DiabetologyPub Date : 2024-08-08DOI: 10.3390/diabetology5030026
Min-Ji Kim, Eun-Jung Choi, In-Kyu Lee
{"title":"Impact of Hyperferritinemia on Immune Modulation in Septic Diabetic Patients","authors":"Min-Ji Kim, Eun-Jung Choi, In-Kyu Lee","doi":"10.3390/diabetology5030026","DOIUrl":"https://doi.org/10.3390/diabetology5030026","url":null,"abstract":"Diabetes significantly impacts the immune system; however, its role in worsening sepsis prognosis remains poorly understood. This study investigated the effect of hyperferritinemia on immune modulation in septic diabetic patients. A cohort study at Kyungpook National University Hospital stratified sepsis patients by diabetes status and followed them for 28 days. Additionally, CD4+ T cells from mice were analyzed for proliferation, apoptosis, and metabolic changes under ferritin treatment. Results from the clinical study showed higher ferritin levels in diabetic patients, and those with lower lymphocyte counts had increased mortality. In the mice study, ferritin inhibited T cell activation and proliferation by shifting metabolism from glycolysis to oxidative phosphorylation without increasing cell death. These findings suggest that the suppression of T cell proliferation due to elevated ferritin levels contributes to an immunosuppressive environment, leading to worse outcomes. In conclusion, hyperferritinemia is a biomarker for sepsis severity, particularly in diabetic patients, highlighting potential therapeutic strategies targeting ferritin levels or glycolytic pathways.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-08-01Epub Date: 2024-08-21DOI: 10.3390/diabetology5030027
KiBeom Kwon, Taylor A Brown, Juan C Arias Aristizábal, David G Armstrong, Tze-Woei Tan
{"title":"Outcomes for Patients with Diabetic Foot Ulcers Following Transition from Medicaid to Commercial Insurance.","authors":"KiBeom Kwon, Taylor A Brown, Juan C Arias Aristizábal, David G Armstrong, Tze-Woei Tan","doi":"10.3390/diabetology5030027","DOIUrl":"10.3390/diabetology5030027","url":null,"abstract":"<p><strong>Objective: </strong>This study investigates the outcomes of Medicaid beneficiaries with diabetic foot ulcers (DFUs) who had transitioned to commercial insurance.</p><p><strong>Methods: </strong>We utilized the PearlDiver claims database to identify adult patients diagnosed with a new DFU between 2010 and 2019. The study cohort comprised 8856 Medicaid beneficiaries who had at least three years of continuous enrollment after DFU diagnosis. Medicaid beneficiaries who transitioned to Medicare during follow-up were excluded. Adjusted comparisons of outcomes were performed by propensity matching the two groups for age, gender, and Charlson Comorbidity Index (CCI) in a 1:1 ratio. We used logistic regression and Kaplan-Meier estimate to evaluate the association between insurance change (from Medicaid to commercial insurance) and major amputation.</p><p><strong>Results: </strong>Among the 8856 Medicaid beneficiaries with DFUs, 66% (<i>n</i> = 5809) had transitioned to commercial insurance coverage during follow-up. The overall major amputation rate was 2.8% (<i>n</i> = 247), with a lower rate observed in patients who transitioned to commercial insurance compared to those with continuous Medicaid coverage (2.6% vs. 3.2%, <i>p</i> < 0.05). In multivariable analysis, Medicaid beneficiaries who transitioned to commercial insurance had a 27% lower risk of major amputation (study cohort: odds ratios [OR] 0.75, 95% CI 0.56-0.97, <i>p</i> = 0.03; matched cohort: OR 0.65, 95% 0.22, 0.55, <i>p</i> = 0.01) compared to those with continuous Medicaid coverage.</p><p><strong>Conclusions: </strong>Transitioning from Medicaid to commercial insurance may be associated with a lower risk of major amputation among Medicaid beneficiaries with DFUs.</p>","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-07-23DOI: 10.3390/diabetology5030023
E. Javor, David Šarčević, A. Rešić
{"title":"Metabolic Syndrome and Pharmacological Interventions in Clinical Development","authors":"E. Javor, David Šarčević, A. Rešić","doi":"10.3390/diabetology5030023","DOIUrl":"https://doi.org/10.3390/diabetology5030023","url":null,"abstract":"Metabolic syndrome prevalence is between 24 and 27% and poses a significant risk for the development of atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes (T2D), or other comorbidities. Currently, no drugs are approved for metabolic syndrome treatment itself, so the risk factors are treated with therapies approved for cardiac and metabolic conditions. These are approved drugs for dyslipidemia treatment such as statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, cornerstone antihypertensive drugs, or novel class glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RA) for T2D and overweight or obesity treatment. We have also evaluated new pharmacological interventions in clinical development that have reached Phase 2 and/or Phase 3 randomized clinical trials (RCTs) for the management of the risk factors of metabolic syndrome. In the pipeline are glucose-dependent insulinotropic polypeptide (GIP), GLP-1, glucagon receptor (GCGR), amylin agonists, and a combination of the latter for T2D and overweight or obesity treatment. Non-entero-pancreatic hormone-based therapies such as ketohexokinase (KHK) inhibitor, growth differentiation factor 15 (GDF15) agonists, monoclonal antibodies (mAbs) as activin type II receptors (ActRII) inhibitors, and a combination of anti-α-myostatin (GFD8) and anti-Activin-A (Act-A) mAbs have also reached Phase 2 or 3 RCTs in the same indications. Rilparencel (Renal Autologous Cell Therapy) is being evaluated in patients with T2D and chronic kidney disease (CKD) in a Phase 3 trial. For dyslipidemia treatment, novel PCSK9 inhibitors (oral and subcutaneous) and cholesteryl ester transfer protein (CETP) inhibitors are in the final stages of clinical development. There is also a surge of a new generation of an antisense oligonucleotide (ASO) and small interfering RNA (siRNA)-targeting lipoprotein(a) [Lp(a)] synthesis pathway that could possibly contribute to a further step forward in the treatment of dyslipidemia. For resistant and uncontrolled hypertension, aldosterone synthase inhibitors and siRNAs targeting angiotensinogen (AGT) messenger RNA (mRNA) are promising new therapeutic options. It would be interesting if a few drugs in clinical development for metabolic syndrome such as 6-bromotryptophan (6-BT), vericiguat, and INV-202 as a peripherally-acting CB1 receptor (CB1r) blocker would succeed in finally gaining the first drug approval for metabolic syndrome itself.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141810441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-07-11DOI: 10.3390/diabetology5030022
A. Kristo, Kübra İzler, Liel Grosskopf, Jordan J. Kerns, A. Sikalidis
{"title":"Emotional Eating Is Associated with T2DM in an Urban Turkish Population: A Pilot Study Utilizing Social Media","authors":"A. Kristo, Kübra İzler, Liel Grosskopf, Jordan J. Kerns, A. Sikalidis","doi":"10.3390/diabetology5030022","DOIUrl":"https://doi.org/10.3390/diabetology5030022","url":null,"abstract":"Lifestyle behaviors and their potential effects on diabetes are being investigated for optimal diabetes management. In patients with type 2 diabetes mellitus (T2DM), the necessary dietary modifications extend to psychological components for consideration. This study aimed to determine the eating behavior of T2DM patients with different sociodemographic characteristics in an urban Turkish population. The Dutch Eating Behavior Questionnaire (DEBQ) was distributed via social media and a smartphone application to 108 T2DM patients, 58 males and 50 females, age 26–40 years (20 individuals, 18.6%) and over 40 years (88 individuals, 81.4 %). Basic component factor analysis varimax rotation was used for the item-total correlation coefficient. The 26–40 years age group exhibited high correlation for both restrained and emotional eating behavior (r > 0.8), while participants over 40 years displayed medium correlation for restrained eating and high correlation for emotional eating (r = 0.6–0.8). Compared to married and single participants, participants with “other” marital status showed significant correlation with all eating behavior categories (r > 0.8). Married participants were less correlated with all categories compared to single participants. Participants with lower education levels exhibited high correlation (r > 0.8) for all forms of eating, more so compared to those with higher levels of education attained. Overweight patients demonstrated moderately high (r = 0.4–0.6) restrictive eating correlation, while normal weight and obese patients exhibited higher correlation (r = 0.6–0.8) for emotional and restrained eating compared to overweight patients. Regardless of demographic factors, when all participants were combined, the strongest correlation was found to be with emotional eating compared to other types of eating.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141658186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-07-05DOI: 10.3390/diabetology5030021
Giancarlo Tonolo, Ariella DeMonte, Maria Antonietta Taras, A. Scorsone, Patrizio Tatti, Battistina Pittui, Salvatore Turco, Riccardo Trentin
{"title":"The Use of Insulin Pen Needles: The Italian Society of Metabolism, Diabetes, and Obesity (SIMDO) Consensus","authors":"Giancarlo Tonolo, Ariella DeMonte, Maria Antonietta Taras, A. Scorsone, Patrizio Tatti, Battistina Pittui, Salvatore Turco, Riccardo Trentin","doi":"10.3390/diabetology5030021","DOIUrl":"https://doi.org/10.3390/diabetology5030021","url":null,"abstract":"A correct injection technique is essential in order to ensure the effectiveness of insulin and to achieve good metabolic control, and the use of suitable needles is fundamental. Today, technological evolution has transformed insulin needles into innovative tools able to guarantee an effective and safe administration of insulin, to reduce local complications, such as lipodystrophies that are an obstacle to the effectiveness of the treatment itself, and to minimize the pain of the injection, a crucial factor in the acceptance of therapy and for compliance. The steering committee of the scientific society SIMDO has commissioned the scientific committee and some members of the board to draw up an official SIMDO point of view/consensus on the use of insulin needles. In this way, a group that has combined the experience gained in their field of expertise—diabetologists operating in the public and private sectors, nurses, psychologists, and patients—was set up. The aim is to give indications regarding insulin injection techniques, combining themes such as technology innovation, education in self-management, and psychological support for the patient into a unified approach based on the priority area of patient quality of life. The document will provide operational recommendations that integrate the directions regarding the standards of care for diabetes resulting from the most recent scientific acquisitions with the concept of quality at 360°, as it emerged from the point of view of all the operators involved, but with the patient’s interests as a central focal point.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141676039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-07-03DOI: 10.3390/diabetology5030020
Inês Fernandes, M. Mariana, Margarida Lorigo, E. Cairrão
{"title":"The Influence of Plant-Based Diets on Metabolic Syndrome","authors":"Inês Fernandes, M. Mariana, Margarida Lorigo, E. Cairrão","doi":"10.3390/diabetology5030020","DOIUrl":"https://doi.org/10.3390/diabetology5030020","url":null,"abstract":"The magnification of Western eating habits has contributed to a large increase in the development of several diseases and conditions, namely cardiovascular disease, obesity, dyslipidemia, and hyperglycemia. These are part of a cluster of metabolic factors involved in metabolic syndrome. However, there are new dietary patterns more focused on the consumption of plant-based foods. Thus, the aim of this review was to investigate the impact of plant-based diets on metabolic syndrome and to achieve the inflammatory mediators and the antioxidant effects involved in this potential health benefits effect. Advanced research was performed for articles published in the last 10 years, which were analyzed and selected according to the defined inclusion and exclusion criteria. Of the articles analyzed, the majority supported the positive impact of plant-based diets on metabolic syndrome. Furthermore, several studies also showed that these diets appear to have an anti-inflammatory and antioxidant role. Thus, plant-based diets appear to have health benefits, contributing to the prevention of metabolic syndrome, and improving the cardiovascular and metabolic markers’ profile, mainly when including healthy foods. The total exclusion of animal source foods (especially meat and fish) from the diet, as well as the consumption of processed and additive plant-based foods, may contribute to an increased prevalence of metabolic syndrome.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141682503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-06-04DOI: 10.3390/diabetology5020017
Matilde Monteiro-Soares, José Dores, Cristina Alves-Palma, Susana Galrito, D. Ferreira-Santos
{"title":"The Utility of Annual Reassessment of the International Working Group on the Diabetic Foot Diabetes-Related Foot Ulcer Risk Classification in the Primary Care Setting—A Cohort Study","authors":"Matilde Monteiro-Soares, José Dores, Cristina Alves-Palma, Susana Galrito, D. Ferreira-Santos","doi":"10.3390/diabetology5020017","DOIUrl":"https://doi.org/10.3390/diabetology5020017","url":null,"abstract":"Background: We assessed the pertinence of updating the International Working Group on the Diabetic Foot (IWGDF) risk classification yearly in people with diabetes by quantifying the changes in the risk group and its accuracy in identifying those developing an ulcer (DFU) in a primary care setting. Methods: In our retrospective cohort study, we included all people with diabetes with a foot assessment registry between January 2016 and December 2018 in the Baixo Alentejo Local Health Unit. Foot-related data were collected at baseline after one and two years. DFU and/or death until December 2019 were registered. The proportion of people changing their risk status each year was calculated. Accuracy measures of the IWGDF classification to predict DFU occurrence at one, two, and three years were calculated. Results: A total of 2097 people were followed for three years, during which 0.1% died and 12.4% developed a DFU. After two years, 3.6% of the participants had progressed to a higher-risk group. The IWGDF classification presented specificity values superior to 90% and negative predictive values superior to 99%. Conclusion: Foot risk status can be safely updated every two years instead of yearly, mainly for those at very low risk. The IWGDF classification can accurately identify those not at risk of DFU.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141388024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-05-22DOI: 10.3390/diabetology5020016
Madison Reddie, Daniel Frey
{"title":"A Resource-Efficient Plantar Pressure Evaluation System for Diabetic Foot Risk Assessment","authors":"Madison Reddie, Daniel Frey","doi":"10.3390/diabetology5020016","DOIUrl":"https://doi.org/10.3390/diabetology5020016","url":null,"abstract":"Diabetic foot complications constitute a large and rapidly growing global health problem, causing one million lower-extremity amputations annually. These amputations are typically preceded by preventable diabetic foot ulcers (DFUs). However, 80% of the world’s diabetics now reside in low- and middle-income countries, where many healthcare settings lack the resources required to implement recommended DFU risk assessment and prevention strategies. There is an unmet need for a more resource-efficient DFU risk assessment method. In this study, a low-cost, purely mechanical plantar pressure evaluation device was designed toward this end. The device consists of a grid of plastic bistable compliant mechanisms, which present a visual series of binary outputs in response to applied pressure. By having diabetic patients step on the device, non-specialist healthcare providers can easily assess patients’ plantar pressures, which are predictive of future DFUs. A prototype was fabricated and pilot-tested with 41 healthy subjects. It demonstrated a sensitivity of 25.6%, although sensitivity reached 60% for heavier subjects. Sensitivity could likely be significantly improved by lowering the device’s profile and increasing the sensing area. Strained health systems may then be able to use this device to allocate scarce healthcare resources more efficiently to prevent costly DFUs and amputations.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141109443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-05-14DOI: 10.3390/diabetology5020015
Aliyanet Isamara Porcayo Ascencio, Evangelina Morales Carmona, Jesús Morán Farías, Dulce Stephanie Guzmán Medina, Rebeca Galindo Salas, Leobardo Sauque Reyna
{"title":"Prevalence of Peripheral Arterial Disease and Principal Associated Risk Factors in Patients with Type 2 Diabetes Mellitus: The IDON-Peripheral Arterial Disease Study","authors":"Aliyanet Isamara Porcayo Ascencio, Evangelina Morales Carmona, Jesús Morán Farías, Dulce Stephanie Guzmán Medina, Rebeca Galindo Salas, Leobardo Sauque Reyna","doi":"10.3390/diabetology5020015","DOIUrl":"https://doi.org/10.3390/diabetology5020015","url":null,"abstract":"The principal purpose of this study is to determine the prevalence of peripheral arterial disease (PAD), as well as the principal associated risk factors, in patients registered in the IDON-PAD database. PAD is a condition characterized by the narrowing or blockage of arteries in the body’s extremities due to plaque buildup, leading to reduced blood flow and tissue ischemia. While PAD primarily affects the lower extremities, it can lead to symptoms such as intermittent claudication and, in severe cases, ulcers and amputations. Risk factors for PAD are numerous and cumulative, including smoking, age over 50, type 2 diabetes mellitus, and hypertension. The prevalence of PAD increases with age, with rates ranging from 2.5% in those over 50 to 60% in those over 85, varying by ethnicity and study population. Diabetic patients face a higher risk of PAD-related complications and have lower success rates with revascularization procedures. The diagnosis of PAD traditionally relied on physical examination and symptoms, but the Ankle–Brachial Index is now a standard diagnostic tool due to its non-invasive nature and reliability. In Mexico, the prevalence of PAD is estimated at 10%, with significant risk factors being the duration of diabetes, hypertension, hypertriglyceridemia, and smoking. Notably, 70% of PAD cases are asymptomatic, emphasizing the importance of proactive screening. This study aimed to determine the prevalence of PAD and associated risk factors in diabetic patients aged 40 and above. The prevalence was found to be 11.2%, with high-risk waist circumference, elevated triglycerides, positive Edinburgh questionnaire, and weak pulses as significant predictors. The detection and management of PAD in diabetic patients require a comprehensive approach, including lifestyle modifications and regular screenings. Prevention strategies should focus on controlling risk factors, including obesity, hypertension, and dyslipidemia. In conclusion, PAD is a prevalent yet underdiagnosed condition in diabetic patients, necessitating proactive screening and comprehensive management to mitigate associated risks and improve patient outcomes. The principal limitation of this study is that, as it uses a cross-sectional methodology and is not an experimental study, although we can establish the prevalence of PAD as well as the associated risk factors, we cannot define causality or determine the hazard ratio for each of these factors. Special thanks to Dr. Leobardo Sauque Reyna and all participants for their contribution to this research.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140980672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DiabetologyPub Date : 2024-05-11DOI: 10.3390/diabetology5020014
Alisah Hussain, Yaw Asare-Amankwah, Shehryar Qureshi, M. J. Thornton, Timothy M. Palmer, I. Bolanle, Ian C. Wood, Neil A. Turner, Karen E. Porter, Andrew Tedder, K. Riches-Suman
{"title":"Defining the miRnome of Saphenous Vein Smooth Muscle Cells from Patients with Type 2 Diabetes Mellitus","authors":"Alisah Hussain, Yaw Asare-Amankwah, Shehryar Qureshi, M. J. Thornton, Timothy M. Palmer, I. Bolanle, Ian C. Wood, Neil A. Turner, Karen E. Porter, Andrew Tedder, K. Riches-Suman","doi":"10.3390/diabetology5020014","DOIUrl":"https://doi.org/10.3390/diabetology5020014","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) patients suffer premature development of cardiovascular disease and commonly require cardiac revascularization using the autologous saphenous vein (SV). Smooth muscle cells (SMCs) are the principal cell type within the vascular wall and are dysfunctional in T2DM SV-SMCs, yet the mechanisms underpinning this are incompletely understood. The purpose of this study was to interrogate differential microRNA (miRNA) expression in SV-SMCs to enhance our understanding of T2DM SV-SMC phenotypic change. miRNA expression in primary human SV-SMCs from T2DM and non-diabetic (ND) donors was determined using an array (n = 6 each of ND and T2DM SV-SMCs). Differentially expressed miRNAs were ranked, and functional annotation of the 30 most differentially expressed miRNAs using DAVID and KEGG analysis revealed pathways related to SMC phenotype, including proliferation, migration, cytokine production and cell signaling. After selecting miRNAs known to be involved in SMC phenotypic regulation, miR-17, miR-29b-2, miR-31, miR-130b and miR-491 were further validated using qRT-PCR (n = 5 each of ND and T2DM SV-SMC), with miR-29b-2 subsequently being removed from further investigation. Potential mRNA targets were identified using mirDIP. Predicted target analysis highlighted likely dysregulation in transcription, epigenetic regulation, cell survival, intracellular signaling and cytoskeletal regulation, all of which are known to be dysfunctional in T2DM SV-SMCs. In conclusion, this paper identified four miRNAs that are dysregulated in T2DM SV-SMCs and are implicated in functional changes in the behavior of these cells. This provides a step forward in our understanding of the molecular and epigenetic regulation of vascular dysfunction in T2DM.","PeriodicalId":72798,"journal":{"name":"Diabetology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140988780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}