-users (8.5 per 100 person years). The weighted hazard ratio for all cause mortality was 0.75 (95% confidence interval 0.66 to 0.85); the weighted incidence rate difference was -1.6 (95% confidence interval -2.5 to -0.8) per 100 person years. Secondary outcomes showed a weighted hazard ratio of 0.94 (0.85 to 1.04) for cardiovascular mortality or hospital admission with heart failure, 0.77 (0.64 to 0.92) for cardiovascular mortality, and 1.03 (0.92 to 1.15) for hospital admission with heart failure. The weighted hazard ratios for all cause mortality were consistent in patients with and without diabetes (0.73 (0.58 to 0.91) and 0.73 (0.63 to 0.85); P=0.99)., Conclusions: In this large database study among patients with heart failure with reduced ejection fraction, SGLT-2 inhibitor use was associated with a 25% lower risk of all cause mortality, supporting their effectiveness in routine clinical practice., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Novo Nordisk Foundation and Karolinska Institutet; HS is a former employee of IQVIA; AH is a scientific advisory board member of VAC4EU and receives unrelated grant support from the Novo Nordisk Foundation, the Lundbeck Foundation, and the Independent Research Foundation Denmark; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent reports have revealed that nephropathy leading to kidney injury (KI) is a prevalent complication of COVID-19 and is linked to high mortality and morbidity in diabetes mellitus type II (DM-T-II) patients. This systematic literature review and meta-analysis aimed to critically analyze existing studies and evidence on the impact of COVID-19 on nephropathy and kidney injury in diabetes mellitus type II (DM-T-II) patients., Method: A systematic search was conducted in the Web of Science (WoS), PubMed and Cochrane databases for relevant studies published between March 2020 and July 2023. To ensure the integrity of the systematic literature review and meta-analysis, observational studies that specifically reported post-COVID-19 kidney injury in DM-T2 patients were included, whereas we did not include articles in the press, meta-analyses, case reports, case series, Diabetes Type-I articles or non-English papers. The primary outcome was kidney injury in patients with type II diabetes after contracting COVID-19. The protocol for this study was published on PROSPERO (registration number CRD42023413887)., Results: Initially, 6,339 articles were included in the search, from which only 6 observational studies were selected by following the 2020 PRISMA statement. The quality of the evidence was assessed by a tool provided by the National Institutes of Health (observational studies). The total number of participants included in the studies was 14,723. Our systematic literature review and meta-analysis provide compelling evidence that kidney injury is a prevalent complication of COVID-19 infection in the type II diabetes population, with a pooled odds ratio of 2.27 (95% CI: 2.05-2.51; p < 0.00001), often necessitating hospitalization and hemodialysis in severe cases., Conclusion: Covid-19 is associated with a two-fold increase in nephropathy and acute kidney injury in diabetes mellitus type 2 patients compared to non-diabetic patients. This implies that kidney injury is more likely to occur in diabetes mellitus type 2 patients post Covid infection., (© 2024. The Author(s).)

Studies have used extensive clinical information to predict time-to-heart failure (HF) in patients with and without diabetes mellitus (DM). We aimed to determine a screening method using only computed tomography calcium scoring (CTCS) to assess HF risk. We analyzed CTCS scans from 1,998 patients (336 with type 2 diabetes) from a no-charge coronary artery calcium score registry (CLARIFY Study, Clinicaltrials.gov NCT04075162). We used deep learning to segment epicardial adipose tissue (EAT) and engineered radiomic features of calcifications ("calcium-omics") and EAT ("fat-omics"). We developed models incorporating radiomics to predict risk of incident HF in patients with and without type 2 diabetes. At a median follow-up of 1.7 years, 5% had incident HF. In the overall cohort, fat-omics (C-index: 77.3) outperformed models using clinical factors, EAT volume, Agatston score, calcium-omics, and calcium-and-fat-omics to predict HF. For DM patients, the calcium-omics model (C-index: 81.8) outperformed other models. In conclusion, CTCS-based models combining calcium and fat-omics can predict incident HF, outperforming prediction scores based on clinical factors.Please check article title if captured correctly.YesPlease check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.Yes., (© 2024. The Author(s).)

Aims: To compare the likelihood of being prescribed an antidepressant in depressed individuals with and without type 2 diabetes., Methods: We performed a matched cohort study using primary care record data from the UK Clinical Practice Research Datalink. We used multivariable logistic regression to compare antidepressant prescribing during the first five years of starting oral antidiabetic medication to a comparison group without type 2 diabetes, matched based on GP practice, age and sex. We performed subgroup analyses stratified by sex, age and ethnicity., Results: People with type 2 diabetes and depression were 75% less likely to be prescribed an antidepressant compared to people with depression alone (odds ratio (OR) 0.25, 95% confidence interval (CI) 0.25 to 0.26). This difference was greater in males (OR 0.23, 95% CI, 0.22 to 0.24), people older than 56 years (OR 0.23, 95% CI, 0.22 to 0.24), or from a minoritised ethnic background (Asian OR 0.14, 95% CI 0.12-0.14; Black OR 0.12, 95% CI 0.09-0.14)., Conclusions: There may be inequalities in access to antidepressant treatment for people with type 2 diabetes, particularly those who are male, older or from minoritised ethnic backgrounds., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aims to discover the association between serum osteocalcin, the Chinese visceral adiposity index (CVAI), and atherosclerotic cardiovascular disease (ASCVD) risk, and their impact on arterial stiffness in T2DM patients. We included 639 T2DM patients aged 30 and older who received the assessment of ASCVD risk using the China-PAR equation, Osteocalcin and arterial stiffness in this cross-sectional study. We found that osteocalcin and CVAI as independent risk factors for both medium-high-risk ASCVD (osteocalcin: men, OR,0.96, 95% CI 0.92, 1.00; women, OR, 0.93, 95% CI 0.8, 1.08, respectively)(CVAI: men, OR,1.01,95% CI 1.00,1.02; women: OR, 1.08, 95% CI 1.02,1.14, respectively) and arterial stiffness (osteocalcin: men, OR, 0.98, 95% CI 0.94,1.01; women, OR, 0.98, 95% CI 0.90,1.06, respectively)(CVAI: men, OR,1.0, 95% CI 0.99,1.01; women, OR, 1.02, 95% CI 1.00,1.04, respectively) in both men and women patients with T2DM. Combining osteocalcin levels and CVAI improved the prediction accuracy of arterial stiffness in men patients with T2DM (difference of AUC (Model 4 vs. Model 1) :1.5%, NRI: 0.06 [0.0,0.4]). All P-values were < 0.05. The results suggested that osteocalcin levels and CVAI are independent risk factors for ASCVD risk and arterial stiffness in T2DM. Combining osteocalcin and CVAI can enhance the early detection of atherosclerosis through male patients with T2DM., (© 2024. The Author(s).)

Studies on the correlation of exposure to metals with diabetic kidney disease (DKD) is scarce, especially concerning the impact of mixed metals on DKD. This study aimed to explore the association of blood heavy metals with DKD risk among type 2 diabetes mellitus (T2DM) patients. This cross-sectional study enrolled patients with T2DM in NHANES 2011-2020. ICP‒MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. At the same time, the impacts of exposure to single and mixed metals on DKD were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age, sex, BMI, hypertension, smoking status and PIR. Totally 2362 participants were enrolled for final analysis. Among them, 634 (26.84%) patients undergoing T2DM had DKD. Logistic regression indicated that, Pb (Q4: OR [95% CI]: 1.557 [1.175, 2.064]) was related to DKD when all covariates were adjusted. The WQS analysis, which was set in a positive directional mode, suggested that Pb was correlated positively with a higher incidence of DKD. In BKMR analysis, linear dose‒response curves were generated for Pb when fixing the other metals in the 50th percentile. In addition, exposure to mixed metals was significantly positively related to DKD. Subgroup analysis during logistic regression demonstrated that Pb was significantly and positively related to DKD in females, over 50 years, those with over 25 kg/m 2 , no hypertension, no smoking status and under PIR. Serum albumin (ALB) did not regulate the indirect impact of blood Pb on DKD risk. The results showed that the increased mixed metal concentration may lead to an increased DKD risk among patients with T2DM. Blood Pb is positively related to the DKD risk in diabetic patients, especially, in females, over 50 years, those with over 25 kg/m 2 , no hypertension, no smoking status and under PIR in T2DM patients. According to our observations, Pb absorption at least slightly influences DKD occurrence and progression. More studies are needed to validate the results in this work and illustrate the relevant biological mechanism., (© 2024. The Author(s).)

Background: The prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM., Methods: Inpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1., Results: Of the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P<0.05 for all). Patients with liver fibrosis had lower TC, TG, hemoglobin (Hb), erythrocyte count (RBC), leukocyte count (WBC) and platelet (PLT) levels (P<0.05 for all). Compared with simple T2DM and SLD-NLF (non-liver fibrosis) groups, for patients over 50 years old, the prevalence of coronary heart disease, stroke, tumor, and diabetic nephropathy was higher in patients with liver fibrosis. Liver fibrosis might be the risk factor of arterial stiffness, stroke, coronary heart disease and numbness based on multivariable logistic regression analysis., Conclusion: Hepatic steatosis and fibrosis were common in patients with T2DM. Liver fibrosis was relevant to many macrovascular and microvascular diabetic complications., (© 2024. The Author(s).)