Microvascular Complications Research Articles

Autoimmune Comorbidity in Endocrinology: Thyroiditis and Type 1 Diabetes Mellitus in Children

Autoimmune thyroid disease and type 1 diabetes mellitus (DM1) often occur simultaneously, especially among children. Due to the lack of scientific data in the Kyrgyz Republic (KR), this report aims to study the relationship between type 1 diabetes and autoimmune thyroiditis by studying influencing factors such as gender, age, and duration of diabetes. Materials and methods. Type 1 diabetes is one of the most common chronic diseases of the endocrine system in children. The incidence of DM1 in childhood and adolescence, including in the Kyrgyz Republic, is steadily increasing. The total number of children with diabetes in the Kyrgyz Republic is 1,249, of whom 190 are newly diagnosed. Type 1 diabetes in combination with an autoimmune process in the thyroid gland reduces the quality of life of children and their family members, threatens the development of microvascular complications and early disability of patients, and is a medical and social problem of our time. Autoimmune diseases of the thyroid gland (thyroid gland) are common in patients with DM1, may be associated with age, long duration of diabetes and may disrupt glycemic control in patients with DM1. These data allow us to trace the dynamics of the disease and to adjust preventive and treatment programs in the Kyrgyz Republic.

Progress in the study of biological factors of aqueous humor in patients with diabetic retinopathy

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus and a leading cause of vision loss in diabetic patients. Pathological processes such as inflammatory response, oxidative stress, and vascular dysfunction play important roles in the pathogenesis of DR. Changes in the levels of cytokines associated with these pathologic processes correlate with the onset, progression, and extent of DR. In this review, we address the role of various potential cytokines in aqueous humor in the pathogenesis of DR, with a view to identifying potential targets that may diagnose and treat DR and providing a basis for developing new therapeutic approaches.

Impact of vitamin D and vitamin D receptor activator in diabetic nephropathy

Vitamin D is a hormone which is involved in many physiological processes in addition to bone metabolism and the muscular system. Based on several animal and human studies, it has been established that vitamin D plays an important role in the development of diabetic nephropathy (DN). DN is a frequent and severe chronic microvascular complication of diabetes mellitus (DM). As such, DN and cardiovascular complications are considered the main risk factors for the death of patients with DM. Recent studies have shown the renoprotective effect of VD and its receptor activators (VDRAs or VD analogs based on its effect on endothelial function, preservation of podocytes, anti-inflammatory effect, and direct influence on the renin-angiotensin aldosterone system. The renoprotective effect of VD has been shown to potentially delay the onset of DN, which is the main cause of end stage renal diseases (ESRD). The impact of vitamin D on the recovery of already existing kidney damage is debatable and doubtful. Increasing evidence has shown that the VD/VDR interaction possesses a series of renoprotective effects in DN patients based on the anti-proteinuric, anti-fibrotic, and anti-inflammatory effect, as well as the preventive effect of podocyte damage. Based on this important renoprotective effect, important data for therapeutic and effective methods for DN have also been presented. It was performed a structured search of published research literature for several databases regarding the impact of VD on the pathophysiology of DN as well as its therapeutic implications in terms of renoprotection of VD and VDRA in animal research and human clinical research as RCT, observational studies, systematic reviews and meta-analyses over the last decade.

LncRNA CASC2 mediates SOCS6 mRNA stabilization via U2AF2 recruitment to modulate macrophage polarisation in diabetic retinopathy

AbstractBackgroundDiabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and a leading cause of vision loss among diabetic individuals. Retinal pigment epithelium (RPE) cells play a crucial role in the pathophysiology of DR by releasing cytokines and exosomal cargo, such as long non‐coding RNAs (lncRNAs), that modulate local immune responses, maintain retinal immune homeostasis and influence macrophage polarisation. Recent studies suggest that lncRNA cancer susceptibility candidate 2 (CASC2) may be involved in the regulation of DR progression. However, the regulatory mechanisms linking CASC2 with RPE cells and its role in macrophage polarisation remain insufficiently understood.MethodsVarious types of cells, including human retinal pigment epithelial cells (ARPE‐19), THP‐1 monocytes and additional retinal cell lines, were cultured under normal glucose and high glucose conditions. ARPE‐19 cells were exposed to oxidative stress, inflammatory stimulation, or hypoxic conditions. Plasma and aqueous humour samples were collected from DR patients and diabetic controls. Exosomes were extracted from AREP‐19 cells and characterised. Various gene and protein expression analyses were performed using techniques including quantitative reverse transcription polymerase chain reaction, Western blot, immunofluorescence, flow cytometry, enzyme‐linked immunosorbent assay, and histological staining. Cell proliferation and migration were assessed using Cell Counting Kit‐8 assays and Transwell migration assays, respectively. The interactions among CASC2, suppressor of cytokine signalling 6 (SOCS6), and U2 small nuclear RNA auxiliary factor 2 (U2AF2) were explored using RNA immunoprecipitation and dual‐luciferase reporter assays. An in vivo diabetic rat model was established.ResultslncRNA CASC2 expression levels were significantly lower in plasma and aqueous humour from DR patients compared to those from diabetic patients without retinopathy. Overexpression of CASC2 significantly attenuated DR and inflammatory damage both in vitro and in vivo. We demonstrated that exosomal CASC2 from ARPE‐19 cells mediated macrophage polarisation by inhibiting M1 polarisation and promoting M2 polarisation. Our findings suggest that CASC2 regulates this polarisation through the stabilisation of SOCS6 mRNA via U2AF2.ConclusionCASC2 derived from RPE cells was transported to macrophages, inducing M2 polarisation by stabilising SOCS6 mRNA through the recruitment of U2AF2. This research may provide a foundation for developing novel therapeutic strategies for DR.

New Markers for the Assessment of Microvascular Complications in Patients with Metabolic Syndrome

Background: Metabolic syndrome is a complex disorder characterized by the coexistence of multiple risk factors, including dysglycemia, hypertension, dyslipidemia, and visceral obesity. Both metabolic syndrome and diabetes mellitus are closely associated with the onset of microvascular complications such as retinopathy, polyneuropathy, and nephropathy. Methods: This narrative review analyzed 137 studies published up to 2025, retrieved from PubMed and Crossref databases. The objective was to identify and evaluate potential biomarkers that could facilitate the early detection of microvascular complications in patients with metabolic syndrome. Results: Several biomarkers demonstrated a strong correlation with microvascular complications in individuals with metabolic syndrome. These findings suggest their potential role in early diagnosis and risk assessment. Conclusions: The identification of reliable biomarkers may enhance early detection and targeted interventions for microvascular complications in metabolic syndrome. Further research is essential to validate these markers and establish their clinical applicability in routine medical practice.

Exploring patient and health care provider perspectives on barriers to diabetic retinopathy screening in public health facilities in North India

Diabetic retinopathy (DR), a prevalent microvascular complication of diabetes mellitus (DM), can be prevented with early detection and timely intervention. DR is asymptomatic in its early stages, highlighting the importance of screening for accurate referral and effective management. Multiple barriers impede access to diabetic retinopathy screening (DRS), creating significant public health challenges in regions with high DM prevalence. This study explores the perspectives of people with DM (PwDM) and healthcare providers (HCP) on these barriers. A qualitative study using in-depth interviews (IDI) was conducted between October 2022 and January 2023 in Punjab and Chandigarh. Through purposive sampling, IDIs were conducted with 7 PwDM and 19 HCPs, including retina specialists, ophthalmologists, optometrists, medical officers (MO), Community Health Officers (CHO), and ASHA workers from various public health facilities. A semi-structured topic guide facilitated the interviews, and thematic analysis was applied, utilizing the healthcare access barrier (HCAB) model as a framework. The study identified financial barriers due to insurance unawareness and employment constraints. Structural challenges included insufficient DRS infrastructure, untrained staff, the need for accompaniment, and limited access to screening sites. Limited awareness and misconceptions about DR characterized cognitive barriers, while psychological barriers involved mistrust of the health system, anxiety, and frustration from low vision. Addressing these issues is essential to improve DRS uptake and eye health outcomes. Managing diabetes and VTDR is challenging, highlighting the need for community-level DRS. Enhancing DR awareness and promoting public health insurance benefits are crucial for overcoming barriers and improving screening rates.

Metformin therapy modifies corneal neuroimmune abnormalities in people with type 2 diabetes.

Diabetic peripheral neuropathy is a debilitating microvascular complication of diabetes mellitus, with limited disease-modifying therapies to date. This study aimed to assess the effect of metformin on the corneal sub-basal nerve plexus as a peripheral neuropathy outcome measure in people with type 2 diabetes. A cohort of 36 participants with type 2 diabetes receiving metformin therapy were recruited and underwent clinical assessment, corneal confocal microscopy and nerve conduction studies. Concurrently, 36 participants with type 2 diabetes not receiving metformin therapy were selected as disease controls and matched to participants on metformin therapy for age, sex, diabetes duration, BMI, eGFR, HbA1c, use of other oral glucose-lowering agents and therapies used for the treatment of the metabolic syndrome. Additionally, 25 healthy control participants were assessed and matched for age and sex. Medical record data over the previous 20 years were analysed for prior and current metformin use in all participants with type 2 diabetes. Participants receiving metformin therapy had higher corneal nerve fibre density (p=0.020), corneal nerve fibre length (p=0.020) and corneal fractal dimension (p=0.003) compared with those not receiving metformin therapy. The inferior whorl dendritic cell density was significantly lower in the metformin group compared with the non-metformin group (p=0.043). Metformin treatment is associated with superior corneal nerve parameters and neuroimmune tone in the corneal sub-basal nerve plexus. This study provides further evidence that metformin may be neuroprotective in diabetic peripheral neuropathy.

Creating a retinal image database to develop an automated screening tool for diabetic retinopathy in India.

Diabetic retinopathy (DR), a prevalent microvascular complication of diabetes, is the fifth leading cause of blindness worldwide. Given the critical nature of the disease, it is paramount that individuals with diabetes undergo annual screening for early and timely detection of DR, facilitating prompt ophthalmic assessment and intervention. However, screening for DR, which involves assessing visual acuity and retinal examination through ophthalmoscopy or retinal photography, presents a significant global challenge due to the massive volume of individuals requiring annual reviews. To counter this challenge, there has been an increasing interest in the potential of artificial intelligence (AI) tools for automated diagnosis of DR. The AI tools primarily utilize deep learning (DL) techniques and are tailored to analyse extensive medical image data and provide diagnostic outputs, essentially streamline the DR screening process. However, the development of such AI tools requires access to a comprehensive retinal image database with a plethora of high-resolution fundus images from various cameras, covering all DR lesions. Additionally, the accurate training of these AI algorithms necessitates skilled professionals, such as optometrists or ophthalmologists, to provide reliable ground truths that ensure the precision of the diagnostic outputs. To address these prerequisites, we have initiated a study involving multiple institutions to establish a large-scale online 'Retinal Image Database' in India, aiming to contribute significantly to DR research. This paper delineates the methodology employed for this significant undertaking, detailing the steps taken to create the large retinal image database, as well as the framework for developing a cost-effective, robust AI-based DR diagnostic tool. Our work is expected to mark a significant stride in DR detection and management, promising a more efficient and scalable solution for tackling this global health challenge.

Advances in Imaging Techniques for Assessing Myocardial Microcirculation in People with Diabetes : An Overview of Current Techniques, Emerging Techniques, and Clinical Applications.

Microangiopathy is a key complication of diabetes, adversely effecting several organs including the heart, kidneys, eyes, and nerves. This review focuses on myocardial microvascular dysfunction, a condition characterized by altered vasomotion and long-term structural changes to coronary arterioles, resulting in impaired regulation of blood flow in response to varying oxygen demands of cardiomyocytes. Presence of myocardial microvascular dysfunction is associated with increased risk of cardiovascular disease, even in the absence of obstructive coronary artery disease. Several noninvasive imaging techniques to assess coronary physiology have significantly enhanced our understanding of the myocardial microcirculation. These methods allow for detailed visualization and quantification of blood flow, endothelial function, and inflammation in the microvasculature, providing critical insights into the early stages of microvascular disease in diabetes. A significant area of development is the use of advanced hybrid imaging techniques such as positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI). The integration of advanced imaging technologies with artificial intelligence is also a key future direction. Overall, these advancements aim to improve the early detection and management of microvascular complications in diabetes, ultimately enhancing outcomes and quality of life. The aim of this review is to provide an overview of both established and emerging noninvasive imaging techniques for assessing myocardial microvascular dysfunction.

The morbidity pattern among children and adolescents with type 1 diabetes attending diabetic clinic in a tertiary care centre

Background: Type 1 diabetes (T1D) is a chronic disease which needs prompt diagnosis, frequent monitoring and appropriate therapy to prevent complications. Objectives: To study the morbidity pattern among children with T1D. Method: For this prospective observational study, 234 children and adolescents aged 1-17 years with T1D, attending the diabetic clinic in a tertiary care centre, were recruited and followed up quarterly for 1 year. Anthropometric measurements and glycaemic status by mean of HbA1c were assessed quarterly, along with annual target organ assessments and documentation of T1D related events during each period. The health outcome measures studied included acute and chronic complications of T1D like hypoglycaemia, diabetic ketoacidosis (DKA), growth faltering, micro-vascular and treatment related complications. Results: Of the participants, 42.7% were in the 6–10-year age group and 74.4% had duration of illness 1-5 years. Acute complications, like hypoglycaemia, were experienced by 52.5% (severe hypoglycaemia by 4.7%) and DKA by 9.4% subjects. Height faltering was observed in 56.1% of the subjects and had a significant association with poor glycaemic control. Among chronic complications, 3.4% had microalbuminuria, 0.9% had nephropathy, 0.9% had retinopathy and 0.9% had cataract. Lipodystrophy was observed in 15.3%. Comorbidities observed included hypothyroidism in 10.3% and coeliac disease in 0.9%. Conclusions: At the time of diagnosis 56.8% had DKA. The major morbidities observed were hypoglycaemia and height faltering. Height faltering was significantly associated with poor glycaemic control. Micro-vascular complications were even detected in children <11years and duration of T1D <2 years.

Diabetes Complications Among Community-Based Health Center Patients with Varying Multimorbidity Patterns.

Multimorbidity with diabetes mellitus (DM and ≥ 1 chronic disease) presents challenges to maintaining adequate DM control. This study evaluates the risk of DM-related complications associated with various multimorbidity/DM patterns for patients seen in community-based health centers (CHCs). Retrospective cohort study from the ADVANCE multi-state practice-based clinical data network. Study included data from 132,765 patients age ≥ 45years with DM seen in 2493 CHCs across 26 states from 10/01/2015 to 12/31/2019. We assessed accrual of conditions and risk of experiencing DM complications during follow-up. Primary outcome of DM complication was categorized into acute, microvascular, microvascular (end-stage), macrovascular, or other. Key exposures included mutually exclusive multimorbidity categories: (1) DM + cardiometabolic, (2) DM + other somatic, (3) DM + mental, (4) DM + mental + somatic. At baseline, 17.2% of patients had DM only, 55.0% had DM + cardiometabolic multimorbidity, 2.3% had DM + other somatic multimorbidity, 3.0% had DM + mental multimorbidity, and 22.5% had DM + mental + somatic multimorbidity. Most DM-only patients (76.5%) developed multimorbidity with DM by study end. Compared with DM-only, adjusted risk differences of DM complications ranged from 1.4% (acute) to 8.8% (microvascular). DM + mental + somatic multimorbidity was associated with 13.4% (95%CI 12.8-14.1%) higher adjusted risk of experiencing any DM complication. CHCs care for increasingly complex populations of patients with DM. Tailoring disease management strategies to address comorbid cardiovascular and/or mental health conditions may be important to prevent acute, microvascular, and macrovascular complications in these settings.

A systematic review and meta analysis of genetic variants and covariates associated with diabetic retinopathy in the Indian population

BackgroundDiabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, is a leading cause of blindness worldwide. Conflicting results of association studies that have explored the contribution of genetic and environmental factors in conferring risk toward DR make it difficult to draw a plausible inference, thus necessitating a meta-analysis of all the concerned data on the risk factors documented from India.MethodsMeta-analysis (using the R software package) was conducted on the genotype data of 3972 cases (NPDR, i.e., non-proliferative diabetic retinopathy and PDR, i.e., proliferative diabetic retinopathy patients), 3407 controls (Type II diabetic individuals without retinopathy), and covariates from 16 studies from India selected through stringent text-mining from PubMed.ResultsTwo out of 12 SNPs from 6 genes, namely rs833061 of the VEGF gene and rs2070600 of the AGER gene showed nominal association with DR that however, did not hold true after FDR (false discovery rate) correction. Analysis carried out on 20 common covariates from all the selected studies revealed a significant association of 17 clinical covariates with DR. A follow-up global meta-analysis of the associated SNPs revealed a suggestive significant association of rs2070600 with DR in the recessive model.ConclusionNo significant association of polymorphic variants even in a meta-analysis among the Indians is probably indicative of the involvement of several rare variants with relatively low impact on DR susceptibility, at least in the Indian context.

Use of artificial intelligence with retinal imaging in screening for diabetes-associated complications: systematic review.

Use of artificial intelligence with retinal imaging in screening for diabetes-associated complications: systematic review.

A study of the association of thyroid-stimulating hormone levels with microvascular complications in type 2 diabetes mellitus patients at a tertiary care center

Background: Diabetes mellitus (DM) and hypothyroidism are two of the most common metabolic diseases worldwide. The prevalence of both conditions is drastically on the rise and if untreated is associated with long-term complications. Several studies have established the association between hypothyroidism and microvascular complications of diabetes. However, with the ever increasing diagnosis of sub-clinical hypothyroidism among diabetics, its association with the microvascular complications of DM needs to be studied. Aims and Objectives: The aims of this study were to study the association between thyroid-stimulating hormone (TSH) levels and microvascular complications of type 2 DM (T2 DM). DM is a metabolic disease which affects various organs of the body. The prevalence of T2 DM is on the rise much more rapidly, which is due to increasing obesity and reduced activity levels. Undiagnosed thyroid dysfunction may affect metabolic control and enhance cardiovascular and other chronic complication in diabetic patients. Materials and Methods: A total of 50 T2 DM patients were enrolled in this cross-sectional study. Subjects were evaluated for thyroid function, microvascular complications such as peripheral neuropathy, diabetic retinopathy, and diabetic kidney disease. TSH was divided into three levels: 0.27–2.49 mU/L, 2.5–4.2 mU/L, and >4.2 mU/L. The association between TSH levels and microvascular complications of T2 DM was studied. Results: Our study found a statistically positive association elevated TSH and microalbuminuria, macroalbuminuria, low GFR, and impaired vibration sense. Our study found no association between elevated TSH and retinopathy. Conclusion: It is ideal to screen all patients with T2 DM for thyroid dysfunction as elevated TSH levels in these patients can be an indicator of underlying microvascular complications.

Correlation Between Triglyceride-Glucose Index and Microvascular Complications in Patients With Early- Onset of Type 2 Diabetes Mellitus.

This study aimed to explore the potential correlation between the triglyceride-glucose (TyG) index and diabetic nephropathy (DN) and diabetic retinopathy (DR) in patients with early-onset type 2 diabetes mellitus (T2DM). This cross-sectional study statistically analysed TyG index levels across DN and DR stages in patients with early-onset and non-early-onset T2DM. A total of 1530 T2DM patients were enrolled between January 2017 and August 2023 at Tianjin Fourth Central Hospital in Tianjin. Correlation analysis and logistic regression were used to examine the association between the TyG index and microvascular complications. Kaplan-Meier plots and Cox regression analyses were employed to evaluate the effects of the TyG index on DN incidence. TyG index's diagnostic ability for DN was explored using the area under the receiver operating characteristic curve. In patients with early-onset T2DM, the TyG index gradually decreased with DR aggravation and gradually increased with DN aggravation, showing a negative correlation with DR and a positive correlation with DN in patients with early-onset T2DM; logistic regression analysis suggested that the TyG index was an independent risk factor for DN (OR = 1.623, 95% CI = 1.175-2.242). The Cox regression analysis and Kaplan-Meier plots suggested that higher TyG was associated with an earlier incidence of DN in patients with early-onset T2DM. In patients with early-onset T2DM, the TyG index could be used to evaluate the risk of microvascular complications, with elevated TyG levels potentially indicating high risk of insulin- resistance related renal injury.

AT1, a small molecular degrader of BRD4 based on proteolysis targeting chimera technology alleviates renal fibrosis and inflammation in diabetic nephropathy.

AT1, a small molecular degrader of BRD4 based on proteolysis targeting chimera technology alleviates renal fibrosis and inflammation in diabetic nephropathy.

Elevated Triglyceride-Glucose Index as a Risk Stratification Marker for Diabetic Retinopathy in Type 2 Diabetes Mellitus: The Influence of Glycemic Control.

Diabetic retinopathy (DR) is a common microvascular complication observed in people with type 2 diabetes mellitus (T2DM). The triglyceride-glucose (TyG) index, an indicator of insulin resistance, has an uncertain role in glycemic management in T2DM patients at risk for DR. This study aimed to evaluate the association between the TyG index and DR risk across different glycemic control status. A total of 4,372 T2DM in-patients from Beijing Tongren Hospital (2013-2024) were included in this study. The patients were categorized into four groups based on TyG index quartiles (Q1-Q4). Participants were stratified by TyG index quartiles (Q1-Q4) and glycemic control status (HbA1c <7%, 7-9%, and >9%). Restricted cubic spline (RCS) analysis, logistic regression, and subgroup analyses were employed to explore the associations among the TyG index, glycemic control and DR risk. Overall, there were positive association of the TyG index and DR risk. The highest TyG Q4 was significantly associated with an increased risk of DR (odds ratio [OR]: 1.289; 95% confidence interval [CI]: 1.008-1.648, P<0.05), compared with the lowest TyG Q1. Significant interaction was observed between the TyG index and glycemic control (P for interaction <0.05). Notably, the association was strongest in patients with HbA1c >9%. The relationship between high TyG index and DR risk was more pronounced in patients with HbA1c >9% group, indicating that TyG index may serve as a useful tool for making risk stratification on glycemic control in T2DM patients.

Bridging Pubertal Changes and Endotype Based Therapy in Type 1 Diabetes

ABSTRACTThe intersection of puberty with the onset of type 1 diabetes (T1D) presents unique pathogenic, clinical and psychosocial challenges, necessitating nuanced management strategies that account for developmental changes and the disease's heterogeneity. The distinction between pre‐pubertal (T1DE1) and pubertal (T1DE2) T1D onset underscores the need for tailored approaches to monitoring and therapy during this critical period. Patients, with severe β‐cell loss and heightened metabolic demands during puberty, require more intensive glycaemic management and screening for growth delays and pubertal disruptions. Meanwhile, pubertal T1D patients, though benefiting from relatively preserved β‐cell function, still face heightened risks of insulin resistance and comorbidities such as obesity that demand vigilant monitoring and individualised interventions. Key actionable recommendations include implementing systematic screening protocols for growth impairment, menstrual abnormalities, and early markers of microvascular complications. Advanced technologies such as continuous glucose monitors and automated insulin delivery systems to reduce the glycaemic burden before and during puberty warrant robust investigation. The integration of behavioural interventions that enhance self‐regulation and family‐centred care into routine diabetes management can yield valuable insights into improving adherence and glycaemic control.

Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations.

Unveiling ferroptosis genes and inhibitors in diabetic retinopathy through single-cell analysis and docking simulations.

Effect of the glucagon-like peptide-1 receptor agonists dulaglutide on kidney outcomes in db/db mice.

Effect of the glucagon-like peptide-1 receptor agonists dulaglutide on kidney outcomes in db/db mice.