Search Results (1,767)

Background: Type 1 diabetes mellitus (T1DM) is associated with an increased risk of fragility fractures that cannot be fully explained by reduced bone mineral density (BMD), highlighting a potential role for bone quality impairment. The purpose of this study was to evaluate the prevalence of altered bone density and microarchitecture and to identify their main clinical correlates in adults with T1DM and seemingly adequate glycemic control at the time of assessment. Methods: Sixty-eight adults aged 18–69 years with T1DM attending a diabetes technology outpatient clinic were enrolled in this single-center, cross-sectional study. BMD at the lumbar spine, femoral neck, and total hip was assessed by dual-energy X-ray absorptiometry (DXA) and classified as reduced based on age and sex: Z-score < −2.0 SD for premenopausal women and men < 50 years, and T-score ≤ −2.5 SD for postmenopausal women and men ≥ 50 years. Bone microarchitecture was evaluated using trabecular bone score (TBS). Clinical, metabolic, and lifestyle variables were collected, including glycated hemoglobin (HbA1c; good control ≈ 7.0%/53 mmol/mol), diabetes duration, microvascular complications, and physical activity (PA) assessed by the International PA Questionnaire (IPAQ; moderate–high PA defined according to combined high and moderate IPAQ categories). Results: Reduced BMD was observed in 35.3% of patients and was associated with older age (p < 0.001), longer disease duration (p = 0.044), lower body mass index (p = 0.031), poorer glycemic control (p = 0.03), microvascular complications such as diabetic peripheral neuropathy (p = 0.028) and retinopathy (p = 0.045), and low PA (p = 0.012). Altered TBS was present in 45.6% of patients and was associated with older age (p < 0.001), longer diabetes duration (p = 0.011), higher HbA1c levels (p < 0.001), diabetic peripheral neuropathy (p = 0.002), retinopathy (p = 0.007), cardiovascular risk factors (dyslipidemia p = 0.002, hypertension p = 0.002), and low PA (p < 0.001). In multivariable analyses, older age and higher HbA1c were independently associated with reduced TBS, whereas moderate–high PA was associated with a lower likelihood of impaired bone microarchitecture. Conclusions: Impaired bone density and bone quality are highly prevalent in adults with T1DM and are frequently associated with longer disease duration, poorer metabolic control, and chronic complications. Our findings support the potential value of a combined assessment of BMD and TBS in fracture risk evaluation, together with strategies aimed at preventing diabetes-related complications and promoting healthy lifestyle behaviors. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is one of the most common metabolic complications during pregnancy. Nutritional and diabetological education constitutes the cornerstone of treatment; however, its actual impact according to maternal knowledge levels requires further evaluation. The objectives of this study were to assess the influence of maternal dietary and lifestyle knowledge on the metabolic control of women diagnosed with GDM and to analyze the effectiveness of nutritional and diabetological education received during pregnancy in achieving favorable obstetric and perinatal outcomes. Methods: A prospective observational cohort study was conducted at a tertiary referral center in women diagnosed with GDM. Participants completed a specific questionnaire to evaluate dietary and lifestyle knowledge relevant to glycemic control. Pregnancy follow-up included anthropometric measurements, maternal biochemical parameters—including oral glucose tolerance tests—and maternal-fetal obstetric outcomes, analyzed in relation to knowledge levels and education received. Results: Results showed that women with lower nutritional knowledge exhibited higher body weight, body mass index, and glucose levels in GDM diagnostic tests. Higher knowledge levels were associated with improved metabolic control. Nutritional and diabetological education during pregnancy proved beneficial, with better maternal-fetal outcomes observed, particularly among women who received reinforced education. Conclusions: Dietary and lifestyle knowledge significantly influenced GDM metabolic control. Nutritional education before and during pregnancy is key to optimizing glycemic management and improving maternal-fetal outcomes, supporting the need for preventive and educational programs targeting women with risk factors. Full article

The oral cavity harbors the second-largest and one of the most diverse microbial communities in the human body, playing a critical role in maintaining local and systemic health. Type 2 diabetes mellitus (T2DM), a chronic metabolic disease accounting for nearly 90% of all diabetes cases, has shown rapidly increasing global prevalence. Growing clinical and experimental evidence indicates a strong bidirectional relationship between oral microbiota dysbiosis and T2DM. Imbalanced oral microbial communities can contribute to systemic inflammation, insulin resistance, and metabolic dysregulation, while hyperglycemia and impaired immunity in T2DM promote oral diseases such as periodontitis, xerostomia, and mucosal infections. This review summarizes current research on the interactions between oral microbiota and T2DM, highlighting their clinical correlations, underlying mechanisms, and mutual influences on inflammation, microbial composition, and metabolic pathways. We also discuss emerging strategies for T2DM prevention and management through oral microbiota modulation. These insights may provide new perspectives for early diagnosis, targeted intervention, and integrative management of T2DM. Full article

Background: The common fat mass and obesity-associated (FTO) gene variant rs9939609 has been linked to elevated risk of obesity and Type 2 diabetes mellitus (T2DM). Eating and sleeping windows gained clinical interest as factors in weight maintenance and have been linked to T2DM risk. Objective: To study the association and interaction between the common FTO rs9939609 variant and eating and sleeping windows to affect T2DM risk in a large community cohort. Methods: This cross-sectional study included 12,254 adult participants. Genetic, anthropometric, and lifestyle behaviors data including eating and fasting windows were analyzed. Logistic and linear regression models, as well as chi-square tests, were applied under additive, dominant, and recessive genetic models (adjusted for age, sex, and BMI). Results: Significant associations between FTO rs9939609 x eating and sleeping window interactions were demonstrated in relation to T2DM risk. Longer eating windows and later last meal timing were associated with an increased risk for T2DM under the additive model (OR = 1.029, 95% CI = 1.002–1.055, and OR = 1.066, 95% CI = 1.012–1.122, respectively), while longer fasting windows were found to be protective under additive model (OR = 0.972, 95% CI = 0.947–0.998). Later bedtime onset was associated with an increased risk for T2DM under additive model (OR = 1.101, 95% CI = 1.005–1.220). Hours of night sleep significantly interacted with FTO rs9939609 under additive genetic model. FTO rs9939609 risk allele carriers with prolonged sleeping windows (OR = 1.137, 95% CI = 1.039–1.354) and poorer sleeping quality (OR = 1.185, 95% CI = 1.038–1.354) had increased risk of T2DM. Conclusions: Eating and fasting windows, late last meal timing, hours of night sleep, late bedtime onset, and poorer sleep quality are significantly associated with T2DM risk among FTO rs9939609 risk carriers and may reflect metabolic vulnerability associated with FTO risk alleles. These findings highlight potential behavioral modification to attenuate genetic risk and provide evidence for actionable prevention strategies in genetically predisposed populations. Full article

Cardiovascular disease remains the leading cause of death and disability worldwide. Coronary artery disease is the most common clinical manifestation. The underlying pathology is largely attributable to atherosclerosis, a chronic inflammatory process that results in the development of atherosclerotic plaques. Coronary artery disease may present as chronic coronary syndrome or acute coronary syndrome, depending on the extent and stability of plaque disruption. The risk of cardiovascular events is modulated by established clinical and metabolic factors, and risk stratification frameworks are provided by international guidelines. Patients undergoing percutaneous coronary intervention are classified as being at very high cardiovascular risk, despite improvements in invasive and non-invasive management. In this population, the residual ischemic risk remains a significant concern, underscoring the need for targeted secondary prevention strategies. The secondary prevention addresses modifiable risk factors, including hypertension, dyslipidemia, diabetes mellitus, overweight and obesity, and tobacco use, along with recommendations for lifestyle modification. Nonetheless, current interventions leave a substantial proportion of patients exposed to future events, indicating a persistent unmet therapeutic need. Emerging evidence highlights the critical roles of lipid metabolism, inflammation, and metabolic dysfunction in the residual risk pathophysiology. This narrative review aims to examine pharmacological strategies targeting metabolic pathways, notably obesity and diabetes, in the context of secondary cardiovascular prevention in patients undergoing percutaneous coronary intervention. Full article

Background/Objectives: Globally, type 2 diabetes mellitus (T2DM) accounts for about 90% of diabetes cases and contributes to hospital admissions and mortality in Malaysia. Identifying the determinants of in-hospital mortality is crucial for improving clinical management and resource allocation. This study aims to determine the clinical and disease-related determinants of in-hospital mortality among T2DM-related admissions in a tertiary teaching hospital. Methods: A cross-sectional study at Hospital Canselor Tuanku Muhriz (HCTM) in Kuala Lumpur involving 2838 T2DM-related admissions from the hospital casemix database. Demographic data, complications, disease group, length of stay, and number of diagnoses were analyzed. Logistic regression assessed factors associated with in-hospital mortality among T2DM-related admissions. Results: The in-hospital mortality rate among T2DM-related admissions was 4.2%. T2DM-related admissions resulting in in-hospital death involved individuals with a higher mean age (67.72 years, SD 12.06) compared to admissions that did not result in death (65.11 years, SD 11.03). Significant determinants of mortality included infections and parasitic diseases (aOR = 8.042; 95% CI: 2.999, 21.569; p < 0.001), respiratory system (aOR = 3.004; 95% CI: 1.192, 7.571; p = 0.020), hepatobiliary/pancreatic (aOR = 3.674; 95% CI: 1.143, 11.871; p = 0.029), and central nervous system (aOR = 3.484; 95% CI: 1.236, 9.826; p =0.018) conditions, and severity level 3 (aOR = 2.994; 95% CI: 1.464, 6.221; p = 0.003). Each additional diagnosis increased the mortality risk (aOR = 1.107; 95% CI: 1.032, 1.189; p = 0.005). Conclusions: Mortality among hospitalized T2DM-related admissions is driven by severe infections, respiratory, hepatobiliary, and neurological conditions, together with overall disease burden. Early identification of high-risk clinical presentations and a timely multidisciplinary approach may reduce preventable deaths among T2DM patients. Full article

Background and Objectives: The combination of resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) accelerates the development of chronic kidney disease (CKD), which may be largely associated with sympathetic hyperactivity. Distal renal denervation (dRDN) effectively reduces sympathetic flow to the kidneys, causing renal vasodilation and increased renal perfusion. However, this effect may be limited by nephrotoxicity due to the multiple increase in the number of contrast injections, as well as a significant blood pressure (BP) reduction, which naturally worsens renal perfusion. This study aimed to test the hypothesis that dRDN prevents the progressive decline in kidney function in patients with RHTN and T2DM. Materials and Methods: The prospective interventional study (REFRAIN, NCT04948918) included men and women > 20 y.o. with true RHTN. Eligible patients underwent dRDN. The primary endpoint was a change in eGFR from baseline to 12 months. Secondary endpoints were changes in 24 h BP, serum lipocalin-2, cystatin C, 24 h urinary albumin excretion, renal blood flow, and kidney volumes (by MRI). Multiple regression analysis was used to find independent predictors of individual estimated glomerular filtration rate (eGFR) change. Results: A total of 29 patients with RHTN and T2DM were included in the study (61.6 ± 7.2 y.o., 10 males, mean 24 h ambulatory BP: 158.1 ± 21.4/81.8 ± 12.4 mmHg (systolic/diastolic, respectively)), HbA1c: 7.8 ± 1.4%, and eGFR 56.7 ± 19.9 mL/min/1.73 m², 23 (79%) patients with CKD, and 2 patients with albuminuria only. There were no perioperative complications. Twenty-seven (93%) participants completed 12 month follow-up. eGFR did not change from baseline: +1.3 mL/min/1.73 m² [95% CI: −9.6, 12.1], despite the expected decrease due to a significant decrease in 24 h systolic BP (−18.2 mmHg [95% CI: −28.6, −7.8]). No changes in other secondary endpoints were observed. Independent predictors of individual eGFR change were baseline 24 h pulse pressure (p = 0.030) and HbA1c (p = 0.010). Conclusions: Distal RDN demonstrates a substantial nephroprotective effect in patients with RHTN and T2DM, which may be partly mediated by a reduction in arterial stiffness and is negatively dependent on baseline hyperglycemia. Full article

Background/Objectives: Inflammation may play a critical role in the pathogenesis of gestational diabetes mellitus (GDM). However, evidence linking early-pregnancy cytokines to subsequent GDM risk remains inconsistent, with most prior research focusing only on CRP, IL6, and TNFα. In this study, we expand on prior work by evaluating a broader range of immune markers and assessing sociodemographic factors as potential moderators. Methods: Data from a prospective U.S. pregnancy cohort (n = 308) were analyzed. Twenty cytokines were quantified in maternal first-trimester plasma using the MILLIPLEX High-Sensitivity Human Cytokine Magnetic Bead Panel. One-hour oral glucose (50 g) tolerance test (OGTT) values assessed at an average gestational age of 27.7 weeks (SD = 2.9) and GDM diagnosis were abstracted from medical records. Multivariable linear and logistic regression models were used to examine associations between cytokines and 1 h 50 g OGTT levels or GDM diagnosis, adjusting for key sociodemographic factors. Interactions terms were included to evaluate whether sociodemographic factors moderated cytokine–GDM relationships. Results: Sixteen women (5.1%) were diagnosed with GDM. Higher first-trimester high-sensitivity-IL6 levels were significantly associated with increased 1 h 50 g OGTT values (b = 3.76; 95% CI: 0.21, 7.32; p = 0.04) and greater odds of GDM (OR = 2.36; 95% CI: 1.17, 4.77; p = 0.02). These associations were more pronounced among Non-Hispanic White women compared to Non-Hispanic Black women (p for interaction = 0.03) and potentially those with normal weight or underweight during early pregnancy compared to overweight or obese women (p for interaction = 0.08). Conclusions: Elevated inflammatory markers, particularly high-sensitivity IL6, in early pregnancy are linked to impaired glucose metabolism and increased GDM risk later in pregnancy. These relationships appeared stronger in Non-Hispanic White women and women with normal weight or underweight during early pregnancy, underscoring the potential to develop serology-based early identification and prevention strategies. Full article

Pediatric tuberculosis (TB) remains a critically underrecognized contributor to global childhood morbidity and mortality, with the highest burden concentrated in low-resource settings. Although children comprise a minority of overall TB cases, mortality is disproportionately high, particularly among those under five years of age, driven largely by delayed diagnosis, inadequate linkage to care, and limited access to effective treatment. The continued rise of pediatric multidrug-resistant TB (MDR-TB), especially in regions with low sociodemographic development, further highlights persistent gaps in current control strategies. This review synthesizes key aspects of pediatric TB pathogenesis and host immune responses that predispose young children to rapid disease progression and severe outcomes, including immune immaturity and paucibacillary infection. We summarize pulmonary and extrapulmonary disease manifestations and identify populations at heightened risk, including children with HIV, malnutrition, type 1 diabetes mellitus, and congenital or treatment-related immunosuppression. Ongoing challenges in diagnosis and treatment are discussed, including limitations of existing microbiologic and immunologic tests, specimen collection constraints, regimen toxicity, and barriers to adherence. Prevention remains central to reducing pediatric TB mortality. We highlight the sustained importance of bacille Calmette–Guérin (BCG) vaccination in preventing severe disease and death, the context-dependent variability in vaccine effectiveness, and the structural and socioeconomic determinants of vaccine coverage. We conclude that integrating equitable vaccine delivery, scalable preventive therapy, and child-adapted diagnostic strategies is essential to meaningfully reduce the global pediatric TB burden. Full article

Diabetic retinopathy (DR) remains the leading cause of preventable blindness among working-age adults worldwide, driven by the growing prevalence of diabetes mellitus. The aim of this comprehensive literature review is to provide an insightful analysis of recent advances in the pathogenesis of DR, followed by a summary of emerging technologies for its diagnosis and treatment. Recent studies have explored the roles of cell death pathways, immune activation, and lipid peroxidation in the pathology of DR. However, at the core of DR pathology lies neovascularization driven by vascular endothelial growth factor (VEGF), and mitochondrial damage due to dysregulated oxidative stress. These dysregulated pathways manifest clinically as DR, with specific subtypes including non-proliferative DR, proliferative DR and diabetic macular edema, which can be diagnosed through various imaging modalities. Recently, novel advances have been made using liquid biopsy and artificial (AI)-based algorithms with the goal of transforming DR diagnostics. AI models show distinct promise with the capacity to provide automated interpretation of retinal imaging. Furthermore, conventional anti-VEGF injectable agents have revolutionized DR treatment in the past decades. Today, as the pathogenesis of DR becomes better understood, new pathways, such as the ROS-VEGF loop, are being elucidated in greater depth, enabling the development of targeted therapies. In addition, new innovations such as intravitreal implants are transforming the delivery of DR-specific medication. This paper will discuss the current understanding of the pathogenesis of DR, which is leading to new diagnostic and therapeutic tools that will transform clinical management of DR. Full article

Background/Objectives: This study aimed to identify risk factors for postoperative wound infections and healing disorders in patients with brain tumors, based on a large, single-center analysis, and to establish an evidence-based foundation for prevention. Methods: A retrospective analysis was conducted on 1480 patients who underwent intracranial tumor resection in our department over a ten-year period, without the influence of anticoagulant or antiplatelet medication. Potential predictors of wound healing disorders were evaluated, focusing on demographic variables and pre-existing conditions. Results: Among the 1480 patients, postoperative wound infections occurred in 47 cases, corresponding to a cumulative incidence of 3.17%. Platelet count (p = 0.018) and partial thromboplastin time (p = 0.011) emerged as potential risk factors for postoperative wound infections. Length of hospital stay appeared as a distinct outcome-associated marker in cases of postoperative wound infection (p = 0.018). In contrast, demographic characteristics (age, sex, blood type), comorbidities (hypertension, diabetes mellitus, cardiovascular disease, kidney disease, chronic inflammatory conditions), and other surgical or laboratory parameters showed no significant association with wound healing disorders. Conclusions: In patients with brain tumors undergoing surgery without the influence of anticoagulant or antiplatelet therapy, most demographic factors, common comorbidities, and selected laboratory parameters were not associated with an increased risk of postoperative wound infections. Awareness of the identified risk factors may help guide preventive strategies and nursing care. Full article

Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy associated with significant short- and long-term risks for both mother and offspring. Increasing evidence indicates that genetic susceptibility plays a central role in GDM pathogenesis, particularly through variants affecting insulin secretion and pancreatic β-cell function. This narrative review integrates molecular, clinical, and epidemiological perspectives, highlighting population-specific effects and gene–environment interactions. Improved understanding of the genetic risk architecture may support earlier risk stratification and enable the future development of personalized strategies for GDM prevention and management, with particular emphasis on genetic polymorphisms in SLC30A8, CDKAL1, and HHEX genes consistently implicated in glucose homeostasis and β-cell integrity. These genes contribute to distinct but complementary molecular pathways underlying GDM, including impaired insulin biosynthesis, defective zinc transport within insulin granules, and altered paracrine regulation within pancreatic islets. While associations between these variants and GDM have been repeatedly demonstrated, their clinical relevance and mechanistic impact remain incompletely understood. Available evidence suggests that CDKAL1 represents the strongest genetic determinant, followed by SLC30A8, while HHEX appears to play a modulatory role. This review summarizes current findings on the molecular functions and clinical significance of these polymorphisms, highlighting population-specific effects and gene–environment interactions. Improved understanding of genetic risk architecture may support earlier risk stratification and enable future development of personalized strategies for GDM prevention and management. Full article

Background and Objectives: Acute and obstructive pyelonephritis (AOP) management, despite advancements in diagnostic imaging and antimicrobial therapy, is characterized by delayed recognition and increasing antimicrobial resistance. This review aimed to summarize current evidence regarding the clinical characteristics, microbiological spectrum, biomarkers, and imaging findings associated with AOP. Materials and Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251162736). Literature searches were performed across the PubMed, Scopus, and Web of Science databases for articles published between January 2014 and 31 March 2025 using the term “acute obstructive pyelonephritis”. Inclusion criteria comprised original full-text English-language studies, published in the last 10 years and conducted in adults, reporting clinical, laboratory, microbiological, and imaging characteristics. Exclusion criteria are letters to the editor, expert opinions, case reports, conference or meeting abstracts, reviews, and redundant publications; having unclear or incomplete data; and being performed on cell cultures or on mammals. The quality of included studies was assessed using the Newcastle–Ottawa Scale. Results: Twenty-three studies met the inclusion criteria. AOP predominantly affected elderly patients with comorbidities, especially diabetes mellitus and urinary tract obstruction. Predictors of septic shock included thrombocytopenia, hypoalbuminemia, elevated procalcitonin (>1.12 µg/L), presepsin, and a neutrophil-to-lymphocyte ratio ≥ 8.7. Escherichia coli remained the leading pathogen (60–95%) with extended-spectrum β-lactamase (ESBL) rates between 20 and 70%, followed by Klebsiella pneumoniae. CT demonstrated 71–100% sensitivity for detecting obstructive complications, confirming its superiority over ultrasound, while MRI provided comparable diagnostic accuracy in selected cases. Source control through double-J stenting or percutaneous drainage significantly improved survival. Conclusions: AOP requires prompt recognition and early decompression to prevent sepsis-related mortality. Biomarkers such as procalcitonin, presepsin, and neutrophil to lymphocyte ratio enhance risk stratification, while CT remains the gold-standard imaging modality. The increasing prevalence of ESBL-producing pathogens underscores the need for antimicrobial stewardship and individualized therapeutic strategies guided by local resistance data. Full article

Neonatal Diabetes Mellitus (NDM) is a rare, heterogeneous monogenic disorder typically presenting within the first six months of life. Unlike type 1 or type 2 diabetes, NDM is caused by single-gene mutations that disrupt pancreatic β-cell function or development. With the advent of next-generation sequencing, the genetic spectrum of NDM has expanded significantly, necessitating a shift from symptomatic management to precision medicine. This narrative review summarizes the genetic basis and pathogenic mechanisms of NDM, categorizing them into three major pathways: (1) ATP-sensitive potassium (K_ATP) channelopathies (e.g., ABCC8, KCNJ11), where gain-of-function mutations inhibit insulin secretion; (2) Transcription factor defects (e.g., GLIS3, PAX6, GATA6), which impair pancreatic development and often present with syndromic features; and (3) Endoplasmic reticulum (ER) stress-mediated β-cell apoptosis, exemplified by WFS1 mutations. Furthermore, we highlight the clinical complexity of these mutations, including the “biphasic phenotype” observed in ABCC8 and HNF1A variants. Understanding these molecular mechanisms is critical for clinical decision-making. We discuss the transformative impact of genetic diagnosis in treatment, particularly the successful transition from insulin to oral sulfonylureas in patients with K_ATP channel mutations, and emphasize the importance of early genetic testing to optimize glycemic control and prevent complications. Full article

Type 2 Diabetes Mellitus (T2DM) is a recognized risk factor for Alzheimer’s Disease (AD), as epidemiological research indicates that those with T2DM have a markedly increased risk of experiencing cognitive decline and dementia. Chronic hyperglycemia and insulin resistance in T2DM hinder cerebral glucose metabolism, reducing the primary energy source for neurons and compromising synaptic function. Insulin resistance impairs signaling pathways crucial for neuronal survival and plasticity, while high insulin levels compete with amyloid-β (Aβ) for breakdown by insulin-degrading enzyme, promoting Aβ buildup. Additionally, vascular issues linked to T2DM impair blood–brain barrier functionality, decrease cerebral blood flow, and worsen neuroinflammation. Elevated oxidative stress and advanced glycation end-products (AGEs) in diabetes exacerbate tau hyperphosphorylation and mitochondrial dysfunction, worsening neurodegeneration. Collectively, these processes create a robust biological connection between T2DM and AD, emphasizing the significance of metabolic regulation as a possible treatment approach for preventing or reducing cognitive decline. Here, we review the relationship between T2DM and AD and discuss the roles insulin, hyperglycemia, and inflammation therapeutic strategies have in successful development of AD therapies. Additionally evaluated are recent therapeutic advances, especially involving the polyflavonoid anthocyanin, against T2DM-mediated AD pathology. Full article