Reverse total shoulder arthroplasty (rTSA) is a widely used procedure for rotator cuff arthropathy, with indications expanding to include fractures, osteoarthritis, and revision arthroplasty. Obesity poses significant challenges in arthroplasty, yet the impact of morbid obesity (BMI ≥40 kg/m2) on rTSA outcomes remains underexplored. This study examines the association between morbid obesity and perioperative outcomes in rTSA patients using a large database.

We conducted a retrospective cohort study using the National Inpatient Sample (NIS) database from 2016 to 2019. Patients aged ≥18 years who underwent rTSA were stratified into morbidly obese (Morbid-Obesity (+)) and non-morbidly obese (Control) cohorts. Outcomes analyzed included demographic factors, length of stay (LOS), discharge disposition, and postoperative complications. Statistical analyses were performed using chi-squared tests, independent t-tests, and multivariate logistic regression to assess associations.

The study included 4850 Morbid-Obesity (+) patients and 55,075 Control patients. The Morbid-Obesity (+) cohort was younger (mean age: 67.74 vs. 71.67 years; p < 0.001) and more likely to be from minority groups, particularly Black patients (7.71 % vs. 3.94 %; p < 0.001). They had significantly longer LOS (mean: 2.23 vs. 1.87 days; p < 0.001) and higher rates of discharge to non-routine facilities. Major complications were more common in the Morbid-Obesity (+) cohort, including periprosthetic dislocation (2.60 % vs. 1.59 %; OR 1.65, p < 0.001), deep vein thrombosis (0.17 % vs. 0.07 %; OR 2.27, p = 0.03), blood loss anemia (11.61 % vs. 10.12 %; OR 1.17, p < 0.001), and acute renal failure (3.53 % vs. 2.11 %; OR 1.69, p < 0.001).

Morbid obesity is associated with higher complication rates, prolonged hospital stays, and increased non-routine discharge rates in rTSA patients. These findings underscore the need for tailored preoperative planning and postoperative management in this high-risk population.

Recent decades have described parallel neuropathological mechanisms increasing the risk for developing late-onset Alzheimer's dementia (LOAD) in type 2 diabetes mellitus (T2DM); however, still little is known of the role of diabetic encephalopathy and brain atrophy in LOAD. The aim of this systematic review is to provide a comprehensive view on diabetic encephalopathy/cerebral atrophy, taking into account neuroimaging data, neuropathology, metabolic and endocrine mechanisms, amyloid formation, brain perfusion impairments, neuroimmunology, and inflammasome activation. Key switches were identified, to further meta-analyze genomic candidate loci and epigenetic modifications. For the qualitative meta-analysis of genomic bases extracted, human linkage studies were examined; for epigenetic mechanisms, data from both human and animal studies are described. For the systematic review of pathophysiological mechanisms, 1,259 publications were evaluated and 93 gene loci extracted for candidate risk linkages. Sixty-six publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight the insulin signaling system, vascular markers, inflammation and inflammasome pathways, amylin interactions, and glycosylation mechanisms. The protocol was registered with PROSPERO (ID: CRD42023440535).

This study aimed to investigate the relationships among urine parameters, systemic inflammation and retinal microvascular changes in patients with type 1 diabetes mellitus (T1DM) without clinical signs of diabetic retinopathy (DR), via optical coherence tomography angiography (OCTA) and the systemic immune-inflammation index (SII).

A total of 64 participants, including 33 patients with T1DM and 31 healthy controls matched by age and sex, were examined. All the subjects underwent detailed eye assessments and OCTA imaging. Retinal and choroidal parameters were measured along with systemic markers such as C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), haemoglobin-A1C (HbA1c), spot urine tests and the SII. Relationships between systemic inflammation, renal and metabolic parameters, and ocular measurements were analyzed.

The T1DM group had significantly higher SII values (381.78 ± 57.30 vs. 284.86 ± 67.88, p < 0.001), HbA1c values (8.21 ± 1.80 vs. 5.15 ± 0.32, p < 0.001), spot microalbumin levels (13.50 ± 26.56 vs. 0.69 ± 0.57, p = 0.009), and albumin/creatinine ratios (0.13 ± 0.31 vs. 0.01 ± 0.01, p = 0.031). No significant differences in macular thickness, vascular density (VD), or foveal avascular zone (FAZ) area were detected between the groups. However, the mean retinal nerve fiber layer (RNFL) thickness and perifoveal ganglion cell complex (GCC) thickness were significantly lower in the diabetic group (p < 0.05). The SII was strongly positively correlated with choroidal thickness (r = 0.686, p < 0.001) and negatively correlated with parafoveal GCC thickness (r=-0.357, p = 0.041). HbA1c was negatively correlated with mean VD (r=-0.261, p = 0.037). No significant correlation was found between the SII and the FAZ or VD. Significant correlations were found between the mean vascular density and both the spot creatinine level (r = -0.527, p = 0.002) and the spot microalbumin level (r = -0.355, p = 0.043).

This study highlights the potential of the SII as a biomarker for detecting early subclinical retinal and choroidal changes in T1DM patients before the onset of retinopathy. The observed correlations among spot urine tests, the SII and OCTA parameters support the role of systemic inflammation in the early microvascular alterations associated with diabetes. These findings may contribute to early diagnosis and novel preventive strategies in DR. However, given the limited sample size, these findings should be interpreted with caution. Larger, well-stratified prospective studies are warranted to validate these preliminary observations.

The escalating prevalence of dementia worldwide necessitates preventive strategies to mitigate its extensive health, psychological, and social impacts. As the prevalence of dementia continues to rise, gaining insights into its risk factors and causes becomes paramount, given the absence of a definitive cure. Cardiovascular disease has emerged as a prominent player in the complex landscape of dementia. Preventing dyslipidaemia, unhealthy western-type diets, hypertension, diabetes, being overweight, physical inactivity, smoking, and high alcohol intake have the potential to diminish not only cardiovascular disease but also dementia. The purpose of this review is to present our current understanding of cardiovascular risk factors for Alzheimer's disease and vascular dementia (VaD) by using clinical human data from observational, genetic studies and clinical trials, while elaborating on potential mechanisms. Hypertension and Type 2 diabetes surface as significant causal risk factors for both Alzheimer's disease and VaD, as consistently illustrated in observational and Mendelian randomization studies. Anti-hypertensive drugs and physical activity have been shown to improve cognitive function in clinical trials. Important to note is that robust genome-wide association studies are lacking for VaD, and indeed more and prolonged clinical trials are needed to establish these findings and investigate other risk factors. Trials should strategically target individuals at the highest dementia risk, identified using risk charts incorporating genetic markers, biomarkers, and cardiovascular risk factors. Understanding causal risk factors for dementia will optimize preventive measures, and the implementation of well-known therapeutics can halt or alleviate dementia symptoms if started early. Needless to mention is that future health policies should prioritize primordial prevention from early childhood to prevent risk factors from even occurring in the first place. Together, understanding the role of cardiovascular risk factors in dementia, improving genome-wide association studies for VaD, and advancing clinical trials are crucial steps in addressing this significant public health challenge.

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related disorder that is associated with macrovascular diseases, such as coronary artery disease and stroke. However, the effects of CHIP on microvascular complication have not been explored in individuals with type 2 diabetes. We wanted to determine whether CHIP is associated with diabetic microvascular complications (DMCs). CHIP was associated with a high risk of DMCs, specifically, diabetic retinopathy and diabetic kidney disease, but not diabetic neuropathy. Gene-specific analyses suggested that some driver genes were associated with risk of developing DMCs. These findings indicated that CHIP may represent a novel risk factor for DMCs among individuals with type 2 diabetes, distinct from traditional risk factors, which may have implications for prevention and management of DMCs.

This study investigates the incidence, predictors, and preventive strategies for microvascular complications in type 2 diabetes patients in community settings.

Data were collected from 3,008 type 2 diabetes patients enrolled across 31 clinics in Beijing and Hebei. Prevalence and incidence of diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN) were assessed. Predictors were identified using XGBoost and Cox regression, and the impact of lifestyle and multifactorial interventions (MFI) was analyzed.

The prevalence of DKD, DR, and DPN were 39.5%, 26.2%, and 27.1%, respectively, with incidences of 74, 21, and 28 per 1000-person year. XGBoost identified that diabetes duration, age, HbA1c, FBG, triglyceride, BP, serum creatinine, proteinuria, aspirin and statin use were associated with those microvascular complications. The risk of DKD increased more rapidly as HbA1c exceeded 7.5% and decreased as blood pressure was maintained below 120/70 mmHg. Cox regression models showed that community-based intervention, including lifestyle modifications, were associated with a lower risk of DR and DPN. The study also found that higher variability in HbA1c and albumin-to-creatinine ratio (ACR) was associated with an increased risk of microvascular complications.

Community-based interventions significantly reduce the of DR and DPN, highlighting the need for individualized glycemic and BP management in primary care. The findings emphasize the importance of comprehensive management strategies to prevent the development and progression of microvascular complications in type 2 diabetes patients.

http://www.chictr.org.cn/, identifier ChiCTR-TRC-13003222.

Rationale: Hyperglycemia-induced endothelial dysfunction is a hallmark of diabetic cardiomyopathy, yet the underlying molecular mechanisms remain incompletely understood. This study aimed to investigate how the DNA damage response (DDR) pathway regulates endothelial cell ferroptosis under hyperglycemic conditions, potentially revealing new therapeutic targets for mitigating cardiac damage in type 2 diabetes mellitus (T2DM). Methods: We performed an integrated analysis of publicly available RNA sequencing datasets (GSE280770, GSE89475, GSE161931, CRA007245) to evaluate the role of DDR in hyperglycemia-induced endothelial dysfunction in vitro and in vivo, including in a T2DM mouse model. Key DDR and ferroptosis markers were validated in cardiac microvascular endothelial cells (CMECs) isolated from mice with streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM, with and without treatment with the DNA-PK inhibitors NU7441 or M9831. Results: Hyperglycemia induced a robust DDR in endothelial cells, characterized by the upregulation of DNA-PK complex genes (PRKDC, XRCC5, XRCC6) and increased markers of DNA damage (γH2AX, 8-oxo-dG). This was accompanied by increased expression of pro-ferroptotic genes (Tfrc, Acsl4, Ptgs2), decreased expression of anti-ferroptotic genes (Gpx4, Slc7a11), and elevated lipid peroxidation (MDA, 4-HNE). Pharmacological inhibition of DNA-PK mitigated these effects, reducing oxidative stress, lipid peroxidation, and endothelial permeability, while improving cardiac contractile and relaxation parameters. Conclusions: Our findings implicate the DNA-PK complex as a key regulator of hyperglycemia-induced endothelial ferroptosis in T2DM cardiomyopathy. Targeting DNA-PK complex may represent a novel therapeutic strategy for mitigating microvascular dysfunction and cardiac decline in T2DM.

The gut microbiota is closely associated with the onset and development of type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and chronic low-grade inflammation. However, despite the widespread use of first-line antidiabetic drugs, IR in diabetes and its complications continue to rise. The gut microbiota and its metabolic products may promote the development of T2DM by exacerbating IR. Therefore, regulating the gut microbiota has become a promising therapeutic strategy, with particular attention given to probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. This review first examines the relationship between gut microbiota and IR in T2DM, summarizing the research progress of microbiota-based therapies in modulating IR. We then delve into how gut microbiota-related metabolic products contribute to IR. Finally, we summarize the research findings on the role of traditional Chinese medicine in regulating the gut microbiota and its metabolic products to improve IR. In conclusion, the gut microbiota and its metabolic products play a crucial role in the pathophysiological process of T2DM by modulating IR, offering new insights into potential therapeutic strategies for T2DM.

Structure-function (SC-FC) coupling may be more sensitive to detecting changes in the brain than any single modality. The aim of this study was to investigate the effects of SC-FC coupling changes on cognition and their interactions in patients with prediabetes and type 2 diabetes mellitus (T2DM).

A total of 493 participants (119 with normal glucose metabolism (NGM), 125 with prediabetes, and 249 with T2DM) were included in the study. Diffusion-weighted MRI and resting state functional MRI data were used to quantify SC-FC coupling. General linear model and linear regression analysis were used to evaluate the relationship between glucose metabolism, SC-FC coupling, and cognition. Mediation models were used to evaluate the mediating role of regional SC-FC coupling between diabetes-related measures and cognition.

The regional coupling strength of SC-FC varied greatly in different brain regions, but was strongest in the ventral attention and somatmotor network areas. Compared with NGM patients, T2DM patients had higher SC-FC coupling in the default mode network but lower SC-FC coupling in the limbic network. In addition, fasting glucose and HbA1c were associated with weaker SC-FC coupling in the limbic network, fasting insulin with higher SC-FC coupling in the limbic network, and HbA1c with higher SC-FC coupling in the dorsal attention network. Furthermore, through mediated models we found that SC-FC coupling in the limbic network suppressed the association between diabetes-related measures and cognition.

T2DM and diabetes-related measures were associated with abnormal SC-FC coupling of the limbic network. The recombination of SC-FC coupling relationships in the limbic network may indicate a potential compensatory mechanism for cognitive decline that begins in prediabetes.

Purpose: To examine the association between diabetic retinopathy (DR) and the atherosclerotic cardiovascular disease (ASCVD) risk score using the "ASCVD Risk Estimator Plus" tool in patients with type 2 diabetes mellitus (DM) and to assess risk factors potentially associated with DR. Methods: Participants in the study included 181 patients with type 2 DM who underwent a thorough ophthalmic examination, including a best-corrected visual acuity (BCVA) measurement, a dilated fundoscopy, fundus photography, an optical coherence tomography (OCT), and an OCT-angiography (OCT-A). DR was graded as no apparent retinopathy (NDR), mild non-proliferative (NPDR), moderate NPDR, severe NPDR, or proliferative DR (PDR). In addition, a detailed medical history of patients was recorded, while the "ASCVD Risk Estimator Plus" tool by the American College of Cardiology was used to calculate the ASCVD risk. Results: The ASCVD score, derived by the "ASCVD Risk Estimator Plus", was not found to be significantly correlated with DR (p = 0.191). Multivariable logistic regression analysis showed that factors associated with DR independently included DM duration (multivariable OR = 3.16, 95% CI: 1.55-6.44, p = 0.002), HbA1c levels (multivariable OR = 2.94, 95% CI: 1.37-6.32, p = 0.006), and the presence of neuropathy (multivariable OR = 3.59, 95% CI: 1.43-9.05, p = 0.007). In the multivariable multinomial logistic regression analysis, NPDR development was associated with duration of DM (multivariable RR = 3.31, 95% CI: 1.57-6.97, p = 0.002), HbA1c levels (multivariable RR = 2.24, 95% CI: 1.00-5.02, p = 0.050), and neuropathy (multivariable RR: 3.94, 95% CI: 1.54-10.11, p = 0.004), while PDR development was only associated with HbA1c levels (multivariable RR = 6.88, 95% CI: 2.19-21.63, p = 0.001). Conclusions: The ASCVD score, as it was calculated using the "ASCVD Risk Estimator Plus" tool, was not found to be significantly associated with DR. Factors significantly associated with DR were DM duration, HbA1c levels, and the presence of neuropathy.

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes (T2D). Lipoprotein(a) [Lp(a)], a known cardiovascular risk factor, has been hypothesized to influence the development of DPN. This meta-analysis aimed to investigate the relationship between Lp(a) levels and DPN in patients with T2D.

Following PRISMA 2020 guidelines, a systematic search of PubMed, Embase, Web of Science, Wanfang, and CNKI databases was performed up to October 12, 2024. Observational studies assessing blood Lp(a) levels in T2D patients with and without DPN or evaluating the association between Lp(a) and DPN risk were included. Data synthesis utilized a random-effects model to calculate standardized mean differences (SMDs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs).

Eleven studies with 18,022 patients were included. Patients with DPN had significantly higher Lp(a) levels than those without DPN (SMD: 0.10, 95% CI: 0.02-0.19, p = 0.01; I² = 43%). High Lp(a) levels were associated with DPN (OR: 1.31, 95% CI: 1.07-1.60, p = 0.009; I² = 62%). Subgroup analyses according to study design, mean age of the patients, methods for measuring Lp(a) concentration, cutoff values of a high Lp(a), and study quality scores showed consistent results (p for subgroup difference all > 0.05). A high Lp(a) was associated with DPN in studies from Asian countries, but not in those from European countries (p for subgroup difference = 0.001).

Elevated Lp(a) levels are associated DPN in T2D patients, particularly in studies from Asian countries.

Recent research has raised concerns about the association between metformin treatment in patients with diabetes mellitus (DM) and an increased risk of diabetic retinopathy. We sought to investigate this relationship, specifically examining if metformin use affects diabetic retinopathy risk in a dose-dependent manner.

This study was a secondary data analysis based on a nationwide population database in Taiwan. Patients with new-onset DM, an age of 20 years or older, and a diagnosis of type 2 DM received at any time during 2002-2013 were included in the study. Patients diagnosed with new-onset type 2 DM between 2002 and 2013 were enrolled as the study population. We divided them into two groups: those treated with metformin and those treated with sulfonylureas. A Cox proportional hazards model was employed to estimate the risk of diabetic retinopathy after 5 years of follow-up, including cumulative defined daily dose and intensity of metformin treatment.

A total of 241,231 patients received treatment with metformin, while 152,617 patients were treated with sulfonylureas. Compared with patients treated with sulfonylureas, patients who received metformin treatment, at a cumulative defined daily dose < 30, had a lower risk of diabetic retinopathy (adjusted hazard ratio = 0.77; 95% confidence interval 0.60-0.98). However, those with varying defined daily doses, especially at a higher metformin treatment level (> 25 defined daily dose), had a 2.43 times higher risk of diabetic retinopathy (95% confidence interval 1.37-4.30) compared with patients treated with sulfonylureas.

Patients with DM treated with a lower cumulative dosage of metformin showed beneficial effects that were associated with a lower risk of diabetic retinopathy. In contrast, a higher intensity of metformin use had a greater risk of diabetic retinopathy.

Diabetes mellitus (DM) is a metabolic condition that is a profound health concern across the globe due to its contribution to the increased mortality rate. It affects millions of people around the world and is associated with severe complications among people diagnosed with it. Among the array of approaches used for the management of DM, inhibition of enzymes viz. α-amylase and α-glucosidase which are responsible for sugars hydrolysis is regarded as a feasible therapeutic protocol for the management of DM. Herein, we report the synthesis of benzylidenehydrazine derivatives as well as their evaluation as α-glucosidase and α-amylase inhibitors including their antioxidant testing. Generally, all the synthesized derivatives were more potent inhibitors of α-amylase than of α-glucosidase. Specifically, 2,4 fluoro substituted analogue 9 (IC50 =116.19 μM) emerged as the strongest α-amylase inhibitor with ~5-fold superior activity in comparison to the standard drug, acarbose (IC50 =600 μM). Compounds 18 (IC50 =240.59) and 19 (IC50 =198.32 μM) displayed the strongest NO scavenging activity compared to Trolox (IC50 =272.36 μM). In addition, the enzyme kinetic studies indicated that compound 9 acts as a non-competitive inhibitor of α-amylase. Finally, density functional theory and molecular docking studies for compound 9 were conducted to explore its structural and electronic properties as well as to determine protein-ligand interactions, respectively to decipher its observed activity. The obtained findings present promising possibilities for developing new drug candidates to control postprandial glucose levels in persons with diabetes.

Myocardial infarction (MI) and diabetes pose significant health challenges globally, necessitating the development of innovative medication strategies to improve outcomes in affected populations. This research aimed to determine the defensive impact of ferulic acid (FA) against isoproterenol-induced myocardial infarction (MI) in diabetic rats.

A group of male rats was partitioned into five distinct groups: control group, diabetic group, diabetic + MI, diabetic + MI + 20 mg/kg FA, and diabetic + MI + 40 mg/kg FA. The experimental groups received isoproterenol (ISO) subcutaneously at a dosage of 50 mg/kg body weight for two consecutive days.

The outcome was severe cardiac toxicity, as shown by changes in electrocardiogram (ECG) rhythm and a substantial increase in blood cardiac enzymes such as creatinine kinase (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Additionally, there was a surge in inflammatory cytokines, like tumor necrosis factor-alpha (TNF-α), and a disruption of the antioxidant system, evidenced by a rise in malondialdehyde (MDA) content. Moreover, there was a rise in cardiac receptor of advanced glycation end products (RAGE). Treatment with FA with escalating dosages of 20 and 40 mg/kg b.w. effectively mitigated changes in serum cardiac enzymes and improved the cellular architecture, which was evaluated by histopathological examination.

In conclusion, in a dose-dependent manner, FA successfully showed a cardioprotective effect against ISO-induced cardiac toxicity in diabetic rats, as shown by the improvement in ECG findings, normalization of serum cardiac biomarkers, and augmentation of the endogenous antioxidant system. Therefore, the aforementioned data indicate that ferulic acid may potentially have a protective effect on MI patients who have diabetes mellitus.

Objectives: This study aimed to explore the demographic and clinical features of tinnitus individuals and analyse its correlation with associated comorbidities. Methods: The study population comprised 147 participants (66 men, 81 women; median age: 52 years) who experienced persistent tinnitus. Comprehensive assessments were carried out, including audiological examinations, scoring using the Tinnitus Handicap Inventory, and thorough medical evaluations. Statistical analyses were applied to explore the correspondences between tinnitus, hearing loss, and various comorbidities, including cardiovascular conditions, metabolic disorders, gastroesophageal reflux disease, autoimmune diseases, pulmonary diseases, and allergic rhinitis. Results: The analysis indicated a slight predominance of females, comprising 55.1% of the participants, with a median onset of tinnitus around the age of 50. Chronic tinnitus was noted, lasting approximately 46 months. Hearing loss was noted in 52.4% of patients, with bilateral tinnitus being the most prevalent type, affecting 44.2% of individuals. Dyslipidaemia was found to significantly predict bilateral tinnitus (p = 0.003*) and left-sided tinnitus (p = 0.023*). Additionally, atherosclerosis was associated with hearing impairment (p = 0.006*) and right-sided tinnitus (p = 0.044*). Dyslipidaemia was also significantly correlated with elevated intensity values (p = 0.04*). Furthermore, atherosclerosis was significantly associated with higher levels of hearing loss (p < 0.00001*). Conclusions: The study emphasises the complex nature of tinnitus and its links to cardiovascular, metabolic, and other comorbidities, highlighting the necessity for comprehensive, interdisciplinary management.

Sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have emerged as a class of agents relevant for managing diabetic nephropathy and cardiopathy. In a previous report, we noticed that these drugs share, with other drugs with "nephroprotective" effects, the ability to reduce the glomerular filtration rate (GFR), thus suggesting the kidney hemodynamic effect as a proxy for optimal drug dosage. We also noticed that all known nephroprotective drugs exert cardioprotective functions, suggesting the possibility of activities not mediated by the kidney. Finally, we observe that nephroprotective drugs can be grouped according to their effects on hemoglobin levels, thus suggesting their mechanism of action. While the primary mechanism of SGLT2i involves glycosuria and natriuria, growing evidence suggests broader therapeutic effects beyond hemodynamic modulation. Specifically, the evidence that SGLT2 can be expressed in several atypical regions under pathological conditions, supports the possibility that its inhibition has several extratubular effects. Evidence supports the hypothesis that SGLT2i influence mitochondrial function in various cell types affected by diabetes, particularly in the context of diabetic nephropathy. Notably, in SGLT2i-treated patients, the extent of albumin-creatinine ratio (ACR) reduction post-treatment may be correlated with mitochondrial staining intensity in glomerular endothelial cells. This implies that the anti-proteinuric effects of SGLT2i could involve direct actions on glomerular endothelial cell. Our investigation into the role of SGLT2 inhibitors (SGLT2i) in endothelial function suggests that the aberrant expression of SGLT2 in endothelial cells in T2DM would lead to intracellular accumulation of glucose; therefore, SGLT2i are the first type of endothelial protective drugs available today, with potential implications for ageing-related kidney disease. The review reveals two major novel findings: SGLT2 inhibitors are the first known class of endothelial-protective drugs, due to their ability to prevent glucose accumulation in endothelial cells where SGLT2 is aberrantly expressed in Type 2 Diabetes. Additionally, the research demonstrates that SGLT2 inhibitors share a GFR-reducing effect with other nephroprotective drugs, suggesting both a mechanism for optimal drug dosing and potential broader applications in ageing-related kidney disease through their effects on mitochondrial function and glomerular endothelial cells.

Diabetes mellitus (DM) and its various complications, including diabetic nephropathy, retinopathy, neuropathy, cardiovascular disease, and ulcers, pose significant challenges to global health. This review investigates the potential of procyanidins (PCs), a natural polyphenolic compound, in preventing and managing diabetes and its complications. PCs, recognized for their strong antioxidant, anti-inflammatory, and anti-hyperglycemic properties, play a crucial role in reducing oxidative stress and enhancing endothelial function, which are essential for managing diabetic complications. This review elucidates the molecular mechanisms by which PCs improve insulin sensitivity and endothelial health, thereby providing protection against the various complications of diabetes. The comprehensive analysis underscores the promising therapeutic role of PCs in diabetes care, indicating the need for further clinical studies to confirm and leverage their potential in comprehensive diabetes management strategies.

The diabetic foot ulcer is among the most serious diabetes-associated complications, with a long disease course considerably increasing the pain and economic burden of patients, leading to amputation and even death. High blood sugar is characteristic of diabetic foot ulcers, with insufficient blood supply, oxidative stress disorder, and high-risk bacterial infection posing great challenges for disease treatment. Advances in hydrogel dressings have shown potential for the management of diabetic foot ulcers involving multisystem lesions. This study comprehensively reviews the pathogenesis of diabetic foot ulcers and advances in hydrogel dressings in treating diabetic foot ulcers, providing innovative perspectives for assessing the nursing care requirements and associated clinical applications.

Cognitive decline and late-onset dementia pose significant challenges in aging societies, and many dementia cases could be prevented or delayed through modification of associated risk factors, many of which are tied to cardiovascular and metabolic dysfunction. As individuals age, the blood-brain barrier becomes more permeable, easing the exchange of molecules between the bloodstream and the brain. Consequently, blood-based biological markers (so-called biomarkers) provide a minimally invasive and accessible means of accessing molecular changes associated with aging and neurodegeneration.

Circulating free fatty acids, also called nonesterified fatty acids (NEFAs), and sphingolipids are associated with cardiovascular disease, insulin resistance, and diabetes; thus, could be promising candidates as biomarkers for cognitive decline and dementia.

The opportunity to study such minimally invasive biomarkers further opens up potential new avenues for improved understanding of the underlying biology of diseases of the brain.

Identifying patterns of metabolic heterogeneity in type 2 diabetes (T2D) can help in the development of optimal treatment strategies. We aimed to identify metabolic patterns in patients with T2D in the Republic of Korea and analyze the risk of developing diabetes-related complications according to patterns. We identified three distinct metabolic patterns and observed that each pattern was associated with a heightened risk of developing various cardiovascular diseases. These findings highlight the necessity of devising treatment strategies based on these patterns to prevent diabetes-related complications.

To evaluate the knowledge, attitude and practice (KAP) regarding screening and managing diabetic microvascular complications, encompassing diabetic retinopathy (DR), diabetic kidney disease (DKD) and diabetic neuropathy (DN), among general practitioners (GPs).

Cross-sectional study.

The online questionnaire survey was conducted between April and July 2023.

GPs from community health centres (CHCs) in all 16 districts of Shanghai were recruited.

The data of sociodemographic characteristics, KAP scales, training experience and screening instruments for community screening and managing diabetic microvascular complications were collected. Multiple stepwise linear regression was used to explore the influencing factors of KAP. Restricted cubic spline curves with four knots (5%, 35%, 65%, 95%) were used to determine the association between KAP score and duration of general practice.

A total of 1243 questionnaires were included in the analysis. The total KAP score was 66.6±8.8/100, and the knowledge, attitude and practice scores were 64.7±8.7, 83.5±10.5 and 51.6+17.8, respectively. Male (β=-2.419, p=0.012), shorter practice duration (β=-1.033, p=0.031), practice in rural area (β=3.230, p=0.001), not attending training in diabetic microvascular complications (β=-6.346, p<0.001), not managing diabetic patients (β=-4.503, p<0.001), less number of diabetes patients under management (β=-0.007, p=0.035), less number of screening instruments based on self-report of GP (β=-1.681, p<0.001), lower knowledge score (β=-0.190, p<0.001) and lower attitude score (β=-0.414, p<0.001) were associated with lower practice score of GPs. The KAP total score increased with the working years of general practice; however, this effect was no longer observed in knowledge score after 15 years, while the attitude and practice scores showed a continuously increasing trend.

GPs showed insufficient knowledge and poor clinical practice on screening and managing diabetic microvascular complications. There is an urgent need to improve their capacity to provide better care for those with diabetic microvascular complications through targeted training.

Fatty acid metabolism, exercise, and insulin action play critical roles in maintaining vascular health, especially relevant in metabolic disorders such as obesity, type 2 diabetes, and cardiovascular disease. Insulin, a vasoactive hormone, induces arterial vasodilation throughout the arterial tree, increasing arterial compliance and enhancing tissue perfusion. These effects, however, are impaired in individuals with obesity and type 2 diabetes, and evidence suggests that vascular insulin resistance contributes to the pathogenesis of type 2 diabetes and its cardiovascular complications. Elevated plasma levels of free fatty acids in people with insulin resistance engender vascular inflammation, endothelial dysfunction, and vascular insulin resistance. Importantly, these effects are both functionally and structurally dependent, with saturated fatty acids as the primary culprits, while polyunsaturated fatty acids may support insulin sensitivity and endothelial function. Exercise enhances fatty acid oxidation, reduces circulating free fatty acids, and improves insulin sensitivity, thereby mitigating lipotoxicity and promoting endothelial function. Additionally, exercise induces beneficial vascular adaptations. This review examines the complex interplay among fatty acid metabolism, exercise training-induced vascular adaptations, and insulin-mediated vascular changes, highlighting their collective impact on vascular health and underlying mechanisms in both healthy and insulin-resistant states. It also explores the therapeutic potential of targeted exercise prescriptions and fatty acid-focused dietary strategies for enhancing vascular health, emphasizing tailored interventions to maximize metabolic benefits. Future research should investigate the pathways linking fatty acid metabolism to vascular insulin resistance, with a focus on how exercise and dietary modifications can be personalized to enhance vascular insulin sensitivity, optimize vascular health, and reduce the risks of type 2 diabetes and associated cardiovascular complications.

This study aimed to explore the association of globulin and albumin-to-globulin ratio (AGR) with diabetic kidney disease (DKD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).

This study used data from the China National Diabetic Chronic Complications Study in Shaanxi Province. From April to May 2019, T2DM patients at disease surveillance sites in Shaanxi Province were investigated using a stratified multi-stage sampling method. The participants completed questionnaire surveys, anthropometric and blood pressure measurements, laboratory tests, and fundus photograph examinations. Multivariate Logistic regression and restricted cubic spline model were used to analyze the association of globulin and AGR with DKD and DR, and subgroup analysis was performed according to age, sex, and diabetes duration to test the stability of the results.

A total of 1494 T2DM patients were enrolled in this study, including 495 patients with DKD (33.1%) and 341 patients with DR (22.8%). After adjusting for all covariates, globulin and AGR were linearly associated with DKD. For every 1g/L increase in globulin level, the risk of DKD increased by 7% (OR=1.07, 95% CI=1.04, 1.10). For every 1 unit increase in AGR, the risk of DKD was reduced by 55% (OR=0.45, 95% CI=0.28, 0.72). Subgroup analysis showed that the association between globulin and DKD was consistent across all subgroups, and the association between AGR and DKD was consistent across subgroups of age and diabetes duration; however, only in males, higher AGR was associated with a reduced risk of DKD. No association was found between globulin and AGR with DR.

Globulin is an independent risk factor and AGR is an independent protective factor for DKD. Screening for DKD should be performed in T2DM patients with high globulin and low AGR levels, especially in men.

Microcirculation is an essential system that regulates oxygen and nutrients to cells and tissues in response to various environmental stimuli and pathophysiological conditions. Diabetes mellitus can cause microvascular complications including nephropathy, neuropathy, and retinopathy. The pathogenesis of microvascular dysfunction in diabetes is associated with hyperglycemia and the result of an interplay of various factors. Research studies have demonstrated that functional microvascular dysfunction appears much earlier than structural alterations in vasculature in diabetes. This finding of the progression from microvascular dysfunction to macrovascular disease establishes a foundation for the screening and early diagnosis of diabetes by assessing the microvascular function. This comprehensive review discusses technologies (laser Doppler, transcutaneous oximetry, infrared thermography and near-infrared spectroscopy) with computational methods (linear (time and frequency domains), nonlinear and machine learning approaches) for diagnosing microvascular dysfunction in diabetes. Pathophysiological changes of microvascular dysfunction leading to impaired vasomotion and blood flow oscillations in diabetes are reviewed. Recent findings in managing microvascular dysfunction using lifestyle modifications and force-based modulations are evaluated. A consensus endorsed by the American Diabetes Association has been reached that an effective exercise program would greatly slow down the progression of microvascular dysfunction and its impact on diabetic foot ulcers, muscle fatigue and weakness and peripheral neuropathy. However, it is imperative to determine the dose-response relationship of exercise and microvascular responses in patients with diabetes. Research studies have demonstrated that local vibration and whole-body vibration can improve microcirculation in various pathological conditions, including diabetes. Due to the complex nature of microvascular regulation, various computational methods have been developed to shed light on the influence of diabetes on microvascular dysfunction. This comprehensive review will contribute to the diagnosis and management of microvascular dysfunction in diabetes.

Coronary microvascular dysfunction (CMD) is a significant complication in type 2 diabetes (T2D) and may be more common in women. We aimed to evaluate the sex differences and sex-specific clinical determinants of CMD in adults with T2D without prevalent cardiovascular disease.

Single center pooled analysis of four prospective studies comparing asymptomatic people with T2D and controls. All subjects underwent comprehensive cardiovascular phenotyping with myocardial perfusion reserve (MPR) quantified with perfusion cardiovascular magnetic resonance (CMR). Participants with silent coronary disease were excluded. Multivariable linear regression was performed to identify determinants of MPR with an interaction term for sex.

Four hundred and seventy-nine T2D (age 57 ± 11 years, 42% [202/479] women) were compared with 116 controls (age 53 ± 11 years, 41% [48/116] women). Men with T2D, but not women, demonstrated worse systolic function and higher extracellular volume fraction than controls. MPR was significantly lower in T2D than controls (women, 2.6 ± 0.9 vs 3.3 ± 1.0, p < 0.001; men, 3.1 ± 0.9 vs 3.5 ± 1.0, p = 0.004), and lower in women than men with T2D (p < 0.001). More women than men with T2D had MPR <2.5 (46% [79/202] vs 26% [64/277], p < 0.001). There was a significant interaction between sex and body mass index (BMI) for MPR (p interaction <0.001). Following adjustment for clinical risk factors, inverse association with MPR were BMI in women (β = -0.17, p = 0.045) and systolic blood pressure in men (β = -0.14, p = 0.049).

Among asymptomatic adults with T2D, women had a greater prevalence of CMD than men. Risk factors modestly but significantly associated with CMD in asymptomatic people with T2D were BMI among women and systolic blood pressure among men.

Non-coding RNAs (ncRNAs), such as microRNA, long non-coding RNA, and circular RNA, are considered essential regulatory molecules mediating many cellular processes. Moreover, an increasing number of studies have investigated the role of ncRNAs in cancers and various metabolic disorders, including diabetes mellitus. Interestingly, some circulating ncRNA detected in body fluids may serve as novel biomarkers. There is still a lack of conventional biomarkers that detect the early stage of type 1 diabetes mellitus. Many circulating microRNA, long non-coding RNA, and circular RNA show aberrant expression in type 1 diabetes patients compared to healthy individuals. However, most studies have focused on circulating microRNA rather than long non-coding RNA or circular RNA. In addition, a few studies have evaluated sex differences in ncRNA biomarkers. Therefore, this article summarises current knowledge about circulating ncRNAs as potential biomarkers for type 1 diabetes and explores the effects of sex on such biomarkers.

Fatty acid metabolism is pivotal for lipid synthesis, cellular signaling, and maintaining cell membrane integrity. However, its diagnostic significance in type 2 diabetes mellitus (T2DM) remains unclear.

Three datasets and fatty acid metabolism-related genes were retrieved. Differential expression analysis, WGCNA, machine learning algorithms, diagnostic analysis, and validation were employed to identify key feature genes. Functional analysis, ceRNA network construction, immune microenvironment assessment, and drug prediction were conducted to explore the underlying molecular mechanisms.

Six feature genes were identified with strong diagnostic performance and were involved in processes such as ribosome function and fatty acid metabolism. Immune cells, including dendritic cells, eosinophils, and neutrophils, may play a role in the progression of T2DM. ceRNA and drug-target network analysis revealed potential interactions, such as RP11-miR-29a-YTHDF3 and BPA-MSANTD1. The expression patterns of the feature genes, except for YTHDF3, were consistently upregulated in T2DM, aligning with trends observed in the training set.

This study investigated the potential molecular mechanisms of six fatty acid metabolism-related genes in T2DM, offering valuable insights that may guide future research and therapeutic development.

Prolonged hyperglycemic conditions in type 2 diabetes mellitus (T2DM) cause pathological and functional damage to many organs and tissues, including the kidneys, retina, skin, and neuronal tissues, resulting in the development of microvascular diabetic complications. The altered renin angiotensin aldosterone system (RAAS) pathway has been reported to play an important role in the development of insulin resistance in T2DM and associated complications. The current study was carried out to evaluate the association of risk factors and altered expression of RAAS genes in T2DM patients without complications and T2DM patients with complications (retinopathy, nephropathy, and neuropathy). Four hundred and twenty subjects including 140 healthy controls, 140 T2DM patients with diabetic complications, and 140 T2DM patients without diabetic complications were included in the study. Risk factors associated with the development of T2DM and diabetic complications were evaluated. Further, expression analysis of RAAS genes (AGT, ACE, ACE2, and AGT1R) was carried out using qRTPCR in healthy controls, T2DM patients with complications, and T2DM patients without complications. Various risk factors like urban background, higher BMI, alcoholism, smoking, and family history of diabetes among others were found to be associated with the development of T2DM as well as diabetic complications. The expression level of AGT, ACE, and AGT1R was found to be upregulated whereas ACE2 was found to be downregulated in T2DM patients with complications and T2DM patients without complications as compared to controls. Altered expression of the studied genes of RAAS pathway is associated with the development of microvascular diabetic complications.

Cellular senescence is a state of permanent cell cycle arrest and plays an important role in many vascular lesions. This study found that the cells of diabetic patients have more characteristics of senescence, which may cause microvascular complications. Cell senescence, as one of the common fates of cells, links microangiopathy and diabetes. Cell senescence in a high-glucose environment can partially elucidate the mechanism of diabetic microangiopathy, and various types of cellular senescence induced by it can promote the progression of diabetic microangiopathy. Still, the molecular mechanism of microangiopathy-related cellular senescence has not yet been clearly studied. Building on recent research evidence, we herein summarize the fundamental mechanisms underlying the development of cellular senescence in various microangiopathies associated with diabetes. We gradually explain how cellular senescence serves as a key driver of diabetic microangiopathy. At the same time, the treatment of basic senescence mechanisms such as cellular senescence may have a great impact on the pathogenesis of the disease, may be more effective in preventing the development of diabetic microangiopathy, and may provide new ideas for the clinical treatment and prognosis of diabetic microangiopathy.

Stem cells from various sources including major salivary glands have been used to establish pancreatic differentiation in an attempt to provide new treatment options for patients with diabetes mellitus. In contrast, the potential of using the more easily accessible intraoral minor salivary glands has not been evaluated so far.

Salivary stem cells were isolated from normal labial minor salivary glands that were removed during the excision of a mucocele and were attempted to differentiate into pancreatic cell lines using a culture medium enriched with activin A, retinoic acid and GLP-1.Real time RT-PCR was used to evaluate the expression of the genes of pancreatic transcription factors MafA, Ptf1a, Hb9 and Arx. Complementary, 22 labial minor salivary gland paraffin-embedded specimens were examined using immunohistochemistry for the presence of the relevant gene products of the pancreatic transcription factors Arx, MafA, Ptf1a and Pdx1.

The differentiated salivary stem cells(cells of passage 3) expressed the genes of the pancreatic transcription factors MafA, Ptf1a, Hb9 and Arx even on the first day of the experiment while immunohistochemistry also confirmed the presence of the protein products of Arx, MafA, Ptf1a as well as Pdx1[> 50% of the specimens for Arx(5/8) and MafA(7/8), < 50% for Ptf1a(5/11) and Pdx1(5/11)] in ducts, mesenchymal connective tissue and acinar cells.

Labial minor salivary glands may share gene and protein characteristics with pancreas suggesting a possible usefulness for pancreatic regeneration or substitution in cases of deficiency.

Irisin is an exercise-induced myokine that alleviates endothelial dysfunction and reduces insulin resistance in type 2 diabetes mellitus (T2DM). The current study aimed to assess the serum level of irisin in T2DM men with erectile dysfunction (ED) compared to T2DM patients with normal erectile function and healthy controls, as well as investigate the association between serum irisin level and the severity of ED in T2DM patients.

A cross-sectional study was conducted on 90 males, divided into three groups: 32 T2DM patients with ED, 24 T2DM patients without ED, and 34 healthy controls. Socio-demographic characteristics and scores of the validated Arabic version of the international Index of Erectile Function-5 (ArIIEF-5), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were obtained. Furthermore, routine laboratory tests employed for diabetes monitoring and serum levels of total testosterone and irisin were assessed within these groups.

T2DM men with ED had significantly lower serum levels of irisin and testosterone, as well as a lower ArIIEF-5 score, but their GAD-7 and PHQ-9 scores were significantly higher than those without ED or controls (p < 0.001). Among T2DM men, serum irisin levels positively associated with ArIIEF-5 scores and serum testosterone (r = 0.413, p = 0.002; r = 0.936, p < 0.001, respectively) but negatively associated with glycosylated hemoglobin levels (r = -0.377, p = 0.004). Multivariate regression analysis to predict ED in T2DM patients found that GAD-7 score was the only most significant predictor for ED (ꞵ = - 1.176, standard error = 0.062, p < 0.001).

The current study had demonstrated that irisin positively correlated with the ArIIEF-5 and serum testosterone but negatively correlated with HbA1c in T2DM men. Nevertheless, further validation of these findings is necessary through cohort studies.

This study aims to investigate the pathogenesis of hyperglycemia and its associated vasculopathy using multiomics analyses in diabetes and impaired glucose tolerance, and validate the mechanism using the cell experiments.

In this study, we conducted a comprehensive analysis of the metagenomic sequencing data of diabetes to explore the key genera related to its occurrence. Subsequently, participants diagnosed with impaired glucose tolerance (IGT), and healthy subjects, were recruited for fecal and blood sample collection. The dysbiosis of the gut microbiota (GM) and its associated metabolites were analyzed using 16S rDNA sequencing and liquid chromatograph mass spectrometry, respectively. The regulation of gene and protein expression was evaluated through mRNA sequencing and data-independent acquisition technology, respectively. The specific mechanism by which GM dysbiosis affects hyperglycemia and its related vasculopathy was investigated using real-time qPCR, Western blotting, and enzyme-linked immunosorbent assay techniques in HepG2 cells and neutrophils.

Based on the published data, the key alterable genera in the GM associated with diabetes were identified as Blautia, Lactobacillus, Bacteroides, Prevotella, Faecalibacterium, Bifidobacterium, Ruminococcus, Clostridium, and Lachnoclostridium. The related metabolic pathways were identified as cholate degradation and L-histidine biosynthesis. Noteworthy, Blautia and Faecalibacterium displayed similar alterations in patients with IGT compared to those observed in patients with diabetes, and the GM metabolites, tauroursodeoxycholic acid (TUDCA) and carnosine (CARN, a downstream metabolite of histidine and alanine) were both found to be decreased, which in turn regulated the expression of proteins in plasma and mRNAs in neutrophils. Subsequent experiments focused on insulin-like growth factor-binding protein 3 and interleukin-6 due to their impact on blood glucose regulation and associated vascular inflammation. Both proteins were found to be suppressed by TUDCA and CARN in HepG2 cells and neutrophils.

Dysbiosis of the GM occurred throughout the entire progression from IGT to diabetes, characterized by an increase in Blautia and a decrease in Faecalibacterium, leading to reduced levels of TUDCA and CARN, which alleviated their inhibition on the expression of insulin-like growth factor-binding protein 3 and interleukin-6, contributing to the development of hyperglycemia and associated vasculopathy.

Heart rate variability (HRV) is an important non-invasive marker for the assessment of an organism's autonomic physiological regulatory pathways. Lower HRV has been shown to correlate with increased mortality. HRV is influenced by various factors or diseases. The aim of this narrative review is to describe the current state of knowledge on factors influencing HRV and their significance for interpretation.

The narrative review only included reviews, meta-analyses, and cohort studies which were published until 2021. HRV confounders were grouped into four categories (non-influenceable physiological factors, diseases, influenceable lifestyle factors and external factors).

The review found that HRV was decreased not only in non-influenceable physiological factors (e.g., age, gender, ethnicity) but also in connection with various number of acute and chronic diseases (e.g., psychiatric diseases, myocardial infarction, heart failure), influenceable lifestyle factors (e.g., alcohol abuse, overweight, physical activity), and external factors (e.g., heat, noise, shift work, harmful- and hazardous substances).

In order to improve the quality of HRV studies and to ensure accurate interpretation, it is recommended that confounders be taken into account in future diagnostic measurements or measurements in the workplace (e.g., as part of health promotion measures) in order to counteract data bias.

The evidence about the acceptability and effectiveness of innovative paediatric models of care for Type 1 diabetes is limited. To address this gap, we synthesised literature on implemented models of care, model components, outcomes, and determinants of implementation and sustainability.

A systematic review was conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Database searches of Medline, CINAHL, EMBASE and Scopus were conducted. Empirical studies focused on Type 1 diabetes paediatric models of care, published from 2010 to 2022 in English were included.

Nineteen extant studies reported on models and their associations with health and psychosocial outcomes, patient engagement with healthcare, and healthcare costs. Thirteen studies described multidisciplinary teamwork, education and capacity building that supported self-care. Four studies involved shared decision making between providers and patients, and two discussed outreach support where technology was an enabler. Fourteen studies reported improvements in health outcomes (e.g. glycaemic control), mostly for models that included multidisciplinary teams, education, and capacity building (11 studies), outreach support or shared care (3 studies). Four studies reported improvements in quality of life, three reported increased satisfaction for patients and carers and, and one reported improved communication. Four of five studies describing shared care and decision-making reported improvements in quality of life, support and motivation. Outreach models reported no negative outcomes, however, accessing some models was limited by technological and cost barriers. Eight studies reported on model sustainability, but only half reported implementation determinants; none reported applying a theoretical framework to guide their research.

Some health and psychosocial benefits were associated with newer models. To address knowledge gaps about implementation determinants and model sustainability, longitudinal studies are needed to inform future adoption of innovative models of care for children with Type 1 diabetes.

Gut microbiota (GM) homeostasis in the human body is closely associated with health, which can be used as a regulator for preventing the onset and progression of disease. Diabetic microvascular complications bring about not only a huge economic burden to society, but also miserable mental and physical pain. Thus, alteration of the GM may be a method to delay diabetic microvascular complications.

A two-sample Mendelian randomization (MR) analysis was conducted to reveal the causal inference between GM and three core diabetic microvascular complications, namely, diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic neuropathy (DNP).

First, genome-wide association study (GWAS) summary statistics for GM from the MiBioGen consortium and three main diabetic microvascular complications acquired from the FinnGen research project were assessed. Second, a forward MR analysis was conducted to assess the causality of GM on the risk of DKD, DR, and DNP. Third, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and leave-one-out analyses, were further conducted to assess the accuracy of MR analysis. Finally, Steiger tests and reverse MR analyses were performed to appraise the possibility of reverse causation.

A total of 2,092 single-nucleotide polymorphisms related to 196 bacterial traits were selected as instrumental variables. This two-sample MR analysis provided strongly reasonable evidence that 28 genetically predicted abundance of specific GM that played non-negligible roles in the occurrence of DKD, DR, and DNP complications were causally associated with 23 GM, the odds ratio of which generally ranged from 0.9 to 1.1. Further sensitivity analysis indicated low heterogeneity, low pleiotropy, and high reliability of the causal estimates.

The study raised the possibility that GM may be a potential target to prevent and delay the progression of diabetic microvascular complications. Further experiments of GM therapy on diabetic microvascular complications are warranted to clarify their effects and specific mechanisms.

Diabetes Mellitus (DM) is a common chronic disease, affecting 435 million people globally. Impaired vasculature in DM patients leads to complications like lower extremity arterial disease (LEAD) and foot ulcers, often resulting in amputations. DM causes additional peripheral neuropathy leading to multifactorial wound problems. Current diagnostics often deem unreliable, but Near-Infrared Fluorescence with Indocyanine Green (ICG NIR) can be used to assess the foot perfusion. Therefore, this study explores DM's impact on foot perfusion using ICG NIR.

Baseline ICG NIR fluorescence imaging was performed in LEAD patients with and without DM. Ten perfusion parameters were extracted and analyzed to assess differences in perfusion patterns.

Among 109 patients (122 limbs) of the included patients, 32.8 % had DM. Six of ten perfusion parameters, mainly inflow-related, differed significantly between DM and non-DM patients (p-values 0.007-0.039). Fontaine stage 4 DM patients had the highest in- and outflow values, with seven parameters significantly higher (p-values 0.004-0.035).

DM is associated with increased in- and outflow parameters. Patients with- and without DM should not be compared directly due to different vascular pathophysiology and multifactorial wound problems in DM patients. Quantified ICG NIR fluorescence imaging offers additional insight into the effect of DM on foot perfusion.

Diabetic microvascular complications such as retinopathy, nephropathy, and neuropathy are primary causes of blindness, terminal renal failure, and neuropathic disorders in type 2 diabetes mellitus patients. Identifying reliable biomarkers promptly is pivotal for early detection and intervention in these severe complications.

This review offers a thorough examination of the latest research concerning serum biomarkers for the prediction and assessment of diabetic microvascular complications. It encompasses biomarkers associated with glycation, oxidative stress, inflammation, endothelial dysfunction, basement membrane thickening, angiogenesis, and thrombosis. The review also highlights the potential of emerging biomarkers, such as microRNAs and long non-coding RNAs.

Serum biomarkers are emerging as valuable tools for the early assessment and therapeutic guidance of diabetic microvascular complications. The biomarkers identified not only reflect the underlying pathophysiology but also align with the extent of the disease. However, further validation across diverse populations and improvement of the practicality of these biomarkers in routine clinical practice are necessary. Pursuing these objectives is essential to advance early diagnosis, risk assessment, and individualized treatment regimens for those affected by diabetes.

Background Diabetes mellitus is one of the most important and common chronic diseases worldwide and is expected to increase in prevalence. Diabetic retinopathy (DR) is one of the most prevalent microvascular sequelae of diabetes mellitus (DM), and ischemic heart disease is a macrovascular sequela. This study was conducted to find out the relation between the degree of DR and ischemic heart disease severity in Indian patients. Materials and methods This cross-sectional, descriptive, hospital-based study was conducted in the ophthalmology department at Dr. D. Y. Patil Medical Hospital, Pune, Maharashtra, India, from September 2022 to June 2024. A total of 200 eyes from 100 patients who were diagnosed with cases of ischemic heart disease and diabetes mellitus were included in the study. Patients with corneal pathology like endothelial dystrophies, corneal degenerations, corneal scars, or trauma preventing good visualization of the posterior segment were excluded from the study. Patients with active uveitis, patients with a history of undergoing any previous vitreoretinal surgery or laser procedures, non-compliant patients, patients not willing to undergo the procedure, or those not consenting to the study were also excluded. Written informed consent was obtained from each patient. Data was entered in Microsoft Excel and statistical analysis was done using IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp. As the continuous variables showed a skewed distribution, we used the Mann-Whitney test and the Kruskal-Wallis test to test the significance of the difference between continuous and categorical variables. A chi-square test was employed to check the association between categorical variables. Significance was assumed at an alpha error of 5%. Results The prevalence of diabetic retinopathy was found to be 95%. The mean age of patients with DR and patients with no diabetic retinopathy was 58.38 and 59.40 years, respectively, with the majority of the patients being in the age group of 60-69 years (46%). The majority of the patients were males (65%), while 35% were females. There was a significant association between the severity of diabetic retinopathy and the higher HbA1c levels, the use of insulin as a treatment modality, and the higher blood sugar levels in our study population. It was observed that the patients in our study with an ejection fraction of <40% had significantly higher severity of diabetic retinopathy in the form of PDR and high-risk PDR. The severity of the DR was directly correlated with the severity of IHD in our study, with most of the IHD patients with a 40-60% ejection fraction having moderate NPDR and patients with a >60% ejection fraction having mild or moderate NPDR. Conclusion The prevalence of diabetic retinopathy among the IHD patients with diabetes was 95% in our study, with moderate NPDR being the most common stage of DR seen among the patients. It was observed that more severe stages of diabetic retinopathy were seen in patients who were on treatment with insulin than in patients who were on treatment with OHA. Severe stages of diabetic retinopathy were associated with higher blood sugar levels (BSL) and higher glycated hemoglobin levels. In the present study, it was observed that a lower ejection fraction (<40%), which is a marker of reduced cardiac function, was associated with more severe stages of diabetic retinopathy.