Diabetic retinopathy (DR) is a major ocular microvascular complication of diabetes mellitus and one of the leading causes of vision loss among working-age populations worldwide. Hyperglycemia-induced metabolic dysregulation has been regarded as a central mechanism underlying DR; accumulating evidence indicates that biomechanical remodeling of the retinal microenvironment also plays an important role in disease progression. Advanced glycation end products (AGEs) serve as key mediators linking metabolic stress to alterations in mechanical signaling. Through non-enzymatic glycation and covalent crosslinking of long-lived proteins, AGEs promote extracellular matrix stiffening, basement membrane thickening, and retinal vascular rigidity. These mechanical alterations can be sensed by retinal vascular cells through mechanotransduction pathways such as Piezo1, YAP/TAZ, and RhoA/ROCK signaling. Aberrant mechanical signals may further exacerbate oxidative stress, inflammatory responses, blood-retinal barrier disruption, vascular dysfunction, and pathological neovascularization. This review summarizes the role of AGEs in DR from an integrated metabolic-mechanical perspective and discusses therapeutic strategies targeting AGEs, providing new insights into potential interventions aimed at biomechanical abnormalities.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder influenced by environmental and genetic factors. The TGF-β1 codon 10 T > C polymorphism has been investigated as a potential genetic factor for T2DM, but evidence from African populations, particularly Ethiopia, remains limited. This study aimed to assess the association between TGF-β1 codon 10 T > C polymorphism and T2DM among patients attending Injibara Comprehensive Hospital, Northwest Ethiopia.

A case-control study was conducted among 230 participants (115 T2DM cases and 115 controls). Sociodemographic, behavioral, and clinical data were collected using a structured questionnaire. DNA was extracted from blood samples, and TGF-β1 codon 10 T > C polymorphism was genotyped using ARMS-PCR. Associations were assessed using bivariate and multivariable logistic regression.

The TC genotype was significantly associated with higher odds of T2DM compared with the TT genotype (AOR = 3.326, 95% CI: 1.009-10.969, p = 0.048). The C allele was also associated with higher odds of T2DM (AOR = 2.361, 95% CI: 1.231-4.528, p = 0.010). However, the CC genotype was not significantly associated with T2DM (p = 0.739). Overweight BMI, elevated blood pressure, and alcohol consumption were also significantly associated with T2DM.

The TGF-β1 codon 10 TC genotype and C allele were associated with T2DM in this study, whereas the CC genotype was not significantly associated. These findings should be interpreted cautiously and require confirmation in larger studies.

Astute observers of health systems are aware that worldwide there is a clinical trend toward integrative and personalized models. Ayurveda, inherently by its theory and practice, a personalized system of healthcare. Evidence from Ayurvedic clinical settings shows its effectiveness in managing chronic diseases; however, a lack of comprehensive multi-centric and retrospective clinical data hampers the credibility of Ayurveda within research circles. Traditional research, particularly Randomized Controlled Trials (RCTs), is deemed unsuitable for evaluating Ayurveda because these trials focus on standardized interventions and do not account for the personalized and multifaceted nature of Ayurvedic practices. This study intends to demonstrate that routine electronic medical record (EMR) data can effectively be transformed into actionable real-world evidence to support Ayurvedic management of chronic conditions.

Analysis was done using digitized Electronic Medical Records (EMR) Practo Insta, from the Institute of Ayurveda and Integrative Medicine, Bengaluru (and IIHNO Indore). Five clinical areas were assessed: Cancer (n = 36), Oral Mucositis (n = 89), Psoriasis (n = 38), Diabetes Mellitus (n = 65), and Infertility (n = 65). We used standardized metrics, including EORTC QLQ-C30, WHO Oral Mucositis grades, PASI, DLQI, and HbA1C, to measure outcomes.

Improvements were observed across all clinical areas. In oncology, global QoL increased by 17%, functional scores rose by 10%, and symptomatic burden dropped by 48%. In Oral Mucositis, at the primary 3-week endpoint 57.3% (51/89) of AGR patients achieved complete Grade 0 resolution versus 0% in PBMT. In Psoriasis, 76.3% of patients showed PASI improvement, and 92.1% reported better QoL. Diabetic participants exhibited noticeable reductions in blood glucose levels, with 85% reporting improved QoL. In infertility management, 58% of female participants successfully conceived within an average of 6 months, alongside improvements in secondary fertility and follicular parameters.

Integrating Ayurveda into mainstream healthcare requires a decisive shift toward robust, data-driven evidence. Evaluating personalized, multi-component interventions solely through conventional RCTs is limited, making the systematic use of Real-World Data (RWD) both necessary and appropriate. Standardizing routine EMR data translates nuanced Ayurvedic assessments into quantifiable metrics, bridging the epistemological gap between ancient clinical wisdom and modern scientific rigor to build the long-term evidence base.

Cyclic Cushing syndrome (CCS) is a rare subtype of Cushing syndrome (CS) characterized by hypercortisolism alternating with periods of physiologic or even low cortisol secretion. Most patients with CCS present with clinical signs of CS; however, in some patients, signs of hypercortisolism may be subtle or even absent. The fluctuating clinical picture and discrepant biochemical findings make CCS difficult to diagnose. We describe a case of a 70-year-old man with well-controlled type 2 diabetes mellitus who experienced recurrent, spontaneous hypercortisolemic episodes resulting in worsening and difficult-to-control hyperglycemia, followed by eucortisolemic phases during which his glycemic control rapidly returned to baseline. Further biochemical evaluation revealed intermittent hypercortisolemia without a clearly identifiable source of an adrenocorticotropic hormone secreting lesion. Data from his continuous glucose monitoring system (CGMS) proved pivotal in detecting the hypercortisolemic phases and tailoring management. After declining bilateral adrenalectomy and opting for a block-and-replace regimen with osilodrostat and hydrocortisone, he was able to anticipate and initiate this treatment based on his CGMS readings, facilitating improved glycemic control during these periods. This case highlights the diagnostic complexity of CCS and the utility of CGMS as both a monitoring tool and treatment guide for CCS in patients with concurrent type 2 diabetes mellitus.

This study investigated potential plasma biomarkers associated with cancer risk and mortality in patients with type 2 diabetes mellitus (T2DM), a population known to have an increased cancer incidence and poorer outcomes compared with non-diabetic individuals. Traditional metabolic indicators, including blood pressure, blood glucose and blood lipids, have limited predictive value for cancer risk, highlighting the need for novel clinical biomarkers. In total, 141 subjects with T2DM were enrolled in this study. Plasma inflammatory and lipid-related biomarkers included cluster of differentiation 147 (CD147), cyclophilin A (CyPA), cytokines, oxidized low-density lipoprotein (oxi-LDL), oxi-LDL antibody and proprotein convertase subtilisin/kexin type 9 (PCSK9). Among all participants, 37.6% were obese (body mass index ≥27 kg/m²). During 10 years of follow-up, all-cause mortality reached 35% and cancer incidence was 16%. Obese diabetic patients exhibit elevated oxi-LDL, soluble intercellular adhesion molecule-1, PCSK9, CD147 and CyPA levels. Deceased patients had a higher incidence of cancer and significantly lower plasma CD147 levels than surviving patients. Receiver operating characteristic curve analysis identified PCSK9 as a potential predictor of cancer occurrence in obese individuals with T2DM [area under the curve (AUC)=0.726], whereas CD147 showed modest predictive value in non-obese patients with diabetes (AUC=0.665). These findings suggest that plasma PCSK9 and CD147 may be associated with cancer occurrence in specific subgroups of patients with T2DM. However, larger prospective studies are required to confirm these associations and to further evaluate their potential value in cancer risk assessment.

Pregnancy is a unique physiological stage characterized by the coordinated remodeling of maternal metabolism, immunity, and endocrine systems. Previous studies have primarily focused on the local uterine microenvironment, neglecting the role of the maternal gut microbiota in mediating distal, cross-organ regulation via the gut-placental axis. The concept of the gut-placental axis was formally proposed in 2018 and has attracted widespread research attention in recent years. Studies using germ-free animals, fecal microbiota transplantation (FMT), and in vitro experiments with human multi-omics cohorts suggest that live gut bacteria generally cannot colonize the placenta, and that soluble microbial metabolites mediate bidirectional signaling between the gut and the placenta. Pregnancy-related factors such as a high-sugar, high-fat diet, antibiotic use, and obesity can induce gut microbiota dysbiosis and intestinal barrier dysfunction, leading to decreased levels of potentially protective metabolites such as short-chain fatty acids (SCFAs) and tryptophan derivatives, while pro-inflammatory molecules such as lipopolysaccharide (LPS), and trimethylamine N-oxide (TMAO) to accumulate in the bloodstream. These substances cross the placental barrier, disrupting maternal-fetal immune homeostasis, inhibiting trophoblast function and spiral artery remodeling, and are statistically associated with adverse pregnancy outcomes such as recurrent spontaneous abortion (RSA), preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and spontaneous preterm birth. This article is a narrative review that systematically elucidates the - placental axis for substance transport and the potential molecular mechanisms by which metabolites regulate maternal-fetal immune balance; it maps out the pathological pathways through which microbiota dysbiosis mediates various adverse pregnancy outcomes; it objectively analyzes controversies and gaps in areas such as placental microbial colonization, bidirectional feedback loops, and evidence for clinical interventions; and it proposes a future research framework centered on multi-omics candidate biomarkers and stratified microbiome interventions. Microbial metabolites are promising candidates for non-invasive biomarkers; stratified microbiome interventions are merely potential prevention and control strategies suggested by laboratory and small-scale clinical studies. There is still a lack of unified, standardized clinical protocols, and large-scale, long-term, randomized controlled trials (RCTs) are needed to validate their safety and efficacy, thereby providing a theoretical foundation for subsequent mechanistic and translational research on maternal-fetal microbiome interactions.

Background: Diabetes mellitus (DM) markedly increases the risk of coronary artery disease (CAD), and myocardial perfusion imaging (MPI) is a key noninvasive tool for risk stratification. Sex-based differences in presentation, referral patterns, and diagnostic accuracy of MPI remain understudied, particularly in Middle Eastern populations with a high prevalence of diabetes. This study evaluated sex-based differences in the indications, results, appropriateness, and diagnostic accuracy of MPI among diabetic Egyptian patients. Methods: This retrospective observational registry study included 1,000 diabetic adults (648 men, 352 women) who underwent gated SPECT-MPI at our university hospitals. Demographic data, risk factors, ECG findings, stress modalities, MPI results, coronary angiography data, and appropriate use criteria (AUC) were analyzed. Results: Men were older than women (59.6 ± 8.0 vs. 57.0 ± 9.4 years, p < 0.001). Hypertension was more prevalent in women (84.1% vs. 67.6%, p < 0.001), whereas smoking was more common in men (30.4% vs. 0.3%, p < 0.001). Positive MPI results were more frequent in men (77.0% vs. 43.2%, p < 0.001), as were appropriate indications (79.3% vs. 53.4%, p < 0.001); inappropriate and uncertain indications were correspondingly more common in women. Reversible perfusion defects did not differ significantly by sex (23.6% in women vs. 21.2% in men, p = 0.523), whereas fixed defects were more prevalent in men (17.0% vs. 7.8%, p < 0.001). MPI accuracy relative to coronary angiography did not differ significantly between the sexes (91.7% in men vs. 86.3% in women, p = 0.103). Conclusion: Substantial sex-based disparities exist in MPI referral patterns, test positivity, and appropriateness among diabetic Egyptians. Women are more likely to receive inappropriate referrals and to have a lower positive diagnostic yield, underscoring the need for sex-sensitive clinical protocols.

Gestational diabetes mellitus (GDM) is a common, inflammatory complication during pregnancy. Women who have GDM are more likely to develop metabolic or cardiovascular disease in the years post-delivery, as are their children. The umbilical cord and placenta provide a unique interface between maternal and foetal circulation and are richly vascularised. However, the molecular and cellular mechanisms that drive metabolic memory and cardiovascular dysfunction in GDM are incompletely understood. This article highlights the clinical presentation of cardiovascular disease post-GDM from mother and child. We investigate histological changes in the vasculature of the umbilical cord and the placenta, and the mechanistic changes in vascular smooth muscle cell and endothelial cell behaviour that may underpin clinical cardiovascular presentations. Finally we suggest areas for future research to increase mechanistic knowledge in this area, which may lead to new personalised medicine approaches for early intervention after delivery to minimise the long-term detrimental effect of GDM on cardiovascular health.

Background: Acute coronary syndrome (ACS) remains a leading cause of cardiovascular morbidity and mortality worldwide, with particularly poor outcomes in low-resource settings. Contemporary prospective data on short-term outcomes and their predictors remain scarce in Ethiopia. This study aimed to describe the clinical characteristics of patients with ACS, determine seven-day mortality, and identify independent predictors of seven-day mortality at Jimma University Medical Center, Southwest Ethiopia. Methods: A prospective hospital-based cohort study was conducted among 200 consecutive adult patients admitted with ACS between September 2024 and September 2025. Sociodemographic, clinical, laboratory, electrocardiographic, echocardiographic, treatment, and outcome data were collected using a structured case report form. Seven-day mortality was the primary outcome. Kaplan-Meier analysis was used to estimate survival probabilities, and bivariable and multivariable logistic regression analyses were performed to identify independent predictors of seven-day mortality. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) are reported, and statistical significance was defined as p < 0.05. Results: Among the 200 participants, 75.5% were male and 61.5% were urban residents. The median age was 58 years (interquartile range [IQR], 48-68 years). ST-segment elevation myocardial infarction was the predominant ACS subtype (78.0%), followed by non-ST-segment elevation myocardial infarction (11.5%) and unstable angina (10.5%). Overall, 60 patients (30.0%) died within seven days of admission. After adjustment for potential confounders, diabetes mellitus (AOR, 17.93; 95% CI [3.44-93.42]; p = 0.001), advancing age (AOR, 1.23 per year; 95% CI [1.11-1.38]; p < 0.001), higher baseline troponin concentration (AOR, 1.41 ng/mL; 95% CI [1.19-1.67]; p < 0.001), and Killip class IV at presentation (AOR, 69.50; 95% CI [4.54-1065.01]; p = 0.002) were independently associated with increased odds of seven-day mortality. Conclusion: Seven-day mortality among patients with ACS at Jimma University Medical Center was substantial. Advancing age, diabetes mellitus, elevated baseline troponin, and Killip class IV independently predicted seven-day mortality. These findings underscore the importance of early risk stratification, prompt recognition of hemodynamic compromise, and timely implementation of evidence-based management strategies to improve short-term outcomes in resource-limited settings.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disease worldwide, affecting nearly one-third of the global population and disproportionately impacting individuals with type 2 diabetes mellitus (T2DM) and obesity. The disease is driven by complex metabolic disturbances, including insulin resistance (IR), hepatic fat accumulation, oxidative stress, and chronic inflammation, which together promote progression from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and cirrhosis. Despite the growing burden of MASLD, therapeutic options remain limited and often constrained by cost, accessibility, or tolerability. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor originally developed for glycemic control in T2DM, has gained attention for its potential hepatoprotective effects. By inducing glucosuria and creating a caloric deficit, dapagliflozin promotes weight reduction, improves insulin sensitivity, and shifts energy metabolism toward fatty acid oxidation. These metabolic effects reduce hepatic de novo lipogenesis, attenuate oxidative stress, and may limit inflammatory pathways involved in MASLD progression. Emerging clinical evidence supports these mechanistic benefits. Prior randomized trials and observational studies have demonstrated improvements in liver enzymes, anthropometric parameters, and metabolic parameters, along with reduction in hepatic fat. Recent biopsy-based evidence, including findings from the DEAN trial, indicates significant improvements in histological endpoints of MASH. Collectively, current data suggest that dapagliflozin may offer a multifaceted therapeutic approach for MASLD by targeting both metabolic and hepatic pathways while providing established cardiovascular and renal benefits. Further large, multicenter trials involving diverse ethnicities, studying key histological endpoints as per regulatory guidance, may confirm these findings and define their role in the evolving treatment landscape of MASLD.