Diabetes-related Complications Research Articles

Utilities for Complications Associated with Type 2 Diabetes: A Review of the Literature.

Utility values are used in health economic modeling analyses of type 2 diabetes (T2D) to quantify the effect of acute and long-term complications on quality of life (QoL). For accurate modeling projections, it is important that the utility values used are up to date, accurate and representative of the simulated model cohort. A literature review was performed to identify utility values for health states representing acute and chronic T2D-related complications including cardiovascular complications, stroke, renal disease, ophthalmic complications, neuropathy, diabetic foot, amputation and hypoglycemia. Searches were performed using the PubMed, Embase and Cochrane Library databases and limited to articles published since 2010. Supplementary searches were performed to identify data published at congresses in 2019-2023. A total of 54 articles were identified that reported utility values for T2D-related complications. The most frequently used elicitation method/instrument was the EQ-5D (n = 42 studies) followed by the Short Form-6 dimensions (n = 6), time tradeoff (n = 5), the Health Utilities Index Mark 2 or Mark 3 (n = 2), 15D (n = 1), visual analog scale (n = 1) and standard gamble (n = 1). Stroke and amputation were consistently associated with the largest decrements in QoL. There is a lack of published data that distinguishes between severity of several complications including renal disease, retinopathy and neuropathy. Diabetes-related complications can have a profound impact on QoL; therefore, it is important that these are captured accurately and appropriately in health economic models. Recently published utility values for diabetes-related complications that can be used to inform health economic models are summarized here.

Classification, Symptoms, Treatment and Preventive Strategies of Diabetes. A guide to the basic

Introduction Diabetes is a chronic metabolic disorder characterized by impaired insulin secretion and action. Risk factors for diabetes include age, obesity, low physical activity, hypertension, lipid disorders, and genetic predisposition. Symptoms of diabetes typically include frequent urination, weight loss, excessive thirst, weakness, fatigue, susceptibility to fungal infections and recurrent boils. Diabetes is a prevalent and significant societal concern, often causing anxiety, uncertainty and a sense of danger upon diagnosis. Aim of the study The aim of the study is to provide a comprehensive analysis of diabetes, including its classification, characteristic symptoms, the most frequently occurring diabetes-related complications, and preventive strategies. Through a detailed discussion of these issues, our goal is to increase public awareness of diabetes and provide readers with comprehensive knowledge about this disease. Material and method This article presents the current state of knowledge about diabetes. A literature review was conducted using the PubMed, Google Scholar and Web of Science databases, utilizing keywords such as "diabetes", "diabetes mellitus", "diabetes complications". Results The number of people with diabetes has continued to rise. Scientists predict that in a few decades, this number could reach more than half a billion globally. Many individuals may not realize that they are at risk for this civilization disease, often due to unhealthy lifestyle choices such as smoking, obesity, and lack of physical activity. Early initiation of treatment is crucial in preventing serious complications. Despite living with diabetes for years, some patients still report insufficient knowledge about their condition. Therefore, educating patients about the nature of the disease and its treatment is essential for improving their quality of life.

Sex differences in risk of incident microvascular and macrovascular complications: a population-based data-linkage study among 25 713 people with diabetes

BackgroundThe global prevalence of diabetes is similar in men and women; however, there is conflicting evidence regarding sex differences in diabetes-related complications. The aim of this study was to investigate...

Cell Therapies and Gene Therapy for Diabetes: Current Progress.

The epidemic of diabetes continues to be an increasing problem, and there is a need for new therapeutic strategies. There are several promising drugs and molecules in synthetic medicinal chemistry that are developing for diabetes. In addition to this approach, extensive studies with gene and cell therapies are being conducted. Gene therapy is an existing approach in treating several diseases, such as cancer, autoimmune diseases, heart disease and diabetes. Several reports have also suggested that stem cells have the differentiation capability to functional pancreatic beta cell development in vitro and in vivo, with the utility to treat diabetes and prevent the progression of diabetes-related complications. In this current review, we have focused on the different types of cell therapies and vector-based gene therapy in treating or preventing diabetes.

Improving foot self-care in people with diabetes in Ghana: A development and feasibility randomised trial of a context appropriate, family-orientated diabetic footcare intervention.

Africa presents a higher diabetic foot ulcer prevalence estimate of 7.2% against global figures of 6.3%. Engaging family members in self-care education interventions has been shown to be effective at preventing diabetes-related foot ulcers. This study culturally adapted and tested the feasibility and acceptability of an evidence-based footcare family intervention in Ghana. The initial phase of the study involved stakeholder engagement, comprising Patient Public Involvement activities and interviews with key informant nurses and people with diabetes (N = 15). In the second phase, adults at risk of diabetes-related foot ulcers and nominated caregivers (N = 50 dyads) participated in an individually randomised feasibility trial of the adapted intervention (N = 25) compared to usual care (N = 25). The study aimed to assess feasibility outcomes and to identify efficacy signals on clinical outcomes at 12 weeks post randomisation. Patient reported outcomes were foot care behaviour, foot self-care efficacy, diabetes knowledge and caregiver diabetes distress. Adjustments were made to the evidence-based intervention to reflect the literacy, information needs and preferences of stakeholders and to develop a context appropriate diabetic foot self-care intervention. A feasibility trial was then conducted which met all recruitment, retention, data quality and randomisation progression criteria. At 12 weeks post randomisation, efficacy signals favoured the intervention group on improved footcare behaviour, foot self-care efficacy, diabetes knowledge and reduced diabetes distress. Future implementation issues to consider include the staff resources needed to deliver the intervention, family members availability to attend in-person sessions and consideration of remote intervention delivery. A contextual family-oriented foot self-care education intervention is feasible, acceptable, and may improve knowledge and self-care with the potential to decrease diabetes-related complications. The education intervention is a strategic approach to improving diabetes care and prevention of foot disease, especially in settings with limited diabetes care resources. Future research will investigate the possibility of remote delivery to better meet patient and staff needs. Pan African Clinical Trials Registry (PACTR) - PACTR202201708421484: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=19363 or pactr.samrc.ac.za/Search.aspx.

Living well with diabetes in Alaska

ABSTRACT Many people with diabetes mellitus experience minimal or no complications. Our objective was to determine the proportion of Alaska Native people who experienced four major complications or mortality and to identify factors that may be associated with these outcomes. We used records in a diabetes registry and clinical and demographic variables in our analyses. We used logistic regression and Cox Proportional Hazards models to evaluate associations of these parameters with death and complications that occurred prior to 2013. The study included 591 Alaska Native people with non-type 1 diabetes mellitus, diagnosed between 1986 and 1992. Over 60% of people in this study remained free of four major diabetes-related complications for the remainder of life or throughout the approximately 20-year study period. Lower BMI, higher age at diagnosis of diabetes, and use of at least one diabetes medication were associated with death and a composite of four complications. A majority of Alaska Native people with DM had none of four major complications over a 20-year period. Lower BMI and use of diabetes medications were associated with higher hazard for some deleterious outcomes. This suggests that goals in care of elders should be carefully individualised. In addition, we discuss several programme factors that we believe contributed to favourable outcomes.

Frequency of Erectile Dysfunction in Patients with Type 2 Diabetes Mellitus Presenting with Peripheral Neuropathy at a Tertiary Care Hospital

Background: Erectile dysfunction (ED) is notably prevalent among patients with type 2 diabetes mellitus (T2DM), especially those suffering from peripheral neuropathy. The condition significantly impacts the quality of life and is often exacerbated by diabetes-related complications. Objective: This study aims to ascertain the frequency and severity of ED among patients with T2DM and peripheral neuropathy, and to examine the association between ED and variables such as age, duration of diabetes, and glycemic control. Methods: A prospective cohort study was conducted at the Baqai Institute of Diabetology and Endocrinology, Karachi, from July 2021 to September 2022. We included 115 male patients aged 35-65 years with T2DM and diagnosed peripheral neuropathy. ED was assessed using the Urdu version of the International Index of Erectile Function-5 (IIEF-5) questionnaire. Demographic details, medical history, and laboratory results were collected and analyzed using SPSS version 25. Statistical tests included chi-squared and one-way ANOVA, with a significance level set at p<0.05. Results: The mean age of the participants was 50.97 ± 7.21 years, and the average duration of diabetes was 9.37 ± 6.56 years. The mean IIEF-5 score was 14.33 ± 6.0, indicating moderate ED. Severe ED was observed in 20% of the participants, moderate ED in 19.1%, and mild to moderate ED in 28.7%. The study found a significant association between the duration of diabetes and ED severity (p < 0.001), while age and HbA1c levels did not show a significant correlation with ED status. Conclusion: ED is highly prevalent and severe among patients with T2DM and peripheral neuropathy, with disease duration being a significant predictor of ED severity. These findings underscore the need for early screening and targeted interventions in this population.

Benfotiamine improves dystrophic pathology and exercise capacity in mdx mice by reducing inflammation and fibrosis.

Duchenne Muscular Dystrophy (DMD) is a progressive and fatal neuromuscular disease. Cycles of myofibre degeneration and regeneration are hallmarks of the disease where immune cells infiltrate to repair damaged skeletal muscle. Benfotiamine is a lipid soluble precursor to thiamine, shown clinically to reduce inflammation in diabetic related complications. We assessed whether benfotiamine administration could reduce inflammation related dystrophic pathology. Benfotiamine (10mg/kg/day) was fed to male mdx mice (n = 7) for 15weeks from 4weeks of age. Treated mice had an increased growth weight (5-7weeks) and myofibre size at treatment completion. Markers of dystrophic pathology (area of damaged necrotic tissue, central nuclei) were reduced in benfotiamine mdx quadriceps. Grip strength was increased and improved exercise capacity was found in mdx treated with benfotiamine for 12weeks, before being placed into individual cages and allowed access to an exercise wheel for 3weeks. Global gene expression profiling (RNAseq) in the gastrocnemius revealed benfotiamine regulated signalling pathways relevant to dystrophic pathology (Inflammatory Response, Myogenesis) and fibrotic gene markers (Col1a1, Col1a2, Col4a5, Col5a2, Col6a2, Col6a2, Col6a3, Lum) towards wildtype levels. In addition, we observed a reduction in gene expression of inflammatory gene markers in the quadriceps (Emr1, Cd163, Cd4, Cd8, Ifng). Overall, these data suggest that benfotiamine reduces dystrophic pathology by acting on inflammatory and fibrotic gene markers and signalling pathways. Given benfotiamine's excellent safety profile and current clinical use, it could be used in combination with glucocorticoids to treat DMD patients.

Bioactive Compounds of Rosa canina L. and Their Effect on Tumor Necrosis Factor-α and Interleukin-1β Activity in Diabetes-Induced Rats

The ethnopharmacological significance of Rosa canina, or dog rose, transcends diverse cultures, with traditional applications in treating various diseases. This study investigates the potential pharmacological application of Rosa canina for diabetes treatment, aiming to assess its antidiabetic properties through in vitro, in vivo, and in silico analyses targeting pro-cytokines. Biochemical profiling utilizing HPLC, and phenolic content analyses were conducted to reveal the antioxidant properties of Rosa canina. In diabetic rats, root extracts influenced the expression of TNF-α and IL-1β, with an exploration of DNA-binding and protective activities. DPPH scavenging and iron chelating activities were measured, identifying significant IC50 values. The chromatographic analysis identified various compounds, with Kaempferol 3-O-glucoside and Rutin exhibiting high inhibitory activity against TNF-alpha. In silico analyses highlighted inhibitory activities by molecular docking against TNF-α and IL-1β (PDB IDs 2AZ5 and 9ILB, respectively) and their drug potential based on ADMET properties. The obtained results have demonstrated a significant decrease in blood glucose levels in mice through the reduction of TNF-α and IL-1β mediated diabetic processes, facilitated by the Rosa canina extract. In conclusion, this study exploring the effects of Rosa canina extracts on diabetic rats have provided valuable insights into its potential therapeutic benefits. The observed reductions in blood glucose levels, improvements in lipid profiles, and modulation of antioxidant activity highlight its promising role in managing diabetes-related complications. Further research is warranted to elucidate the underlying mechanisms and optimize the dosage regimens for harnessing the full therapeutic potential of Rosa canina extracts in diabetes management.

Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy.

Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications. In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods. Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)]. The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.

Proactive Identification of Patients with Diabetes at Risk of Uncontrolled Outcomes during a Diabetes Management Program: Conceptualization and Development Study Using Machine Learning.

The growth in the capabilities of telehealth have made it possible to identify individuals with a higher risk of uncontrolled diabetes and provide them with targeted support and resources to help them manage their condition. Thus, predictive modeling has emerged as a valuable tool for the advancement of diabetes management. This study aimed to conceptualize and develop a novel machine learning (ML) approach to proactively identify participants enrolled in a remote diabetes monitoring program (RDMP) who were at risk of uncontrolled diabetes at 12 months in the program. Registry data from the Livongo for Diabetes RDMP were used to design separate dynamic predictive ML models to predict participant outcomes at each monthly checkpoint of the participants' program journey (month-n models) from the first day of onboarding (month-0 model) up to the 11th month (month-11 model). A participant's program journey began upon onboarding into the RDMP and monitoring their own blood glucose (BG) levels through the RDMP-provided BG meter. Each participant passed through 12 predicative models through their first year enrolled in the RDMP. Four categories of participant attributes (ie, survey data, BG data, medication fills, and health signals) were used for feature construction. The models were trained using the light gradient boosting machine and underwent hyperparameter tuning. The performance of the models was evaluated using standard metrics, including precision, recall, specificity, the area under the curve, the F1-score, and accuracy. The ML models exhibited strong performance, accurately identifying observable at-risk participants, with recall ranging from 70% to 94% and precision from 40% to 88% across the 12-month program journey. Unobservable at-risk participants also showed promising performance, with recall ranging from 61% to 82% and precision from 42% to 61%. Overall, model performance improved as participants progressed through their program journey, demonstrating the importance of engagement data in predicting long-term clinical outcomes. This study explored the Livongo for Diabetes RDMP participants' temporal and static attributes, identification of diabetes management patterns and characteristics, and their relationship to predict diabetes management outcomes. Proactive targeting ML models accurately identified participants at risk of uncontrolled diabetes with a high level of precision that was generalizable through future years within the RDMP. The ability to identify participants who are at risk at various time points throughout the program journey allows for personalized interventions to improve outcomes. This approach offers significant advancements in the feasibility of large-scale implementation in remote monitoring programs and can help prevent uncontrolled glycemic levels and diabetes-related complications. Future research should include the impact of significant changes that can affect a participant's diabetes management.

The role of emotion dysregulation in self-management behaviors among adults with type 2 diabetes.

Suboptimal disease self-management among adults with type 2 diabetes is associated with greater risk of diabetes related health complications and mortality. Emotional distress has been linked with poor diabetes self-management; however, few studies have examined the role of emotion dysregulation in diabetes management. The purpose of this study was to examine the relations between different facets of emotion dysregulation and diabetes self-management behaviors among a sample of 373 adults with type 2 diabetes. Separate median regression and binary logistic regression models were used to examine the association of emotion dysregulation facets and each diabetes self-care behavior (i.e., medication nonadherence, diet, exercise, self-monitoring of blood glucose (SMBG), foot care, and smoking). Generally, greater difficulties in emotion regulation were associated with poorer self-management behaviors. However, several facets of emotion dysregulation were linked with better self-management behaviors. Addressing emotion dysregulation among adults with type 2 diabetes has the potential to improve diabetes related self-management.

NAMPT, IL-6, and vaspin gene expressions and serum protein levels in type 2 diabetes mellitus and related complication

NAMPT, IL-6, and vaspin gene expressions and serum protein levels in type 2 diabetes mellitus and related complication

Exosomal MALAT1 from macrophages treated with high levels of glucose upregulates LC3B expression via miR-204-5p downregulation.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a critical role in the pathophysiology of diabetes-related complications. However, whether macrophage-derived MALAT1 affects autophagic activity under hyperglycemic conditions is unclear. Therefore, we investigated the molecular regulatory mechanisms of macrophage-derived MALAT1 and autophagy under hyperglycemic conditions. Hyperglycemia was induced by culturing macrophages in 25 mM glucose for 1 h. Exosomes were extracted from the culture media. A rat model of carotid artery balloon injury was established to assess the effect of MALAT1 on vascular injury. Reverse transcription, real-time quantitative polymerase chain reaction, western blotting, immunohistochemical staining, and luciferase activity assays were performed. Stimulation with high levels of glucose significantly enhanced MALAT1 expression in macrophage-derived exosomes. MALAT1 inhibited miR-204-5p expression in macrophage-derived exosomes under hyperglycemic conditions. siRNA-induced silencing of MALAT1 significantly reversed macrophage-derived exosome-induced miR-204-5p expression. Hyperglycemic treatment caused a significant, exosome-induced increase in the expression of the autophagy marker LC3B in macrophages. Silencing MALAT1 and overexpression of miR-204-5p significantly decreased LC3B expression induced by macrophage-derived exosomes. Overexpression of miR-204-5p significantly reduced LC3B luciferase activity induced by macrophage-derived exosomes. Balloon injury to the carotid artery in rats significantly enhanced MALAT1 and LC3B expression, and significantly reduced miR-204-5p expression in carotid artery tissue. Silencing MALAT1 significantly reversed miR-204-5p expression in carotid artery tissue after balloon injury. MALAT1 silencing or miR-204-5p overexpression significantly reduced LC3B expression after balloon injury. This study demonstrated that hyperglycemia upregulates MALAT1. MALAT1 suppresses miR-204-5p expression and counteracts the inhibitory effect of miR-204-5p on LC3B expression in macrophages to promote vascular disease.

Development of Syringaldehyde as an Agonist of the GLP-1 Receptor to Alleviate Diabetic Disorders in Animal Models.

The phenolic aldehyde syringaldehyde (SA) has been shown to have an antihyperglycemic effect in diabetic rats due to increased glucose utilization and insulin sensitivity. To understand the direct effect of SA on the GLP-1 receptor, STZ-induced diabetic rats were used. The levels of pro-inflammatory cytokines, liver enzymes, and renal function were measured using specific ELISA kits. The mechanisms of SA effects were investigated using CHO-K1 cells, pancreatic Min-6 cells, and cardiomyocyte H9c2 cells. The results indicated that the antihyperglycemic effect of SA in diabetic rats was abolished by blocking the GLP-1 receptor with an antagonist. SA has a direct effect on the GLP-1 receptor when using CHO-K1 cells transfected with the exogenous GLP-1 receptor gene. In addition, SA stimulated insulin production in Min-6 cells by activating GLP-1 receptors. SA caused a dose-dependent rise in GLP-1 receptor mRNA levels in cardiac H9c2 cells. These in vitro results support the notion that SA has a direct effect on the GLP-1 receptor. Otherwise, SA inhibited the increase of pro-inflammatory cytokines, including interleukins and tumor TNF-α, in type 1 diabetic rats in a dose-dependent manner. Moreover, as with liraglutide, SA reduced plasma lipid profiles, including total cholesterol and triglyceride, in mixed diet-induced type 2 diabetic rats. Intriguingly, chronic treatment with SA (as with liraglutide) reversed the functions of both the liver and the kidney in these diabetic rats. SA displayed less efficiency in reducing body weight and food consumption compared to liraglutide. In conclusion, SA effectively activates GLP-1 receptors, resulting in a reduction in diabetic-related complications in rats. Therefore, it is beneficial to develop SA as a chemical agonist for clinical applications in the future.

Benchmarking docking, density functional theory and molecular dynamics studies to assess the aldose reductase inhibitory potential of Trigonella foenum-graecum compounds for managing diabetes-associated complications

Inhibition of aldose reductase (AR) could be a beneficial strategy for managing diabetes-associated complications. Trigonella foenum-graecum (TFG) is used around the globe as a traditional medicine for the management of diabetes. Our study aimed to assess the potential of TFG phytocompounds as inhibitors of AR in the context of diabetes-related complications. Our research work employed molecular docking, density functional theory (DFT) and molecular dynamics (MD) to evaluate the efficacy of TFG compounds. The study compared the predictive power of AutoDock and AutoDock Vina docking software and found that AutoDock Vina performs better in ranking and discriminating actives and decoys. The research identified five compounds as potential AR inhibitors from fifty-eight reported TFG phytoconstituents. Tigogenin and Gitogenin stood out as the most promising AR inhibitors. The electronic properties of the compounds were analysed through DFT studies and provided insights into their binding potential. Finally, the results of MD simulations indicated that Tigogenin and Gitogenin bound robustly with AR throughout the simulation period. This study predicted the AR inhibitory potential of TFG compounds for managing diabetes-associated complications and supports further drug development from TFG. The benchmarking approach used in this study improves the accuracy and dependability of bioactivity prediction.

Frequency of Peripheral Arterial Disease in Type-II Diabetic Patients presenting with Diabetic Retinopathy

Background: Type-II Diabetes Mellitus (T2DM) often leads to Diabetic Retinopathy (DR), but the prevalence of coexisting Peripheral Arterial Disease (PAD) in these patients is unclear, creating controversy in existing literature. This study aims to fill this gap by investigating the frequency of PAD in T2DM patients with DR, enhancing our understanding of diabetes-related complications. Objective: To determine frequency of peripheral arterial disease in T2DM patients presenting with diabetic retinopathy. Study Design: It was a cross sectional study. Settings: This study was conducted at the Department of Medicine, DHQ Teaching Hospital, KMU Institute of Medical Sciences, Kohat Pakistan. Duration: Six months from 05-01-2022 to 04-07-2022. Methods: A total 165 T2DM patients presenting with diabetic retinopathy and meeting inclusion criteria were enrolled in this study after taking informed written consent. Ankle brachial pressure index was measured. Two blood pressure readings were taken 5 minutes apart and average was calculated for analysis. Peripheral arterial disease was labeled. SPSS version 26.0 was used for data analysis. Results: The mean age of the participants was 51.1±14.69. There were 63 (38.2%) females and 102 (61.8%) males. Mean BMI was 26.87±3.73 kg/m2. The mean duration of diabetes in the participants was 6.43±2.36 years. As regards type of retinopathy, 62 (37.6%) had Proliferative Diabetic Retinopathy (PDR), and 103 (62.4%) had Non-Proliferative Diabetic Retinopathy (NPDR). Mean Ankle Brachial Pressure Index (ABPI) among the participants was 1.01±0.25. Peripheral arterial disease was noticed in 28.5% of the T2DM patients presenting with diabetic retinopathy. Stratification of frequency of PAD for various sub groups of age, gender, BMI, duration of disease and type of retinopathy produced insignificant difference between sub groups (p-value&gt;0.05). Conclusion: In conclusion, our investigation of Type 2 diabetic patients with diabetic retinopathy uncovers a significant 28.5% prevalence of peripheral arterial disease (PAD). Stratification across age, gender, BMI, disease duration, and retinopathy type reveals no substantial differences. These results underscore the systemic nature of vascular complications, emphasizing the importance of comprehensive care strategies.

Trajectories of clinical characteristics, complications and treatment choices in data-driven subgroups of type 2 diabetes.

This study aimed to explore the added value of subgroups that categorise individuals with type 2 diabetes by k-means clustering for two primary care registries (the Netherlands and Scotland), inspired by Ahlqvist's novel diabetes subgroups and previously analysed by Slieker et al. METHODS: We used two Dutch and Scottish diabetes cohorts (N=3054 and 6145; median follow-up=11.2 and 12.3 years, respectively) and defined five subgroups by k-means clustering with age at baseline, BMI, HbA1c, HDL-cholesterol and C-peptide. We investigated differences between subgroups by trajectories of risk factor values (random intercept models), time to diabetes-related complications (logrank tests and Cox models) and medication patterns (multinomial logistic models). We also compared directly using the clustering indicators as predictors of progression vs the k-means discrete subgroups. Cluster consistency over follow-up was assessed. Subgroups' risk factors were significantly different, and these differences remained generally consistent over follow-up. Among all subgroups, individuals with severe insulin resistance faced a significantly higher risk of myocardial infarction both before (HR 1.65; 95% CI 1.40, 1.94) and after adjusting for age effect (HR 1.72; 95% CI 1.46, 2.02) compared with mild diabetes with high HDL-cholesterol. Individuals with severe insulin-deficient diabetes were most intensively treated, with more than 25% prescribed insulin at 10 years of diagnosis. For severe insulin-deficient diabetes relative to mild diabetes, the relative risks for using insulin relative to no common treatment would be expected to increase by a factor of 3.07 (95% CI 2.73, 3.44), holding other factors constant. Clustering indicators were better predictors of progression variation relative to subgroups, but prediction accuracy may improve after combining both. Clusters were consistent over 8 years with an accuracy ranging from 59% to 72%. Data-driven subgroup allocations were generally consistent over follow-up and captured significant differences in risk factor trajectories, medication patterns and complication risks. Subgroups serve better as a complement rather than as a basis for compressing clustering indicators.

Activation of heme oxygenase-1 by laminar shear stress ameliorates high glucose-induced endothelial cell and smooth muscle cell dysfunction.

High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications.

Glycemic control and its associated factors among adult diabetic patients in Southern Ethiopia: a cross-sectional study

Background: Diabetes mellitus is a group of common metabolic disorders that share the phenotype of hyperglycemia. Chronic hyperglycemia causes vascular complications, mortality, and life-threatening disabilities in low-income countries including Ethiopia. Glycemic control status in diabetic patients is crucial to maintain the blood glucose level at the optimal level and to reduce the risk of diabetes-related complications and mortality. However, there is limited data on poor glycemic control status and its associated factors among diabetic patients in southern Ethiopia, particularly in the study area. Thus, this study aimed to determine glycemic control status and its associated factors using glycated hemoglobin among adult diabetic patients at Nigist Elleni Mohammad Memorial Referral Hospital, Hossana, southern Ethiopia. Materials and methods: A facility-based cross-sectional study was conducted from May 1 to June 30, 2020. A systematic random sampling technique was used to recruit 307 diabetic patients at follow-up. Interviewer administered questionnaire was used to collect data on sociodemographic, clinical, and behavioral characteristics. Five milliliters of venous blood samples were collected to determine lipid profiles and hemoglobin A1C. Lipid profiles and hemoglobin A1C were measured by Cobas c311 analyzer. The data were analyzed by SPSS version 20.Bivariable and multivariable logistic regression were used to determine associated factors with poor glycemic control status. P-value &lt;0.05 was considered statistically significant. Result: The overall prevalence of poor glycemic control among the study participants based on hemoglobin A1C ≥7% was 82.4%. Having a history of diabetic complications (AOR: 7.09, 95%CI: 1.72-29.16), duration of diabetes ≥7 years (AOR: 4.09, 95%CI: 1.38-12.08), insulin and oral hypoglycemic agents (AOR: 0.106 95%CI: 0.02-0.44), lack of self-glucose monitoring (AOR: 8.27, 95%CI: 1.61-42.46), lack of physical exercise (AOR: 5.5, 95%CI: 1.6-18.9) and dyslipidemia (AOR: 2.74, 95%CI: 1.12-6.66) were significantly associated with poor glycemic control. Conclusion: A high prevalence of poor glycemic control status (82.4%) was observed among diabetic patients in this study area, and disease-related factors like duration of diabetes, complication, treatment type and lack of self-glucose monitoring, physical exercise, and dyslipidemia were identified as factors significantly associated with poor glycemic control status. The finding of the current study should be taken into account to conduct a strategic and timely intervention on significantly associated factors to delay diabetic complications and to improve the health outcome of diabetic patients. Routine screening and monitoring of dyslipidemia and providing health education on behavioral factors were the necessary measures that should be conducted to reduce the burden of poor glycemic control status among diabetic patients. Keywords: Diabetes mellitus; Glycemic control; Glycated hemoglobin; Hossana; Ethiopia.