Development Of Microvascular Complications Research Articles

Связь однонуклеотидного полиморфизма rs4880 гена SOD2 с развитием микрососудистых осложнений сахарного диабета 2-го типа

Связь однонуклеотидного полиморфизма rs4880 гена SOD2 с развитием микрососудистых осложнений сахарного диабета 2-го типа

The Impact of Body Mass Index, Residual Beta Cell Function and Estimated Glucose Disposal Rate on the Development of Double Diabetes and Microvascular Complications in Patients With Type 1 Diabetes Mellitus.

Background The clinical impact of body mass index (BMI), residual beta cell function and estimated glucose disposal rate (eGDR) in the development of double diabetes (DD) and microvascular complications are largely unknown. We aimed to assess whether BMI, residual beta cell function measured by plasma "C" peptide and insulin resistance measured by eGDR have any impact on the development of DDand microvascular complications in patients with type 1 diabetes mellitus (T1DM). Methods It is a cross-sectional observational study involving 113 T1DM patients of more than five years duration who were classified into two groups: normal BMI (18.5-22.9 kg/m2) and overweight/obese group (≥ 23kg/m2) based on Asian BMI classification. Based on their eGDR values, they were grouped into four categories: ≥ 8, 6-7.99, 4-5.99, and < 4 mg/kg/min. The prevalence of DD based on eGDR values was determined. Their BMI and different eGDR categories were compared with the prevalence of diabetic retinopathy and nephropathy and their odds ratio (OR) was calculated. Results The median and interquartile range (IQR) of the eGDR of the overweight/obese group was significantly lower than the normal BMI group (5.3 [3.96-8.15] vs 8.72 [6.50-9.77 mg/kg/min], p < 0.001). The prevalence of DD in the overweight/obese T1DM group and normal BMI group was 75% and 33.3% respectively. The ORof retinopathy and nephropathy in the overweight/obese group was 3.28 (p = 0.007) and 3.01 (p = 0.015) respectively when compared to the normal BMI group. The OR of retinopathy and nephropathy in T1DM patients with eGDR < 4 mg/kg/min was 17.13 (p = 0.001) and 18.5 (p = 0.001) respectively. The lower the eGDR values, the higher the prevalence of retinopathy and nephropathy regardless of HbA1c levels. Conclusion As overweight and obesity are increasingly becoming more prevalent in T1DM, the eGDR will better predict the development of DD and microvascular complications irrespective of HbA1c levels. It is more useful as a variable and easily inducted into routine clinical practice. However, residual beta cell function was not useful in predicting the development of microvascular complications.

Does prediabetes diagnosed by hemoglobinA1c or oral glucose tolerance test predict coronary artery disease in patients suspected of chronic coronary syndrome?

Abstract Introduction The presence of prediabetes worsens the prognosis of coronary artery disease, as patients with prediabetes are known to have an almost doubled cardiovascular mortality risk compared to normoglycemic patients. In clinical practice, HemoglobinA1c (HbA1c) has replaced the oral glucose tolerance test (OGTT) in the diagnosis of prediabetes. However, the background for the HbA1c threshold is based on the development of microvascular complications and progression to established diabetes. It remains unclear whether the substitution of OGTT with HbA1c results in an underestimation of prediabetics with a high risk of coronary artery disease, or if HbA1c is associated with macrovascular complications in prediabetic patients. Purpose We aimed to investigate whether HbA1c- or OGTT-diagnosed prediabetes could predict presence and severity of coronary artery disease in patients suspected of chronic coronary syndrome. Methods This was a descriptive cross-sectional study of 702 patients referred to a coronary CT angiography due to suspicion of chronic coronary syndrome. Coronary artery calcification (CAC)-score, presence of plaque and significant stenosis (&amp;gt;50%), and plaque characteristics were evaluated. All patients had a fasting OGTT and blood samples performed. Patients were categorized according to glycemic status by HbA1c and OGTT, and compared to their test-specific range. Results Prediabetes was detected by HbA1c 167 (24%) or OGTT 272 (39%), and an overlap in classification by both tests was seen in 98 (22%) of participants. Both classifications of prediabetes showed increased presence of plaques, significant stenosis, calcified plaques, and correspondingly, a low frequency of a CAC-score=0 compared to their test-specific normal. Additionally, the HbA1c-prediabetics had an increased frequency of a high CAC score &amp;gt;400 compared to normal HbA1c (23% vs. 10%, p&amp;lt;0.0001). In the multiple logistic regression analysis the HbA1c-prediabetics had an odds ratio (OR) of 1.5 for plaque presence (confidence interval (CI) 1.0;2.4) and OR 2.1 for a CAC-score &amp;gt;400 (CI 1.3;3.5). None of the associations for the OGTT-prediabetics were significant in the logistic regression analysis. Receiver operating characteristic curves were applied to the significant logistic associations. The HbA1c-prediabetics had an area under the curve (AUC)=0.77 for plaque presence and AUC=0.81 for CAC-score &amp;gt;400. Conclusion Prediabetes defined by HbA1c can predict presence and severity of coronary artery disease. Although OGTT identified more patients as having prediabetes, their risk of coronary artery disease was not attributable to prediabetes. Thus, our results support the replacement of OGTT with HbA1c in clinical practice.

Proliferative diabetic retinopathy as the initial presenting feature of type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the destruction of the pancreatic beta cells, which produce insulin. Individuals with T1DM usually require at least 3-5 years to develop microvascular complications in comparison to people with type 2 diabetes (T2DM), who may develop complications even before the diagnosis of diabetes. We discuss a patient who presented with proliferative diabetic retinopathy subsequently diagnosed with T1DM and diabetic neuropathy following investigations. Diabetic retinopathy or other microvascular complications as the presenting feature of T1DM is rarely known or reported in the literature. A 33-year-old healthcare worker had been seen by the opticians due to 1-week history of blurred vision. The ophthalmology assessment had confirmed proliferative retinopathy in the right eye and severe non-proliferative retinopathy in the left eye with bilateral clinically significant macular oedema. His BMI was 24.9 kg/m2. The nervous system examination revealed bilateral stocking type peripheral neuropathy. The random venous glucose was 24.9 mmol/L. Plasma ketones were 0.7 mmol/L and HbA1c was 137 mmol/mol. On further evaluation, the anti-glutamic acid decarboxylase (GAD) antibody was positive, confirming the diagnosis of T1DM. He was started on aflibercept injections in both eyes, followed by panretinal photocoagulation. Subsequent nerve conduction studies confirmed the presence of symmetrical polyneuropathy. The pathogenesis of the development of microvascular complications in T1DM is multifactorial. Usually, the development of complications is seen at least a few years following the diagnosis. The occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important in preventing the progression of the disease. The pathogenesis of the development of microvascular complications in type 1 diabetes mellitus is multifactorial. The development of complications is seen at least a few years following the diagnosis. Occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important to prevent the progression of the disease.

Vitamin D deficiency and development of complications in individuals with type 1 and type 2 diabetes: A cohort study

AimsTo investigate vitamin D deficiency as a risk marker for complications in individuals with type 1 and type 2 diabetes. MethodsA cohort study including 1448 adults with type 1 and 770 with type 2 diabetes. Individuals in the decile with lowest vitamin D level were classified as vitamin D deficient. Outcomes based on medical records and registers included mortality, major adverse cardiovascular event (MACE), heart failure, a composite kidney endpoint, albuminuria progression and sight-threatening eye disease. Risk in individuals with vitamin D deficiency was compared to the remaining using adjusted Cox proportional hazards models. ResultsVitamin D deficiency was associated with higher risk of MACE (adjusted hazard ratio (HR): 2.6; 95 % confidence interval (CI): 1.3–5.2) in type 1, but not in type 2 diabetes. Risk of heart failure was higher in individuals with vitamin D deficiency in both cohorts (HR (95%CI): 16 (4.8–50) in type 1 and 2.4 (1.1–5.5) in type 2 diabetes). Vitamin D deficiency was not associated with development of microvascular complications or mortality. ConclusionsVitamin D deficiency was a risk marker for MACE and heart failure in type 1 and for heart failure in type 2 diabetes, but not for microvascular complications or all-cause mortality.

The Potential of West Sumatran Dadiah as The Novel to Alleviate Hyperglycemia, Hypercholesterolemia, and Reducing NF-kB Expression in Nephropathy Diabetes Rat Model

Diabetic nephropathy (DN) is the most common microvascular complication in diabetes mellitus (DM) patients. The main mechanism for the development of DN is an inflammatory reaction as indicated by increased expression of NF-kB in kidney tissue due to chronic hyperglycemia and hypercholesterolemia. Hyperglycemia is related to changes in the composition of the microbiota which can cause dysbiosis. The therapeutic approach in DM sufferers using probiotics needs attention. Dadiah is a naturally fermented buffalo milk product in bamboo tubes. Even though this probiotic has health benefits, its mechanism as an antidiabetic is not widely known. This study aims to reduce blood sugar, cholesterol, and inflammatory marker NF-kB levels after Dadiah treatment. This study was an experimental animal study using 7 groups, each group of 6 rats, 8 weeks of intervention, and evaluation of serum glucose and cholesterol every 2 weeks. NF-kB expression in kidney tissue was examined after 8 weeks of the termination phase. We examined their effect on blood glucose levels, serum cholesterol, and NF-kB antibody expression in kidney tissue using immunohistochemical assays. probiotic metabolites in intraperitoneal Alloxan-induced diabetic rats 100 mg/kg b. w. The results showed the potential of Dadiah and its metabolites to significantly (one-way ANOVA test) reduce hyperglycemia and serum cholesterol and inhibit oxidative stress by reducing NF-kB expression in kidney tissue after treatment. Dadiah probiotics should be considered as a nutritional companion in DN and as a future therapeutic target for DM patients to prevent the development of microvascular complications and hypercholesterolemia. HIGHLIGHTS Dadiah is a naturally fermented buffalo milk product in bamboo tubes. Dadiah (Probiotic) originating from West Sumatra, Indonesia acts as an antidiabetic. Dadiah and its metabolites significantly reduced hyperglycemia and serum cholesterol and inhibited oxidative stress by reducing NF-kB expression in kidney tissue after treatment. Dadiah probiotics should be considered as a nutritional companion in diabetic nephropathy and as a future therapeutic target for DM patients to prevent the development of microvascular complications and hypercholesterolemia. GRAPHICAL ABSTRACT

Computational Analysis of ZINC Analogues for Antidiabetic Phytochemical with Inhibitory Activity against Aldose Reductase Enzyme

The pathognomonic role of sorbitol pathway in the development of microvascular complications cannot go underappreciated; while it may not be a sole independent initiator, it remains a key contributor to the initiation and progression of diabetic microangiopathies, particularly retinopathy, neuropathy, and nephropathy. The sorbitol pathway is a two-step reaction process initiated by the rate-limiting enzyme aldose reductase. This study aimed to screen ZINC databases for chemical compounds similar to Ellagic acid, Kaempferol, and Mangiferin and analyze their pharmacokinetic, toxicological and docking profile using computational methods. These phytochemicals were chosen based on literature review of ethnobotanical studies and validated via SwissTargetPrediction. An in-silico study design was employed using computational algorithms. Molecular structures of analogues were obtained from ZINC database and prepared using Avogadro software. Docking analysis was carried out using AutoDock Vina embedded in Chimera. Visualization of ligand-enzyme interactions was done using Discovery studio. SWISSADME and Protox-II were used to profile pharmacokinetic and toxicity of the analogs. A total of 44 analogs were analyzed. Sulindac and parent phytochemicals were used as comparators. Kaempferol had strongest binding affinity (-8.7) followed by Ellagic acid and Mangiferin tying at -8.4. Kaempferol analogs had highest binding affinity compared to analogues of Ellagic acid and Mangiferin. In terms of Pharmacokinetic profile, analogues of Ellagic acid demonstrated a favorable profile with no Lipinski rule violations, high GI absorption, and inhibition limited to CYP1A2, which plays a minor role in drug metabolism compared to other enzymes. Toxicology predictions indicated that Kaempferol exhibited a higher safety profile compared to Ellagic acid and Mangiferin, with LD50 values of 3919 mg/kg, 2991 mg/kg, and 2 mg/kg, respectively. Ellagic acid analogues demonstrated chemical safety, absence of mutagenicity, hepatotoxicity, cytotoxicity, and activation of various pathways. Among the Kaempferol analogues, a subset was potentially carcinogenic and mutagenic, while all exhibited potential pathway activation. Mangiferin analogues, except for a few compounds, did not activate specific pathways, nor did they demonstrate hepatotoxicity or cytotoxicity. However, some analogues exhibited potential immunogenicity and mutagenicity. Kaempferol and some of its ZINC analogues had strongest binding affinity compared to Ellagic acid, Mangiferin and their analogues. This can be attributed to the simpler structure of Kaempferol, allowing it to fit snugly into the hydrophobic pocket of aldose reductase. Ellagic acid, with its planar and rigid structure, interacted primarily with the outer surface of the hydrophobic pocket. Similarly, due to its complex and large structure, Mangiferin demonstrated a relatively lower affinity. Analogues ZINC000005004393, ZINC000003872446, and ZINC000031156069 for Kaempferol, Ellagic acid, and Mangiferin respectively depicted the best optimal characteristics required for further development. We recommend an in vitro study be conducted to assess and validate the claims arrived at in this study

Both LDL and HDL particle concentrations associate positively with an increased risk of developing microvascular complications in patients with type 2 diabetes: lost protection by HDL (Zodiac-63)

BackgroundTriglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL) are associated positively whereas high-density lipoproteins (HDL) are associated inversely with the development of new-onset type 2 diabetes (T2D). Here we studied potential associations between these lipoprotein particle concentrations and the risk of developing microvascular complications in patients with established T2D.MethodsLipoprotein particle concentrations (TRLP, LDLP, and HDLP) were determined in 278 patients with T2D participating in a primary care-based longitudinal cohort study (Zwolle Outpatient Diabetes project Integrating Available Care [ZODIAC] study) leveraging the Vantera nuclear magnetic resonance (NMR) platform using the LP4 algorithm. Associations between lipoprotein particles and incident microvascular complications (nephropathy, neuropathy, and retinopathy) were assessed using Cox proportional hazards regression models.ResultsIn total, 136 patients had microvascular complications at baseline. During a median follow-up of 3.2 years, 49 (34.5%) of 142 patients without microvascular complications at baseline developed new-onset microvascular complications. In multivariable Cox proportional hazards regression analyses, both total LDLP and HDLP concentrations, but not total TRLP concentrations, were positively associated with an increased risk of developing any microvascular complications after adjustment for potential confounding factors, including age, sex, disease duration, HbA1c levels, history of macrovascular complications, and statin use (adjusted hazard ratio [HR] per 1 SD increment: 1.70 [95% CI 1.24–2.34], P < 0.001 and 1.63 [95% CI 1.19–2.23], P = 0.002, respectively). When analyzing each microvascular complication individually, total LDLP concentrations were positively associated with retinopathy (adjusted HR 3.35, 95% CI 1.35–8.30, P = 0.009) and nephropathy (adjusted HR 2.13, 95% CI 1.27–3.35, P = 0.004), and total HDLP concentrations with neuropathy (adjusted HR 1.77, 95% CI 1.15–2.70, P = 0.009). No significant associations were observed for lipoprotein particle subfractions.ConclusionsTotal lipoprotein particle concentrations of both LDL and HDL associate positively with an increased risk of developing microvascular complications in T2D. We propose that the protective role of HDL on the development of microvascular complications may be lost in established T2D.

FAKTOR DETERMINAN PENGETAHUAN, SIKAP, DAN PRAKTIK PASIEN DIABETES TERHADAP DIABETIK NEUROPATI, NEFROPATI DAN RETINOPATI

Background: The contribution of potential knowledge, attitudes and practices related to microvascular complications of diabetes is a determinant factor to consider. Objectives: Research is projected to determine the prevalence of DM characteristics and microrvascular complications, the potential for KAP to complications, health-seeking behaviors, follow-up problems, stigma and sources of information. Method: The cross-sectional approach is the main choice of research design in this study. This study took place in February – November 2021 which succeeded in recruiting the research subjects of 375 patients in Makassar City with diabetes observed. Results: The characteristics of DM type in this study included 3 types (DM type 1, DM type 2 and gestational DM), which were dominated by DM type 2, 310 (82.23%), followed by DM type 1, 59 (15.65%) and the smallest was Gestational diabetes 6 (2.12%) from 375 patients. The correlation of significance between quality of life and DM was shown to have positive values in aspects of knowledge and practice (r = 0.1; p = 0.002 ; r = 0.3;  p=0.02), only the negative attitude aspect (r=-0.2;  p=0.002). The correlation of knowledge of DM patients is directly proportional to the absence of: microvascular complications of diabetes (5.10 ± 2.64 versus 1.12 ± 0.33;  P&lt;0.001), coronary artery disease (3.69 ± 2.65 versus 2.08 ± 2.25;  P&lt;0.001), dyslipidemia (2.85 ± 2.58 versus 1.89 ± 2.07; p&lt;0.001), hypertension (2.86 ± 2.62 versus 1.98 ± 2.11; p&lt;0.001). Conclusion: This study provides invaluable information in helping to design and develop a supporting program model to educate and train DM patients and health workers professionally, especially in health service facilities in Makassar City in order to minimize the development of microvascular complications of diabetes

Altered high-density lipoprotein composition is associated with risk for complications in type 2 diabetes mellitus in South Asian descendants: A cross-sectional, case-control study on lipoprotein subclass profiling.

Composition of high-density lipoproteins (HDL) is emerging as an important determinant in the development of microvascular complications in type 2 diabetes mellitus (T2DM). Dutch South Asian (DSA) individuals with T2DM display an increased risk of microvascular complications compared with Dutch white Caucasian (DwC) individuals with T2DM. In this study, we aimed to investigate whether changes in HDL composition associate with increased microvascular risk in this ethnic group and lead to new lipoprotein biomarkers. Using 1 H nuclear magnetic resonance spectroscopy and Bruker IVDr Lipoprotein Subclass Analysis (B.I.LISA) software, plasma lipoprotein changes were determined in 51 healthy individuals (30 DwC, 21 DSA) and 92 individuals with T2DM (45 DwC, 47 DSA) in a cross-sectional, case-control study. Differential HDL subfractions were investigated using multinomial logistic regression analyses, adjusting for possible confounders including BMI and diabetes duration. We identified HDL compositional differences between healthy and diabetic individuals in both ethnic groups. Specifically, levels of apolipoprotein A2 and HDL-4 subfractions were lower in DSA compared with DwC with T2DM. Apolipoprotein A2 and HDL-4 subfractions also negatively correlated with waist circumference, waist-to-hip ratio, haemoglobin A1c, glucose levels and disease duration in DSA with T2DM, and associated with increased incidence of microvascular complications. While HDL composition differed between controls and T2DM in both ethnic groups, the lower levels of lipid content in the smallest HDL subclass (HDL-4) in DSA with T2DM appeared to be more clinically relevant, with higher odds of having diabetes-related pan-microvascular complications such as retinopathy and neuropathy. These typical differences in HDL could be used as ethnicity-specific T2DM biomarkers.

Utility of apolipoprotein ratio in predicting metabolic risk and microvascular complications in Indian children and young adults with type 1 diabetes mellitus.

To assess the relationship of apolipoproteins with glycemic control and insulin resistance (IR) in Indian children and youth with type-1 diabetes (T1D) and to assess its utility in predicting metabolic risk (MR) and microvascular complications in these subjects. This cross-sectional study included 152 participants aged 6-23 years with T1D. Demographic, anthropometric, clinical, biochemical and body composition data were obtained using standard protocols. IR was calculated using estimated glucose disposal rate (eGDR) and metabolic syndrome (MS) was diagnosed using the international diabetes federation consensus definition 2017. Apolipoprotein ratio in subjects with T1D had negative and positive correlation with eGDR and HbA1c respectively. Positive correlation of Apolipoproten B and apolipoprotein ratio with urinary albumin creatinine ratio is noted. The ratio had area under curve of 0.766 and 0.737 to predict MR and microvascular complications respectively. The ratio cut-off of 0.536 yielded 77.1 % sensitivity and 61 % specificity to predict MR. On adding the apolipoprotein ratio as a predictor to the regression model developed to predict MR, the R2 and accuracy improved. The apolipoprotein ratio had significant correlation with IR, microalbuminuria and glycaemic control. The ratio also predicts risk of development of microvascular complications and maybe used to predict MR in subjects with T1D.

Vitamin D Levels and Microvascular Complications in Type 2 Diabetes Mellitus Patients: A Study from North Keral

Introduction: Vitamin D plays an important role in glucose metabolism. Several pleiotropic effects of Vitamin D have been studied like regulation of cell proliferation, suppression of cell mediated immunity, Glial cell line-derived neurotrophic factor, stimulation of nerve growth factor, suppression of Renin-angiotensin-aldosterone system (RAAS), reduction of albuminuria, immunomodulatory effects, and anti-inflammatory effects.(1)Thus, vitamin D is implicated in the pathogenesis of retinopathy, neuropathy and nephropathy.&#x0D; Materials and Methods: A Cross-sectional case-control study of 206 patients (&gt;30 years), who met the American Diabetes Association, 2011 criteria (2) for type 2 DM, was conducted. Subjects were evaluated for the presence of microvascular complications by clinical evaluation, urine examination, fundus examination, clinical neuropathy scoring, and various biochemical tests. 25-OH cholecalciferol levels were done and cut off level for vitamin D deficiency was 30 ng/ml. 72 Vitamin D sufficient and 134 Vitamin D deficient cases were studied.&#x0D; Results: A total of 134 T2DM cases with Vitamin D deficiency were studied. 72 age matched T2DM patients with sufficient Vitamin D levels served as controls. The mean age of cases under study was 47.58 ± 9.63 years compared to 51.24 ± 8.75 years of controls. 61.2% were females, whereas 38.8% were males in the case group while in the control group, 69.4% were males, and 30.5% were females. The mean duration of diabetes in the cases studied was 57.08 ± 18.13 months. It was 52.69 ± 17.98 months in the Vitamin D sufficient controls.  Significant statistical associations were established using Chi square test between Vitamin D status and development of microvascular complications like Diabetic nephropathy, retinopathy and neuropathy in Type 2 Diabetes Mellitus at p &lt; 0.05.&#x0D; Conclusion and Implication: Vitamin D is an important factor in modifying the risk of Type 2 DM and its microvascular complications, especially Diabetic retinopathy, neuropathy and nephropathy. Administration of vitamin D supplements may prove to be a beneficial adjuvant therapy in mitigating microvascular complications. Frequent Monitoring of Vitamin D status can decrease the burden of co-morbidities in T2DM and thus can decrease the mortality rate associated with T2DM. However; the exact role of vitamin D in these processes requires further investigations.&#x0D; Keywords:&#x0D; Diabetes, Nephropathy, Neuropathy, Retinopathy, Vitamin D

Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling

Hyperglycemia plays a key role in the development of microvascular complications, endothelial dysfunction (ED), and inflammation. It has been demonstrated that cathepsin S (CTSS) is activated in hyperglycemia and is involved in inducing the release of inflammatory cytokines. We hypothesized that blocking CTSS might alleviate the inflammatory responses and reduce the microvascular complications and angiogenesis in hyperglycemic conditions. In this study, we treated human umbilical vein endothelial cells (HUVECs) with high glucose (HG; 30 mM) to induce hyperglycemia and measured the expression of inflammatory cytokines. When treated with glucose, hyperosmolarity could be linked to cathepsin S expression; however, many have mentioned the high expression of CTSS. Thus, we made an effort to concentrate on the immunomodulatory role of the CTSS knockdown in high glucose conditions. We validated that the HG treatment upregulated the expression of inflammatory cytokines and CTSS in HUVEC. Further, siRNA treatment significantly downregulated CTSS expression along with inflammatory marker levels by inhibiting the nuclear factor-kappa B (NF-κB) mediated signaling pathway. In addition, CTSS silencing led to the decreased expression of vascular endothelial markers and downregulated angiogenic activity in HUVECs, which was confirmed by a tube formation experiment. Concurrently, siRNA treatment reduced the activation of complement proteins C3a and C5a in HUVECs under hyperglycemic conditions. These findings show that CTSS silencing significantly reduces hyperglycemia-induced vascular inflammation. Hence, CTSS may be a novel target for preventing diabetes-induced microvascular complications.

The association of cell adhesion molecules and selectins (VCAM-1, ICAM-1, E-selectin, L-selectin, and P-selectin) with microvascular complications in patients with type 2 diabetes: A follow-up study.

Chronic hyperglycemia induces pathogenic changes in the vascular endothelium and leads to the development of microvascular complications in patients with type 2 diabetes mellitus. Early identification of markers of diabetes complications may help to minimize the risk of the development and progression of microvascular complications. This follow-up study was conducted in type 2 diabetic cohort aged between 30-70 years. Out of 160 eligible participants, 70 of them completed follow-up. Levels of cell adhesion molecules and selectins (VCAM-1, ICAM-1, E-selectin, L-selectin and P-selectin) at baseline and follow-up were measured using Randox Evidence biochip analyzer (UK). Development of microvascular complications (diabetic neuropathy, retinopathy and nephropathy) was evaluated. During the follow-up (2 years, median), 31 (44.3%) developed diabetic neuropathy, 10 (14.3%) developed diabetic retinopathy and, 27 (38.6%) developed diabetic nephropathy. A significant difference in levels of cell adhesion molecules and selectins were found in type 2 diabetic patients with and without microvascular complications. Multiple logistic regression analysis reveals that baseline level of VCAM-1 is significantly associated with microvascular complications; diabetic neuropathy(p=0.028), retinopathy (p=0.007) and nephropathy(p=<0.001). Additionally, levels of P-selectin (p=0.05) and L-selectin (p=0.008) is associated with diabetic nephropathy while retinopathy associated with L-selectin (p=0.005) only. Cell adhesion molecules and selectins are indicators of microvascular complication among patients with type 2 diabetes (T2D). Association of these markers with the development of microvascular complications may provide additive information for developing strategies for diabetes management and prediction of microvascular complications.

Plasma levels of GlycA, a pro-inflammatory glycoprotein biomarker, associate with an increased risk of microvascular complications in patients with type 2 diabetes (Zodiac-62).

GlycA, a pro-inflammatory glycoprotein biomarker, associates with newly developed type 2 diabetes (T2D). We determined the association of plasma GlycA with the development of microvascular complications in patients with established T2D. Plasma GlycA was measured by nuclear magnetic resonance spectrometry in T2D patients without microvascular complications at baseline (n = 145) participating in a longitudinal cohort study of primary care-treated T2D patients (Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study). Associations of GlycA with incident microvascular complications including nephropathy, retinopathy, and neuropathy, were determined by Cox proportional hazards regression analyses. After a median follow-up of 3.2 (interquartile range [IQR]: 2.9-3.4) years, 49 patients (33.8%) developed one or more microvascular complications. Median GlycA levels were 453.5 (IQR: 402.0-512.8) μmol/l. GlycA was associated with incident microvascular complications (hazard ratio [HR] per 1-SD increment: 1.28 [95% confidence interval [CI]:1.00-1.63], P = 0.048]), even after adjustment for potential confounders and high-sensitive C-reactive protein (hs-CRP), HR 1.79 [95%CI:1.25-2.57], P = 0.001). In contrast, hs-CRP levels were not significantly associated with the risk of developing microvascular complications (P = 0.792). Higher plasma GlycA is associated with an increased risk of developing microvascular complications in T2D patients. Altered N-glycan branching associated with acute-phase reactive proteins may represent a preferred biomarker of systemic low-grade inflammation in predicting diabetic complications.

THE IMPACT OF TOTAL PHYSICAL ACTIVITY ON MICROVASCULAR COMPLICATIONS IN TYPE 1 DIABETES MELLITUS PATIENTS.

The incidence of diabetes is increasing worldwide, emphasizing an emerging need for blood glucose control optimization to prevent the development of chronic complications and improve the quality of life. This retrospective cohort study aimed to investigate the effects of total physical activity on microvascular diabetic complication development in patients with type 1 diabetes mellitus (T1DM). The study included 71 T1DM patients, average age 41 years and HbA1c 7.78%. Most patients (82.1%) reported having hypoglycemia, while the minority of patients developed microvascular complications, mostly nonproliferative retinopathy (17.7%). All subjects included in the study were moderately or vigorously physically active. No association was observed between total physical activity and regulation of glycemia, hypoglycemic incidents, or development of microvascular complications. Until sufficient data from prospective studies become available, our data support the findings of no negative effect of higher intensity physical activity on the development of microvascular complications in T1DM patients.

Immunothrombosis and Complement Activation Contribute to Disease Severity and Adverse Outcome in COVID-19

Severe COVID-19 is characterized by systemic inflammation and multiple organ dysfunction syndrome (MODS). Arterial and venous thrombosis are involved in the pathogenesis of MODS and fatality in COVID-19. There is evidence that complement and neutrophil activation in the form of neutrophil extracellular traps are main drivers for development of microvascular complications in COVID-19. Plasma and serum samples were collected from 83 patients infected by SARS-CoV-2 during the two first waves of COVID-19, before the availability of SARS-CoV-2 vaccination. Samples were collected at enrollment, day 11, and day 28; and patients had differing severity of disease. In this comprehensive study, we measured cell-free DNA, neutrophil activation, deoxyribonuclease I activity, complement activation, and D-dimers in longitudinal samples of COVID-19 patients. We show that all the above markers, except deoxyribonuclease I activity, increased with disease severity. Moreover, we provide evidence that in severe disease there is continued neutrophil and complement activation, as well as D-dimer formation and nucleosome release, whereas in mild and moderate disease all these markers decrease over time. These findings suggest that neutrophil and complement activation are important drivers of microvascular complications and that they reflect immunothrombosis in these patients. Neutrophil activation, complement activation, cell-free DNA, and D-dimer levels have the potential to serve as reliable biomarkers for disease severity and fatality in COVID-19. They might also serve as suitable markers with which to monitor the efficacy of therapeutic interventions in COVID-19.

Potential Roles of Anti-Inflammatory Plant-Derived Bioactive Compounds Targeting Inflammation in Microvascular Complications of Diabetes.

Diabetes mellitus (DM) is a group of metabolic disorders, the characteristics of which include chronic hyperglycemia owing to defects in insulin function, insulin secretion, or both. Inflammation plays a crucial role in DM pathogenesis and innate immunity in the development of microvascular complications of diabetes. In addition, hyperglycemia and DM mediate a proinflammatory microenvironment that can result in various microvascular complications, including diabetic nephropathy (DNP), diabetic neuropathy (DN), and diabetic retinopathy (DR). DNP is a major cause of end-stage renal disease. DNP can lead to albuminuria, decreased filtration, mesangium expansion, thickening of the basement membrane, and eventually renal failure. Furthermore, inflammatory cells can accumulate in the interstitium and glomeruli to deteriorate DNP. DN is another most prevalent microvascular complication of DM and the main cause of high mortality, disability, and a poor quality of life. DNs have a wide range of clinical manifestations because of the types of fiber dysfunctions and complex structures of the peripheral nervous system. DR is also a microvascular and multifactorial disease, as well as a major cause of visual impairment globally. Pathogenesis of DR is yet to be fully revealed, however, numerous studies have already confirmed the role of inflammation in the onset and advancement of DR. Despite evidence, and better knowledge regarding the pathogenesis of these microvascular complications of diabetes, there is still a deficiency of effective therapies. Bioactive compounds are mainly derived from plants, and these molecules have promising therapeutic potential. In this review, evidence and molecular mechanisms regarding the role of inflammation in various microvascular complications of diabetes including DNP, DN, and DR, have been summarized. The therapeutic potential of several bioactive compounds derived from plants in the treatment of these microvascular complications of diabetes has also been discussed.

Prediction of microvascular complications in diabetic patients without obstructive coronary stenosis based on peri-coronary adipose tissue attenuation model.

To investigate the predictive value of peri-coronary adipose tissue (PCAT) attenuation for microvascular complications in diabetic patients without significant stenosis and to develop a prediction model for early risk stratification. This study retrospectively included patients clinically identified for coronary computed tomography angiography (CCTA) and type 2 diabetes between January 2017 and December 2020. All patients were followed up for at least 1 year. The clinical data and CCTA-based imaging characteristics (including PCAT of major epicardial vessels, high-risk plaque features) were recorded. In the training cohort comprising of 579 patients, two models were developed: model 1 with the inclusion of clinical factors and model 2 incorporating clinical factors + RCAPCAT using multivariable logistic regression analysis. An internal validation cohort comprising 249 patients and an independent external validation cohort of 269 patients were used to validate the proposed models. Microvascular complications occurred in 69.1% (758/1097) of the current cohort during follow-up. In the training cohort, model 2 exhibited improved predictive power over model 1 based on clinical factors (AUC = 0.820 versus 0.781, p = 0.003) with lower prediction error (Brier score = 0.146 versus 0.164) compared to model 1. Model 2 accurately categorized 78.58% of patients with diabetic microvascular complications. Similar performance of model 2 in the internal validation cohort and the external validation cohort was further confirmed. The model incorporating clinical factors and RCAPCAT predicts the development of microvascular complications in diabetic patients without significant coronary stenosis. • Hypertension, HbA1c, duration of diabetes, and RCAPCAT were independent risk factors for microvascular complications. • The prediction model integrating RCAPCAT exhibited improved predictive power over the model only based on clinical factors (AUC = 0.820 versus 0.781, p = 0.003) and showed lower prediction error (Brier score=0.146 versus 0.164).

Evaluation of Morphological Changes in Retinal Vessels in Type 1 Diabetes Mellitus Patients with the Use of Adaptive Optics.

Introduction. Diabetes mellitus contributes to the development of microvascular complications in the eye. Moreover, it affects multiple end organs, including brain damage, leading to premature death. The use of adaptive optics technique allows to perform non-invasive in vivo assessment of retinal vessels and to identify changes in arterioles about 100 μm in diameter. The retinal vasculature may be a model of the cerebral vessels both morphologically and functionally. Aim. To evaluate morphological parameters of retinal arterioles in patients with type 1 diabetes mellitus (DM1). Material and methods. The study included 22 DM1 patients (13 females) aged 43.00 ± 9.45 years with a mean diabetes duration of 22.55 ± 10.05 years, and 23 healthy volunteers (10 females) aged 41.09 ± 10.99 years. Blood pressure, BMI, waist circumference, and metabolic control markers of diabetes were measured in both groups. Vascular examinations were performed using an rtx1 adaptive optics retinal camera (Imagine Eyes, Orsay, France); the vessel wall thickness (WT), lumen diameter (LD), wall-to-lumen ratio (WLR), and vascular wall cross-sectional area (WCSA) were assessed. Statistical analysis was performed with the application of IMB SPSS version 23 software. Results. The DM1 group did not differ significantly in age, BMI, waist circumference, blood pressure, or axial length of the eye compared to the control group. Intraocular pressure (IOP) in both groups was normal, but in the DM1 group it was significantly higher. The DM1 group had significantly higher WT, WLR, and WCSA. These parameters correlated significantly with the duration of diabetes, but not with IOP. Conclusions. The presented study demonstrates the presence of significant morphological changes in retinal vessels in DM1 patients without previously diagnosed diabetic retinopathy. Similar changes may occur in the brain and may be early indicators of cardiovascular risk, but further investigation is required to confirm that.