Exploring the World of Membrane Proteins: Techniques and Methods for Understanding Structure, Function, and Dynamics.

In eukaryotic cells, membrane proteins play a crucial role. They fall into three categories: intrinsic proteins, extrinsic proteins, and proteins that are essential to the human genome (30% of which is devoted to encoding them). Hydrophobic interactions inside the membrane serve to stabilize integral proteins, which span the lipid bilayer. This review investigates a number of computational and experimental methods used to study membrane proteins. It encompasses a variety of technologies, including electrophoresis, X-ray crystallography, cryogenic electron microscopy (cryo-EM), nuclear magnetic resonance spectroscopy (NMR), biophysical methods, computational methods, and artificial intelligence. The link between structure and function of membrane proteins has been better understood thanks to these approaches, which also hold great promise for future study in the field. The significance of fusing artificial intelligence with experimental data to improve our comprehension of membrane protein biology is also covered in this paper. This effort aims to shed light on the complexity of membrane protein biology by investigating a variety of experimental and computational methods. Overall, the goal of this review is to emphasize how crucial it is to understand the functions of membrane proteins in eukaryotic cells. It gives a general review of the numerous methods used to look into these crucial elements and highlights the demand for multidisciplinary approaches to advance our understanding.

Prevalence and Co-prevalence of Comorbidities Among Patients with Type 2 Diabetes Mellitus in the MENA Region: A Systematic Review.

AIM: The management of type 2 diabetes mellitus is affected by the presence of comorbidities. This meta-analysis aimed to determine how likely it is for individuals with type 2 diabetes in the Middle East and North Africa (MENA) to be living with additional chronic health conditions. METHODS: We searched for studies published from January 2010 to December 2020 in PubMed, Ovid MEDLINE®, Cochrane CENTRAL, Scopus, and Web of Science. Studies of adults with type 2 diabetes in the MENA region were included. We performed a random-effects meta-analysis of single proportions to calculate each comorbidity's overall prevalence/co-prevalence. RESULTS: Statistically significant co-prevalence was detected at p < 0.01 for angina (pooled proportion: 0.24, 95% CI: 0.06, 0.49), cerebrovascular accident (pooled proportion: 0.16, 95% CI: 0.08, 0.26), coronary artery disease (pooled proportion: 0.25, 95% CI: 0.16, 0.35), coronary heart disease (pooled proportion: 0.05, 95% CI: 0.01, 0.12), peripheral vascular disease (pooled proportion: 0.19, 95% CI: 0.13, 0.26), hypertension (pooled proportion: 0.56, 95% CI: 0.43, 0.69), renal impairment (pooled proportion: 0.19, 95% CI: 0.10, 0.29), in addition to hyperlipidemia and overweight/obesity. CONCLUSION: There is evidence of co-prevalence of several comorbidities in patients with type 2 diabetes. This highlights the importance of enhancing communication among healthcare professionals to develop the optimal management plan for each patient.

Urinary 20-HETE: A prospective Non-Invasive prognostic and diagnostic marker for diabetic kidney disease.

INTRODUCTION: The identification and validation of a non-invasive prognostic marker for early detection of diabetic kidney disease (DKD) can lead to substantial improvement in therapeutic decision-making. OBJECTIVES: The main objective of this study is to assess the potential role of the arachidonic acid (AA) metabolite 20-hydroxyeicosatetraenoic (20-HETE) in predicting the incidence and progression of DKD. METHODS: Healthy patients and patients with diabetes were recruited from the Hamad General Hospital in Qatar, and urinary 20-HETE levels were measured. Data analysis was done using the Statistical Package for Social Sciences (SPSS). RESULTS: Our results show that urinary 20-HETE-to-creatinine (20-HETE/Cr) ratios were significantly elevated in patients with DKD when compared to patients with diabetes who did not exhibit clinical signs of kidney injury (p < 0.001). This correlation was preserved in the multivariate linear regression accounting for age, diabetes, family history of kidney disease, hypertension, dyslipidemia, stroke and metabolic syndrome. Urinary 20-HETE/Cr ratios were also positively correlated with the severity of kidney injury as indicated by albuminuria levels (p < 0.001). A urinary 20-HETE/Cr ratio of 4.6 pmol/mg discriminated between the presence and absence of kidney disease with a sensitivity of 82.2 % and a specificity of 67.1%. More importantly, a 10-unit increase in urinary 20-HETE/Cr ratio was tied to a 10-fold increase in the risk of developing DKD, suggesting a 20-HETE prognostic efficiency. CONCLUSION: Taken together, our results suggest that urinary 20-HETE levels can potentially be used as non-invasive diagnostic and prognostic markers for DKD.

Recommendations for Early and Comprehensive Management of Type 2 Diabetes and Its Related Cardio-Renal Complications.

Type 2 diabetes (T2D) is a global health problem accompanied by an elevated risk of complications, the most common being cardiac and renal diseases. In Lebanon, the prevalence of T2D is estimated at 8-13%. Local medical practice generally suffers from clinical inertia, with gaps in the yearly assessment of clinical manifestations and suboptimal screening for major complications. The joint statement presented here, endorsed by five Lebanese scientific medical societies, aims at providing physicians in Lebanon with a tool for early, effective, and comprehensive care of patients with T2D. Findings from major randomized clinical trials of antidiabetic medications with cardio-renal benefits are presented, together with recommendations from international medical societies. Optimal care should be multidisciplinary and should include a multifactorial risk assessment, lifestyle modifications, and a regular evaluation of risks, including the risks for cardiovascular (CV) and renal complications. With international guidelines supporting a shift in T2D management from glucose-lowering agents to disease-modifying drugs, the present statement recommends treatment initiation with metformin, followed by the addition of sodium-glucose cotransporter 2 inhibitors or glucagon-like peptide-1 receptor agonists due to their CV and renal protection properties, whenever possible. In addition to the selection of the most appropriate pharmacological therapy, efforts should be made to provide continuous education to patients about their disease, with the aim to achieve a patient-centered approach and to foster self-management and adherence to the medical plan. Increasing the level of patient engagement is expected to be associated with favorable health outcomes. Finally, this statement recommends setting an achievable individualized management plan and conducting regular follow-ups to monitor the patients' glycemic status and assess their risks every 3-6 months.

Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases.

The intricate interplay of one-carbon metabolism (OCM) with various cellular processes has garnered substantial attention due to its fundamental implications in several biological processes. OCM serves as a pivotal hub for methyl group donation in vital biochemical reactions, influencing DNA methylation, protein synthesis, and redox balance. In the context of aging, OCM dysregulation can contribute to epigenetic modifications and aberrant redox states, accentuating cellular senescence and age-associated pathologies. Furthermore, OCM's intricate involvement in cancer progression is evident through its capacity to provide essential one-carbon units crucial for nucleotide synthesis and DNA methylation, thereby fueling uncontrolled cell proliferation and tumor development. In neurodegenerative disorders like Alzheimer's and Parkinson's, perturbations in OCM pathways are implicated in the dysregulation of neurotransmitter synthesis and mitochondrial dysfunction, contributing to disease pathophysiology. This review underscores the profound impact of OCM in diverse disease contexts, reinforcing the need for a comprehensive understanding of its molecular complexities to pave the way for targeted therapeutic interventions across inflammation, aging and neurodegenerative disorders.

Wearable flexible body matched electromagnetic sensors for personalized non-invasive glucose monitoring.

This work introduces novel body-matched, vasculature-inspired, quasi-antenna-arrays that act as electromagnetic sensors to instantaneously, continuously, and wirelessly sense glucose variations in the bloodstream. The proposed sensors are personalized, leverage electromagnetic waves, and are coupled with a custom machine-learning-based signal-processing module. These sensors are flexible, and embedded in wearable garments such as socks, which provide conformity to curved skin surfaces and movement resilience. The entire wearable system is calibrated against temperature, humidity, and movement resulting in high accuracy in glucose variations tracking. In-Vivo experiments on diabetic rats and pigs exhibit a 100% diagnostic accuracy over a wide range of glucose variations. Human trials on patients with diabetes and healthy individuals reveal a clinical accuracy of continuous glucose monitoring of 99.01% in twenty-eight subjects who underwent Oral Glucose Tolerance Tests. Hence, our approach ensures the continuous tracking of glucose variations from hypo-to-hyper glycemic levels with great fidelity.

Activation of 20-HETE Synthase Triggers Oxidative Injury and Peripheral Nerve Damage in Type 2 Diabetic Mice.

Diabetic Peripheral Neuropathy (DPN), highly prevalent among patients with diabetes, is characterized by peripheral nerve dysfunction. Reactive Oxygen Species (ROS) overproduction has been suggested to orchestrate diabetic complications including DPN. Untargeted antioxidant therapy has exhibited limited efficacy, highlighting a critical need to explore ROS sources altered in a cell-specific manner in DPN. Cytochromes P450 (CYP) enzymes are prominent sources of ROS. Particularly, the 20-HETE synthase, CYP4A, is reported to mediate diabetes-induced renal, retinal, and cardiovascular injuries. This work investigates the role of CYP4A/20-HETE in DPN and their mechanisms of action. Non-obese type 2 Diabetic mice (MKR) were used and treated with a CYP4A-inhibitor (HET0016) or AMPK-activator (Metformin). Peripheral nerves of MKR mice reflect increased CYP4A and 20-HETE levels, concurrent with altered myelin proteins and sensorimotor deficits. This was associated with increased ROS production and altered Beclin-1 and LC3 protein levels, indicative of disrupted autophagic responses in tandem with AMPK inactivation. AMPK activation via Metformin restored nerve integrity, reduced ROS production, and regulated autophagy. Interestingly, similar outcomes were revealed upon HET0016 treatment whereby ROS production, autophagic responses, and AMPK signaling were normalized in diabetic mice. Altogether, the results highlight hyperglycemia-mediated oxidative injury in DPN through a novel CYP4A/20-HETE/AMPK pathological axis. PERSPECTIVE: To our knowledge, this is the first study to highlight the role of CYPs/20-HETE-induced oxidative injury in the pathogenesis of diabetic peripheral neuropathy. Targeting the identified pathological axis CYP4A/20-HETE/AMPK may be of clinical potential in predicting and alleviating peripheral nerve injury in patients with Type 2 Diabetes Mellitus.

Reno-Protective Effect of GLP-1 Receptor Agonists in Type1 Diabetes: Dual Action on TRPC6 and NADPH Oxidases.

Diabetic kidney disease (DKD), a serious diabetic complication, results in podocyte loss and proteinuria through NADPH oxidases (NOX)-mediated ROS production. DUOX1 and 2 are NOX enzymes that require calcium for their activation which enters renal cells through the pivotal TRPC channels. Hypoglycemic drugs such as liraglutide can interfere with this deleterious mechanism imparting reno-protection. Herein, we aim to investigate the reno-protective effect of GLP1 receptor agonist (GLP1-RA), via its effect on TRPC6 and NADPH oxidases. To achieve our aim, control or STZ-induced T1DM Sprague-Dawley rats were used. Rats were treated with liraglutide, metformin, or their combination. Functional, histological, and molecular parameters of the kidneys were assessed. Our results show that treatment with liraglutide, metformin or their combination ameliorates DKD by rectifying renal function tests and protecting against fibrosis paralleled by restored mRNA levels of nephrin, DUOX1 and 2, and reduced ROS production. Treatment with liraglutide reduces TRPC6 expression, while metformin treatment shows no effect. Furthermore, TRPC6 was found to be directly interacting with nephrin, and indirectly interacting with DUOX1, DUOX2 and GLP1-R. Our findings suggest that treatment with liraglutide may prevent the progression of diabetic nephropathy by modulating the crosstalk between TRPC6 and NADPH oxidases.

Diabetic Nephropathy and COVID-19: The Potential Role of Immune Actors.

Nowadays, type II diabetes mellitus, more specifically ensuing diabetic nephropathy, and severe COVID-19 disease are known to be closely associated. The exact mechanisms behind this association are less known. An implication for the angiotensin-converting enzyme 2 remains controversial. Some researchers have started looking into other potential actors, such as neuropilin-1, mitochondrial glutathione, vitamin D, and DPP4. In particular, neuropilin-1 seems to play an important role in the underlying mechanism linking COVID-19 and diabetic nephropathy. We suggest, based on the findings in this review, that its up-regulation in the diabetic kidney facilitates viral entry in this tissue, and that the engagement of both processes leads to a depletion of neuropilin-1, which was demonstrated to be strongly associated with the pathogenesis of DN. More studies are needed to confirm this hypothesis, and research should be directed towards elucidating the potential roles of all these suggested actors and eventually discovering new therapeutic strategies that could reduce the burden of COVID-19 in patients with diabetic nephropathy.

Experts' opinion on the detection and management of prediabetes in Lebanon.

Given that the complications of type 2 diabetes can start at an early stage, early detection and appropriate management of prediabetes are essential. We aimed to develop an expert opinion on prediabetes in Lebanon to pave the way for national guidelines tailored for the Lebanese population in the near future. A panel of seven diabetes experts conducted a thorough literature review and discussed their opinions and experiences before coming up with a set of preliminary recommendations for the detection and management of prediabetes in Lebanon. Lebanese physicians employ multiple tests for the diagnosis of prediabetes and no national cut-off values exist. The panel agreed that prediabetes screening should be focused on patients exceeding 45 years of age with otherwise no risk factors and on adults with risk factors. The panel reached that fasting plasma glucose (FPG) and HbA1c should be used for prediabetes diagnosis in Lebanon. FPG values of 100-125 mg/dL or HbA1c values of 5.7%-6.4% were agreed upon as indicative of prediabetes. For the management of prediabetes, a three-step approach constituting lifestyle modifications, pharmacological treatment and bariatric surgery is recommended. There should be more focus on research on prediabetes in Lebanon. This preliminary report will be further discussed with the Lebanese Society of Endocrinology, Diabetes and Lipids in 2021 in order to come up with the first Lebanese national guidelines for the detection and management of prediabetes in Lebanon.

Characteristics and treatment patterns of patients with type 2 diabetes in Lebanon: the DISCOVER study.

BACKGROUND: Lebanon is part of the global DISCOVER study, a global, noninterventional, multicentre, prospective study with 3-years of follow-up. AIMS: The aim of this study is to describe real-world clinical practice in terms of type 2 diabetes mellitus (T2DM) disease management and treatment patterns within Lebanon. METHODS: Baseline demographic and clinical parameters were captured on a standardized case report form, according to routine clinical practice at each clinical site. RESULTS: We recruited 348 patients. At the initiation of second-line therapy, mean duration of diabetes was 6.7 [standard deviation (SD) 6.5] years; mean HbA1c and fasting plasma glucose levels were 8.5% (SD 1.6%) and 178.7 (SD 56.5) mg/dL respectively. Almost half the patients were hypertensive (45.1%) or had dyslipidaemia (48.6%). Metformin monotherapy was used as first-line therapy in 56.9% of the patients and upfront dual therapy in 25%. The primary reason for changing firstline therapy was poor glycaemic control. The main factors in choosing the second-line therapy were efficacy, tolerability and hypoglycaemia. CONCLUSION: Clinical inertia was evident in this cohort of patients as they had suboptimal glycaemic control at the time of enrolment and the initiation of second-line therapy. Treatment intensification is required to reduce diabetes-related adverse outcomes.

Immune Checkpoint Inhibitor-Induced Diabetes Mellitus: Potential Role of T Cells in the Underlying Mechanism.

Immunotherapy is now a recognized treatment option for several types of cancer. However, some cancer patients treated with immune checkpoint inhibitors (ICIs) are subject to immune-related adverse events, including induced diabetes mellitus. The exact role and molecular/genetic action of ICIs in diabetes are still not well understood. Elucidating the underlying mechanisms in a proper fashion would allow better refining of biomarkers that would help diagnose patients at risk of altered immune system homeostasis, but would also hold the potential of new therapeutic options for diabetes. In the present narrative review, we propose to discuss the case of autoimmune diabetes following treatment with ICIs and the role of ICIs in the pathophysiology of diabetes. We also present some scarce available data on interesting potential immune therapies for diabetes.

Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome.

Atrial fibrillation (AF) and cardiometabolic syndrome (CMS) have been linked to inflammation and fibrosis. However, it is still unknown which inflammatory cytokines contribute to the pathogenesis of AF. Furthermore, cardiometabolic syndrome (CMS) risk factors such as obesity, hypertension, insulin resistance/glucose intolerance are also associated with inflammation and increased level of cytokines and adipokines. We hypothesized that the inflammatory immune response is exacerbated in patients with both AF and CMS compared to either AF or CMS alone. We investigated inflammatory cytokines and fibrotic markers as well as cytokine genetic profiles in patients with lone AF and CMS. CMS, lone AF patients, patients with both lone AF and CMS, and control patients were recruited. Genetic polymorphisms in inflammatory and fibrotic markers were assessed. Serum levels of connective tissue growth factor (CTGF) were tested along with other inflammatory markers including platelet-to-lymphocyte ratio (PLR), monocyte-to-HDL ratio (MHR) in three groups of AF+CMS, AF, and CMS patients. There was a trend in the CTGF levels for statistical significance between the AF and AF+CMS group (P = 0.084). Genotyping showed high percentages of patients in all groups with high secretor genotypes of Interleukin-6 (IL-6) (P = 0.037). Genotyping of IFN-γ and IL-10 at high level showed an increase in expression in the AF + CMS group compared to AF and CMS alone suggesting an imbalance between the inflammatory and anti-inflammatory cytokines which is exacerbated by AF. Serum cytokine inflammatory cytokine levels showed that IL-4, IL-5, IL-10, IL-17F, and IL-22 were significant between the AF, AF+CMS, and CMS patients. Combination of both CMS and AF may be associated with a higher degree of inflammation than what is seen in either CMS or AF alone. Thus, the identification of a biomarker capable of identifying metabolic syndrome associated with disease will help in identification of a therapeutic target in treating this devastating disease.

Thyroid Dysfunctions Due to Immune Checkpoint Inhibitors: A Review.

AIM: Immune checkpoint inhibitors are anti-cancer drugs associated with adverse events that result from releasing the immune system against self-antigens while attacking cancer cells. Thyroid dysfunctions are among the most common associated adverse events. MATERIALS AND METHODS: We conducted a systematic search of the literature in 2 databases: PubMed and Medline. Articles that reported thyroid adverse events of immune checkpoint inhibitors were reviewed. Thyroid disorders include hyperthyroidism and hypothyroidism and are most commonly seen with programmed cell death protein 1 and programmed death-ligand 1 inhibitors. CONCLUSIONS: Thyroid disorders are common side effects seen with check point inhibitors and are treated, depending on the clinical situation, by adequate hormonal replacement, thionamides, corticosteroids or observation only. The use of high dose corticosteroids has not been established as a treatment of thyroid toxicities. Thyroid function tests screening should be a part of baseline laboratory testing of all patients undergoing treatment with immune checkpoint inhibitors.

NETosis contributes to the pathogenesis of diabetes and its complications.

NETosis, a novel form of neutrophil-related cell death, acts as a major regulator of diabetes and diabetes-associated complications. In this review, we show that the extrusion of neutrophil extracellular traps, termed NETs, plays an important role in the pathogenesis of type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and diabetes-induced complications. In T1DM, ß-cell death induces the sequestration of neutrophils in the pancreas and seems to be correlated with increased NETosis. In T2DM patients, products of NETs release are significantly elevated. Increased levels of dsDNA are correlated with the presence of cardiovascular disease and diabetic kidney disease, further supporting the role of NETosis in the pathogenesis of other diabetes-induced complications such as impaired wound healing and diabetic retinopathy. NETosis is induced by high glucose through incompletely understood mechanisms, but it also appears to be elevated in patients with diabetes who have tightly controlled glucose levels. We hypothesize that hyperglycemia worsens the already elevated baseline of NETosis in diabetic patients to further increase its detrimental effects.

COVID-19 and diabetes mellitus: how one pandemic worsens the other.

In light of the most challenging public health crisis of modern history, COVID-19 mortality continues to rise at an alarming rate. Patients with co-morbidities such as hypertension, cardiovascular disease, and diabetes mellitus (DM) seem to be more prone to severe symptoms and appear to have a higher mortality rate. In this review, we elucidate suggested mechanisms underlying the increased susceptibility of patients with diabetes to infection with SARS-CoV-2 with a more severe COVID-19 disease. The worsened prognosis of COVID-19 patients with DM can be attributed to a facilitated viral uptake assisted by the host's receptor angiotensin-converting enzyme 2 (ACE2). It can also be associated with a higher basal level of pro-inflammatory cytokines present in patients with diabetes, which enables a hyperinflammatory "cytokine storm" in response to the virus. This review also suggests a link between elevated levels of IL-6 and AMPK/mTOR signaling pathway and their role in exacerbating diabetes-induced complications and insulin resistance. If further studied, these findings could help identify novel therapeutic intervention strategies for patients with diabetes comorbid with COVID-19.

Safety of lixisenatide plus basal insulin treatment regimen in Indian people with type 2 diabetes mellitus during Ramadan fast: A post hoc analysis of the LixiRam randomized trial.

AIMS: Hypoglycemia is one of the most important complications associated with Ramadan fasting in people with type 2 diabetes. LixiRam (NCT02941367) was the first randomized trial comparing safety and efficacy of lixisenatide + basal insulin (BI) vs. sulphonylurea + BI in people with type 2 diabetes who fast during Ramadan. This post hoc analysis focuses on the LixiRam study population from India. METHODS: Adults with type 2 diabetes insufficiently controlled with sulphonylurea + BI ± another oral anti-hyperglycemic drug were randomized 1:1 to receive lixisenatide + BI or to continue sulphonylurea + BI treatment. RESULTS: In total, 150 participants were randomized in India. One participant (1.3%) with lixisenatide + BI vs. 5 participants (6.8%) with sulphonylurea + BI experienced ≥1 documented symptomatic hypoglycemic event during the Ramadan fast (odds ratio [OR]: 0.22; 95% confidence interval [CI]: 0.02-1.93). Incidence of any hypoglycemia was numerically lower with lixisenatide + BI vs. sulphonylurea + BI during Ramadan fasting (1.3% [1/75] vs. 14.7% [11/75], respectively; OR: 0.09; 95% CI: 0.01-0.69). No new safety signals were identified. CONCLUSIONS: A combination of lixisenatide prandial GLP1-RA + BI may be a suitable treatment option for people with type 2 diabetes who elect to fast during Ramadan. Clinical Trial Registry: clinicaltrials.gov (NCT02941367).

SGLT2 Inhibitors, GLP-1 Agonists, and DPP-4 Inhibitors in Diabetes and Microvascular Complications: A Review.

The prevalence of diabetes and its associated complications is increasing throughout the decades. Promising diabetes medications were introduced to the market including GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors aiming to target these complications. The literature lacks sufficient data regarding these new medications and their influence on nephropathy, retinopathy, and neuropathy. This review expands on the major results of effects of the 3 drug classes on microvascular complications. In our review, both SGLT2 inhibitors and GLP-1 agonists appear to have promising nephroprotective outcomes at this stage, with less promising outcomes seen with DPP-4 inhibitors. Moreover, the retinoprotective outcomes of both SGLT2 inhibitors and DPP-4 inhibitors were only tested on mice, while those of GLP-1 agonists were assessed in few trials. In addition, the results of both GLP-1 agonists and DPP-4 inhibitors showed discrepancies in these studies. On the contrary, conclusions regarding the effect of these medications on neuroprotective outcomes cannot be drawn at the time due to the lack of clinical trials targeting these complications. Hence, a clearer picture of the microvascular outcomes will manifest over time with the release of multiple upcoming clinical trials.

Role of the Nox4/AMPK/mTOR signaling axe in adipose inflammation-induced kidney injury.

Diabetic kidney disease is one of the most serious complications of diabetes worldwide and is the leading cause of end-stage renal disease. While research has primarily focused on hyperglycemia as a key player in the pathophysiology of diabetic complications, recently, increasing evidence have underlined the role of adipose inflammation in modulating the development and/or progression of diabetic kidney disease. This review focuses on how adipose inflammation contribute to diabetic kidney disease. Furthermore, it discusses in detail the underlying mechanisms of adipose inflammation, including pro-inflammatory cytokines, oxidative stress, and AMPK/mTOR signaling pathway and critically describes their role in diabetic kidney disease. This in-depth understanding of adipose inflammation and its impact on diabetic kidney disease highlights the need for novel interventions in the treatment of diabetic complications.

Diabetes without Manifest Cardiovascular Disease: A Novel Approach in Risk Stratification and Treatment Selection.

BACKGROUND: Cardiovascular disease (CVD), the main macro vascular complication of type 2 diabetes (T2D), increases the risk of death significantly in patients with T2D. INTRODUCTION: Most of the patients with T2D do not have obvious CVD symptoms. Due to the paucity of data, CVD screening in asymptomatic patients with T2D remains highly controversial. METHODS: This has driven a panel of experts to establish a novel consensus on how to approach patients with T2D at high CVD risk. The panel formulated a stepwise algorithm by which patients with T2D undergo initial risk stratification into low, intermediate and high risk using the ASCVD calculator. In patients with intermediate risk, coronary artery calcium measurement is used to further stratify those patients into new low and high-risk categories. RESULTS AND CONCLUSION: The panel recommends using standard diabetes care in low risk patients and using SGLT2 inhibitors and GLP1 agonists with cardio protective effect, on top of standard care, in high risk individuals.