Role Of DM Research Articles

Impact of Diabetes Duration and Control on the Extent and Severity of Coronary Artery Disease in Egyptian Patients: Evaluation by Coronary CT Angiography

Abstract Background Diabetes mellitus (DM) has reached epidemic proportions worldwide and approximately 40% of diabetics die due to ischemic heart disease, 15% from other forms of heart disease, principally congestive heart failure, and about 10% from stroke. The role of DM in CAD progression is now universally accepted. Aim of the Work To explore the association between diabetes duration and control on the extent of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA). Patients and Methods This study is a cross sectional observational study that included 100 diabetic patients who were eligible for CT coronary angiography. They were evaluated in the diabetic outpatient clinic of the internal affairs ministry Hospitals for symptoms suggestive of CAD or for preoperative cardiovascular system risk stratification. CT coronary angiography was performed in all patients, and CACS was calculated using Agatston score. CCTA was analyzed for the site and severity of stenosis. For each patient, the number of diseased vessels was calculated through the assignment of one, two, and three or left main (LM) coronary artery vessels. Results The prevalence of atherosclerotic coronary artery disease among diabetics in the studied population was 78%, moderate to severe degree of obstructive lesions was found in 81% of them as detected by CTCA. Coronary calcification was found in 65% of diabetic patients. Coronary calcium score showed a significant positive correlation with age (p-value =0.002), HB1c level and the Triglycerides, cholesterol and LDL levels. The severity of atherosclerotic coronary artery disease was significantly associated with dyslipidemia. On the other hand, the extent of coronary affection was associated with the duration of diabetes. Among the studied subjects, the LAD was the most frequently affected artery (60% of patients). Low risk diabetics (zero calcium and no atherosclerotic plaques) had a mean duration of DM < 10 years with controlled lipid profile. Conclusion Based on the results of the current study, we can draw several conclusions. Diabetic patients are at risk for significant CAD with or without calcium burden. Extensive significant CAD is associated with long standing diabetes. Uncontrolled diabetes mellitus and the presence of dyslipidemia augment the process of atherosclerosis and the severity of the disease. Younger patients with controlled diabetes and lipid profile have a more favorable coronary anatomy profile and a favorable outcome. The LAD is the artery of predilection in diabetics. Abbreviations ASCVD: Atherosclerotic cardiovascular disease; BP: Blood pressure; CABG: Coronary artery bypass graft; CAD: Coronary artery disease; CCTA: Coronary computed tomography angiography; CVD: Cardiovascular disease; DM: Diabetes mellitus; HDL-c: High density lipoprotein cholesterol; HS: Highly significant; IQR: Inter-quartile range; LAD: Left anterior descending; LCX: Left circumflex; LDL-c: Low density lipoprotein cholesterol; LM: Left main; MDCT: Multidetector coronary CT angiography; MSCT: Multi-slice computed tomography; NS: Non significant; PCI: Percutaneous coronary intervention; RCA: Right coronary artery; S: Significant; TC: Total cholesterol; TG: Triglycerides

CLINICAL FEATURES OF ISCHEMIC STROKE IN PATIENTS WITH TYPE II DIABETES

This article discusses the clinical features of ischemic stroke in patients with type II diabetes. It should be noted that type II diabetes mellitus (DM 2) is one of the main risk factors and has a special place among all diseases that lead to stroke. The role of DM 2 in the development of the first stroke was presented as a result of a 10-year follow-up in Framingham (USA). A population study of people aged 55-84 years showed that people with diabetes have a significantly higher rate of death from stroke.

Prevalence of Low Level of Vitamin D Among COVID-19 Patients and Associated Risk Factors in India – A Hospital-Based Study

BackgroundThe world is facing the most challenging pandemic in the 21st century. The developed and developing countries are facing the burden equally and no proven treatment options available. Recent studies suggest the plausibility of vitamin D therapy and prophylaxis for COVID-19, in the setting where the deficiency is more prevalent. Though evaluation of vitamin D status is not a routine in India, the present study focuses on the level of Vitamin d among COVID-19 patients.MethodsThe study was a hospital-based cross-sectional to find the status of vitamin D among COVID-19 patients in a tertiary care hospital, Patna, Bihar, India. The demographic, comorbidity data were taken, and the level of vitamin D was measured by a chemiluminescence-based immunoassay analyzer. The analysis compared the level of deficiency and insufficiency among different groups of COVID-19 patients. The role of DM and HTN as risk factors for mortality was compared.ResultsAmong the total study participants (156), 42.31% were obese and 17.31% were severe as per clinical severity. The total prevalence of vitamin D deficiency was 58.97% and insufficiency was 89.1%. The prevalence was found high among male (61.02%), overweight (65.52%), and severe (62.96%) patients. The severity increases with advanced age (p<0.05) and important risk factors for mortality are DM, HTN, and advanced age.ConclusionThe level of vitamin D can be assessed for the prognosis of COIVD-19 patients and help to modify the treatment protocol. Appropriate therapeutic/preventive intervention of vitamin D can alter the course and severity of COVID-19.

462-P: Diabetes Is Associated with Progression of Coronary Arterial Calcification in Patients New to Dialysis

Background and Objective: Coronary artery calcification is a risk marker of atherosclerosis. Recently, a large multicenter, prospective observational study showed the CAC density was inversely related to the occurrence of cardiac vascular events. The proposed hypothesis is that low density area is more prone to rupture due to large lipid core and a marker of plaque instability. However, high CAC density in 125 chronic hemodialysis patients was associated with increased mortality. Our aim was to determine CAC density in new dialysis patients, and the role of DM in the progression of CAC density. Design, Setting, Participants, and Measurements: Ninety-eight initial dialysis patients were enrolled. CAC density was calculated by Agatson score divided by calcium volume score. CAC density progression was measured by the difference in score between CT/time. Sixty-seven study participants had repeat CAC measures at one year. Results: The mean age of study participants was 50.1 ± 12.7 years. A third were women, and 64.7% were black. The baseline CAC density for DM group was 85.2 (interquartile range (IQR), 10.3-452) compared to 0(IQR, 0-90.3) for non-DM group was (P=0.01). Seventy percent of diabetes patients had progression of calcium density while forty one percent of nondiabetic patients had progression of calcium density score. (P=0.02). Hazard ratio for DM after adjust for age and smoke is 2.0 (1.05-72.6). Conclusions: Our results indicate that DM is a risk factor for high calcium density of individuals new to dialysis patients and is a risk factor for progression of calcium density score. Increased calcium density in new dialysis patient is a risk factor for CAC progression, rather than a marker of plaque stabilization. Disclosure N. Roy: None. D. Yang: None. S. Rosas: Research Support; Self; Bayer US, Ironwood Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.

Comparison of outcomes after everolimus-eluting stent implantation in diabetic versus non-diabetic patients in the Tokyo-MD PCI study

BackgroundDiabetes mellitus (DM), especially in those requiring insulin for treatment, is known to be a risk factor for adverse events after percutaneous coronary intervention using first-generation drug-eluting stents. However, the role of DM in patients treated with everolimus-eluting stents (EES) is less known. The purpose of the present analysis was to evaluate the outcomes of treatment with EES for DM patients both requiring and not requiring insulin, and to compare them with non-DM patients. MethodsOf patients treated with EES in the Tokyo-MD PCI study, an all-comer, multicenter, observational cohort study, we identified 199 insulin-requiring diabetics (IRDM), 575 non-insulin requiring diabetics (NIRDM), and 1092 non-diabetics (non-DM). The main outcomes were major adverse cardiovascular events (MACE) defined as a composite of all-cause death, myocardial infarction, and stroke, and target lesion revascularization (TLR). ResultsThe cumulative incidence of MACE and TLR was significantly greater in patients with IRDM than non-DM [MACE: hazard ratio 1.97, 95% confidence interval (CI) 1.31–2.90, p<0.01; TLR: hazard ratio 3.43, 2.07–5.55, p<0.0001] according to univariate Cox proportional hazards model. After adjusting for confounders using the multivariate Cox proportional hazard model, the risk of IRDM versus non-DM for TLR remained significant (hazard ratio 1.92, 1.10–3.29, p=0.02). The incidence of TLR in NIRDM was slightly greater than that in non-DM according to univariate analysis (hazard ratio 1.65, 1.07–2.54, p=0.02). However, the risk was not statistically different in the multivariate analysis (hazard ratio 1.52, 0.97–2.35, p=0.06). ConclusionsIn this all-comer, observational study, the risk of TLR was greater in IRDM compared with non-DM after EES implantation, while the increased risk for TLR from NIRDM did not reach statistical significance.

HLA-DM Constrains Epitope Selection in the Human CD4 T Cell Response to Vaccinia Virus by Favoring the Presentation of Peptides with Longer HLA-DM–Mediated Half-Lives

HLA-DM (DM) is a nonclassical MHC class II (MHC II) protein that acts as a peptide editor to mediate the exchange of peptides loaded onto MHC II during Ag presentation. Although the ability of DM to promote peptide exchange in vitro and in vivo is well established, the role of DM in epitope selection is still unclear, especially in human response to infectious disease. In this study, we addressed this question in the context of the human CD4 T cell response to vaccinia virus. We measured the IC(50), intrinsic dissociation t(1/2), and DM-mediated dissociation t(1/2) for a large set of peptides derived from the major core protein A10L and other known vaccinia epitopes bound to HLA-DR1 and compared these properties to the presence and magnitude of peptide-specific CD4(+) T cell responses. We found that MHC II-peptide complex kinetic stability in the presence of DM distinguishes T cell epitopes from nonrecognized peptides in A10L peptides and also in a set of predicted tight binders from the entire vaccinia genome. Taken together, these analyses demonstrate that DM-mediated dissociation t(1/2) is a strong and independent factor governing peptide immunogenicity by favoring the presentation of peptides with greater kinetic stability in the presence of DM.

Metformin and cancer mortality

The author analyses recent publications supporting the ability of metformin to decrease the risk of cancer morbidity and mortality in patients with type 2diabetes mellitus. Pre-history of the problem (including the use of biguanides for metabolic rehabilitation of oncological patients), the role of DM as a riskfactor of cancer morbidity and mortality, mechanisms and targets of metformin anticancer effects, and potential use of this agent in non-diabetic patientsare discussed. The need for the search of the markers of sensitivity and resistance to metformin to be used in oncological practice is emphasized.

A point mutation in the groove of HLA-DO allows egress from the endoplasmic reticulum independent of HLA-DM

B lymphocytes express the nonclassical class II molecule HLA-DO, which modulates the peptide loading activity of HLA-DM in the endocytic pathway. Binding to HLA-DM is required for HLA-DO to egress from the endoplasmic reticulum (ER). To gain insights into the mode of action of DO and on the role of DM in ER release, we sought to identify DM-binding residues on DO. Our results show that DOalpha encompasses the binding site for HLA-DM. More specifically, mutation of residue DOalpha41 on an exposed lateral loop of the alpha1 domain affects the binding to DM, ER egress, and activity of DO. Using a series of chimeric DR/DO molecules, we confirmed the role of the alpha chain and established that a second DM-binding region is located C-terminal to the DOalpha80 residue, most probably in the alpha2 domain. Interestingly, after mutation of a buried proline (alpha11) on the floor of the putative peptide-binding groove, HLA-DO remained functional but became independent of HLA-DM for ER egress and intracellular trafficking. Collectively, these results suggest that the binding of HLA-DM to DOalpha allows the complex to egress from the ER by stabilizing intramolecular contacts between the N-terminal antiparallel beta-strands of the DOalphabeta heterodimer.