Search Results (29)

Background/Objectives: Ochronosis is an uncommon metabolic condition caused by a deficiency of homogentisate 1,2-dioxygenase, leading to the accumulation of homogentisic acid (HGA) in connective tissues. This deposition of HGA in the joints can result in cartilage degeneration and advanced ochronotic arthritis. Although this condition is usually asymptomatic, it can demonstrate devastating articular destruction characterized by dark pigmentation of the tissues. Methods: A 64-year-old female with a medical history consisting of diabetes mellitus type 2, hypertension, and thoracic aortic aneurysm, with no personal or family history of ochronosis or related symptoms, has been diagnosed with progressive knee osteoarthritis, Kellgren and Lawrence grade III, unresponsive to conservative treatment. Results: The patient underwent staged bilateral, bicompartmental, cemented total knee arthroplasty (TKA), during which several pathological changes were incidentally discovered: black-pigmented, weakened articular cartilage and darkened synovial fluid, as well as brittle metaphyseal bone necessitating increased cement application to ensure prosthetic stability. Postoperative recovery was significant for anemia requiring a blood transfusion. Improved knee function was observed in the first month follow-up visit, and the patient was referred for diagnostic confirmation of her condition. Conclusions: This case underscores the importance of recognizing ochronosis as a potential cause of advanced joint degeneration in patients undergoing arthroplasty. Furthermore, the diagnosis might be of clinical relevance, since this case demonstrated postoperative anemia which required blood transfusion. This, combined with the brittleness of bone, highlights the need for meticulous surgical planning and tailored approaches by the unaware surgeon who might encounter such not-so-pleasant findings. Full article

Diabetic retinopathy (DR), a complication of type 2 diabetes mellitus (T2DM), is typically asymptomatic in its early stages. Diagnosis typically relies on routine fundoscopy for the clinical detection of microvascular abnormalities. However, permanent retinal damage may occur well before clinical signs are appreciable. In the early stages of DR, the retina undergoes distinct epigenetic changes, including DNA methylation and histone modifications. Recent evidence supports unique epigenetic ‘signatures’ in patients with DR compared to non-diabetic controls. These DNA ‘signature’ sequences may be specific to the retina and may circulate in peripheral blood in the form of cell-free DNA (cfDNA). In this review, we explore the literature and clinical application of cfDNA sampling as an early, non-invasive, accessible assessment tool for early DR detection. First, we summarize the known epigenetic signatures of DR. Next, we review current sequencing technologies used for cfDNA detection, such as magnetic bead-based enrichment, next-generation sequencing, and bisulfite sequencing. Finally, we outline the current research limitations and emerging areas of study which aim to improve the clinical utility of cfDNA for DR evaluation. Full article

Background/Objectives: Patients with coronary artery disease undergoing coronary artery bypass grafting (CABG) have a high prevalence of type 2 diabetes mellitus (T2DM) and prediabetes. Glucose metabolism disorders (GMDs) are often asymptomatic and remain undetected, but untreated they can have adverse effects. To evaluate the possibilities of active screening in identifying T2DM and prediabetes before CABG and to assess the impact of GMD on the incidence of postoperative complications. Methods: This study included 1021 patients who underwent CABG in 2016–2018 at the department of cardiovascular surgery, whose glycemic status was determined. All patients had their glycated hemoglobin (HbA1c) levels measured; those without a previous diagnosis of diabetes underwent an oral glucose tolerance test. The frequency of newly diagnosed diabetes and prediabetes was evaluated. Postoperative complication rates were analyzed among patient groups with various types of GMDs and normal blood glucose levels. Results: Screening before CABG increased the number of patients with established type 2 diabetes from 20.9 to 27.8% and the number of people with prediabetes from 2.7% to 31.7%. When analyzing hospital complications, patients with type 2 diabetes compared to patients with normoglycemia were significantly more likely to develop heart failure (p = 0.010), multiple organ failure (p = 0.002), require extracorporeal homeostasis correction (p = 0.011), and wound dehiscence (p = 0.004). Nine patients (0.9%) died following CABG without being discharged from the hospital, with 90% of these deaths occurring in patients with GMDs. Any GMD (diabetes or prediabetes) was associated with an increased incidence of postoperative heart failure (OR 1.259; p = 0.011), rhythm disturbances (OR 1.236; p = 0.010), major cardiovascular complications and/or heart failure (OR 1.193; p = 0.039), and all cardiovascular complications (OR 1.455; p = 0.002). In the presence of any GMD, the risk of multiple organ failure increased by 2.5 times (OR 2.506; p = 0.014), extracorporeal correction of homeostasis increased by 1.8 times (OR 1.821; p = 0.034), and diastasis of the wound edges increased by 1.3 times (OR 1.266; p = 0.005). It is important that, when adjusting for gender and age, the effect of GMD on the described complications remained significant. Conclusions: Active preoperative detection established an extremely high prevalence of GMD in patients with multivessel coronary artery disease (59.5%). T2DM and prediabetes are significant predictors of postoperative complications of coronary artery bypass grafting. Full article

The COVID-19 pandemic represents a major global health crisis, with clinical manifestations ranging from asymptomatic infection to fatal outcomes. While all individuals are susceptible, specific populations, particularly those with pre-existing medical conditions, face a heightened risk of severe disease. This study aimed to assess the prevalence of severe COVID-19 among hospitalized patients with comorbidities in the Central Region of Romania, and to analyze the association between these conditions and mortality. We conducted a retrospective cohort study using data from the Corona Forms platform (2020–2022), encompassing hospitalized cases across three Romanian counties. A total of 1458 patients with confirmed SARS-CoV-2 infection and documented comorbidities were included. Demographic characteristics, comorbid conditions, and hospitalization outcomes were analyzed. The overall mortality rate among comorbid patients was 89.3%. Renal, neurologic, hepatic disease, cardiovascular conditions, obesity, type 2 diabetes mellitus, and cerebrovascular accidents are significant risk factors for death outcomes in the SARS-CoV-2-infected study population. The strength of their association varies, with odds ratios ranging from 25.32 to 1. The findings underscore the critical impact of comorbidities on COVID-19 severity and mortality among the Central Romanian population, emphasizing the necessity of targeted clinical interventions and public health strategies to protect high-risk populations. Full article

Background/Objectives: Prior research has identified a significant association between heart disease and metabolic-dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms are unclear. This study aimed to identify predictive biomarkers associated with grade I left ventricular diastolic dysfunction (LVDD) in patients with type 2 diabetes mellitus (T2DM). Methods: This single-center, cross-sectional study evaluated 73 T2DM patients for grade 1 LVDD and MASLD using 2D echocardiography, tissue analysis, spectral color Doppler, and Fibromax. Results: This study analyzed 50 patients (mean age 58.0 ± 11.3 years) with a median diabetes duration of 7 years, abdominal obesity (mean body mass index (BMI) 34.4 ± 5.9 kg/m²), and a mean HbA1c of 7.9 ± 1.5%. The prevalence of grade I LVDD, fibrosis, mild steatosis, moderate-to-severe liver steatosis, mild MASLD, and moderate MASLD was 54%, 44%, 14%, 80%, 43%, and 34%, respectively. Regression analysis revealed that grade 1 LVDD was positively associated with age, Fibrotest, α2-macroglobulin, epicardiac adipose tissue (EAT), and negatively associated with lateral s′, E wave, E/e′, E/A, medium E′, and septal e′ (p < 0.05 for all). α2-macroglobulin > 1.92 g/L (area under the receiver operating characteristic curve (AUROC) = 0.782, sensitivity 70.4%, specificity 81.2%) and fibrotest score > 0.11 (AUROC 0.766, sensitivity 92.6%, specificity 56.2%) were significant predictors of grade I LVDD. Conclusions: Although the underlying mechanisms remain unclear, innovative non-invasive biomarkers, such as α2-macroglobulin or fibrotest, could concurrently indicate liver stiffness and the likelihood of grade I LVDD, an early, asymptomatic HF stage in T2DM patients. Full article

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels of N-terminal brain natriuretic pro-peptide (NT-proBNP) > 125 pmol/mL and followed them for 52 weeks. Structural cardiac abnormalities were used as the minimum from the following criteria: abnormal left ventricular (LV) global longitudinal strain (GLS) < −16%, LV hypertrophy, left atrial volume index > 34 mL/m², abnormal ratio of early transmitral diastolic filling velocity/early mitral annular velocity ≥ 13 units. All the patients underwent echocardiographic and Doppler examinations by two blinded, highly experienced echocardiographers. NT-proBNP, irisin, TNF-alpha, and hs-CRP were quantified in the serum at baseline, at 26 weeks, and at the end of the study. The kidney-related outcomes consisted of an eGFR reduction by 40% from baseline, or end-stage kidney disease, or kidney replacement therapy. We found that levels of irisin at baseline < 4.15 ng/mL and/or its decrease > 20% from baseline in T2DM patients predicted kidney-related events better than baseline levels/dynamic NT-proBNP and the use of SGLT2 inhibitors. In conclusion, we established that a low baseline level of irisin and its 20% decrease correlated with newly kidney-related events in T2DM patients with asymptomatic HFpEF/HFmrEF. Full article

In patients with type 2 diabetes mellitus (T2DM), asymptomatic adverse cardiac remodeling plays a pivotal role in the development of heart failure (HF). Patients with T2DM often have low or near-normal levels of natriuretic peptides, including N-terminal brain natriuretic peptide (NT-proBNP), which have been inconclusive in predicting the transition from asymptomatic adverse cardiac remodeling to HF with preserved ejection fraction (HFpEF). The aim of this study was to elucidate the predictive ability of adropin for HFpEF depending on the circulating levels of NT-proBNP. We prospectively enrolled 561 T2DM patients (glycated hemoglobin < 6.9%) with echocardiographic evidence of structural cardiac abnormalities and left ventricular ejection fractions >50%. All patients underwent B-mode transthoracic echocardiographic and Doppler examinations. Circulating biomarkers, i.e., NT-proBNP and adropin, were assessed at baseline. All individuals were divided into two groups according to the presence of low levels (<125 pmol/mL; n = 162) or elevated levels (≥125 pmol/mL; n = 399) of NT-proBNP. Patients with known asymptomatic adverse cardiac remodeling and elevated NT-proBNP were classified as having asymptomatic HFpEF. A multivariate logistic regression showed that low serum levels of adropin (<3.5 ng/mL), its combination with any level of NT-proBNP, and use of SGLT2 inhibitors were independent predictors of HFpEF. However, low levels of adropin significantly increased the predictive ability of NT-proBNP for asymptomatic HFpEF in patients with T2DM, even though the concentrations of NT-proBNP were low, while adropin added discriminatory value to all concentrations of NT-proBNP. In conclusion, low levels of adropin significantly increase the predictive ability of NT-proBNP for asymptomatic HFpEF in patients with T2DM. Full article

With around one billion of the world’s population affected, the era of the metabolic-associated fatty liver disease (MAFLD) pandemic has entered the global stage. MAFLD is a chronic progressive liver disease with accompanying metabolic disorders such as type 2 diabetes mellitus and obesity which can progress asymptomatically to liver cirrhosis and subsequently to hepatocellular carcinoma (HCC), and for which to date there are almost no approved pharmacologic options. Because MAFLD has a very complex etiology and it also affects extrahepatic organs, a multidisciplinary approach is required when it comes to finding an effective and safe active substance for MAFLD treatment. The optimal drug for MAFLD should diminish steatosis, fibrosis and inflammation in the liver, and the winner for MAFLD drug authorisation seems to be the one that significantly improves liver histology. Saroglitazar (Lipaglyn^®) was approved for metabolic-dysfunction-associated steatohepatitis (MASH) in India in 2020; however, the drug is still being investigated in other countries. Although the pharmaceutical industry is still lagging behind in developing an approved pharmacologic therapy for MAFLD, research has recently intensified and many molecules which are in the final stages of clinical trials are expected to be approved in the coming few years. Already this year, the first drug (Rezdiffra™) in the United States was approved via accelerated procedure for treatment of MAFLD, i.e., of MASH in adults. This review underscores the most recent information related to the development of drugs for MAFLD treatment, focusing on the molecules that have come furthest towards approval. Full article

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. Full article

Background and Objectives: Screening for type 2 diabetes mellitus (DM2) aims to identify asymptomatic individuals who may be at a higher risk, allowing proactive interventions. The objective of this study was to predict the incidence of DM2 and prediabetes in the Saudi population over the next five years. Materials and Methods: The study was conducted in the Aseer region through August 2023 using a cross-sectional survey for data collection. A multistage stratified random sampling technique was adopted, and data were collected through face-to-face interviews using the validated Arabic version of the Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK). Results: In total, 652 individuals were included in the study. Their mean age was 32.0 ± 12.0 years; 53.8% were male, 89.6% were from urban areas, and 55.8% were single. There were statistically significant differences between males and females in AUSDRISK items, including age, history of high blood glucose, use of medications for high blood pressure, smoking, physical activity, and measurements of waist circumference (p < 0.05). Based on AUSDRISK scores, 46.2% of the included participants were predicted to develop impaired glucose tolerance within the coming five years (65.8% among females vs. 23.6%), and 21.9% were predicted to develop DM2 (35.6% among males vs. 6.0% among females); this difference was statistically significant (p = 0.0001). Conclusions: Urgent public health action is required to prevent the increasing epidemic of DM2 in Saudi Arabia. Full article

Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)—the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease. Full article

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes (PreDM) is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on PreDM is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as PreDM is a reversible condition if it is detected in the early stages. The literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes are not well elucidated. In this review, we seek to review the existing literature on PreDM- and T2DM-associated changes in skeletal muscle function. Full article

Diabetes mellitus is a complex and widespread metabolic disease, having extremely complex implications (biological, psychological, social) for patients. Understanding the pathophysiology of diabetes (majorly influenced by various factors such as genetic predisposition, age, lifestyle choices, etc.) is essential for the prevention of this condition and the establishment of effective treatment strategies. The latest and relevant literature data related to the epidemiology, pathophysiology, and treatment of diabetes are presented, after an exhaustive review of the articles published on this topic and indexed in the WOS, PubMed, Scopus and Google Scholar databases. Preventing or delaying the onset of diabetes can be achieved in some patients with type 2 diabetes. After onset, treatment of diabetes is complex, involving a comprehensive approach (pharmacological interventions, lifestyle changes, surgical interventions in selected cases, as well as psychological support), depending on the stage of the disease and possible associated complications. Finally, diabetes is often asymptomatic in the initial stages, so an early diagnosis remains the essential element for the best subsequent therapeutic control. Full article

Background: Perioperative myocardial infarction (PMI) is a life-threatening complication in major non-cardiac surgeries (NCS) and constitutes the most common cause of postoperative morbidity and mortality. A PMI that is associated with prolonged oxygen supply–demand imbalance and its etiology is defined as a type 2 MI. Asymptomatic myocardial ischemia can occur in patients with stable coronary artery disease (CAD), especially those with comorbidities such as diabetes mellitus (DM), hypertension, or, in some cases, without any risk factors. Case: We report a case of asymptomatic PMI in a 76-year-old patient with underlying hypertension and DM without a previous history of CAD. During the induction of anesthesia, abnormal electrocardiography was discovered, and the surgery was postponed after further studies revealed almost completely occluded three-vessel CAD and type 2 PMI. Conclusions: Anesthesiologists should closely monitor and evaluate the associated cardiovascular risk, including cardiac biomarkers of each patient before surgery, to minimize the possibility of PMI. Full article

One of the most common and deadly types of pancreatic cancer (PC) is pancreatic ductal adenocarcinoma (PDAC), with most patients succumbing to the disease within one year of diagnosis. Current detection strategies do not address asymptomatic PC; therefore, patients are diagnosed at an advanced stage when curative treatment is often no longer possible. In order to detect PC in asymptomatic patients earlier, the risk factors that could serve as reliable markers need to be examined. Diabetic mellitus (DM) is a significant risk factor for this malignancy and can be both a cause and consequence of PC. Typically, DM caused by PC is known as new-onset, pancreatogenic, pancreoprivic, or pancreatic cancer-related diabetes (PCRD). Although PCRD is quite distinct from type 2 DM (T2DM), there are currently no biomarkers that differentiate PCRD from T2DM. To identify such biomarkers, a better understanding of the mechanisms mediating PCRD is essential. To this end, there has been a growing research interest in recent years to elucidate the role of tumour-derived exosomes and their cargo in the pathogenesis of PCRD. Exosomes derived from tumours can be recognized for their specificity because they reflect the characteristics of their parent cells and are important in intercellular communication. Their cargo consists of proteins, lipids, and nucleic acids, which can be transferred to and alter the behaviour of recipient cells. This review provides a concise overview of current knowledge regarding tumour-derived exosomes and their cargo in PCRD and discusses the potential areas worthy of further study. Full article