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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.)

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.)

Objective: Diabetes-related kidney disease reduces patients' quality of life, increases the risk of death, and is associated with insulin resistance (IR). The triglyceride-glucose (TyG) index is a simple and inexpensive alternative to IR measurement. Furthermore, the relationship between albuminuria and chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we aimed to investigate the association of TyG index with albuminuria and CKD in patients with T2DM., Methods: Data from 01/2013-12/2017 period were obtained from the Population Health Data Archive's Diabetes Complications Data Set. A total of 1048 patients with T2DM were included in this study. CKD is defined as an estimated glomerular filtration rate < 60 ml/min-1.1.73 m-2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Albuminuria is defined as a UACR ≥ 30 mg/g. The TyG index is calculated by measuring the triglyceride and fasting blood glucose levels. Logistic regression models were used to analyze the association between albuminuria, CKD with T2DM and TyG index., Results: We identified 1048 subjects, 63.03% of whom were men. The mean age was 46.21 years, and the mean body mass index was 26.742 kg/m2. CKD and albuminuria detection rates showed an increasing trend in the different TyG subgroups. (p = 0.008, p = 0.006). Using the Q1 group as a baseline, the risk of albuminuria and CKD was significantly greater in the group Q3 (OR = 1.514, 95% CI 1.121-2.047 P = 0.05), and the same result was obtained after adjusting for covariates (OR = 2.241, 95% CI 1.245-4.034, P = 0.007). Subgroup analyses revealed a significant increase in the incidence of albuminuria and CKD in the group Q3 compared to that in the Q1 group., Conclusions: The TyG index is positively associated with albuminuria and CKD in patients with T2DM and may be a marker for predicting the occurrence of early kidney injury in patients with T2DM. Clinicians should test this indicator early to detect lesions and improve patient prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li, Wang. 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: Diabetes mellitus is characterized by insulin resistance (IR) and dysfunctional insulin secretion from pancreatic β-cells. However, little research has been conducted on the relationship between IR and β-cell function in relation to diabetic complications among Korean diabetic patients. This study aimed to examine the differential associations between IR and β-cell function and various diabetic complications among Korean diabetic patients., Methods: The analysis employed a common data model (CDM). IR and β-cell function were quantified using the homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), respectively. Hazard ratios for diabetic nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) events were calculated., Results: The study cohort consisted of 2,034 diabetic patients aged over 20 years who visited EUMC between January 2001 and December 2019. Among diabetic patients in the highest quartile of HOMA-IR, the adjusted hazard ratio for total CVD events was 1.76 (95% confidence interval [CI], 1.20-2.57) compared with those in the lowest quartile of HOMA-IR (P = 0.004). In contrast, diabetic patients in the lowest quartile of HOMA-β exhibited an adjusted hazard ratio of 3.91 (95% CI, 1.80-8.49) for diabetic retinopathy compared to those in the highest quartile of HOMA-β (P = 0.001)., Conclusion: Insulin resistance and β-cell function exhibited different associations with diabetic complications among Korean diabetic patients. Specifically, lower β-cell function was associated with an increased risk of diabetic retinopathy, whereas higher IR was associated with an increased risk of CVD events. Individuals with pronounced IR should prioritize CVD prevention measures, and those with significant β-cell dysfunction may benefit from early, intensive surveillance for diabetic retinopathy., Competing Interests: We declare that we have no conflict of interests., (Copyright: © 2024 Song 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: Diabetic foot ulcers are challenging to heal, increase the risk of lower extremity amputation, and place a significant burden on patients, families, and healthcare systems. Prioritizing preventive interventions holds the promise of reducing patient suffering, lowering costs, and improving quality of life. This study describes a scoping review protocol that will be used to delineate the preventive interventions for diabetic foot ulcers employed in different healthcare settings., Methods: The scoping review methodology was formulated in accordance with the PRISMA extension guidelines for scoping reviews and informed by the procedural insights provided by the JBI methodology group. Studies with participants diagnosed with type 1 and type 2 diabetes, aged 18 years or older, without an active ulcer at baseline, and studies of preventive interventions for foot ulcers in various healthcare settings will be screened. The search strategy was developed in collaboration with a research librarian using the PRESS checklist and no time or language limitations were applied. Data will be analyzed and summarized descriptively, including characteristics of studies, participants, and interventions., Discussion: Understanding the strategies and gaps in diabetic foot ulcer prevention is critical. The literature can provide valuable insights for developing tailored interventions and strategies to effectively address these gaps, potentially accelerating progress toward improved outcomes in diabetic foot ulcer prevention., Review Registration: Open Science Framework DOI 10.17605/OSF.IO/FRZ97 [June 19, 2023]., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Araújo 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 & Aims: Current screening pathways, developed from tertiary care cohorts, underestimate the presence of Metabolic-dysfunction associated steatotic liver disease (MASLD) in patients with type 2 diabetes mellitus (T2DM) in the community. We developed, validated, and assessed cost-effectiveness of a new score for screening the presence of fibrosis due to MASLD in primary care., Methods: Consecutive T2DM patients underwent screening for liver diseases with transient elastography (TE). Based on predictors of significant/advanced fibrosis, we generated the BIMAST score (based on aspartate aminotransferase (AST) and body mass index (BMI)) and validated it internally and externally (Royal Free Hospital, London and Palermo Hospital). For cost-effectiveness analysis, 6 screening strategies were compared against standard of care: BIMAST score, ultrasound plus abnormal liver function tests, FIB-4, NAFLD fibrosis score, ELF and transient elastography (TE). A Markov model was built based on fibrosis status. Cost per quality-adjusted life year (QALY) gained and the incremental cost-effectiveness ratio (ICER) were estimated over a lifetime., Results: Among 300 patients enrolled, 64% (186) had MASLD and 10% (28) other causes of liver disease. In the whole population, patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287), and 3% (8/287), respectively. In primary care, BIMAST performed better than other non-invasive markers at predicting significant and advanced fibrosis. Moreover, BIMAST reduced false negatives from 54% (ELF) and 38% (FIB-4) to 10%. In both validation cohorts, BIMAST performance was as good as FIB-4. In the cost-utility analysis, ICER was £2,337.92/QALY for BIMAST., Conclusion: The BIMAST predicts the presence of significant fibrosis in the community, reduces false negatives and is cost-effective. The BIMAST score should be included in the holistic assessment of diabetic patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Forlano 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.)

Introduction: Type 2 diabetes mellitus (T2DM) is a frequent chronic condition among the elderly, which increasing their susceptibility to infection. Urinary tract infection (UTI) is one of the most prevalent infections among older people with T2DM. However, the association between geriatric T2DM and the risk of UTI has not been thoroughly researched and is still contentious. Consequently, this protocol describes a systematic review to pinpoint the primary risk factors for UTI among elderly T2DM. Our goal is to improve recommendations for the creation of targeted treatment interventions by examining risk factors for UTI in elderly individuals with T2DM., Methods and Analysis: We will search 4 English literature databases (PubMed, Embase, Web of Science, and Cochrane Library) and 3 major Chinese databases (CNKI, WanFang, and VIP) from the establishment of the database to June 20, 2024. Systematic evaluation and meta-analysis will be conducted on cohort and case-control studies exploring the occurrence and risk determinants of UTI in individuals diagnosed with T2DM. The main focus will be on identifying the risk factors for UTI in elderly diabetic patients. Two researchers will independently review articles, collect data, and evaluate the quality and potential bias of study inclusion. We will use RevMan V.5.4 software to analyze the data. The quality of the included studies will be assessed using the Newcastle-Ottawa scale. In addition, the GRADE (Grade of Recommendations, Assessment, Development, Evaluation) method will be used to examine the quality of evidence for each exposure and outcome of interest., Discussion: This study aims to illuminate the various risk factors associated with UTI in older patients diagnosed with T2DM. By this thorough investigation, we hope to provide a more comprehensive reference for medical professionals and researchers, thereby supporting the implementation of effective preventive strategies against UTI and improving overall nursing outcomes for this specific patient population., Trail Registration: PROSPERO (CRD42024559129)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jia 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.)

Introduction: Diabetic Foot Complications (DFCs) are a growing cause of morbidity and mortality with less than one third of physicians able to discern the signs of diabetes related peripheral neuropathy. DFCs and resultant amputations account for a considerable proportion of surgeries in Fiji, with very limited literature available to verify the factors that influence these alarming figures. This study aimed to explore Health Care Workers' (HCWs) perspectives on diabetic foot complications and challenges of foot care management in Fiji., Method: An exploratory descriptive qualitative design was used among HCWs at the Sigatoka Sub Divisional Hospital (SDH), Fiji in 2021. HCWs at the SDH were required to have a minimum work experience of at least six months in public health. All participants who met the inclusion criteria were selected through purposive sampling. Data was collected using a focus group discussion guide composed of semi-structured open-ended questions to guide the Focus Group Discussions (FGDs). Focus discussions were audio recorded and transcribed with thematic analysis applied to derive the themes and sub-themes outlined in the study., Results: Twenty HCWs participated in four FGDs with four major themes identified. The first theme was HCWs' perceptions and practice of foot care which revealed that all participants had adequate diabetic foot care knowledge. The second theme was factors affecting foot care which was mainly focused on identified barriers such as inadequate patient foot care knowledge, the lack of resources such as manpower, and health system challenges like the COVID-19 pandemic. The third theme is creating awareness among patients and HCWs to improve foot care practices. The fourth theme is strengthening foot care practices at the different levels of health care that is aimed at optimizing diabetic foot outcomes., Conclusion: Various foot care barriers namely patient factors and the lack of resources is a concern depicted in this study. There is a need to address health system barriers and enforce diabetic foot education, screening and care for patients and the community., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Saverio 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.)

Purpose: Bladder dysfunction associated with type 2 diabetes mellitus (T2DM) includes urine storage and voiding disorders. We examined pathological conditions of the bladder wall in a rat T2DM model and evaluated the effects of the phosphodiesterase-5 (PDE-5) inhibitor tadalafil., Materials and Methods: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats were used as the T2DM and control groups, respectively. Tadalafil was orally administered for 12 weeks. Micturition behavior was monitored using metabolic cages, and bladder function was evaluated by cystometry. Bladder blood flow was evaluated by laser speckle imaging, and an organ bath bladder distention test was used to measure adenosine triphosphate (ATP) release from the bladder urothelium. The expression levels of vesicular nucleotide transporter (VNUT), hypoxia markers, pro-inflammatory cytokines and growth factors in the bladder wall were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Bladder wall contractions in response to KCl and carbachol were monitored using bladder-strip tests., Results: With aging, OLETF rats had higher micturition frequency and greater urine volume than LETO rats. Although bladder capacity was not significantly different, non-voiding bladder contraction occurred more frequently in OLETF rats than in LETO rats. Bladder blood flow was decreased and ATP release was increased with higher VNUT expression in OLETF rats than in LETO rats. These effects were suppressed by tadalafil administration, with accompanying decreased HIF-1α, 8-OHdG, IL-6, TNF-α, IGF-1, and bFGF expression. The impaired contractile responses of bladder strips to KCl and carbachol in OLETF rats with aging were restored by tadalafil administration., Conclusions: The T2DM rats had polyuria, increased ATP release induced by decreased bladder blood flow and impaired contractile function. PDE5 inhibition improved these changes and may prevent T2DM-associated urinary frequency and bladder storage and voiding dysfunctions., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Kabuto 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: Diabetes Mellitus is a prevalent disease with a growing impact on individuals worldwide. Evaluating the prevalence of subclinical left ventricular dysfunction and understanding its associations with microvascular complications, uncontrolled glycemia, diabetes duration, and patient age is crucial. Our aim is to determine the utility of screening for this condition., Methods: We conducted a retrospective cohort study involving 159 asymptomatic individuals with type 2 diabetes. Bivariate analysis was employed to assess potential factors and their associations with subclinical left ventricular dysfunction. Patients with a history of cardiac disease or interventions were excluded., Results: The average age of our sample was 61.5 years. Almost half of the patients exhibited an HbA1c exceeding 7% (50.3%), and approximately half had an ejection fraction (EF) of less than 55% (50.9%). In the bivariate analysis, a notable difference in microvascular diabetic complications was observed among different EF groups. Specifically, nephropathy (62%), neuropathy (57.5%), and retinopathy (74.4%) were significantly more prevalent among patients with an EF < 55%. We also identified a significant age difference between groups, with a higher mean diabetes duration (14.1 ± 7.7 years) in the lower EF group. Notably, 63.7% of patients with an HbA1c exceeding 7% exhibited an EF < 55%. Older patients were associated with a lower EF, with an adjusted odds ratio (aOR) of 0.94. An HbA1c of 7% or less was linked to a higher likelihood of an EF > 55%., Conclusion: We established a correlation between subclinical left ventricular systolic dysfunction and microvascular complications. However, further extensive prospective research is necessary to deepen our understanding of these associations and their clinical implications., Competing Interests: all authors declare no competing interest exists., (Copyright: © 2024 El Tawil 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.)

Myocardial fibrosis can trigger heart failure in diabetic cardiomyopathy (DCM), and irisin, an exercise-induced myokine, may have a beneficial effect on cardiac function. However, the specific molecular mechanism between exercise and irisin in the diabetic heart remains not fully explored. This study aimed to investigate how miR-34a mediates exercise-induced irisin to ameliorate myocardial fibrosis and its underlying mechanisms. Type 2 diabetes mellitus (T2DM) with DCM was induced in adult male rats with high-fat diet and streptozotocin injection. The DCM rats were subjected to swimming (60 min/d) and recombinant irisin (r-irisin, 500 μg/kg/d) interventions for 8 weeks, respectively. Cardiac function, cardiomyocyte structure, myocardial fibrosis and its correlated gene and protein expression were analyzed. Swimming intervention alleviated insulin resistance, myocardial fibrosis, and myocardial hypertrophy, and promoted blood glucose homeostasis in T2DM model rats. This improvement was associated with irisin upregulation and miR-34a downregulation in the myocardium, thus enhancing cardiac function. Similar efficacy was observed via intraperitoneal injection of exogenous recombinant irisin. Inhibition of miR-34a in vivo exhibited an anti-myocardial fibrotic effect by promoting irisin secretion through activating sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α)/fibronectin type III domain-containing protein 5 (FNDC5) signal pathway and downregulating myocardial fibrosis markers (collagen I, collagen III, and transforming growth factor-β1). Therefore, swimming-induced irisin has the potential therapeutic effect on diabetic myocardial fibrosis through activating the miR-34a-mediated SIRT1/PGC-1α/FNDC5 signal pathway., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Guo 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.)

Objective: This study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs)., Methods: Twenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO+N group), sildenafil positive control group (GO+S group), and PI3K inhibitor group (GO+N+E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group., Results: (1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in penile cavernous tissue., Conclusions: Nesfatin-1 not only effectively improves body weight and blood glucose levels in diabetic mice but also enhances erectile function and regulates the phenotypic switching of corpus cavernosum smooth muscle. The potential mechanism involves Nesfatin-1 activating the PI3K/AKT/mTOR signaling pathway to induce the conversion of CCSMCs to a contractile phenotype., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen 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: The prevalence of type 2 diabetes (DM) has been increasing globally, particularly among older adults who are more susceptible to DM-related complications. Elderly individuals with diabetes are at higher risk of developing hypoglycemia compared with younger diabetes patients. Hypoglycemia in elderly patients can result in serious consequences such as cognitive changes, increased risk of falls, heart and other vascular problems, and even high mortality rate., Objective: To assess prevalence, and factors associated with hypoglycemia events among geriatric outpatients with type 2 diabetes mellitus., Methods: The study was conducted at King Abdullah University Hospital (KAUH) at the outpatient diabetes clinic from October 1st, 2022 to August 1st, 2023. Variables such as socio-demographics, medication history, and comorbidities were obtained using electronic medical records. The prevalence of hypoglycemia was determined through patient interviews during their clinic visit. Patients were prospectively monitored for hospital admissions, emergency department visits, and mortality using electronic medical records over a three-month follow-up period. Logistic regression models were conducted to identify factors associated with hypoglycemia and hospital admissions/ emergency visits. Ethical Approval (Reference # 53/151/2022) was obtained on 19/9/2022., Results: Electronic medical charts of 640 patients who have type 2 diabetes mellitus and age ≥ 60 years were evaluated. The mean age ± SD was 67.19 (± 5.69) years. Hypoglycemia incidents with different severity levels were prevalent in 21.7% (n = 139) of the patients. Insulin administration was significantly associated with more hypoglycemic events compared to other antidiabetic medication. Patients with liver diseases had a significantly higher risk of hypoglycemia, with odds 7.43 times higher than patients without liver diseases. Patients with dyslipidemia also had a higher risk of hypoglycemia (odd ratio = 1.87). Regression analysis revealed that hypoglycemia and educational level were significant predictors for hospital admission and emergency department (ER) visits. Hypoglycemia was a positive predictor, meaning it increased the odds of these outcomes, while having a college degree or higher was associated with reduced odds of hospital admission and ER visits., Conclusion: Current study identified a considerable prevalence of hypoglycemia among older patients with type 2 diabetes, particularly, among those with concurrent liver diseases and dyslipidemia. Furthermore, hypoglycemia was associated with an increased rate of emergency department visits and hospital admissions by 2 folds in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Al-Azayzih 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.)

Introduction: Diabetic peripheral neuropathy (DPN), a widely prevalent complication in patients with type 2 diabetes, exerts a significant influence on patients' overall health and financial circumstances. Photobiomodulation therapy is one of the means of physical therapy for DPN. Although preliminary findings suggest the efficacy of photobiomodulation therapy in alleviating peripheral neuropathy, the existing literature lacks substantial evidence regarding its safety and effectiveness specifically in the context of diabetes-related peripheral neuropathy. Therefore, we plan to arrive at more distinct findings through systematic evaluation and meta-analysis., Methods: We will conduct a comprehensive search for studies published from the beginning until October 1, 2023, using various databases including Web of Science, Embase, Cochrane Library, PubMed, AMED, Wanfang database, VIP database, China National Knowledge Infrastructure, and the Chinese Biomedical Literature database. Simultaneously, we will also search for the WHO International Clinical Trial Registration Platform, China Clinical Trial Registration Platform, and Clinical Trials.gov. Gray literature will be retrieved using Google Scholar and opengrey.edu. Only randomized controlled trials in Chinese and English were included, with no restrictions on publication status. The primary outcomes will include change of symptom scores, change of nerve conduction velocity. Additional outcomes will encompass quality of life, change in pain, blood glucose levels after fasting and 2 hours after eating, levels of glycosylated hemoglobin, and any adverse events associated with photobiomodulation therapy. Reman V.5.4 and R language will be used for the meta-analysis. Assessment of potential bias will be conducted through Cochrane risk of bias 2 tool (RoB 2.0) and Physiotherapy Evidence Database (PEDro) scale. Registration: PROSPERO (registration number: CRD42023466586)., Discussion: This meta-analysis aims to assess the efficacy and safety of photobiomodulation therapy as a potential treatment for diabetic peripheral neuropathy (DPN), and providing a straightforward and convenient therapeutic for patients. Additionally, it expands the range of treatment alternatives available to healthcare professionals managing DPN., Competing Interests: The authors have declared that no competing interests exist., (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: Western guidelines often recommend biguanides as the first-line treatment for diabetes. However, dipeptidyl peptidase-4 (DPP-4) inhibitors, alongside biguanides, are increasingly used as the first-line therapy for type 2 diabetes (T2DM) in Japan. However, there have been few studies comparing the effectiveness of biguanides and DPP-4 inhibitors with respect to diabetes-related complications and cardio-cerebrovascular events over the long term, as well as the costs associated., Objective: We aimed to compare the outcomes of patients with T2DM who initiate treatment with a biguanide versus a DPP-4 inhibitor and the long-term costs associated., Methods: We performed a cohort study between 2012 and 2021 using a new-user design and the Shizuoka Kokuho database. Patients were included if they were diagnosed with T2DM. The primary outcome was the incidence of cardio-cerebrovascular events or mortality from the initial month of treatment; and the secondary outcomes were the incidences of related complications (nephropathy, renal failure, retinopathy, and peripheral neuropathy) and the daily cost of the drugs used. Individuals who had experienced prior events during the preceding year were excluded, and events within 6 months of the start of the study period were censored. Propensity score matching was performed to compare between two groups., Results: The matched 1:5 cohort comprised 529 and 2,116 patients who were initially treated with a biguanide or a DPP-4 inhibitor, respectively. Although there were no significant differences in the incidence of cardio-cerebrovascular events or mortality and T2DM-related complications between the two groups (p = 0.139 and p = 0.595), daily biguanide administration was significantly cheaper (mean daily cost for biguanides, 61.1 JPY; for DPP-4 inhibitors, 122.7 JPY; p<0.001)., Conclusion: In patients with T2DM who initiate pharmacotherapy, there were no differences in the long-term incidences of cardio-cerebrovascular events or complications associated with biguanide or DPP-4 use, but the former was less costly., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nakatani 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.)

Objective: To assess the risk of all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes newly initiating glucagon-like peptide-1 receptor agonists (GLP-1-RAs) versus dipeptidyl peptidase-4 inhibitors (DPP-4is)., Methods: We performed a population-based cohort study using administrative health data from British Columbia. Patients with an IMID (i.e., rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or a systemic autoimmune rheumatic disease) and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i between January 1, 2010, and December 31, 2021 were identified using ICD-9/10 codes. The primary outcome was all-cause mortality. Secondary outcomes included MACE and its components (i.e., cardiovascular death, myocardial infarction, and ischemic stroke). Cox proportional hazard regressions were used with propensity score overlap weighting. The analysis was repeated in age- and sex-matched adults without IMIDs., Results: We identified 10,855 adults with IMIDs and type 2 diabetes who newly initiated a GLP-1-RA or DPP-4i. All-cause mortality rate was lower among initiators of GLP-1-RAs compared to initiators of DPP-4is, with a weighted hazard ratio (HR) of 0.48 (95% confidence interval [CI], 0.31-0.75) and rate difference (RD) of -9.4 (95% CI, -16.0 to -2.7) per 1000 person-years. Rate of MACE was also lower with GLP-1-RA exposure (HR 0.66 [0.50-0.88], RD -10.5 [-20.4 to -0.8]). Effect sizes were similar in adults without IMIDs., Conclusion: In patients with IMIDs and type 2 diabetes, GLP-1-RA exposure is associated with a lower risk of all-cause mortality and MACE compared to a cardioneutral active comparator., Competing Interests: The authors have declared that no competing interests exist. HKC reports research support from Horizon and consulting fees from ANI and LG Chem outside of the submitted work. HKC has participated on an advisory board for Shanton, unrelated to the submitted work., (Copyright: © 2024 Karacabeyli 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: Diabetes mellitus (DM) is well known for related micro and macrovascular complications. Uncontrolled hyperglycemia in diabetes mellitus leads to endothelial dysfunction, inflammation, microvascular impairment, myocardial dysfunction, and skeletal muscle changes which affect multiple organ systems. This study was designed to take an extensive view of cardiorespiratory dynamics in patients with type 2 DM., Methods: One hundred healthy controls (HC) and 100 DM patients were enrolled. We measured and compared the breathing patterns (spirometry), VO2 max levels (heart rate ratio method) and self-reported fitness level (international fitness scale) of individuals with and without diabetes. Data was analyzed in SPSS v.22 and GraphPad Prism v8.0., Results: We observed restrictive spirometry patterns (FVC <80%) in 22% of DM as compared to 2% in HC (p = 0.021). There was low mean VO2 max in DM as compared to HC(32.03 ± 5.36 vs 41.91 ± 7.98 ml/kg/min; p value <0.001). When evaluating physical fitness on self-reported IFiS scale, 90% of the HC report average, good, or very good fitness levels. In contrast, only 45% of the DM shared this pattern, with a 53% proportion perceiving their fitness as poor or very poor (p = <0.05). Restrictive respiratory pattern, low VO2 max and fitness level were significantly associated with HbA1c and long-standing DM., Conclusion: This study shows decreased pulmonary functions, decreased cardiorespiratory fitness (VO2 max) and IFiS scale variables in diabetic population as compared to healthy controls which are also associated with glycemic levels and long-standing DM. Screening for pulmonary functions can aid optimum management in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abbas 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.)

Distal sensorimotor polyneuropathy (DSPN) is the earliest detectable and the most frequent microvascular complication in diabetes mellitus. Several studies have previously demonstrated correlations between cardiovascular risk factors in diabetic patients and independent risk factors for diabetic neuropathy. Our objective was to retrospectively analyze data from diabetic patients in the North-East region of Hungary who underwent neuropathy screening at the Diabetic Neuropathy Center, University of Debrecen, between 2017 and 2021. We aimed to investigate the correlations between cardiovascular risk factors and microvascular complications among patients with DSPN. The median age of the patients was 67 years, 59,6% were female, and 91,1% had type 2 diabetes. The prevalence of DSPN among the study subjects was 71.7%. A significantly longer duration of diabetes (p<0.01) was noted in patients with DSPN. Those with DSPN demonstrated a significantly higher HbA1c level (p<0.001) and a greater frequency of insulin use (p = 0.001). We observed a significantly elevated albumin/creatinine ratio (p<0.001) and a significantly lower eGFR (p<0.001) in patients with DSPN. Diabetic retinopathy exhibited a significantly higher prevalence in patients with DSPN (p<0.001). A higher prevalence of myocardial infarction (p<0.05), ischemic heart disease (p<0.001), peripheral arterial disease (p<0.05) and a history of atherosclerosis (p<0.05) was observed in patients with DSPN. In a multivariate logistic regression analysis, the following factors were independently associated with the presence of DSPN: higher HbA1c (OR:2.58, 95% CI:1.89-3.52, p<0.001), age (OR:1.03, 95% CI:1.01-1.05, p = 0.006), albumin/creatinine ratio above 3 mg/mmol (OR:1.23, 95% CI:1.06-1.45, p = 0.008), retinopathy (OR:6.06, 95% CI:1.33-27.53, p = 0.02), and composite cardiovascular endpoint (OR:1.95, 95% CI:1.19-3.19, p = 0.008). Our study revealed that age, elevated HbA1c levels, significant albuminuria, retinopathy, and cardiovascular complications may increase the risk of DSPN. Further investigation of these associations is necessary to understand the impact of patient characteristics during the treatment of diabetic neuropathy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pető 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: The dual existence of Type 2 Diabetes Mellitus (T2DM) and obesity within a single individual may describe a combined adverse health effects, including impaired quality of life and increased risk for cardiovascular diseases (CVDs). Oxidative stress is a contributing factor to the pathogenesis of obesity. Meanwhile, dietary antioxidants may improve the antioxidant defense system and thereby decrease oxidative injury. Dietary total antioxidant capacity (TAC) is usually used to investigate the potential health effects of dietary antioxidant intake on several oxidative stress induced chronic diseases. This study aimed to examine the association of dietary TAC with obesity-related features in T2DM patients., Methods: The present study included 254 type 2 diabetes outpatients with a mean (SD) age of 54.52 (7.21) years and mean (SD) diabetes duration of 8.2 (6.4) years. Data on dietary intake was assessed using a validated food frequency questionnaire. Dietary TAC was estimated by ferric reducing antioxidant potential (FRAP) method. Anthropometric, clinical and lifestyle characteristics were all collected., Results: In linear regression analyses, dietary antioxidant capacity was inversely associated with body mass index (β = -0,231; 95% CI, -0,419 to -0,042), waist circumference (β = -0,427; 95% CI, -0,849 to -0,006) and fat mass percentage (β = -0,328; 95% CI, -0,545 to -0,112) independently of the assessed confounding variables. Interestingly, dietary TAC showed positive and significant associations with vitamin A, vitamin C, β-carotene, magnesium, folic acid and iron intakes, after adjusting for age and daily energy intake., Conclusions: Higher intake of dietary TAC was in association with lower indices of general and central obesity in T2DM patients. Therefore, dietary recommendations for counteracting obesity in patients with T2DM should take into account a high dietary TAC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 El Frakchi 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: Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and disability within this patient demographic. Presently, numerous studies have been conducted to investigate the underlying causes of stroke in individuals with T2DM, yet the findings exhibit inconsistencies., Objective: This paper aims to consolidate and summarize the available evidence concerning the influential factors contributing to stroke among patients diagnosed with T2DM., Methods: We conducted a comprehensive search across multiple databases, including Cochrane Library, PubMed, Web Of Science, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Weipu up to August 2023. Google Scholar was also searched to retrieve gray literature. We calculated odds ratios (OR) and 95% confidence intervals (CI) using Stata software., Results: Our analysis encompassed 43 observational studies, exploring factors across sociodemographic, biochemical, complications, and hypoglycemic agent categories. The findings identified several risk factors for stroke in patients with T2DM: age, gender, T2DM duration, hypertension, body-mass index (BMI), smoking, Glycated hemoglobin (HbA1c), estimated Glomerular Filtration Rate (eGFR), albuminuria, Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), Coronary heart disease (CHD), Atrial fibrillation (AF), diabetic retinopathy (DR), Peripheral vascular disease (PVD), and carotid plaque. Conversely, exercise, High density lipoprotein cholesterol (HDL-C), metformin (MET), pioglitazone, and metformin combination therapy emerged as protective factors., Conclusion: This study underscores the multitude of influencing factors contributing to stroke in people with T2DM patients, among which the microvascular complications of T2DM play an most important role. Therefore, we emphasize the importance of screening for microvascular complications in patients with T2DM. However, due to limitations arising from the number of articles reviewed, there remain areas where clarity is lacking. Further research efforts are warranted to expand upon and reinforce our current findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhao 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.)

The aim of this study was to determine plasma levels of three adhesion molecules that may contribute to the development of diabetic retinopathy; soluble endothelial selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), in young adults, aged 15-34 years at diagnosis of diabetes, to find potential predictors for development of retinopathy, and to evaluate their relation to diabetes associated autoantibodies. Participants with type 1 (n = 169) and type 2 diabetes (n = 83) were selected from the complications trial of the Diabetes Incidence Study in Sweden and classified in two subgroups according to presence (n = 80) or absence (n = 172) of retinopathy as determined by retinal photography at follow-up 8-10 years after diagnosis of diabetes. Blood samples were collected at diagnosis in 1987-88. The levels of sE-selectin, sICAM-1, and sVCAM-1 were analysed by enzyme-linked immunosorbent assay and islet cell antibodies by a prolonged two-colour immunofluorescent assay. Mean HbA1c (p<0.001) and clinical characteristics: mean body mass index (p = 0.019), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.003), male gender (p = 0.026), and young age at diagnosis of diabetes (p = 0.015) remained associated with development of retinopathy in type 1 diabetes. However, in a multivariate analysis only HbA1c remained as a risk factor. sE-selectin was significantly higher in the group with type 2 diabetes and retinopathy, compared to the group with type 2 diabetes without retinopathy (p = 0.04). Regarding sE-selectin, sICAM-1, and sVCAM-1 in participants with type 1 diabetes, no differences were observed between the groups with or without retinopathy. This trial confirmed the role of HbA1c and clinical characteristics as predictors for development of retinopathy in type 1 diabetes. sE-selectin stands out as a potential predictor for development of retinopathy in type 2 diabetes, whereas a predictive role for sICAM-1 and sVCAM-1 could not be identified neither for type 1 nor type 2 diabetes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: When the research was conducted, Jonatan Dereke was affiliated to Lund University. Thereafter, he has been employed by Novo Nordisk Scandinavia AB in Malmö, Sweden. Charlotte Ekelund, Charlotta Nilsson and Mona Landin-Olsson have declared that no competing interests exist., (Copyright: © 2024 Ekelund 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.)

Introduction: Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder, significantly increases cardiovascular disease (CVD) risk. Integrative care (IC) offers a personalized health management approach, utilizing various interventions to mitigate this risk. However, the impact of IC on CVD risk in newly diagnosed T2Dm patients remains unclear. This study aims to assess the differences in CVD risk development within 120 months following a new diagnosis of T2DM, using real-world data from Bumrungrad International Hospital and Vitallife Scientific Wellness Center., Methods: This study utilized the BI-VitalLife Cohort dataset that contains de-identified demographics, vitals, diagnoses and clinical information, laboratory and radiological data, medications, and treatments of more than 2.8 million patients who visited Bumrungrad International Hospital and/or VitalLife Scientific Wellness Center from June 1, 1999, to May 31, 2022. This study focused on newly diagnosed T2DM patients, defined according to American Diabetes Association criteria. We compared CVD risk between the IC and conventional care (CC) groups using the Kaplan-Meier curve and Cox proportional hazard model, adjusted for age, sex, and laboratory values. Propensity score matching was employed to enhance comparability., Results: Of the 5,687 patients included, 236 were in the IC group and 5,451 in the CC group. The IC group, characterized by a lower age at T2DM diagnosis, showed favorable hematological and metabolic profiles. The Cox proportional hazard ratios revealed a significantly lower CVD risk in the IC group within 120 months post-T2DM diagnosis compared to the CC group, consistent even after adjusting for confounding factors. Propensity score-matched analysis supported these findings., Conclusion: Personalized integrative care may offer a significant advantage in reducing CVD risk among newly diagnosed T2DM patients compared to conventional care, even when considering various confounding factors. This study sheds light on the potential of integrative care in informing treatment strategies for T2DM patients at risk of developing CVD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Khunlertkit 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: Attempts to subtype, type 2 diabetes (T2D) have mostly focused on newly diagnosed European patients. In this study, our aim was to subtype T2D in a non-white Emirati ethnic population with long-standing disease, using unsupervised soft clustering, based on etiological determinants., Methods: The Auto Cluster model in the IBM SPSS Modeler was used to cluster data from 348 Emirati patients with long-standing T2D. Five predictor variables (fasting blood glucose (FBG), fasting serum insulin (FSI), body mass index (BMI), hemoglobin A1c (HbA1c) and age at diagnosis) were used to determine the appropriate number of clusters and their clinical characteristics. Multinomial logistic regression was used to validate clustering results., Results: Five clusters were identified; the first four matched Ahlqvist et al subgroups: severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), and a fifth new subtype of mild early onset diabetes (MEOD). The Modeler algorithm allows for soft assignments, in which a data point can be assigned to multiple clusters with different probabilities. There were 151 patients (43%) with membership in cluster peaks with no overlap. The remaining 197 patients (57%) showed extensive overlap between clusters at the base of distributions., Conclusions: Despite the complex picture of long-standing T2D with comorbidities and complications, our study demonstrates the feasibility of identifying subtypes and their underlying causes. While clustering provides valuable insights into the architecture of T2D subtypes, its application to individual patient management would remain limited due to overlapping characteristics. Therefore, integrating simplified, personalized metabolic profiles with clustering holds greater promise for guiding clinical decisions than subtyping alone., Competing Interests: All authors declare that they do not have any financial support or relationships that might have posed conflict of interest in this study., (Copyright: © 2024 Bayoumi 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.)

Aims: Shorter and longer sleep durations are associated with adverse health consequences. However, available evidence on the association of sleep duration with constipation is limited, especially in patients with diabetes, who are at a high risk of both conditions. This study aimed to examine the association between sleep duration and constipation in patients with type 2 diabetes., Methods: A total of 4,826 patients with type 2 diabetes were classified into six groups according to sleep duration: <4.5, 4.5-5.4, 5.5-6.4, 6.5-7.4, 7.5-8.4, and ≥8.5 hours/day. The odds ratios for the presence of constipation, defined as a defecation frequency <3 times/week and/or laxative use, were calculated using a logistic regression model., Results: Shorter and longer sleep durations were associated with a higher likelihood of constipation than an intermediate duration (6.5-7.4 hours/day). This U-shaped association persisted after adjusting for confounding factors, including lifestyle behavior, measures of obesity and glycemic control, and comorbidities. Broadly identical findings were observed when decreased defecation frequency and laxative use were individually assessed., Conclusions: This study shows a U-shaped association between sleep duration and constipation in patients with type 2 diabetes, and highlights the importance of assessing sleep duration in daily clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ohkuma 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.)

The primary objective of this study was to isolate bacteria from diabetic foot ulcers and subsequently assess their antibiotic resistance capabilities. Seventy-five patients diagnosed with diabetic foot ulcers were investigated. A number of these patients (97.33%) had type 2 diabetes, with a significant proportion of them having been diagnosed for 1-5 years (29.33%). Notably, a substantial number of these individuals were on insulin usage (78.66%). Among the patients under examination, 49.33% reported having no use of tobacco products, alcohol, or betel leaf. The ulcers analyzed in this study were classified into grades 1-5 according to the Wagner scale. Wagner grade 2 diabetic foot ulcers had the highest number of culture-positive patients, at 33.33%. Pus samples collected from patients were cultured on selective media, and bacterial identity was confirmed by biochemical tests and polymerase chain reaction. A total of 141 isolates were isolated. Among the isolates, 82.97% gram-negative bacteria and 17.02% gram-positive bacteria were detected. Klebsiella pneumoniae was the most common isolate. Proteus spp., Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also detected. Approximately 61.33% of the ulcers exhibited were polybacterial. In this study, it was observed that all bacterial isolates, except for Proteus spp., were primarily detected in patients classified under Wagner's grade 2. Moreover, antibiotic susceptibility was also tested on these 141 isolates. Among them, Escherichia coli showed the highest multidrug resistance, 81.81%. Most of the gram-negative bacteria were resistant to ampicillin. All of the gram-negative isolates exhibited high levels of susceptibility to piperacillin-tazobactam, and these levels were Klebsiella pneumoniae (97.56%), Pseudomonas aeruginosa (95.24%), Escherichia coli (81.82%), and Proteus spp. (80%). On the other hand, gram-positive Staphylococcus aureus mostly showed sensitivity towards vancomycin and norfloxacin (79.17%)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Baral 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.)

The goal of this study was to evaluate the relationship between serum lipoprotein(a) [Lp(a)] levels and diabetic nephropathy (DN) among Han Chinese individuals with type 2 diabetes mellitus (T2DM). This retrospective analysis comprised a consecutive case series of 767 grown-up patients with T2DM (199 among them with DN) hospitalized in the Department of Endocrinology at the The First Affiliated Hospital of Anhui Medical University from February 20220 to February 2021. Clinical data and other laboratory measurements, such as glycated hemoglobin (HbA1c), were extracted from medical records and compared among groups. Clinical characteristics according to Lp(a) quartiles were also studied. Univariate and multivariate regression analysis were used to examine the relationship between serum Lp(a) and DN. Patients with DN had a longer disease duration, higher HbA1c, higher level of Lp(a), and were more likely to have diabetic retinopathy (DR) than those without DN (P < 0.005 for each). With regard to the Lp(a) quartile group, patients with a higher Lp(a) concentration were more likely to have DN and have higher level of HbA1c during the study (P for trend < 0.005 for each). After adjusting for several confounding factors, the development of DN was significantly associated with the serum Lp(a) level (P = 0.026, comparing the 4th vs 1st quartile of Lp(a)) according to multivariate regression analysis. The receiver operating characteristic (ROC) curves for DN development using serum Lp(a) showed that the area under the receiver operating characteristic curves (AUC) was 0.590 (P < 0.001). Findings from this study demonstrated that the DN was independently associated with the serum Lp(a) level in patients with T2DM in this retrospective study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ting Wang. 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: Older adults with HIV are at increased risk of developing certain chronic health conditions including type 2 diabetes mellitus (T2DM). As the number and complexity of conditions increases, so do treatment and health care needs. We explored patient and clinician preferences for HIV+T2DM care and perceived solutions to improving care., Methods: We conducted an exploratory qualitative study comprised of individual in-depth interviews. Participants included English-speaking patients aged 50 and older living with HIV and T2DM and infectious disease (ID) and primary care (PC) clinicians from a large academic health center in Chicago. Thematic analysis drew from the Framework Method., Results: A total of 19 patient and 10 clinician participants were interviewed. Many patients reported seeking HIV and T2DM care from the same clinician; they valued rapport and a 'one-stop-shop'. Others reported having separate clinicians; they valued perceived expertise and specialty care. Nearly all clinicians reported comfort screening for T2DM and initiating first line oral therapy; ID clinicians reported placing referrals for newer, complex therapies. Patients would like educational support for T2DM management; clinicians would like to learn more about newer therapies and easier referral processes., Conclusions: Patient-centered care includes managing T2DM from a variety of clinical settings for individuals with HIV, yet strategies are needed to better support clinicians. Future research should examine how best to implement these strategies., Competing Interests: APP reports grants from RRF Foundation for Aging and commercial funders Merck, Pfizer, Gordon and Betty Moore Foundation, Lundbeck, Gilead, and Eli Lilly through her institution; and personal fees from commercial funder Gilead. SCB reports grants from the NIH and RRF Foundation for Aging, and commercial funders Merck, Pfizer, Gordon and Betty Moore Foundation, Lundbeck, Gilead and Eli Lilly through her institution; and personal fees from commerical funders Gilead, Sanofi, Pfizer, University of Westminster, Lundbeck, and Luto outside the submitted work. MCM reports grants from the NIH and commerical funder Merck through her institution. AW reports grants from commerical funder NovoNordisk through her institution, and research salary support from UnitedHealth Group. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Pack 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.)

There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bertran 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.)

Carpal tunnel syndrome (CTS) occurs more often among individuals with diabetes. The aim of this retrospective observational registry study was to examine whether individuals with diabetes and CTS are treated surgically to the same extent as individuals with CTS but without diabetes. Data on CTS diagnosis and surgery were collected from the Skåne Healthcare Register (SHR). A total of 35,105 individuals (age ≥ 18 years) diagnosed with CTS from 2004-2019 were included. Data were matched to the Swedish National Diabetes Register (NDR. Cox regression models were used to calculate the risk of the use of surgical treatment. Of the 35,105 included individuals with a CTS diagnosis, 17,662 (50%) were treated surgically, and 4,966 (14%) had diabetes. A higher number of individuals with diabetes were treated surgically (2,935/4,966, 59%) than individuals without diabetes (14,727/30,139, 49%). In the Cox regression model, diabetes remained a significant risk factor for surgical treatment (PR 1.14 (95% CI 1.11-1.17)). Individuals with type 1 diabetes were more frequently treated surgically (490/757, 65%) than individuals with type 2 diabetes (2,445/4,209, 58%). There was no difference between the sexes and their treatment. The duration of diabetes was also a risk factor for surgical treatment in diabetes type 2, but high HbA1c levels were not. Individuals with diabetes are more likely to be treated surgically for CTS than individuals without diabetes. Individuals with type 1 diabetes are more likely to be treated surgically for CTS than individuals with type 2 diabetes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MZ has been a consultant for Ansell Medical on hand problems in dentistry., (Copyright: © 2024 Svensson 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: Treating comorbid depression does not always improve outcomes for people with type 2 diabetes. Evidence is lacking on potential psychological and behavioural intermediaries of the impact of depression on diabetes outcomes., Objective: To synthesise evidence on the impact of comorbid depression on self-efficacy, illness perceptions, and self-management in people with type 2 diabetes., Data Sources: We searched PubMed, Embase, PsycINFO, and Global Health databases from inception up to 29th March 2023., Study Eligibility Criteria: Only prospective studies (cohort or intervention studies) were included, with no restrictions on language. The outcomes were self-efficacy, illness perceptions, and self-management., Participants: People with type 2 diabetes in community or health settings., Exposure: Comorbid depression or depressive symptoms in people with type 2 diabetes., Synthesis of Results: A narrative review of heterogeneous studies., Risk of Bias: The risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) quality assessment tool for quantitative studies., Results: Twenty-five studies were included, all from high-income countries. Depression was associated with lower self-efficacy (2 studies), poor illness perception (1 study), and poor self-management practices (17 studies) in people with type 2 diabetes. In 6/7 studies, depressive symptoms predicted less adherence to dietary recommendations, 8/10 studies found depressive symptoms were associated with poor medication adherence, 1/3 study found that depressive symptoms were associated with poor weight control, 3/4 with less physical exercise, and 2/3 with general self-care practices., Limitations: There were no studies from low- and middle-income countries and non-Western settings, and we cannot assume the mechanisms linking comorbid depression with diabetes outcomes are similar., Conclusions: Comorbid depression was associated with lower self-efficacy, poorer self-management, and less adaptive illness perceptions among people with diabetes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Derese 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: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM., Methods: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed., Discussion: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM., Trial Registration: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lin 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: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM., Method: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms., Results: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023-1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004-1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006-1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012-1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002-1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively., Conclusion: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sun 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.)

Objective: To compare the serum levels of brain-derived neurotrophic factor (BDNF) in type 2 diabetes mellitus (T2DM) patients with healthy controls (HC) and evaluate the BDNF levels in T2DM patients with/without cognitive impairment., Methods: PubMed, EMBASE, and the Cochrane Library databases were searched for the published English literature on BDNF in T2DM patients from inception to December 2022. The BDNF data in the T2DM and HC groups were extracted, and the study quality was evaluated using the Agency for Healthcare Research and Quality. A meta-analysis of the pooled data was conducted using Review Manager 5.3 and Stata 12.0 software., Results: A total of 18 English articles fulfilled with inclusion criteria. The standard mean difference of the serum BDNF level was significantly lower in T2DM than that in the HC group (SMD: -2.04, z = 11.19, P <0.001). Besides, T2DM cognitive impairment group had a slightly lower serum BDNF level compared to the non-cognitive impairment group (SMD: -2.59, z = 1.87, P = 0.06)., Conclusion: BDNF might be involved in the neuropathophysiology of cerebral damage in T2DM, especially cognitive impairment in T2DM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 He 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.)

Psoriasis has been related to metabolic dysfunction-associated fatty liver disease and, liver fibrosis. This study aimed to evaluate the prevalence of liver fibrosis in psoriasis and identify predictors for fibrosis. This is a cross-sectional study conducted from December 2012 to June 2016 assessing psoriasis and psoriatic arthritis patients attended at four centers in Mexico City. Data regarding history of the skin disease, previous and current medication, and previously diagnosed liver disease was collected. Liver fibrosis was assessed with four different non-invasive methods (FIB4, APRI, NAFLD score and elastography). We compared data based on the presence of fibrosis. Adjusted-logistic regression models were performed to estimate OR and 95% CI. A total of 160 patients were included. The prevalence of significant fibrosis using elastography was 25% (n = 40), and 7.5% (n = 12) for advanced fibrosis. Patients with fibrosis had higher prevalence of obesity (60% vs 30.8%, P = 0.04), type 2 diabetes (40% vs 27.5%, P = 0.003), gamma-glutamyl transpeptidase levels (70.8±84.4 vs. 40.1±39.2, P = 0.002), and lower platelets (210.7±58.9 vs. 242.8±49.7, P = 0.0009). Multivariate analysis showed that body mass index (OR1.11, 95%CI 1.02-1.21), type 2 diabetes (OR 3.44, 95%CI 1.2-9.88), and gamma-glutamyl transpeptidase (OR 1.01, 95%CI1-1.02) were associated with the presence of fibrosis. The use of methotrexate was not associated. Patients with psoriasis are at higher risk of fibrosis. Metabolic dysfunction, rather than solely the use of hepatotoxic drugs, likely plays a major role; it may be beneficial to consider elastography regardless of the treatment used. Metabolic factors should be assessed, and lifestyle modification should be encouraged., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chavez-Tapia 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.)

Introduction: Health state utility values (HSUV) for Type 2 diabetes mellitus (T2DM) complications are useful in economic evaluations to determine cost effectiveness of an intervention. However, there is a lack of reference ranges for different severity and stages of individual complications. This study aimed to provide an overview of HSUV decrement ranges for common T2DM complications focusing on different severity and stages of complications., Method: A systematic search was conducted in MEDLINE, SCOPUS, WEB OF SCIENCE. (Jan 2000 to April 2022). Included studies for HSUV estimates were from outpatient setting, regardless of treatment types, complication stages, regions and HRQoL instruments. Health Related Quality of Life (HRQoL) outcomes was to be presented as HSUV decrement values, adjusted according to social demographics and comorbidities. Adjusted HSUV decrements were extracted and compiled according to individual complications. After which, subsequently grouped into mild or severe category for comparison., Results: Searches identified 35 studies. The size of the study population ranged from 160 to 14,826. The HSUV decrement range was widest for cerebrovascular disease (stroke): -0.0060 to -0.0780 for mild stroke and -0.035 to -0.266 for severe stroke; retinopathy: mild (-0.005 to -0.0862), moderate (-0.0030 to -0.1845) and severe retinopathy (-0.023 to -0.2434); amputation: (-0.1050 to -0.2880). Different nature of complication severity defined in studies could be categorized into: those with acute nature, chronic with lasting effects, those with symptoms at early stage or those with repetitive frequency or episodes., Discussion: Overview of HSUV decrement ranges across different stages of each T2DM diabetes-related complications shows that chronic complications with lasting impact such as amputation, severe stroke with sequelae and severe retinopathy with blindness were generally associated with larger HSUV decrement range. Considerable heterogeneities exist across the studies. Promoting standardized complication definitions and identifying the most influential health state stages on HSUV decrements may assist researchers for future cost-effectiveness studies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tan 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.)

Objectives: This systematic review aimed to assess the prevalence and incidence of diabetic retinopathy in patients with diabetes of Latin America and the Caribbean., Methods: We searched Web of Science (WoS)/Core Collection, WoS/MEDLINE, WoS/Scielo, Scopus, PubMed/Medline and Embase databases until January 16, 2023. We meta-analyzed prevalences according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM)., Results: Forty-three prevalence studies (47 585 participants) and one incidence study (436 participants) were included. The overall prevalence of retinopathy in patients with T1DM was 40.6% (95% CI: 34.7 to 46.6; I2: 92.1%) and in T2DM was 37.3% (95% CI: 31.0 to 43.8; I2: 97.7), but the evidence is very uncertain (very low certainty of evidence). In meta-regression, we found that age (T1DM) and time in diabetes (T2DM) were factors associated with the prevalence. On the other hand, one study found a cumulative incidence of diabetic retinopathy of 39.6% at 9 years of follow-up., Conclusions: Two out of five patients with T1DM or T2DM may present diabetic retinopathy in Latin America and the Caribbean, but the evidence is very uncertain. This is a major public health problem, and policies and strategies for early detection and opportunely treatment should be proposed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Medina-Ramirez 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: Multiple risk factors contribute jointly to the development and progression of cardiometabolic diseases. Therefore, joint longitudinal trajectories of multiple risk factors might represent different degrees of cardiometabolic risk., Methods: We analyzed population-based data comprising three examinations (Exam 1: 1999-2001, Exam 2: 2006-2008, Exam 3: 2013-2014) of 976 male and 1004 female participants of the KORA cohort (Southern Germany). Participants were followed up for cardiometabolic diseases, including cardiovascular mortality, myocardial infarction and stroke, or a diagnosis of type 2 diabetes, until 2016. Longitudinal multivariate k-means clustering identified sex-specific trajectory clusters based on nine cardiometabolic risk factors (age, systolic and diastolic blood pressure, body-mass-index, waist circumference, Hemoglobin-A1c, total cholesterol, high- and low-density lipoprotein cholesterol). Associations between clusters and cardiometabolic events were assessed by logistic regression models., Results: We identified three trajectory clusters for men and women, respectively. Trajectory clusters reflected a distinct distribution of cardiometabolic risk burden and were associated with prevalent cardiometabolic disease at Exam 3 (men: odds ratio (OR)ClusterII = 2.0, 95% confidence interval: (0.9-4.5); ORClusterIII = 10.5 (4.8-22.9); women: ORClusterII = 1.7 (0.6-4.7); ORClusterIII = 5.8 (2.6-12.9)). Trajectory clusters were furthermore associated with incident cardiometabolic cases after Exam 3 (men: ORClusterII = 3.5 (1.1-15.6); ORClusterIII = 7.5 (2.4-32.7); women: ORClusterII = 5.0 (1.1-34.1); ORClusterIII = 8.0 (2.2-51.7)). Associations remained significant after adjusting for a single time point cardiovascular risk score (Framingham)., Conclusions: On a population-based level, distinct longitudinal risk profiles over a 14-year time period are differentially associated with cardiometabolic events. Our results suggest that longitudinal data may provide additional information beyond single time-point measures. Their inclusion in cardiometabolic risk assessment might improve early identification of individuals at risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Niedermayer 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.)

Introduction: Patients with diabetes mellitus type 2 and chronic kidney disease (T2DM-CKD) have a 5 times higher risk of developing severe SARS-CoV-2 infection than those without these 2 diseases. The goal of this study is to provide information on T2DM-CKD and COVID-19 outcomes, with an emphasis on the association with anti-diabetic medications., Methodology: Study is designed as a retrospective cohort analysis covering the years 2020 and 2021. Data from the National Diabetes Registry (CroDiab) were linked to hospital data, primary healthcare data, Causes of Death Registry data, the SARS-CoV-2 vaccination database, and the SARS-CoV-2 test results database. Study outcomes were cumulative incidence of SARS-CoV-2 positivity, COVID-19 hospitalizations, and COVID-19 deaths. For outcome predictors, logistic regression models were developed., Results: Of 231 796 patients with diabetes mellitus type 2 in the database, 7 539 were T2DM-CKD (3.25%). The 2-year cumulative incidences of all three studies' outcomes were higher in T2DM-CKD than in diabetes patients without CKD (positivity 18.1% vs. 14.4%; hospitalization 9.7% vs. 4.2%; death 3.3% vs. 1.1%, all p<0.001). For COVID-19 hospitalization, protective factors were SGLT-2 inhibitors use (OR 0.430; 95%CI 0.257-0.719) and metformin use (OR 0.769; 95% CI 0.643-0.920), risk factors were insulin use (1.411; 95%CI 1.167-1.706) and sulfonylureas use (OR 1.226; 95% CI 1.027-1.464). For SARS-CoV-2 positivity protective factors were SGLT-2 inhibitors (0.607; 95% CI 0.448-0.823), repaglinide use (OR 0.765; 95% CI 0.593-0.986) and metformin use (OR 0.857; 95% CI 0.770-0.994). DPP-4 inhibitors showed a non-significant decrease in risk for COVID-19 death (OR 0.761; 95% CI 0.568-1.019)., Conclusion: T2DM-CKD are heavily burdened by COVID-19 disease. Our results suggest no association between antidiabetic drugs and COVID-19 death outcome while SGLT-2 and metformin show to be protective against COVID-19 hospitalization and infection, repaglinide against infection, and insulin and sulfonylureas show to be risk factors for COVID-19 hospitalization and infection. Further research in T2DM-CKD is needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dimnjaković 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: Type 2 diabetes mellitus (T2DM) is a common condition that is characterized by metabolic impairments. Exercise therapy has proven effective in improving the physiological and psychological states of patients with T2DM; however, the influence of different exercise modalities on metabolic profiles is not fully understood. This study first aimed to investigate the metabolic changes associated with T2DM among patients and then to evaluate the potential physiological effects of different exercise modalities (Tai Chi and brisk walking) on their metabolic profiles., Methods: This study included 20 T2DM patients and 11 healthy subjects. Patients were randomly allocated to either the Tai Chi or walking group to perform Dijia simplified 24-form Tai Chi or brisk walking (80-100 m/min), with 90 minutes each time, three times per week for 12 weeks, for a total of 36 sessions. The healthy group maintained daily living habits without intervention. Glycemic tests were conducted at the baseline and after 12 weeks. Serum and urine samples were collected for untargeted metabolomic analyses at baseline and 12 weeks to examine the differential metabolic profiles between T2DM and healthy subjects, and the metabolic alterations of T2DM patients before and after exercise therapy., Results: Compared to the healthy group, T2DM patients exhibited metabolic disturbances in carbohydrates (fructose, mannose, galactose, glycolysis/gluconeogenesis), lipids (inositol phosphate), and amino acids (arginine, proline, cysteine, methionine, valine, leucine, and isoleucine) metabolism, including 20 differential metabolites in the serum and six in the urine. After exercise, the glycemic results showed insignificant changes. However, patients who practiced Tai Chi showed significant improvements in their post-treatment metabolic profiles compared to baseline, with nine serum and six urine metabolites, including branch-chained amino acids (BCAAs); while those in the walking group had significantly altered nine serum and four urine metabolites concerning steroid hormone biosynthesis and arachidonic acid metabolism compared to baseline., Conclusion: T2DM patients displayed impaired carbohydrate, lipid, and amino acid metabolism, and exercise therapy improved their metabolic health. Different modalities may act through different pathways. Tai Chi may improve disrupted BCAAs metabolism, whereas brisk walking mainly regulates steroid hormone biosynthesis and arachidonic acid metabolism., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang 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.)

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis., Competing Interests: This work was funded by Eli Lilly and Company and all authors are employees of Eli Lilly and Company. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Alan J.M. Brnabic was involved with the conceptualization, methodology, investigation and formal analysis of the data for the work and contributed to the original draft preparation, review and editing of the manuscript. Sarah E. Curtis was involved with the conceptualization, methodology, investigation and formal analysis of the data for the work and contributed to the review and editing of the manuscript. Joseph A. Johnston was involved with the conceptualization, methodology and investigation of the data for the work, and contributed to the original draft preparation, review and editing of the manuscript. Albert contributed to the review and editing of the manuscript. Anthony J. Zagar was involved with the methodology and investigation of the data for the work and contributed to the original draft preparation of the manuscript. Ilya Lipkovich was involved with the methodology and validation of the data for the work and contributed to the original draft preparation of the manuscript. Zbigniew Kadziola was involved with the formal analysis of the data for the work and contributed to the review and editing of the manuscript. Megan H. Murray was involved with the investigation, methodology and formal analysis of the data for the work and contributed to the original draft preparation of the manuscript. Timothy Ryan was involved with the conceptualization and investigation of the data for the work and contributed to the original draft preparation, review and editing of the manuscript. All authors have participated sufficiently in the work to agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors give final approval of the manuscript to be published., (Copyright: © 2024 Brnabic 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: COVID-19-related acute hypoxic respiratory failure patients often use high-flow nasal cannula (HFNO) oxygen therapy. COVID-19 HFNO intubation and mortality risk factors are understudied in the Mexican population, so the aim was to study them., Methods: This retrospective study searched electronic medical records from March 2020 to June 2022 for patients with COVID-19 who required hospitalization and HFNO. Descriptive statistics, a survival curve analysis, and Cox proportional hazard models were used to determine predictor factors for intubation and mortality in patients with HFNO and COVID-19, respectively., Results: A total of 134 patients received HFNO treatment. Ninety-one (67.9%) were men with a mean (SD) age of 54.5 (17.9) years. Common medical history included obesity (n = 89, 66.4%) with a Body Mass Index (BMI) mean (SD) of 31.8 (5.9), hypertension (n = 67, 50.0%), type 2 diabetes (n = 55, 41.0%), and dyslipidemias (n = 43, 32.1%). The variables associated with a greater risk of requiring intubation after high-flow therapy were age (HR = 1.018, 95% CI 1.003-1.034, p = 0.022) and BMI (HR = 1.071, 95% CI 1.024-1.120, p = 0.003). No variables were associated with lower risk. Increased mortality was associated with increasing age (HR = 1.151, 95% CI 1.102-1.201, p = <0.001), hypertension (HR = 4.092, 95% CI 1.369-12.236, p = 0.012), and dyslipidemia (HR = 3.954, 95% CI 1.395-11.209, p = 0.010). Patients with type 2 diabetes had a lower risk of mortality (HR = 0.235, 95% CI 0.080-0.688, p = 0.008)., Conclusions: A higher age and BMI were associated with an increased risk of intubation in patients with HFNO and COVID-19. Hypertension and dyslipidemias were associated with a higher risk of mortality., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Luviano-García 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: Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits., Methods: The summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480). The DIAGRAM and MAGIC consortia offered summary data pertaining to T2D and glycemic characteristics, including fasting glucose (FG) (n = 133,010), glycosylated hemoglobin (HbA1c) (n = 46,368), and homeostatic model assessment-estimated insulin resistance (HOMA-IR) (n = 37,037). A series of MR analyses (univariable MR, multivariable MR, and reverse MR) were used to investigate the causal association of different WBC subtypes with T2D and glycemic traits., Results: Using the inverse-variance weighted method, we found one standard deviation increases in genetically determined neutrophil [odd ratio (OR): 1.086, 95% confidence interval (CI): 0.877-1.345], lymphocyte [0.878 (0.766-1.006)], monocyte [1.010 (0.906-1.127)], eosinophil [0.995 (0.867-1.142)], and basophil [0.960 (0.763-1.207)] were not causally associated with T2D risk. These findings were consistent with the results of three pleiotropy robust methods (MR-Egger, weighted median, and mode-based estimator) and multivariable MR analyses. Reverse MR analysis provided no evidence for the reverse causation of T2D on WBC subtypes. The null causal effects of WBC subtypes on FG, HbA1c, and HOMA-IR were also identified., Conclusions: WBCs play no causal role in the development of insulin resistance and T2D. The observed association between these factors may be explained by residual confounding., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bi 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: Since patients with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular events, interventions addressing risk factors reduce the incidence of cardiovascular disease (CVD) events. This study aimed to evaluate the difference in the incidence of CVD events according to risk factor control in patients with diabetes with and without cardio-renal disease., Methods: We analyzed 113,909 patients with diabetes and 290,339 without diabetes using data released by the National Health Insurance Service (NHIS)., Results: Among patients with diabetes with four or five poorly controlled risk factors, hazard ratio for CVD events was 1.19 (95% confidence interval [CI], 1.06-1.34) in patients with cardio-renal disease and 2.31 (95% CI, 1.95-2.74) in patients without cardio-renal disease compared to patients with diabetes without risk factors. In subjects with diabetes and cardio-renal disease, patients with four or five poorly controlled risk factors had a higher risk of CVD mortality compared to subjects without risk factors (hazard ratio, 1.64; 95% CI, 1.18-2.30)., Conclusion: Controlling cardiovascular risk factors reduced the incidence of CVD events in patients with diabetes, especially those without cardio-renal disease. The degree of risk control was strongly associated with CVD mortality in patients with diabetes with baseline cardio-renal disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song 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.)

Introduction: With an incidence rate as high as 46%-58%, hypoglycemia is a common complication of glycemic management among those suffering from type 2 diabetes mellitus(T2DM). According to preclinical research, hypoglycemia episodes may impair cognition by harming neurons. However, there is still controversy regarding the clinical evidence for the relationship between hypoglycemic events and the likelihood of cognitive impairment. Furthermore, little research has been done on the dose-response association between hypoglycemia incidents and the possibility of cognitive impairment. To address these knowledge gaps, the present research intends to update the comprehension of the association among hypoglycemic events and the risk of cognitive impairment and to clarify the correlation between dose and response by incorporating the most recent investigations., Method and Analysis: This work has developed a protocol for a systematic review and meta-analysis that will examine, via a well-organized assessment of several databases, the relationship between the incidence of hypoglycemia and the probability of cognitive impairment. Observational studies investigating the connection between hypoglycemia episodes and cognitive impairment will be included. The databases that will be searched are PubMed, Web of Science, the Chinese Biomedical Literature Database (CBM), Cochrane Library, Embase, the China National Knowledge (CNKI), Wan Fang, the Chinese Science and Technology Periodical Database (VIP), and Du Xiu. Literature from the establishment of each database to December 2023 will be included in the search. Two researchers will independently screen the studies that satisfy the requirements for both inclusion and exclusion. A third researcher will be asked to mediate any disputes. The methodological caliber of the studies included will be assessed utilizing the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) critical appraisal method. With regard to GRADE, which stands for Grading of Recommendations, Assessment, Development, and Evaluation, the quality of the evidence will be evaluated. ROBIS Tool will be used to evaluate the risk of bias in the development of the systematic review. If the data is accessible, meta-analysis and dose-response curve analysis will be employed by Stata software. However, if the data does not allow for such analysis, a descriptive review will be performed., Discussion and Conclusion: Hypoglycemic episodes may raise the likelihood of cognitive impairment, according to earlier investigations. This study will update the relevant evidence and explore the dose-response connection between hypoglycemic episodes and cognitive impairment. The results of this review will have significant effects on decision-making by individuals with diabetes, healthcare providers, and government policy institutions., Trial Registration: Prospero registration number: CRD42023432352., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ye 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.)

Introduction: Diabetic nephropathy (DN) is a long-term kidney disease among diabetic patients. It is the leading cause of end-stage renal failure. In Ethiopia, DN affects the majority of diabetic populations, but there were inconsistent findings about the determinant factors across the studies., Methods: We have accessed studies using PubMed, Embase, EBSCO, Web of Science, OVID, and search engines including Google and Google Scholar published up to June 2023. The study populations were diabetic patients with nephropathy. The quality of each included article was assessed using the Newcastle-Ottawa quality assessment scale. The odds ratios of risk factors were pooled using a random-effect meta-analysis model. Heterogeneity was assessed using the Cochrane Q statistics and I-Square (I2). The publication bias was detected using the funnel plot and/or Egger's test (p< 0.05). Trim and fill analysis was carried out to treat the publication bias. The protocol has been registered with the reference number CRD42023434547., Results: A total of sixteen articles were used for this reviewed study. Of which, eleven articles were used for advanced age, ten articles for duration of diabetic illness, ten articles for poor glycemic control, and eleven articles for having co-morbid hypertension. Diabetic patients with advanced age (AOR = 1.11, 95% CI: 1.03-120, I2 = 0.0%, p = 0.488), longer duration of diabetic illness (AOR = 1.23, 95% CI = 1.05-1.45, I2 = 0.0%, p = 0.567), poor glycemic control (AOR = 2.57, 95% CI: 1.07-6.14; I2 = 0.0%, p = 0.996), and having co-morbid hypertension (AOR = 4.03, 95% CI: 2.00-8.12, I2 = 0.0%, p = 0.964) were found to be factors associated with DN., Conclusions: The findings of the study revealed that diabetic patients with advanced age, longer duration of diabetic illness, poor glycemic control status, and co-morbid hypertension were the determinant factors of DN. Therefore, treatment of co-morbid hypertension and high blood glucose and regular screening of renal function should be implemented to detect, treat, and reduce the progression of DN. Furthermore, healthcare workers should give due attention to diabetes with advanced age and a longer duration of diabetes illness to prevent the occurrence of DN., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Azagew 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: Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD)., Objective and Rationale: This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease. A comprehensive systematic review provides a clear conclusion and high-level evidence for the association between ELMO1 gene and DKD for future application in personalized medicine., Methods: A comprehensive search of electronic databases, per PRISMA instructions, was conducted in Scopus, EMBASE, Web of Science, and PubMed databases from 1980 to January 2023. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using appropriate models. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and assess the robustness of the findings., Results: A total of 5794 diabetes patients with DKD, 4886 diabetes patients without DKD, and 2023 healthy controls were included in the 17 studies that made up this systematic review. In the investigation of DM (Diabetes Mellitus) with DKD vs. DM without DKD, the susceptibility for DKD for the EMLO1 rs741301 polymorphism indicated a significant difference under the dominant, homozygote, and recessive genetic models. The susceptibility for DKD for the EMLO1 rs1345365, rs10255208, and rs7782979 polymorphisms demonstrated a significant difference under the allele genetic models in the analysis of DM with DKD vs. DM without DKD groups. There was a considerable increase in DKD risk in the Middle East when the population was stratified by the region., Conclusion: The findings of the meta-analysis show that there are a significant connection between the EMLO1 rs741301 polymorphism and DKD susceptibility in overall analyses; as well as rs1345365, rs10255208, and rs7782979 polymorphisms; especially in the Middle East region., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Azarboo 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.)

The biological mechanisms underlying the pathogenesis of type 2 diabetes (T2DM)-related periodontitis remain unclear. This cross-sectional study evaluated the distinctive transcriptomic changes between tissues with periodontal health and with periodontitis in patients with T2DM. In this cross-sectional study, whole transcriptome sequencing was performed on gingival biopsies from non-periodontitis and periodontitis tissues from non-diabetic and diabetic patients. A differentially expressed gene (DEG) analysis and Ingenuity Pathway Analysis (IPA) assessed the genes and signaling pathways associated with T2DM-related periodontitis. Immunohistochemistry was performed to validate selected DEGs possibly involved in T2DM-related periodontitis. Four hundred and twenty and one thousand five hundred and sixty-three DEGs (fold change ≥ 2) were uniquely identified in the diseased tissues of non-diabetic and diabetic patients, respectively. The IPA predicted the activation of Phagosome Formation, Cardiac β-adrenergic, tRNA Splicing, and PI3K/AKT pathways. The IPA also predicted the inhibition of Cholesterol Biosynthesis, Adrenomedullin, and Inositol Phosphate Compounds pathways in T2DM-related periodontitis. Validation of DEGs confirmed changes in protein expression of PTPN2, PTPN13, DHCR24, PIK3R2, CALCRL, IL1RN, IL-6R and ITGA4 in diseased tissues in diabetic subjects. Thus, these preliminary findings indicate that there are specific genes and functional pathways that may be involved in the pathogenesis of T2DM-related periodontitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Observational studies show that liver enzymes are diabetes risk factors. However, previous observational investigations on the relationship between liver enzymes and diabetic microvascular complications produced contradictory results. The purpose of this research is to examine the independent causal effects of liver enzymes on diabetic microvascular complications., Methods: Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to disentangle the causal effects. The genome-wide association study (GWAS) summary-level statistics were collected from the UK biobank and the FinnGen consortium. Single nucleotide polymorphisms (SNPs) were selected as genetic instruments with genome-wide significance (p < 5 ×10-8). Five UVMR approaches, including inverse variance weighted (IVW), Bayesian weighted Mendelian randomization, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), weighted median, and MR-Egger, and three MVMR approaches, including the extended versions of IVW, MR-Egger, and the Q-minimization methods, were performed to evaluate the causal effects. The robustness of the MR results was further confirmed using several sensitivity analyses., Results: UVMR revealed that a genetically predisposed per standard deviation increase in serum alanine aminotransferase (ALT) level increased the risk of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) (IVW OR = 1.489, 95% CI = 1.206-1.772, p = 0.006). Likewise, serum aspartate aminotransferase (AST) levels showed similar results (IVW OR = 1.376, 95% CI = 1.115-1.638, p = 0.017). Furthermore, these effects were consistent after controlling for glycemia and blood pressure using MVMR analysis. Additionally, sensitivity analyses further strengthened the causality. However, no significant associations were found between alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and diabetic microvascular complications., Conclusions: Robust evidence was demonstrated for an independent causal effect of serum ALT or AST concentration on the risk of DR in T2DM. Further investigations are necessary to elucidate the potential biological mechanisms and confirm their clinical significance for early prevention and intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li, Zhang. 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.)