Cardiovascular Risk In Diabetic Patients Research Articles

Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis.

Cardiovascular disease (CVD) remains a prominent cause of global mortality, primarily driven by atherosclerosis. Diabetes mellitus, as a modifiable risk factor, significantly contributes to atherogenesis. Monocyte recruitment to the intima is a critical step in atherosclerotic plaque formation, involving chemokines and adhesion molecules such as selectins, ICAM-1, and MCP-1. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a promising group of drugs for reducing cardiovascular risk in diabetic patients, prompting investigation into their mechanisms of action. This interventional study enrolled 50 diabetes patients with atherosclerotic plaque, administering GLP-1RA for 180 days. Serum concentrations of MCP-1, ICAM-1, and L-selectin were measured before and after treatment. Anthropometric and biochemical parameters were also assessed. GLP-1RA treatment resulted in significant improvements in anthropometric parameters, glycemic control, blood pressure, and biochemical markers of liver steatosis. Biomarker laboratory analysis revealed higher baseline levels of MCP-1, ICAM-1, and L-selectin in diabetic patients with atherosclerotic plaque compared to healthy controls. Following treatment, MCP-1 and L-selectin levels decreased significantly (p < 0.001), while ICAM-1 levels increased (p < 0.001). GLP-1RA treatment in diabetic patients with atherosclerotic plaque leads to favorable changes in serum molecule levels associated with monocyte recruitment to the endothelium. The observed reduction in MCP-1 and L-selectin suggests a potential mechanism underlying GLP-1RA-mediated cardiovascular risk reduction. Further research is warranted to elucidate the precise mechanisms and clinical implications of these findings in diabetic patients with atherosclerosis.

Impact of glycated hemoglobin A1c on cardiovascular risk in diabetes patients with and without coronary artery disease

Abstract Background Guidelines recommend a haemoglobin A1c (HbA1c) target &amp;lt;53 mmol/mol (7%) to achieve microvascular risk reduction. However, the impact of HbA1c target levels on macrovascular complications is less certain. Moreover, we have previously shown that the risk of macrovascular complications is dependent on presence of coronary artery disease (CAD). Purpose We tested the hypothesis that HbA1c ≥53 mmol/mol is associated with cardiovascular risk in diabetes patients with and without CAD. Methods We conducted a contemporary cohort study including diabetes patients examined by coronary angiography in Western Denmark from 2011-2021. The association between HbA1c and major adverse cardiovascular events (MACE, a composite outcome of myocardial infarction, ischemic stroke, and cardiovascular death) was modeled using restricted cubic splines. Patients were followed for up to 10 years. We estimated adjusted hazards ratios (aHR) using HbA1c of 52 mmol/mol as reference. We also performed stratified analyses by presence of CAD. Results We included 15,825 patients with diabetes, of whom 12,200 (77%) had CAD. Median HbA1c was 52 mmol/mol in patients with CAD and 51 mmol/mol in patients without CAD. Using restricted cubic splines, we observed significantly increased MACE rates with HbA1c ≥53 mmol in the entire cohort (Figure 1A). MACE rates plateaued with increasing HbA1c above 65 mmol/mol. When stratifying by presence of CAD, this association between HbA1c and MACE was sustained in patients with CAD (Figure 1B). In contrast, we did not observe any relation between HbA1c and MACE rates in patients without CAD (Figure 1C). Conclusions The current study suggest two novel findings. Firstly, a HbA1c &amp;lt;53 mmol/mol target is associated with a reduced risk of macrovascular complications in patients with diabetes. Thus, the impact of glucose control on macrovascular complications corresponds to the HbA1c levels recommended for avoidance of microvascular complications. Secondly, the association between HbA1c and MACE is restricted to diabetes patients with CAD while not observed in those without CAD.Figure 1,A-C

A mathematical model for thrombotic risk assessment in type 2 diabetes.

Hyperglycaemia is known to alter the circulating lipids in diabetics. Combinatorial effect of in vivo synthesis of lipids and dietary lipids leads to atherosclerosis. Uncontrolled diabetes is linked with the cardiovascular outcome. This data has correlated the Castelli's Risk Index (CRI-I and CRI-II), Atherogenic Index of Plasma and Atherogenic Coefficient with microvascular complications of T2DM. Etio-pathogenesis of cardiovascular risk factors and lipid biomarkers speaks of the thrombotic events of cerebrovascular accidents and also the reno-vascular mechanisms of renal arterial thrombotic events. Documentary evidence have proved that the micro albuminuria is a "cutting edge" to assess the microvascular complications of renal and retina. Uncontrolled diabetes is known to alter the triglycerides, lower HDL-cholesterol and elevate LDL-cholesterol. Alteration of lipid profile mimics a major link between diabetes and the increased cardiovascular risk in diabetic patients.

NSAID cardiovascular risk in diabetic patients not impacted by HbA1c level

NSAID cardiovascular risk in diabetic patients not impacted by HbA1c level

SIRT3-and FAK-mediated acetylation-phosphorylation crosstalk of NFATc1 regulates Nε-carboxymethyl-lysine-induced vascular calcification in diabetes mellitus

Background and aimsArterial calcification is the predictor of cardiovascular risk in diabetic patients. Nε-carboxymethyl-lysine (CML), a toxic metabolite, is associated with accelerated vascular calcification in diabetes mellitus (DM). However, the mechanism remains elusive. This study aims to explore the key regulators involved in CML-induced vascular calcification in DM. MethodsWe used Western blot and immuno-staining to test the expression and localization of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) in human samples, a diabetic apolipoprotein E-deficient (ApoE−/−) mouse model, and a vascular smooth muscle cells (VSMC) model. Further, we confirmed the regulator of NFATc1 phosphorylation and acetylation induced by CML. The role of NFATc1 in VSMCs calcification and osteogenic differentiation was explored in vivo and in vitro. ResultsIn diabetic patients, CML and NFATc1 levels increased in the severe calcified anterior tibial arteries. CML significantly promoted NFATc1 expression and nuclear translocation in VSMCs and mouse aorta. Knockdown of NFATc1 significantly inhibited CML-induced calcification. CML promoted NFATc1 acetylation at K549 by downregulating sirtuin 3 (SIRT3), which antagonized the focal adhesion kinase (FAK) induced NFATc1 phosphorylation at the Y270 site. FAK and SIRT3 affected the nuclear translocation of NFATc1 by regulating the acetylation-phosphorylation crosstalk. NFATc1 dephosphorylation mutant Y270F and deacetylation mutant K549R had opposite effects on VSMC calcification. SIRT3 overexpression and FAK inhibitor could reverse CML-promoted VSMC calcification. ConclusionsCML enhances vascular calcification in DM through NFATc1. In this process, CML increases NFATc1 acetylation by downregulating SIRT3 to antagonize FAK-induced NFATc1 phosphorylation.

#4655 IMPACT OF MAGNESIUM ASPARTATE AND L-CARNITINE ON INFLAMMATION, INSULIN RESISTANCE AND ATHEROSCLEROSIS PROGRESSION IN DIABETIC HEMODIALYSIS PATIENTS

Abstract Background and Aims The development of new pathogenetic treatment programs to reduce cardiovascular risk in diabetic patients with end-stage kidney disease is an important task of modern nephrology. In these conditions, considering the essential role of magnesium and L-carnitine deficiency in the mechanisms (via endothelial and metabolic disorders) of cardiovascular diseases, we evaluated the effect of the combined use of magnesium aspartate and L-carnitine on inflammation, insulin resistance and the atherosclerosis progression of carotid arteries in type 2 diabetic hemodialysis (HD) patients. Method 42 type 2 diabetic HD patients were included in this prospective cohort study (male, 26; age, 59.5 ± 0.7 years; HD duration, 31.2 ± 4.6 month; diabetes mellitus duration, 174.6 ± 7.8 month). Depending on the treatment programme, patients were divided into two groups: the 1st (main) group (n = 22) in addition to basic treatment (hypoglycemic, antihypertensive therapy, correction of anemia, hyperparathyroidism, hyperphosphatemia) was treated by combination of magnesium aspartate (0.5 g/day orally) and L-carnitine (1 g/day parenterally after each HD session (three times weekly); the 2nd (comparison) group (n = 20) was only on the standard therapy. Complex treatment lasted 12-months; administration of L-carnitine was performed continuously throughout the year, while magnesium aspartate – by three 2-months’ courses per year. Serum content of tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP) and fibrinogen as inflammatory biomarkers were determined. The homoeostasis model of assessment-insulin resistance (HOMA-IR) as an index of insulin resistance was estimated. Common carotid artery intima-media thickness (CСА IMT) as an index of the atherosclerosis severity was measured by ultrasound. Data are expressed as means ± SEM. Wilcoxon T-test was used for comparison of the dependent variables, Mann-Whitney U-test – for independent ones. Results In diabetic HD patients undergoing complex treatment with a combination of magnesium aspartate and L-carnitine after 12 months of observation CCA IMT did not change (0.88 ± 0.05 vs. 0.88 ± 0.05 mm; Z = 0.09, p = 0.925), while a significant increase (by 9.1%) in the CCA IMT was determined in subjects, who were on basic therapy (0.98 ± 0.04 vs. 1.07 ± 0.04 mm; Z = 2.27, p = 0.023). In addition, after 12 months of treatment, the indicated index between 1st and 2nd groups differed (p = 0.006). By the end of follow-up, the TNF-α, CRP and fibrinogen contents in patients who were on modified therapy were 44.7, 56.4 and 78.2% from baseline, a similar indices in patients receiving standard treatment – 70.7, 77.3 and 88.8% respectively, and after one year the main group and the comparison group on the serum concentrations of TNF-α (p = 0.089), CRP (p = 0.030) and fibrinogen (p = 0.026) differed. Magnesium aspartate and L-carnitine supplementation significantly improve HOMA-IR, and after 12 months of observation, the indicated index in the 2nd group exceeded (p = 0.003) that in the 1st one (Table 1). Conclusion (1) The combined use of magnesium aspartate and L-carnitine, in addition to the basic 12-month treatment, prevents the atherosclerosis progression of CCA, provides an effective reduction of the activity of chronic inflammation, improves insulin resistance in type 2 diabetic HD patients. (2) Long-term modified treatment may reduce the cardiovascular risk in these subjects.

Development of a biomarker panel for assessing cardiovascular risk in diabetic patients with chronic limb-threatening ischemia (CLTI): a prospective study

BackgroundLower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI.MethodsIn this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes’ incidence was evaluated after 1, 3, 6 and 12 months.ResultsDuring the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events.ConclusionsElevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER.

Evaluating Diagnostic Ultrasound of the Vagus Nerve as a Surrogate Marker for Autonomic Neuropathy in Diabetic Patients.

Background and Objectives: Diagnostic ultrasound of the vagus nerve has been used to examine different polyneuropathies, and it has been suggested to be useful as a marker of autonomic dysfunction in diabetic patients. Materials and Methods: We analyzed the cross-sectional area (CSA) of the right vagus nerve of 111 patients with type 2 diabetes in comparison to 104 healthy adults and 41 patients with CIDP (chronic inflammatory demyelinating polyneuropathy). In the diabetes group, sympathetic skin response (SSR) was measured as an indicator for autonomic neuropathy. Carotid intima-media thickness (CIMT) was measured as a surrogate for atherosclerosis. Clinical symptoms of polyneuropathy were assessed using the Neuropathy Symptom Score and the Neuropathy Disability Score. Results: In total, 61.3% of the diabetes patients had clinical signs of polyneuropathy; 23.4% had no SSR at the feet as an indicator of autonomic neuropathy. Mean vagus nerve CSA did not differ in patients with and without diabetic polyneuropathy or in diabetic patients with and without SSR at the feet. No significant correlation was found between vagus nerve CSA and CIMT or SSR parameters in diabetic patients. Mean CSA of the right vagus nerve was slightly larger in diabetic patients (p = 0.028) and in patients with CIDP (p = 0.015) than in healthy controls. Conclusions: Effect sizes and mean differences were rather small so that a reliable diagnosis cannot be performed based on the vagus nerve measurement of a single person alone. Vagus nerve CSA seems not suitable as an indicator of autonomic dysfunction or cardiovascular risk in diabetic patients.

The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients.

The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts. We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine. A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., <0.9, 0.9-1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9-1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9-1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9-1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD). We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.

The Effect of Clinically Indicated Liraglutide on Pericoronary Adipose Tissue in Type 2 Diabetic Patients.

Vascular inflammation can be detected in the pericoronary adipose tissue (PCAT) by coronary computed tomography angiography (CCTA) attenuation. Treatment with liraglutide is associated with anti-inflammatory effects and reduces cardiovascular risk in diabetic patients. This study is aimed at examining the effect of clinically indicated liraglutide on PCAT attenuation. Asymptomatic patients with type 2 diabetes mellitus (T2DM) and without known ischemic heart disease underwent clinical examination, blood analysis, and CCTA. The main coronary arteries were outlined and PCAT attenuation was measured on the proximal 40 mm. Patients treated with liraglutide on a clinical indication were compared to patients not receiving liraglutide. The study included 190 patients; 53 (28%) received liraglutide (Lira+) and 137 (72%) did not (Lira-). There were no significant differences in PCAT attenuation between the two groups in either artery. However, PCAT attenuation measured around the left anterior descending artery (LAD) was lower in the Lira+ group after adjustment for age, sex, body mass index, and T2DM duration (b coefficient -2.4, p = 0.029). In a population of cardiac asymptomatic T2DM patients, treatment with clinically indicated liraglutide was not associated with differences in PCAT attenuation compared to nonliraglutide treatment in the unadjusted model. An association was seen in the adjusted model for the left anterior descending artery, possibly indicating an anti-inflammatory effect.

Lipids-Diagnosis and therapy in diabetes mellitus (Update 2023)

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.

ARTERIAL STIFFNESS ASSESSMENT IN DIABETIC PATIENTS IN A CARDIOLOGY CLINIC

Objective: Arterial stiffness is a complex phenomenon characterized by decreased compliance of the great arteries. In diabetes, the arterial wall undergoes a series of biomechanical changes, which can result in arterial stiffness. The mechanisms of these structural and functional arterial alterations in diabetes include insulin resistance, collagen accumulation due to inadequate enzymatic glycation, endothelial and autonomic nervous system dysfunction. Increased arterial stiffness is a marker of cardiovascular risk in diabetic patients. We aimed to evaluate the arterial stiffness of diabetic pateients in a private cardiology clinic Design and method: We evaluated 46 patients in cardiology service, who underwent central pressure assessment with the Mobil O’Graph device. All additional information about the patients conditions were taken from their medical records. Results: A total of 46 patients underwent the examination, being 26 of them women (56%), with a mean age of 58.93 years (+-35). Of these patients, 22 (47.8%) were diabetic, reported by their medical records. The mean central systolic pressure of diabetic patients was 142.9mmHg (+-35.1) and the central diastolic pressure was 86.9mmHg (+-19.9). The mean pulse wave velocity was 9.68 (+-5.31), with 11 (50%) above the normal value, according to the Brazilian Guideline of Hypertension 2020. Conclusions: As seen in the analyzed patients, diabetic patients are at high risk for an increase in arterial stiffness. This is possibly because the mechanisms that cause changes in endothelial collagen loss, such as advanced glycation end products and the inhibitor of formation of these products, aminoguanidine, are exacerbated in diabetic patients. The importance of assessing arterial stiffness, through pulse wave velocity, in diabetic patients is evident.

Fibroblast Growth Factor 23 and Cardiovascular Risk in Diabetes Patients-Cardiologists Be Aware.

Numerous clinical studies have indicated that elevated FGF23 (fibroblast growth factor 23) levels may be associated with cardiovascular (CV) mortality, especially in patients with chronic kidney disease. The purpose of this study was to examine the hypothesis that FGF23 may be a potent CV risk factor among patients with long-standing type 2 diabetes mellitus (T2DM). Research was performed utilizing patients with T2DM and regular outpatient follow-up care. Baseline characteristics determined by laboratory tests were recorded. Serum FGF23 levels were detected using a sandwich enzyme-linked immunosorbent assay. All patients underwent echocardiograms and 12-lead electrocardiograms. Data records of 102 patients (males: 57%) with a median age of 69 years (interquartile range (IQR) 66.0–74.0) were analyzed. Baseline characteristics indicated that one-third (33%) of patients suffered from ischemic heart disease (IHD), and the median time elapsed since diagnosis with T2DM was 19 years (IQR 14.0–25.0). The hemoglobin A1c, estimated glomerular filtration rate, and FGF23 values were, respectively, as follows: 6.85% (IQR 6.5–7.7), 80 mL/min/1.73 m2 (IQR 70.0–94.0), and 253.0 pg/mL (IQR 218.0–531.0). The study revealed that FGF23 was elevated in all patients, regardless of IHD status. Thus, the role of FGF23 as a CV risk factor should not be overestimated among patients with T2DM and good glycemic control.

Cardiovascular risk in diabetic patients with chronic kidney disease: One more turn of the screw

Cardiovascular risk in diabetic patients with chronic kidney disease: One more turn of the screw

IDF21-0547 Cardiovascular risk in diabetic patients with chronic kidney disease: One more turn of the screw

Background: Poor glycemic control in patients with diabetes mellitus (DM) is a well-documented responsible factor for microvascular complications, especially eye and kidney damage. The onset of chronic kidney disease (CKD) marks a serious turning point in the clinical history of DM in terms of cardiovascular prognosis. Aim: Our study aims to assess the cardiovascular risk (CVR) in diabetic patients with CKD. Method: We conducted a retrospective descriptive study on 88 type 2 diabetic patients with CKD, admitted during 2019-2020 to the Endocrinology-Diabetology Department of Hedi Chaker University Hospital, Sfax, Tunisia. Results: The mean age was 68.7±10.9 years with a male predominance (52.3%). Active smokers represented 12.5%. We noted a family history of CKD and early cardiovascular events in 12.5% and 5.7% of cases, respectively. The mean duration of the evolution of diabetes was 13±9 years. We highlighted a glycemic imbalance in 80.2% of patients with a mean fasting plasma glucose of 2.78 ±1.5g/L and an average HbA1C level of 9.68±2.5%. Dyslipidemia and hypertension were encountered in 94% and 86.4% of cases, respectively. Obesity affected 35.7% of the patients with a mean BMI of 28,53 ± 5.11 kg/m2. Macroangiopathy was documented in 29.5%, mainly ischemic heart disease (19.3%) and stroke (9.1%). Diabetic retinopathy was diagnosed in 53.5%. The mean glomerular filtration rate (GFR) was 32.2±13.81 mL/min/1.73 m2. Most patients were Stage 3 CKD (56.8%) whereas 30.5% were stage 4 and 12.5% stage 5. Hemodialysis was undergone for 7.9%. Albuminuria was positive in 52.2% with mean proteinuria of 1.46 ± 2.4 g/24H. According to the European Society of Cardiology 2019 CVR assessment, all patients are among the very high CVR range. Discussion: Diabetic nephropathy (DN) is the first leading cause of CKD in the world. Chronic hyperglycemia is responsible for the vascular damage and progression of CKD to terminal-stage and recourse to hemodialysis. In addition to traditional CVR factors, GFR impairment and albuminuria are independent markers of CVR and overall morbidity in diabetic patients. This risk is proportional to the severity of CKD and would be maximal in hemodialysis patients. We recommend screening annually for DN using a urine dipstick test and serum creatinine measurement. Achieving the best glycemic control (A1c <7%), treating high blood pressure (<130/80 mmHg or <125/75 mmHg if proteinuria >1.0 g/24 h and increased serum creatinine), using nephroprotective renin-angiotensin-aldosterone system blockers, and treating dyslipidemia (LDL cholesterol <0.55g/l) are effective measures for preventing the development of microalbuminuria, delaying the progression to more advanced stages of CKD and reducing the overall cardiovascular mortality in diabetic patients.

Alpha-lipoic acid improved anemia, erythropoietin resistance, maintained glycemic control, and reduced cardiovascular risk in diabetic patients on hemodialysis: a multi-center prospective randomized controlled study.

To investigate the impact of alpha-lipoic acid (ALA) on inflammation, oxidative stress, anemia, and glycemic parameters and their association with cardiovascular risk in diabetic patients on hemodialysis. In this multi-center, randomized, controlled study, 60 diabetic patients on hemodialysis were randomized into control group (n=30) which received Epoetin-alpha plus insulin therapy, and alpha-lipoic acid group (n=30) which received the same treatment plus alpha-lipoic acid (ALA) 600 mg once daily. Serum levels of high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), creatinine, urea, blood urea nitrogen (BUN), hemoglobin (Hb), iron parameters, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and fructosamine were measured at baseline and six months after intervention. The ankle-brachial index (ABI) was used to evaluate the clinical outcome. Erythropoietin resistance index (ERI), the weekly cost of Epoetin-alpha doses, and the total cost were calculated. The two groups were statistically similar at baseline. After the intervention, as compared to the control group, ALA group showed significant reductions in serum levels of hs-CRP, TNF-α, 8-OHdG (p<0.001), urea, and BUN (p=0.029) with significant elevations in Hb concentration (p<0.001), serum iron (p=0.037) and transferrin saturation (p<0.001). ALA group showed a significant decline in FBG (p=0.004), HbA1c (p<0.001), fructosamine (p=0.005), ERI (p<0.001), weekly doses, and the weekly cost of Epoetin-alpha, and the total cost (p<0.001). ALA provided a cardio-protective effect, whereas the percentage of patients with acceptable ABI (0.9-1) was significantly higher in ALA group than in the control group (p=0.024), and those with abnormally low ABI (<0.9) were lower in the ALA group. Due to its efficacy and safety, alpha-lipoic acid represents a pharmaco-economic supplement for diabetic patients on hemodialysis. Further trials are needed for complete evaluation of ALA effects.

Dipeptidyl peptidase-4 inhibitors reduced long-term cardiovascular risk in diabetic patients after percutaneous coronary intervention via insulin-like growth factor-1 axis

Dipeptidyl-peptidase-4 inhibitors (DPP4i) have been the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, large cardiovascular outcome trials (CVOTs) have not shown any significant the prognostic superiority. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. The aim of this study was thus to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4. This single-center analysis involved consecutive Japanese diabetic patients who underwent PCI for the first time between 2008 and 2018 (n = 885). Primary and secondary endpoints were set as cardiovascular (CV) death and the composite of CV death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (insulin-like growth factor binding protein-3: IGFBP-3) were measured. In consequences, unadjusted Kaplan–Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤ 25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV death by DPP4i at PCI (hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.16–0.82, p = 0.01) and 3P-MACE (HR 0.47, 95% CI 0.25–0.84, p = 0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p < 0.0001). In conclusion, the findings of the present study indicate beneficial effects of DPP4i to improve outcomes in Japanese diabetic patients following PCI, which might be mediated by DPP4–IGF-1 axis.

Pharmacological Treatment of Diabetic and Non-Diabetic Patients With Coronary Artery Disease in the Real World of General Practice.

Type 2 diabetes mellitus (T2DM) severely increases the probability of developing coronary artery disease (CAD), and diabetic patients with CAD should be considered at very high cardiovascular risk. The complexity of this clinical scenario makes very hard the appropriateness of the pharmacological treatment in the real world. To investigate the implementation of guideline recommendations for the treatment of patients affected by CAD with or without T2DM, a retrospective observational study was carried out between 2018 and 2020, by using the computerized clinical medical record of 10 general practitioners (GPs) including 13,206 subjects. A total of 926 patients (7.0%) were affected by CAD and 393 (42.4%) of them were also diabetic. LDLc, SBP, DBP, and FPG were recorded in 77.4%, 65.4%, 66.5%, and 82.6% of patients, respectively. Comorbidities (median; IQR = 8; 6–10 vs. 5; 3–7: p < 0.001) were significantly high in diabetic patients. Specialist counselling has been observed in 59.9% of diabetic and 57% of non-diabetic patients (p = 0.400). Antithrombotic drugs, statins, β-blockers, or RAASs were prescribed in 67.2%, 59.6%, and 75.9% of patients, respectively. Overall, 462 (49.9%) patients used the treatment suggested by guidelines. Dyslipidemia, hypertension, atherosclerosis, and specialist counselling were predictors of suggested drugs use both in diabetic and non-diabetic patients. Diabetes was not an independent factor related to the likelihood to be properly treated, according to the guidelines. Glucose lowering drugs were prescribed in 69.5% of diabetic patients, but only 39 (14.3%) were treated with the proper GLP-1 or SGLT2-i, whereas 45 patients (16.5%) received the improper sulphonylureas. Our results showed that a “non-ideal” therapeutic approach was adopted in patients affected by diabetes and CAD. ADA and ESC guidelines recommend the use of at least one hypoglycemic agent belonging to the GLP-1 or SGLT2-i class in diabetic patients with high/very high cardiovascular risk, regardless of the glycemic target (HbA1c <7%). However, only a few diabetic patients on hypoglycemic therapy were appropriately treated. These data suggest that a closer collaboration between the GPs, clinical pharmacologist, and specialists is needed in the real world scenario of the general practice in order to effectively improve adherence to guidelines and overall management of global cardiovascular risk in diabetic patients.

The Evaluation of Cardiovascular Risk in Diabetic Patients

Abstract AIM The aim of the study was to evaluate cardiovascular risk in patients with diabetes mellitus type 2 according to gender. METHODS The monitoring was designed as a retrospective analysis of data obtained from the documentation of the diabetic outpatients treated with the dipeptidyl peptidase-4 inhibitors (DPP4is) or sodium–glucose co-transporter-2 (SGLT2). Cardiovascular risk was assessed according to UKPDS risk engine. RESULTS The levels of HbA1c decreased throughout the whole study. Sixty per cent of patients achieved an HbA1c level &lt;8% after 18 months. Both men and women had similar glycaemic compensation. Men had a significantly higher risk of fatal coronary heart disease (CHD) (p &lt; 0.001), stroke (p &lt; 0.01) and fatal stroke (p &lt; 0.01) compared to women. We found the risk of fatal CHD to be 38-fold higher in men compared to women (p &lt; 0.01). CONCLUSION Potential cardiovascular effects of antidiabetic treatment should be clearly defined with possible different effects according to gender. We found a much higher risk in men than women, even when their glycaemic compensation was comparable.

Association of Fibroblast Growth Factor 21 with Lipid Profile, MDA and AOPP in Patients with Type 2 Diabetes Mellitus

Background: Diabetes mellitus is rising all over the world due to population growth, aging, urbanisation, and the increase of obesity due to physical inactivity, characterized by persistent high blood glucose levels associated with aberrations in lipid, carbohydrate, and protein metabolisms leading to water and electrolyte imbalance. Cardiovascular diseases are the leading causes of mortality in diabetic patients. Mechanisms such as oxidative stress, lipid metabolism imbalance, as well as myocardial cell apoptosis are key factors to facilitate the progression of Diabetic cardiomyopathy.&#x0D; Aim: The aim of this study was to assess FGF-21 levels and their association with lipid profile parameters and oxidative stress in patients with type 2 diabetes mellitus.&#x0D; Methods: A patient based cross-sectional study was conducted among the subjects with history of type 2 DM for the past 10 years.&#x0D; Results: Variations in FBS, T.C, TG, LDL, HDL, VLDL, FGF-21, MDA and AOPP levels among cases and controls were depicted in Table 2. There was an increase in all these parameters in cases compared to controls whereas HDL showed a decrease among cases.&#x0D; Conclusion: Our study concluded that there is a significant correlation between fibroblast growth factor 21 (FGF-21), oxidative stress, and abnormal lipid profile in type 2 diabetic patients. We would recommend further studies to explore the role of FGF21 as an important marker in predicting cardiovascular risk in diabetic patients.