Vascular Complications In Type Research Articles

Role of platelet indices and vitamin D in forecasting deterioration of glycemic control and vascular complications in type 2 diabetes

Role of platelet indices and vitamin D in forecasting deterioration of glycemic control and vascular complications in type 2 diabetes

The Potential of Neuregulin 4 as a Novel Biomarker and Therapeutic Agent for Vascular Complications in Type 2 Diabetes Mellitus.

Neuregulin 4 (Nrg4), a novel adipokine produced primarily by brown adipose tissue (BAT), has beenfunctionallycharacterized to exert beneficial effects on modulating energy homeostasis and glucolipid metabolism, and is closely associatedwith the development and progressionof obesity and obesity-associated metabolic diseases, such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Recently, there has been a growing focus on the relationship between circulating Nrg4 levels and T2DM-related vascular complications. In this review, we discussed the known and potential roles of Nrg4 in various physiological and pathological processes, and its association with vascular complications in T2DM, in the aim of finding a potential biomarker recommended for the clinical diagnosis, prognosis and follow-up of T2DM patients at high risk of developing vascular complications as well as providing new therapeutic approaches.

Movement pattern definitions for resistance training behavior measurement in diabetes.

Type 2 diabetes can result in debilitating vascular complications, and resistance training (RT) is an effective therapy for improving cardiovascular outcomes. However, only 10-30% of adults meet the public health guidance for RT. While current RT guidelines focus on targeting major muscle groups, guidance specific to simplified movement categorization may augment understanding of RT programming and improve uptake and outcomes. Current movement pattern definitions and descriptions lack clarity, accuracy, and consistency. This paper proposes movement definitions and descriptions to be used for RT intervention design and prescription, and includes the following categories: hip, knee, ankle, vertebral column, vertical push, horizontal push, vertical pull, and horizontal pull. These categories are intended to aid clinicians, researchers, and trainers in RT surveillance and RT intervention design for improving vascular complications in type 2 diabetes. Simplified RT program design using these categories may also facilitate greater RT program understanding and adherence for patients.

1786-LB: Twenty-Four-Hour Ambulatory Blood Pressure and Vascular Complications in Type 1 Diabetes Subjects—Systematic Review and Meta-analysis of Prospective Studies

1786-LB: Twenty-Four-Hour Ambulatory Blood Pressure and Vascular Complications in Type 1 Diabetes Subjects—Systematic Review and Meta-analysis of Prospective Studies

1799-LB: Identification of Proteomics Signature for Vascular Complications in Type 2 Diabetes

1799-LB: Identification of Proteomics Signature for Vascular Complications in Type 2 Diabetes

Glucoselysine, a unique advanced glycation end-product of the polyol pathway and its association with vascular complications in type 2 diabetes

Glucoselysine (GL) is a unique advanced glycation end-product derived from fructose. The main source of fructose in vivo is the polyol pathway, and an increase in its activity leads to diabetic complications. Here, we aimed to demonstrate that GL can serve as an indicator of the polyol pathway activity. Additionally, we propose a novel approach for detecting GL in peripheral blood samples using LC-MS/MS and evaluate its clinical usefulness. We successfully circumvent interference from fructoselysine, which shares the same molecular weight as GL, by performing ultrafiltration and hydrolysis without reduction, successfully generating adequate peaks for quantification in serum. Furthermore, using immortalized aldose reductase knockout mouse Schwann cells, we demonstrate that GL reflects the downstream activity of the polyol pathway and that GL produced intracellularly is released into the extracellular space. Clinical studies reveal that GL levels in patients with type 2 diabetes are significantly higher than those in healthy participants, while Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1) levels are significantly lower. Both GL and MG-H1 show higher values among patients with vascular complications; however, GL varies more markedly than MG-H1 as well as hemoglobin A1c, fasting plasma glucose, and estimated glomerular filtration rate. Furthermore, GL remains consistently stable under various existing drug treatments for type 2 diabetes, whereas MG-H1 is impacted. To the best of our knowledge, we provide important insights in predicting diabetic complications caused by enhanced polyol pathway activity via assessment of GL levels in peripheral blood samples from patients.

G6PD activity in whole blood distinguishes the pattern of vascular complications in type 2 diabetes

G6PD activity in whole blood distinguishes the pattern of vascular complications in type 2 diabetes

Glucose Promotes EMMPRIN/CD147 and the Secretion of Pro-Angiogenic Factors in a Co-Culture System of Endothelial Cells and Monocytes.

Vascular complications in Type 2 diabetes mellitus (T2DM) patients increase morbidity and mortality. In T2DM, angiogenesis is impaired and can be enhanced or reduced in different tissues ("angiogenic paradox"). The present study aimed to delineate differences between macrovascular and microvascular endothelial cells that might explain this paradox. In a monoculture system of human macrovascular (EaHy926) or microvascular (HMEC-1) endothelial cell lines and a monocytic cell line (U937), high glucose concentrations (25 mmole/L) increased the secretion of the pro-angiogenic factors CD147/EMMPRIN, VEGF, and MMP-9 from both endothelial cells, but not from monocytes. Co-cultures of EaHy926/HMEC-1 with U937 enhanced EMMPRIN and MMP-9 secretion, even in low glucose concentrations (5.5 mmole/L), while in high glucose HMEC-1 co-cultures enhanced all three factors. EMMPRIN mediated these effects, as the addition of anti-EMMPRIN antibody decreased VEGF and MMP-9 secretion, and inhibited the angiogenic potential assessed through the wound assay. Thus, the minor differences between the macrovascular and microvascular endothelial cells cannot explain the angiogenic paradox. Metformin, a widely used drug for the treatment of T2DM, inhibited EMMPRIN, VEGF, and MMP-9 secretion in high glucose concentration, and the AMPK inhibitor dorsomorphin enhanced it. Thus, AMPK regulates EMMPRIN, a key factor in diabetic angiogenesis, suggesting that targeting EMMPRIN may help in the treatment of diabetic vascular complications.

Association between irisin and vascular complications of type 2 diabetic patients: a prospective case–control study

BackgroundDiabetes vascular complications are classified as either macrovascular (cardiovascular disease) or microvascular (nephropathy). These complications considerably raise the risk of morbidity and death. Irisin is a myokine that has been linked to metabolic disorders and cardiovascular disease. The purpose of this study was to look at the relationship between irisin and vascular complications among type 2 diabetic (T2DM) individuals. In this case–control study, the patients were put into four groups based on the occurrence of a diabetic cardiovascular complications and the presence of diabetic nephropathy into group 1: twenty T2DM cases without complications, group 2: twenty T2DM cases with diabetic nephropathy, group 3: twenty T2DM cases with cardiovascular complications, and group 4: thirty controls. History was taken, and clinical examination was done. Laboratory investigations (fasting blood glucose, 2-h postprandial blood glucose, HbA1C, cholesterol, triglycerides, HDL-C and LDL-C, serum urea and creatinine, albumin/creatinine ratio, eGFR, serum irisin) were analyzed.ResultsSerum level of irisin was significantly lower in T2DM patients than in control. Also, irisin level was significantly lower in diabetic cases with vascular complications versus those without complications. Irisin level had a negative correlation to BMI and lipid profile in diabetic cases and had a positive correlation to eGFR in diabetic patients with cardiovascular complications.ConclusionsIrisin level was significantly lower in T2DM patients than control and in diabetic patients with vascular complications than patients without complications. So, irisin may have a role as a marker of vascular complications in T2DM.

Plasma Citrate Levels Are Associated with an Increased Risk of Cardiovascular Mortality in Patients with Type 2 Diabetes (Zodiac-64).

Circulating citrate may represent a proxy of mitochondrial dysfunction which plays a role in the development of vascular complications in type 2 diabetes (T2D). Here, we determined the associations between plasma citrate levels and cardiovascular (CV) mortality in T2D patients. In this prospective cohort study, 601 patients were included who participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC). Plasma citrate levels were measured by nuclear magnetic resonance spectroscopy. Cox proportional hazards regression models were used to evaluate the associations between plasma citrate and the risk of CV mortality. Over a median follow-up of 11.4 years, 119 (19.8%) of the 601 patients died from a CV cause. In multivariable Cox proportional hazards regression models, adjusting for conventional risk factors, plasma citrate was associated with an increased risk of CV mortality (the hazard ratio (HR) per 1-SD increment was 1.19 (95%CI: 1.00-1.40), p = 0.048). This association was prominent in males (n = 49 with CV mortality) (HR 1.52 (95%CI: 1.14-2.03), p = 0.005), but not in females (n = 70 with CV mortality) (HR 1.11 (95%CI: 0.90-1.37), p = 0.319) (age-adjusted Pinteraction = 0.044). In conclusion, higher plasma citrate levels are associated with an increased risk of CV mortality in patients with established T2D. Future studies are warranted to unravel the potential role of citrate-related pathways in the pathogenesis of T2D-related vascular complications.

Impact of ABO/Rhesus (D, C, c, E, e) blood type on development of vascular complications in type 2 diabetes

Introduction: Many studies on type 2 diabetes had conflicting results about the prognostic importance of the ABO or Rhesus (Rh) D expression, and in this context, the other important types of Rh were never studied. Objective: The purpose of this study was to investigate whether ABO and Rh phenotype has an association with vascular complications in type 2 diabetes. Methods: 390 individuals were included in this study (194 were type 2 diabetic patients and 196 were healthy persons). 159 of diabetic patients were classified into two groups: group DC which included 98 diabetic patients with vascular complications, and group D which included 61 diabetic patients without vascular complications. A slide agglutination test was done to determine the ABO and Rh types. Results: While no difference was observed between the frequency of any ABO or Rh types between patients and healthy people, the frequency of A-type and each Rh+ type was higher in the DC group compared to the D group. In addition, the prevalence of the Rh DCceand Rh DcEphenotypes was higher in the DC group. Conclusion: Determining the phenotype of the Rhesus blood group may be a cheap and easy prognostic test for vascular complications development in type 2 diabetes.

The skin autofluorescence of advanced glycation end-products relates to the development of foot ulcers in type 2 diabetes: A longitudinal observational study

ObjectivesThe long-term glycemic memory contributes to vascular complications in type 2 diabetes, including those patients with Diabetic Foot Ulcers (DFU). We investigated whether the skin autofluorescence (SAF) of Advanced Glycation End-products related to later DFUs. Research design & methodsSAF was measured with an AGE-Reader in a retrospective cohort of patients hospitalized from 2009 to 2017 for Type 2 Diabetes. New DFUs were registered until the year 2020 and survival analyses were performed. ResultsThe 517 patients (men: 58.0 %), were 62 ± 9 years old at baseline, with a duration of diabetes of 14 ± 10 years, HbA1c: 8.7 ± 1.8 %, complications included 33.8 % macroangiopathies, 44.9 % diabetic kidney diseases and 26.7 % retinopathies. According to the IWGDF classification, the grades of risk for DFU were 0 for 43.2 %, 1 for 23.9 %, 2 for 7.2 %, and 3 for 25.7 %. During the 53 months of follow-up, 58 new DFUs occurred, mostly in patients with SAF higher than its median value (2.65 AU). Adjusted for age and sex, conventional risk factors (duration and control of diabetes, arterial hypertension, dyslipidemia, smoking), and other complications (macroangiopathy, diabetic kidney disease, retinopathy), SAF related to later DFUs. Adjusted for the IWGDF classification, SAF related to new DFUs (HR: 1.81, 95%CI:1.25–2.62). This relationship was significant for the 403 subjects without previous history of DFU (HR: 2.32, 95%CI: 1.36–3.95). SAF did not predict recurrence for patients with a previous history of DFUs. ConclusionSAF, a simple non-invasive marker of glycemic memory, independently predicts the occurrence of a first foot ulcer in patients with Type 2 Diabetes.

Molecular Link between Glo-1 Expression and Markers of Hyperglycemia and Oxidative Stress in Vascular Complications of Type 2 Diabetes Mellitus.

Chronic hyperglycemia and oxidative stress in Type 2 Diabetes Mellitus trigger cellular dysfunction via the formation of Advanced Glycation End Products (AGEs), resulting in dicarbonyl stress. Glyoxalase-1 (Glo-1) is the main defense against dicarbonyl stress. The aim of this study was to explore any cross-talk between Glo-1 and markers of hyperglycemia and oxidative stress. The siRNA-mediated downregulation of Glo-1 was performed in human microvascular endothelial cell line (HMEC-1). A Glo-1 transgenic rat model was developed. Glo-1 activity, as determined spectrophotometrically, and methylglyoxal were quantified using UPLC-MS/MS and the expression of representative markers of hyperglycemia and oxidative stress was performed using quantitative real-time PCR. A significant increase in the expression of Vascular Cell Adhesion Molecule-1 (VCAM-1) was observed in the case of the siRNA-mediated downregulation of Glo-1 in the microvasculature model under hyperglycemic conditions (p-value < 0.001), as well the as overexpression of Glo-1 in the macrovasculature (p-value = 0.0125). The expression of thioredoxin interacting protein (TXNIP) was found to be significantly upregulated in wildtype diabetic conditions vs. Glo-1 transgenic control conditions (p-value = 0.008), whereas the downregulation of Glo-1 had no impact on TXNIP expression. These findings substantiate the role of VCAM as an important marker of dicarbonyl stress (represented by Glo-1 downregulation), as well as of hyperglycemia, in diabetic vascular complications. Our findings also suggest a potential feedback loop that may exist between Glo-1 and TXNIP, as the highest expression of TXNIP is observed in cases of wildtype diabetic conditions, and the lowest expression of TXNIP is observed when Glo-1 transgene is being expressed in absence of dicarbonyl stress.

Serum MicroRNA-191-5p Levels in Vascular Complications of Type 1 Diabetes: The EURODIAB Prospective Complications Study.

MicroRNA-191-5p regulates key cellular processes involved in the pathogenesis of diabetic complications such as angiogenesis, extracellular matrix deposition, and inflammation. However, no data on circulating microRNA-191-5p in the chronic complications of diabetes are available. To assess whether serum levels of microRNA-191-5p were associated with micro- and macrovascular disease in a large cohort of subjects with type 1 diabetes mellitus (DM1) from the EURODIAB Prospective Complication Study. Levels of microRNA-191-5p were measured by quantitative PCR in 420 patients with DM1 recruited as part of the cross-sectional analysis of the EURODIAB Prospective Complication Study. Cases (n = 277) were subjects with nephropathy and/or retinopathy and/or cardiovascular disease (CVD). Controls (n = 143) were patients without complications. Logistic regression analysis was performed to evaluate the potential independent association of microRNA-191-5p levels with chronic complications of diabetes. Levels of microRNA-191-5p were significantly reduced (P < .001) in cases compared with controls even after adjustment for age, sex, and diabetes duration. Logistic regression analysis revealed that microRNA-191-5p was negatively associated with a 58% reduced odds ratio (OR) of chronic diabetes complications, specifically CVD, micro-macroalbuminuria, and retinopathy (OR, 0.42; 95% CI, 0.23-0.77), independent of age, sex, physical activity, educational levels, diabetes duration, glycated hemoglobin, total insulin dose, hypertension, smoking, total cholesterol, albumin excretion rate, estimated glomerular filtration rate, serum vascular cell adhesion molecule-1, and tumor necrosis factor-α. Analyses performed separately for each complication demonstrated a significant independent association with albuminuria (OR, 0.36; 95% CI, (0.18-0.75) and CVD (OR, 0.34; 95% CI, 0.16-0.70). In DM1 subjects, microRNA-191-5p is inversely associated with vascular chronic complications of diabetes.

Bisphenol A instigates diminished sirtuin-1 mediated vascular complications in type 2 diabetes mellitus

Endocrine society has evidence that plastics can disrupt the endocrine system to cause severe diseases in humans and animals. However, plastics are still used in a variety of models for their applications. The overproduction of plastics simultaneously increases health hazards in human and animal living society. The pancreas is an endocrine system to produces insulin to maintain the glucose level in the blood when that insulin level resists or does not synthesize causing diabetes mellitus. It is one of the highest prevalence diseases occurred in worldwide. Sirtuin-1 is a protein involved in glucose homeostasis and it regulates insulin action. In the human body, hampered the level of insulin, sirtuin-1, and glucose cause diabetes and its vascular complications. Furthermore, many researchers evidenced that the endocrine disruptor of bisphenol A (BPA) causes diabetes mellitus and its vascular complications. Nevertheless, the biological pathway is unclear. This review discusses the linkage between the endocrine disruptor of BPA and diabetes and explores Sirtuin-1 mediated BPA-induced diabetic vascular complications.

POSTPRANDIAL HYPERTRIGLYCERIDEMIA AS A RISK FACTOR FOR MACROVASCULAR COMPLICATIONS IN TYPE 2 DIABETES MELLITUS

Diabetes mellitus is a common endocrine disorder characterized by chronic hyperglycemia, and disturbances of carbohydrate, fat and protein metabolism. The prevalence of diabetes has been increasing widely in India and worldwide. Diabetes is a cause of signicant mortality and morbidity due to macro and micro vascular complications. Dyslipidemia accompanying type 2 Diabetes plays an important role in pathogenesis of atherosclerotic vascular disease. Post prandial hypertriglyceridemia, irrespective of fasting triglyceride levels, has emerged as a signicant risk factor for symptomatic and asymptomatic macro vascular disease It is a case control study, conducted for a period of 1 year from November 2020 to October 2021, on patients visiting the Out-patient department of NRI institute of Medical Sciences, Sangivalasa, Visakhapatnam. The cases and controls were subjected to clinical and biochemical evaluation to detect presence of macro vascular complications. The cases were subjected to a high fat meal, and plasma triglycerides were measured two and four hours after a fat challenge. It was observed that post prandial hypertriglyceridemia correlated better than fasting triglycerides in patients with macro vascular complications. Persistent and signicant post prandial hypertriglyceridemia was observed in diabetic patients with macro vascular complications; and can be used as a marker for predicting vascular complications in type 2 Diabetes mellitus

Association between low‐carbohydrate diets and continuous glucose monitoring‐derived time in ranges

ABSTRACTAimsLow‐carbohydrate diets have become popular in the general community. The mutual relationship between the percentage of total energy intake from carbohydrates (CHO/E), glycemic control indices, and diabetes complications remains unclear.Materials and MethodsThis cross‐sectional study included 177 patients with type 2 diabetes mellitus who regularly visited outpatient clinics. In this study, dietary questionnaires were used to assess the intake ratio of the three macronutrients, and the low‐carbohydrate‐diet score was calculated. We investigated the association between the low‐carbohydrate‐diet score, continuous glucose monitoring (CGM)‐derived short‐term glycemic control indices, and diabetes complications in patients with type 2 diabetes mellitus.ResultsThe results are presented as medians (interquartile ranges) unless otherwise stated. Hemoglobin A1c was 7.1% (6.6–7.7%), CGM‐derived time in range (TIR) was 75.3% (62.8–87.0%), body mass index (BMI) was 24.0 (22.1–26.3) kg/m2, and CHO/E was 49.8% (44.8–55.6%). BMI, triglycerides, and CGM‐derived time above range decreased significantly with increasing low‐carbohydrate‐diet scores. However, no significant association was found between the low‐carbohydrate‐diet score and glycemic control indices, including TIR, mean amplitude of glycemic excursions, and vascular complications of type 2 diabetes mellitus.ConclusionModerate‐carbohydrate diets positively impact weight control and lipid metabolism but may have a limited effect on short‐term glycemic variability in Japanese patients with type 2 diabetes mellitus.

Abstract MP57: Coagulation Factor IX and Incident Diabetes Risk: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: A prothrombotic state is implicated in the vascular complications of type 2 diabetes (DM), and such complications disproportionately affect Black compared to White adults. However, it is not known if this is due to DM or whether coagulation factor levels are related to DM incidence. Higher coagulation factor IX (FIX) was related to increased risk of CHD and stroke among Black but not White participants in the REGARDS cohort. We hypothesized higher FIX antigen would be associated with incident DM risk, with stronger relationships in Black versus White adults. Methods: REGARDS enrolled 30,239 Black and White adults from across the contiguous US from 2003-2006 with a second in-home visit from 2013-2016. The Biomarkers as MEDiators of Racial Disparities in Risk Factors (BioMedioR) nested cohort study included 4,400 participants who completed both visits, balanced on race and sex. Modified Poisson regression models estimated the RR of incident DM per 1-SD increment log FIX. We tested for a FIX-by-race interaction a priori due to differential associations of FIX with CHD and stroke by race in REGARDS. Results: Among 3,381 participants without baseline DM (mean age 63 years, 44% Black race, 51% women), 456 (13.5%) developed incident DM over 9.5-years. Adjusting for age, sex, and race, there was a significant difference in the association of FIX with DM by race (p-interaction&lt;0.01). As shown in the Figure, adjusted for age and sex (Model 1), the RR (95% CI) for incident DM was 1.19 (1.05, 1.34) for Black adults and 1.49 (1.23, 1.81) for White adults. Adjusting for clinical risk factors (Model 2) fully attenuated this association for Black adults, and further adjusting for behavioral factors (Model 3) fully attenuated this association for Black and White adults. Conclusions: Higher FIX levels were associated with incident DM risk. Relationships between FIX and incident DM were stronger for White than Black adults. The FIX-DM association may be due to adverse clinical and behavioral risk factors.

Assessment of endothelial dysfunction and inflammation in type 2 diabetic postmenopausal women

Objective: Vascular complications in type 2 diabetes mellitus are an important cause of morbidity and mortality. Also, endothelial dysfunction arises with vascular ageing during the postmenopausal period. Our objective in this study was to evaluate inflammation and endothelial function parameters and their possible diagnostic roles in type 2 diabetic postmenopausal patients. Material and Methods: The study was conducted on four groups, including type 2 diabetic premenopausal (n:20), non-diabetic premenopausal (n:20), type 2 diabetic postmenopausal (n:20), and non-diabetic postmenopausal subjects (n:20). Serum endothelin-1 (ET-1), endothelial nitric oxide synthetase (eNOS), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and chitinase-3-like protein 1 (YKL-40) levels were determined as inflammatory and endothelial function markers using ELISA kits. Results: Serum ET-1, IL-6, and YKL-40 levels were higher in the type 2 diabetic postmenopausal group compared to the non-diabetic premenopausal group (p&lt;0.01, p&lt;0.05, and p&lt;0.01, respectively). ET-1, IL-6, and YKL-40 levels were higher in the type 2 diabetic postmenopausal group compared to the non-diabetic postmenopausal group (p&lt;0.001, p&lt;0.05, and p&lt;0.01 respectively). ROC analysis revealed serum ET-1 (AUC 0.933, sensitivity 87.5%, specificity 85.7%), IL-6 (AUC 0.812, sensitivity 56.3%, specificity 92.8%), and YKL-40 (AUC 0.880, sensitivity 81.2%, specificity 92.8%), as good diagnostic parameters, especially in the type 2 diabetic premenopausal vs. non-diabetic premenopausal cohorts. Conclusion: Serum ET-1, IL-6, and YKL-40 levels were at the highest levels in the 2 diabetic postmenopausal group, and the increase in these markers was remarkable in diabetes compared with menopausal periods. Also, ET-1, IL-6, and YKL-40 were good diagnostic parameters for detecting endothelial function and inflammation in type 2 diabetic postmenopausal and non-diabetic premenopausal cohorts.

A correlation biomarker between BMI and lipid peroxidation in type 2 diabetes mellitus with and without other complications

Objectives: Body mass index (BMI) is a traditional measurement practice that divides a person’s weight by their height to find out whether they have a healthy range of weight. The objective of this study is to understand the relation between BMI and prevalence of diabetes mellitus, hypertension, and dyslipidemia. Material and Methods: BMI distribution among these patients was compared with and without hypertension and dyslipidemia. The improper of secretion of insulin leads to changes in metabolism of lipids, proteins, and carbohydrates also characterized hyperglycemia generally considered as diabetes mellitus (DM). Results: The excessive formation of free radicals induces oxidative stress, and the antioxidant defense system becomes weaken and hence arises diabetic disorder and overproduction of malondialdehyde (MDA). In cells, the polyunsaturated fatty acid peroxidation is considered as the final product and marker of oxidative stress. Conclusion: In this study, significantly increased BMI is observed in diabetic victims in comparison with control group. A significant positive correlation was noticed between glycated hemoglobin, cholesterol, and MDA. In conclusion, for the prevention and management of vascular complication in type 2 diabetes mellitus, maintaining normal levels of MDA and body weight are very important. Further large-scale studies are required to confirm it.