Macrovascular Complications Of Diabetes Research Articles

Prediction of Micro- and Macrovascular Complications in Type 2 Diabetes Mellitus using Heart Rate Variability.

To explore the utility of heart rate variability (HRV), a noninvasive marker of cardiac autonomic activity, as a prescreening tool for the prediction of micro- and macrovascular complications in type 2 diabetes mellitus (T2DM). Consenting type 2 diabetic patients of both genders between 30 and 70 years, without known micro- and macrovascular complications of diabetes, were enrolled. Patients with medications affecting the HRV were excluded. Prior to other screening tests, 15 minutes of resting electrocardiogram (ECG) (1 kHz) was recorded in enrolled patients, followed by an exercise stress test and assessment for nephropathy, retinopathy, and peripheral neuropathy. The patients with positive stress tests were referred for coronary angiography to confirm coronary artery disease. Based on screening test results, patients were grouped as Group I-T2DM without complications (n = 31) and Group II-T2DM with micro/macrovascular complications (n = 29), (total = 60). Group comparison and test for association were employed, and p-value of <0.05 was considered significant. Significantly reduced HRV (decreased standard deviation of NN interval) between groups and a strong association of HRV indices with complications of diabetes were observed. Logistic regression to classify complicated vs noncomplicated group was used, and an accuracy of 0.78 with 85% sensitivity, 74% specificity with area under the curve (AUC) of 0.83 was observed. Significantly reduced HRV, stronger association with complications, and 85% sensitivity, 74% specificity, and 78% accuracy of classification make HRV indices a promising prescreening tool to predict micro- and macrovascular complications in type 2 diabetes.

Weight Change and the Risk of Micro and Macro Vascular Complications of Diabetes: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a metabolic disease that can be a significant cause of cardiovascular disease (CVD), leading to macrovascular and microvascular diseases. Many researchers around the world have investigated the effects of weight change on micro and macro CVD in patients with T2DM. This study aimed to investigate the effect of weight change (weight gain and loss) on microvascular and macrovascular complications in patients with T2DM. We searched PubMed, Scopus and Google Scholar from the database until January 2023. We screened the title, abstract, and full text of articles, and after quality assessment, we extracted data from interrelated ones into this systematic review. Reviewing the results of 11 cohort studies with 219,839 individuals (T2DM patients) showed that weight loss caused an increase in the mortality rate in diabetic patients, while weight gain after diabetes diagnosis increased the risk of CVD, chronic kidney disease (CKD), microvascular disease, stroke and mortality. It should be noted that severe body weight variability increases the mortality rate and the risk of microvascular disease. Unlike other studies, one study showed that more than 5% weight gain positively affected CVD and coronary heart disease in T2DM patients. Generally, weight change in patients with T2DM is an essential sign of cardiovascular complications. According to our findings, the risk of cardiovascular complications in patients with weight loss is seen to be higher than in patients with weight gain. In regular patients with body mass index (BMI), stable weight in a healthy range is reported to decrease the risk of CVD.

The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR=4.58, 95% CI: 1.89-11.07, P<0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR=0.57, 95% CI: 0.41-0.78, P<0.001), macrovascular complications incidence (HR=0.59, 95% CI: 0.50-0.70, P<0.001) and mortality (HR=0.53, 95% CI: 0.53-0.79, P=0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.

Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes. Animal study: Subcutaneous PP infusion for 4weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up. Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p=0.001; hazard ratio (HR) 1.259 (1.035-1.531) p=0.0213), albuminuria (OR 1.277 (1.124-1.454), p=0.0002; HR 1.608 (1.208-2.141) p=0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p=0.0068; HR 1.324 (1.089-1.61), p=0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p=0.0109). Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.

Noninvasive Liver Fibrosis Indices as Indicators of Microvascular and Macrovascular Complications in Type 2 Diabetes.

Objective: Nonalcoholic fatty liver disease (NAFLD) is more prevalent in patients with obesity, diabetes, and metabolic syndrome, which are risk factors for nonalcoholic steatohepatitis and liver fibrosis. NAFLD is related to cardiovascular outcomes in diabetes. We aimed to investigate the relationship between diabetic complications and NAFLD fibrosis score (NFS) and Fibrosis-4 score (FIB-4). Methods: Three hundred patients with type 2 diabetes mellitus (T2DM) were retrospectively evaluated according to NAFLD diagnosis on ultrasound in outpatient clinic. Risk of advanced fibrosis was estimated using FIB-4 and NFS. Diabetic complications of the patients were noted. Results: Presence of diabetic retinopathy is related to FIB-4 (P = 0.001) and NFS (P < 0.001) scores. NFS score (P = 0.037), not FIB-4 (P = 0.517), is related to diabetic nephropathy. Among macrovascular complications, only coronary artery disease is related to NFS and FIB-4 scores (P = 0.037 and P = 0.004, respectively). Although we cannot establish any association between fasting blood glucose, glycosylated hemoglobin (HbA1c) values and noninvasive liver fibrosis scores (P > 0.05), diabetes duration, and age positively correlated with the FIB-4 score (P = 0.033, P = 0.001). In logistic regression analysis, NFS > 0.676 values are associated with increased rates of diabetic retinopathy, independent of age, sex, HbA1c, and duration diabetes (odds ratio: 1.155, P = 0.030). FIB-4 has no relation with microvascular complications according to logistic regression analysis (P > 0.05 for all). Neither FIB-4 nor NFS has an effect on the presence of macrovascular complications (P > 0.05 for all). Conclusion: Our findings suggest that increase in NFS score is associated with the presence of diabetic retinopathy, independent of confounding factors. Further studies are needed on the applicability of noninvasive fibrosis scores in monitoring the presence of diabetic microvascular and macrovascular complications.

Correlation of Serum Magnesium Level in Type 2 Diabetes Mellitus Patient with Microalbuminuria

Diabetic nephropathy is the leading cause of end stage renal disease world wide. Approximately one third of patients with type 2 diabetes have hypomagnesemia, mainly caused by enhanced renal excretion. Magnesium deficit in the diet would induce insulin resistance in humans. If it is chronic, this may lead to macro-vascular and micro-vascular complications of diabetes. This study was designed to know the relationship of serum magnesium level in type 2 diabetic patients with microalbuminuria. This study was conducted at the Department of Laboratory Medicine in Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. In this study, serum magnesium level and urine microalbumin level of 60 type 2 diabetic patients were measured. Both serum magnesium and urine microalbumin levels were measured by biochemical auto analyzer (Siemens Dimension RL Max). The mean serum magnesium level is lower in type 2 diabetes mellitus patient. There was a negative correlation between serum magnesium level and urinary microalbumin in hypomagnesemia diabetic patients. Identifying and treating hypomagnesemia can delay end stage renal disease in diabetic patient and reduce the clinical and economic burden of diabetic complications in future. The potential benefits of supplementing magnesium in type 2 diabetic patients with hypomagnesemia need to be evaluated further.

Apolipoprotein-CIII O-Glycosylation Is Associated with Micro- and Macrovascular Complications of Type 2 Diabetes.

Apolipoprotein-CIII (apo-CIII) inhibits the clearance of triglycerides from circulation and is associated with an increased risk of diabetes complications. It exists in four main proteoforms: O-glycosylated variants containing either zero, one, or two sialic acids and a non-glycosylated variant. O-glycosylation may affect the metabolic functions of apo-CIII. We investigated the associations of apo-CIII glycosylation in blood plasma, measured by mass spectrometry of the intact protein, and genetic variants with micro- and macrovascular complications (retinopathy, nephropathy, neuropathy, cardiovascular disease) of type 2 diabetes in a DiaGene study (n = 1571) and the Hoorn DCS cohort (n = 5409). Mono-sialylated apolipoprotein-CIII (apo-CIII1) was associated with a reduced risk of retinopathy (β = -7.215, 95% CI -11.137 to -3.294) whereas disialylated apolipoprotein-CIII (apo-CIII2) was associated with an increased risk (β = 5.309, 95% CI 2.279 to 8.339). A variant of the GALNT2-gene (rs4846913), previously linked to lower apo-CIII0a, was associated with a decreased prevalence of retinopathy (OR = 0.739, 95% CI 0.575 to 0.951). Higher apo-CIII1 levels were associated with neuropathy (β = 7.706, 95% CI 2.317 to 13.095) and lower apo-CIII0a with macrovascular complications (β = -9.195, 95% CI -15.847 to -2.543). In conclusion, apo-CIII glycosylation was associated with the prevalence of micro- and macrovascular complications of diabetes. Moreover, a variant in the GALNT2-gene was associated with apo-CIII glycosylation and retinopathy, suggesting a causal effect. The findings facilitate a molecular understanding of the pathophysiology of diabetes complications and warrant consideration of apo-CIII glycosylation as a potential target in the prevention of diabetes complications.

Prevalence and determinants of microvascular and macrovascular complications of diabetes in acromegaly patients: A prospective case-control cross-sectional study

Prevalence and determinants of microvascular and macrovascular complications of diabetes in acromegaly patients: A prospective case-control cross-sectional study

Management of macrovascular diabetic complications: a single-center case series analysis of consecutively attending patients in primary care

Management of macrovascular diabetic complications: a single-center case series analysis of consecutively attending patients in primary care

CircZNF609 inhibits miR-150-5p to promote high glucose-induced damage to retinal microvascular endothelial cells

Hyperglycemia is a key contributor to diabetic macrovascular and ocular complications. It triggers a cascade of cellular damage, particularly in the retinal microvascular endothelial cells (RMECs). However, the underlying molecular mechanisms remain only partially understood. This study hypothesizes that CircZNF609 plays a pivotal role in mediating high glucose-induced damage in RMECs by modulating miR-150-5p and its downstream target genes, thereby affecting cellular survival, apoptosis, and oxidative stress. Gene expression datasets (GSE193974 and GSE160308) and clinical samples were used to investigate the expression levels of CircZNF609 and its interaction with miR-150-5p in the context of diabetic retinopathy (DR). Our results demonstrate that CircZNF609 is upregulated in both peripheral blood stem cells from DR patients and high glucose-stimulated hRMECs. Functional experiments reveal that silencing CircZNF609 improves cell viability, reduces apoptosis, inhibits tube formation, and modulates oxidative stress markers, whereas CircZNF609 overexpression exacerbates these effects. Moreover, miR-150-5p, a microRNA, was found to be negatively regulated by CircZNF609 and downregulated in DR. Its overexpression mitigates high glucose-induced cell injury. Our findings suggest a novel mechanism whereby CircZNF609 exacerbates high glucose-induced endothelial cell damage by sponging miR-150-5p, implicating the CircZNF609/miR-150-5p axis as a potential therapeutic target in diabetic retinopathy.

Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents.

Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. Twenty-three type 1 diabetic patients, aged 12-16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity. Proinflammatory cytokines' concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. There were no statistically significant differences between the proinflammatory cytokines' concentrations in the two groups. PWV [6.63 (6.23-7.07) vs. 6.07 (5.15-6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=-0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=-0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.

Platelet bioenergetic profiling uncovers a metabolic pattern of high dependency on mitochondrial fatty acid oxidation in type 2 diabetic patients who developed in-stent restenosis

Although platelet bioenergetic dysfunction is evident early in the pathogenesis of diabetic macrovascular complications, the bioenergetic characteristics in type 2 diabetic patients who developed coronary in-stent restenosis (ISR) and their effects on platelet function remain unclear. Here, we performed platelet bioenergetic profiling to characterize the bioenergetic alterations in 28 type 2 diabetic patients with ISR compared with 28 type 2 diabetic patients without ISR (non-ISR) and 28 healthy individuals. Generally, platelets from type 2 diabetic patients with ISR exhibited a specific bioenergetic alteration characterized by high dependency on fatty acid (FA) oxidation, which subsequently induced complex III deficiency, causing decreased mitochondrial respiration, increased mitochondrial oxidant production, and low efficiency of mitochondrial ATP generation. This pattern of bioenergetic dysfunction showed close relationships with both α-granule and dense granule secretion as measured by surface P-selectin expression, ATP release, and profiles of granule cargo proteins in platelet releasates. Importantly, ex vivo reproduction of high dependency on FA oxidation by exposing non-ISR platelets to its agonist mimicked the bioenergetic dysfunction observed in ISR platelets and enhanced platelet secretion, whereas pharmaceutical inhibition of FA oxidation normalized the respiratory and redox states of ISR platelets and diminished platelet secretion. Further, causal mediation analyses identified a strong association between high dependency on FA oxidation and increased angiographical severity of ISR, which was significantly mediated by the status of platelet secretion. Our findings, for the first time, uncover a pattern of bioenergetic dysfunction in ISR and enhance current understanding of the mechanistic link of high dependency on FA oxidation to platelet abnormalities in the context of diabetes.

Wait Times for Scheduling Appointments for Prevention of Macrovascular and Microvascular Complications of Diabetes: Cross-Sectional Descriptive Study.

Diabetes is a chronic disease that requires lifelong management and care, affecting around 422 million people worldwide and roughly 37 million in the United States. Patients newly diagnosed with diabetes must work with health care providers to formulate a management plan, including lifestyle modifications and regular office visits, to improve metabolic control, prevent or delay complications, optimize quality of life, and promote well-being. Our aim is to investigate one component of system-wide access to timely health care for people with diabetes in New York City (NYC), namely the length of time for someone with newly diagnosed diabetes to obtain an appointment with 3 diabetes care specialists: a cardiologist, an endocrinologist, and an ophthalmologist, respectively. We contacted the offices of 3 different kinds of specialists: cardiologists, endocrinologists, and ophthalmologists, by telephone, for this descriptive cross-sectional study, to determine the number of days required to schedule an appointment for a new patient with diabetes. The sampling frame included all specialists affiliated with any private or public hospital in NYC. The number of days to obtain an appointment with each specialist was documented, along with "time on hold" when attempting to schedule an appointment and the presence of online booking capabilities. Of the 1639 unique physicians affiliated with (private and public) hospitals in the 3 subspecialties, 1032 (cardiologists, endocrinologists, and ophthalmologists) were in active practice and did not require a referral. The mean wait time for scheduling an appointment was 36 (SD 36.4; IQR 12-51.5) days for cardiologists; 82 (SD 47; IQR 56-101) days for endocrinologists; and 50.4 (SD 56; IQR 10-72) days for ophthalmologists. The median wait time was 27 days for cardiologists, 72 days for endocrinologists, and 30 days for ophthalmologists. The mean time on hold while attempting to schedule an appointment with these specialists was 2.6 (SD 5.5) minutes for cardiologists, 5.4 (SD 4.3) minutes for endocrinologists, and 3.2 (SD 4.8) minutes for ophthalmologists, respectively. Over 46% (158/341) of cardiologists enabled patients to schedule an appointment on the web, and over 55% (128/228) of endocrinologists enabled patients to schedule an appointment on the web. In contrast, only approximately 25% (117/463) of ophthalmologists offered web-based appointment scheduling options. The results indicate considerable variation in wait times between and within the 3 specialties examined for a new patient in NYC. Given the paucity of research on wait times for newly diagnosed people with diabetes to obtain an appointment with different specialists, this study provides preliminary estimates that can serve as an initial reference. Additional research is needed to document the extent to which wait times are associated with complications and the demographic and socio-economic characteristics of people served by different providers.

Enrollment in High-Deductible Health Plans and Incident Diabetes Complications

Preventing diabetes complications requires monitoring and control of hyperglycemia and cardiovascular risk factors. Switching to high-deductible health plans (HDHPs) has been shown to hinder aspects of diabetes care; however, the association of HDHP enrollment with microvascular and macrovascular diabetes complications is unknown. To examine the association between an employer-required switch to an HDHP and incident complications of diabetes. This retrospective cohort study used deidentified administrative claims data for US adults with diabetes enrolled in employer-sponsored health plans between January 1, 2010, and December 31, 2019. Data analysis was performed from May 26, 2022, to January 2, 2024. Adults with a baseline year of non-HDHP enrollment who had to switch to an HDHP because their employer offered no non-HDHP alternative in that year were compared with adults who were continuously enrolled in a non-HDHP. Mixed-effects logistic regression models examined the association between switching to an HDHP and, individually, the odds of myocardial infarction, stroke, hospitalization for heart failure, lower-extremity complication, end-stage kidney disease, proliferative retinopathy, treatment for retinopathy, and blindness. Models were adjusted for demographics, comorbidities, and medications, with inverse propensity score weighting used to account for potential selection bias. The study included 42 326 adults who switched to an HDHP (mean [SD] age, 52 [10] years; 19 752 [46.7%] female) and 202 729 adults who did not switch (mean [SD] age, 53 [10] years; 89 828 [44.3%] female). Those who switched to an HDHP had greater odds of experiencing all diabetes complications (odds ratio [OR], 1.11; 95% CI, 1.06-1.16 for myocardial infarction; OR, 1.15; 95% CI, 1.09-1.21 for stroke; OR, 1.35; 95% CI, 1.30-1.41 for hospitalization for heart failure; OR, 2.53; 95% CI, 2.38-2.70 for end-stage kidney disease; OR, 2.23; 95% CI, 2.17-2.29 for lower-extremity complication; OR, 1.17; 95% CI, 1.13-1.21 for proliferative retinopathy; OR, 2.35; 95% CI, 2.18-2.54 for blindness; and OR, 2.28; 95% CI, 2.15-2.41 for retinopathy treatment). This study found that an employer-driven switch to an HDHP was associated with increased odds of experiencing all diabetes complications. These findings reinforce the potential harm associated with HDHPs for people with diabetes and the importance of affordable and accessible chronic disease management, which is hindered by high out-of-pocket costs incurred by HDHPs.

Use of Diabetes Technologies and Retinopathy in Adults With Type 1 Diabetes

Diabetic retinopathy (DR) is a complication of diabetes that can lead to vision loss. Outcomes of continuous glucose monitoring (CGM) and insulin pump use in DR are not well understood. To assess the use of CGM, insulin pump, or both, and DR and proliferative diabetic retinopathy (PDR) in adults with type 1 diabetes (T1D). A retrospective cohort study of adults with T1D in a tertiary diabetes center and ophthalmology center was conducted from 2013 to 2021, with data analysis performed from June 2022 to April 2023. Use of diabetes technologies, including insulin pump, CGM, and both CGM and insulin pump. The primary outcome was development of DR or PDR. A secondary outcome was the progression of DR for patients in the longitudinal cohort. Multivariable logistic regression models assessed for development of DR and PDR and association with CGM and insulin pump use. A total of 550 adults with T1D were included (median age, 40 [IQR, 28-54] years; 54.4% female; 24.5% Black or African American; and 68.4% White), with a median duration of diabetes of 20 (IQR, 10-30) years, and median hemoglobin A1c (HbA1c) of 7.8% (IQR, 7.0%-8.9%). Overall, 62.7% patients used CGM, 58.2% used an insulin pump, and 47.5% used both; 44% (244 of 550) of the participants had DR at any point during the study. On univariate analysis, CGM use was associated with lower odds of DR and PDR, and CGM with pump was associated with lower odds of PDR (all P < .05), compared with no CGM use. Multivariable logistic regression adjusting for age, sex, race and ethnicity, diabetes duration, microvascular and macrovascular complications, insurance type, and mean HbA1c, showed that CGM was associated with lower odds of DR (odds ratio [OR], 0.52; 95% CI, 0.32-0.84; P = .008) and PDR (OR, 0.42; 95% CI, 0.23-0.75; P = .004), compared with no CGM use. In the longitudinal analysis of participants without baseline PDR, 79 of 363 patients (21.8%) had progression of DR during the study. In this cohort study of adults with T1D, CGM use was associated with lower odds of developing DR and PDR, even after adjusting for HbA1c. These findings suggest that CGM may be useful for diabetes management to mitigate risk for DR and PDR.

Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis

BackgroundPlatelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes.MethodsWe enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system.ResultsAmong groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters.ConclusionsIn the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

The Study of Relationship between Plasma Fibrinogen Level and the Macrovascular Complications in Type 2 Diabetes Mellitus patients in a Tertiary Health Care Centre in Eastern India

Introduction: The macrovascular complications in patients of Type 2 Diabetes Mellitus (T2DM) are an expression of the generalized atherosclerotic process affecting the blood vessels of the body. Studies have revealed cardinal role of inflammation in the development of atherosclerosis. Literature review suggests that the level of plasma fibrinogen, an inflammatory marker, is elevated in T2DM and more so in those with the macrovascular complications. Therefore, this study was taken up with the aim to determine the association of plasma fibrinogen level with the macrovascular complications in patients of T2DM. Methods and aterials: This was a prospective observational study undertaken in Tata Main Hospital from November 2020 to October 2022. It included T2DM out-patients and those admitted in the Department of Medicine between the age group of 40 to 80 years. Patient’s clinical history and detailed physical examination were noted. Relevant blood tests (including HbA1c, lipid profile) and plasma fibrinogen levels were done. All patients were evaluated for complications of Coronary Artery Disease (CAD), cerebrovascular disease and peripheral vascular disease using appropriate investigations. The statistical association was determined by chi -square (χ2) and independent sample t-tests where appropriate. The relationship between plasma fibrinogen level and the macrovascular complications was determined using binary logistic regression. Results: The study involved 180 patients. Their mean age was 58.63 ± 7.177 years with most patients in 51-60 years age group. Male preponderance was seen and the male to female ratio was 1.86:1. While the average duration of T2DM in the study population was 6.744 ± 2.376 years, mean HbA1c level was 8.2 ± 1.9% (range: 6.2% to 9.8%). The mean Body Mass Index (BMI) was 24.57 ± 2.49 Kg/m2, with 61.67 % of cases having BMI of 25-29.9. The mean fibrinogen level in patients was 446.50 ± 28.449 mg/dl (ranged: 358.3 mg/dl to 513.0 mg/d). Diabetics without complications had mean fibrinogen level of 443.3 ± 28.3 mg/dl while those with complications had level of 469.6 ± 16.8 mg/dl (P = 0.000). 43 (23.9%) patients had macrovascular complications. Peripheral vascular disease was observed in 31(17.2%), cerebrovascular disease in 16 (8.9%) and CAD in 20 (11.1%) patients while hypertension was observed in 68 (37.8%) patients. Fibrinogen level showed a positive relation with age (R- 0.541, P &lt;0.001), male gender, BMI (R- 0.515, P=0.0001), total cholesterol levels more than 200 mg/dl (R-0.365, P = 0.0001) and HbA1c (R-0.355 with P = 0.0001). Binomial logistic regression demonstrated significant association between plasma fibrinogen level with macrovascular complications of diabetes (Wald test: 7.482, odds ratio-1.062, P&lt;0.01). Furthermore, the association was found to be independent after adjusting for the confounding factors. Conclusion: Our study suggests that plasma fibrinogen level may be viewed as an independent risk factor for the development of macrovascular complications in T2DM patients. Hence, in these patients, it can be used as a marker for the prediction of the macrovascular complications.

Salvianolic Acid B Alleviates High Glucose-Induced Vascular Smooth Muscle Cell Inflammation by Upregulating the miR-486a-5p Expression.

The macrovascular complications of diabetes cause high mortality and disability in patients with type 2 diabetes mellitus (T2DM). The inflammatory response of vascular smooth muscle cell (VSMC) runs through its pathophysiological process. Salvianolic acid B (Sal B) exhibits beneficial effects on the cardiovascular system. However, its role and mechanism in diabetic vascular inflammatory response remain unclear. In this study, we found that Sal B reduced vascular inflammation in diabetic mice and high glucose- (HG-) induced VSMC inflammation. Subsequently, we found that Sal B reduced HG-induced VSMC inflammation by downregulating FOXO1. Furthermore, miR-486a-5p expression was obviously reduced in HG-treated VSMC. Sal B attenuated HG-induced VSMC inflammation by upregulating miR-486a-5p. Loss- and gain-of-function experiments had proven that the transfection of the miR-486a-5p mimic inhibited HG-induced VSMC inflammation whereas that of the miR-486a-5p inhibitor promoted HG-induced VSMC inflammation, thereby leading to the amelioration of vascular inflammation in the diabetic mice. Furthermore, studies had shown that miR-486a-5p inhibited FOXO1 expression by directly targeting its 3'-UTR. In conclusion, Sal B alleviates the inflammatory response of VSMC by upregulating miR-486a-5p and aggravating its inhibition of FOXO1 expression. Sal B exerts a significant anti-inflammatory effect in HG-induced VSMC inflammation by modulating the miR-486a-5p/FOXO1 axis.

Effect of aminoguanidine on plasminogen activator inhibitor-1 and receptor of advanced glycation endproduct in the liver of streptozotocin-induced diabetic rats

Objectives: Advanced glycation end products (AGEs) play an important role in the development and progression of diabetic complications. The receptor for AGE (RAGE) is the ligand-binding site of AGE that initiates and accelerates the atherosclerotic process. Plasminogen activator inhibitor-1 (PAI-1) is a prothrombotic factor that has been proposed as a biological marker for prognostic assessment, monitoring of microvascular and macrovascular complications in diabetes. The purpose of this study is to investigate the effects of aminoguanidine on RAGE and PAI-1 expression levels in the liver of streptozotocin-induced diabetic rats.&#x0D; Methods: Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ, 50 mg/kg). On day 3, diabetic rats were administered 50, 100, and 200 mg/kg/day of aminoguanidine. The expression of PAI-1 and RAGE in the liver tissue was evaluated using real-time PCR.&#x0D; Results: PAI-1 and RAGE gene expression levels were higher in the liver of the diabetic rats compared to the control group. Aminoguanidine at 50, 100, and 200 mg/kg decreased PAI-1 and RAGE gene expression in the liver (p&lt;0.001 at all doses). However, these genes were downregulated only at a dose of 200 mg/kg in healthy rats (p&lt;0.0001). In addition, hepatic AGE protein levels were significantly decreased following treatment of the diabetic rats with aminoguanidine (p&lt;0.001). There was also a significant correlation between AGE protein concentration and the expression of PAI-1 and RAGE.&#x0D; Conclusion: In summary, the data of the present study suggest that aminoguanidine reduced the expression of PAI-1 and RAGE in the liver of the diabetic rats.

Evaluation of association between time in range, a continuous glucose monitoring metric, and cardiac autonomic neuropathy in type 2 diabetes patients.

Time in range (TIR), a metric of continuous glucose monitoring (CGM) provides better information regarding the individual's glycemic variability than a static measure like glycated hemoglobin (HbA1c). TIR is emerging as an independent risk factor for diabetic complications, both microvascular and macrovascular complications independent of HbA1c. Hence, this study evaluates the association between TIR and cardiac autonomic neuropathy (CAN) in type 2 diabetic patients. A total of 42 patients with type 2 diabetes mellitus were enrolled in this study and underwent a 3-day CGM using the "FreeStyle Libre Pro Flash Glucose Monitoring System Sensor" along with tests for CAN within the 3 days of attaching the CGM. Out of 42 patients, 36 patients (85.7%) were diagnosed with CAN (early CAN 57.1% and definite CAN 28.6%) and the mean TIR was 64.4% ±23.5%. Out of those with TIR <70%, 42.9% were affected with definite CAN compared to only 14.3% among those with TIR >70%. Patients with more severe CAN were found to have a lower TIR (P = 0.115). The study found a high prevalence of cardiac autonomic neuropathy (CAN) of around 85.7% in type 2 diabetes patients. Lower TIR values were associated with a higher incidence of definite CAN (42.9% vs. 14.3% in TIR <70% vs. >70% groups). The findings suggest TIR is inversely associated with the presence and severity of cardiac autonomic neuropathy in type 2 diabetic patients and also a potential link between TIR and CAN severity.