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.

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.

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.

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.

Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer.

Cancer was recently annexed to diabetic complications. Furthermore, recent studies suggest that cancer can increase the risk of diabetes. Consequently, diabetes and cancer share many risk factors, but the cellular and molecular pathways correlating diabetes and colon and rectal cancer (CRC) remain far from understood. In this study, we assess the effect of hyperglycemia on cancer cell aggressiveness in human colon epithelial adenocarcinoma cells in vitro and in an experimental animal model of CRC. Our results show that Nox (NADPH oxidase enzyme) 4-induced reactive oxygen species (ROS) production is deregulated in both diabetes and CRC. This is paralleled by inactivation of the AMPK and activation of the mammalian target of rapamycin (mTOR) C1 signaling pathways, resulting in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulation, induction of DNA damage, and exacerbation of cancer cell aggressiveness, thus contributing to the genomic instability and predisposition to increased tumorigenesis in the diabetic milieu. Pharmacologic activation of AMPK, inhibition of mTORC1, or blockade of Nox4 reduce ROS production, restore the homeostatic signaling of 8-oxoguanine DNA glycosylase/8-oxodG, and lessen the progression of CRC malignancy in a diabetic milieu. Taken together, our results identify the AMPK/mTORC1/Nox4 signaling axis as a molecular switch correlating diabetes and CRC. Modulating this pathway may be a strategic target of therapeutic potential aimed at reversing or slowing the progression of CRC in patients with or without diabetes.-Mroueh, F. M., Noureldein, M., Zeidan, Y. H., Boutary, S., Irani, S. A. M., Eid, S., Haddad, M., Barakat, R., Harb, F., Costantine, J., Kanj, R., Sauleau, E.-A., Ouhtit, A., Azar, S. T., Eid, A. H., Eid, A. A. Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer.

Tolerability of canagliflozin in patients with type 2 diabetes mellitus fasting during Ramadan: Results of the Canagliflozin in Ramadan Tolerance Observational Study (CRATOS).

AIMS: There is a large population of people with type 2 diabetes mellitus (T2DM) who are Muslim and fast during Ramadan. Changes in the pattern and amount of meal and fluid intake during Ramadan, in addition to the long fasting hours, may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. The Canagliflozin in Ramadan Tolerance Observational Study (CRATOS) evaluated the tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with sulphonylureas among patients with T2DM who fast during Ramadan. METHODS: This non-randomised, parallel-cohort, prospective, comparative, observational study was conducted in the Middle East during Ramadan and enrolled patients who were taking canagliflozin (n=162) or any sulphonylurea (n=159) added to metformin±dipeptidyl peptidase-4 inhibitor. The proportion of patients who experienced hypoglycaemia events was assessed as the primary end-point. Between-cohort comparisons were adjusted using propensity score analysis. RESULTS: During Ramadan, fewer patients experienced symptomatic hypoglycaemia with canagliflozin vs sulphonylurea (adjusted odds ratio: 0.273 [95% CI: 0.104, 0.719]). Of hypoglycaemia events for which blood glucose was measured, two of six with canagliflozin and 27 of 37 with sulphonylurea were confirmed by blood glucose <3.9 mmol/L. More patients treated with canagliflozin experienced volume depletion events compared with sulphonylurea (adjusted odds ratio: 3.5 [95% CI: 1.3, 9.2]). Missed fasting days were few and medication adherence was high in both groups. No patients treated with canagliflozin and 9.4% treated with sulphonylurea adjusted their medication dose near the beginning of Ramadan. Both treatments were generally well tolerated, with low rates of adverse events and no serious adverse events in either group. CONCLUSIONS: Overall, these findings support the use of canagliflozin for the treatment of adults with T2DM who fast during Ramadan. CLINICALTRIALS. GOV IDENTIFIER: NCT02737657.

Low-density lipoprotein levels and not mutation status predict intima-media thickness in familial hypercholesterolemia.

BACKGROUND: Intima-media thickness (IMT) is a well-described marker of cardiovascular disease. In this study we aim to determine whether low-density lipoprotein (LDL) levels and disease-related mutation status can predict IMT in patients with severe familial hypercholesterolemia (FH) referred for or on LDL apheresis. METHODS: Genetic screening, lipid profile testing, and IMT measurements were performed on a series of 33 severe FH patients (19 homozygous) on LDL apheresis treatments (LDL 447 ± 151 mg/dL, age range 6-60 years). Data were then compared with literature IMT-LDL data for normal subjects, mild FH patients, and severe FH patients (18, 41, and 6 studies, respectively). RESULTS: Age-adjusted IMT was linearly related to LDL levels over a wide range of values (<500 mg/dL), except for the severe FH no-apheresis cohort. Alternatively, our severe FH population (mostly on apheresis) did follow the mild FH/control age-adjusted IMT-LDL relation. CONCLUSIONS: In severe FH, measuring LDL levels is more predictive of increased IMT than genetic screening.

Management and control of patients with type 2 diabetes mellitus in Lebanon: results from the International Diabetes Management Practices Study (IDMPS).

BACKGROUND: The IDMPS is a study to identify changes in diabetes treatment practice in several developing countries. This paper focuses on diabetes management and compliance with guidelines in a Middle Eastern country like Lebanon. METHODS: The cross-sectional data from the 2006 wave of two weeks duration on the Lebanese population along with the longitudinal data of a 9-month follow-up study were collected. RESULTS: A large proportion of Lebanese patients were not adequately controlled or followed up. A slight proportion was managed by diet and exercise alone while most patients were on two or more oral anti-hyperglycemics. Metformin was the most common monotherapy followed by sulfonylureas. 22.6% of Lebanese patients were on insulin, most commonly basal insulin alone followed by premix insulin alone. Blood glucose self-monitoring was more frequently done by insulinized patients and was associated with better glycemic control. Glycemic control was reached in 29.6% of type 2 patients (HbA1c < 7%) with poorest outcome for patients on insulin and was more frequently achieved in patients who had more frequent monitoring of HbA1c levels. CONCLUSION: For a proper assessment of diabetic control, maintaining adherence to international guidelines needs to be evaluated. Promoting patient education, improving physician knowledge with better implementation of guidelines is recommended.

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.

Possible role of GLP-1 and its agonists in the treatment of type 1 diabetes mellitus.

Unfortunately, the only approved medical treatment for type 1 diabetes mellitus (DM) is insulin, despite the fact that tight control cannot be reached without some serious side effects such as hypoglycemia and weight gain. More and more importance is now shifted towards developing new drugs that can reach a better glycemic control with lesser side effects. Some of these promising drugs are the glucagon-like peptides 1 (GLP-1) and their agonists, which have been FDA approved for the treatment of type 2 DM. The purpose of this article is to review all of the relevant literature on the potential role of GLP-1 in the treatment of type 1 DM. The major source of data acquisition included Medline search strategies, using the words "type 1 diabetes mellitus" and "GLP-1." Articles published in the last 20 years were screened. GLP-1 increases insulin secretion in humans with existing beta cells; it also decreases glucagon secretion, and blunts appetite. Of note, new animal studies demonstrate a role in beta cell-proliferation and decreased apoptosis. Because of all the effects mentioned above, GLP-1 seems to be a promising drug for type 1 DM treatment, but more studies are still needed before solid conclusions can be drawn.

Vocal characteristics in patients with thyroiditis.

OBJECTIVE: The aim of the present study was to describe the vocal characteristics of patients with thyroiditis in a clinical setting. MATERIALS AND METHODS: A total of 17 consecutive patients with the diagnosis of thyroiditis presenting to the endocrinology clinic were invited to participate in the study. A group of 29 healthy subjects were used as controls. They underwent acoustic analysis and a perceptual evaluation using the GRABS classification. The mean score of each parameter was computed, and the distribution of severity of each perceptual parameter were listed. RESULTS: There was no significant difference in any of the acoustic parameters between the patients and the controls, and there was no significant difference in the mean score of all the perceptual parameters between the patients and the controls. Even when examining the distribution of the severity of evaluation, there was no significant difference between the patients and the controls, as well. CONCLUSION: Patients with thyroiditis do not have abnormal perceptual vocal evaluation or acoustic findings compared with controls.

Vocal characteristics in patients with type 2 diabetes mellitus.

The objective of this study is to report the vocal characteristics of patients with type 2 diabetes mellitus in relation to disease duration, glycemic control, and neuropathy. This is a prospective study. The setting is institutional setting. A total of 82 patients were recruited for this study, and a healthy control group matched according to age and gender was recruited. Subjects underwent acoustic analysis and perceptual evaluation using the GRABS classification where G stands for grading, R for roughness, A for asthenia, B for breathiness, and S for straining using a scale of 0­3 where o stands for normal and three for severe deviation from normal. There was no significant difference in any of the acoustic variables between diabetic patients and control. There was no significant difference in the mean score of any of the perceptual evaluation parameters between diabetic patients and control, despite the fact that the mean scores were all higher in the diseased group except for roughness. When looking at subgroups, we see that diabetic patients with poor glycemic control and with neuropathy had significantly higher mean score for the G overall grade of the voice compared to controls with P values of 0.005 and 0.009, respectively. What is also worth noting is that diabetic patients with poor glycemic control had more straining compared to controls, P value 0.043. Patients with type 2 diabetes mellitus and poor glycemic control or neuropathy have a significant difference in the grade of their voice compared to controls.

Homozygous familial hypercholesterolemia in Lebanon: a genotype/phenotype correlation.

Familial hypercholesterolemia (FH) is an inherited disease characterized by the deposition of LDL in tissues causing premature atherosclerosis. Many genes are implicated in FH resulting in a large variability in the phenotype. DNA sequencing of the LDLR gene was done for forty patients clinically diagnosed with homozygous FH and forty family members variably affected. Patients underwent noninvasive heart and vascular studies. Statistical and pedigree analyses were used to correlate the different genotypes with the phenotypes. The prevalence of homozygosity at the Lebanese allele (2043C>A) is 45%. However, 27.5% of the patients have no mutations at all in the LDLR gene, and 27.5% are either heterozygous for the 2043C>A mutation, heterozygous for a mutation in another exon of the LDLR gene, or combined heterozygous for two different mutations. We confirm previous reports on the higher prevalence of FH in Lebanon. Our results do, however contradict previous reports on an assumed higher prevalence among the Christian Lebanese. Mutations in the LDLR especially combined heterozygosity can cause a severe phenotype similar to the homozygous mutation in the Lebanese allele. This information is particularly important in targeting the more prevalent heterozygotes in the general population with early diagnosis and intervention.

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.

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.

WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon.

Most cases of juvenile-onset diabetes (JOD) are diagnosed as type 1 diabetes (T1D), for which genetic studies conducted in outbred Caucasian populations support the concept of multifactorial inheritance. However, this view may be partly challenged in particular population settings. In view of the suggestive evidence for a high prevalence of Wolfram syndrome (WFS) in Lebanon, the phenotypic variability associated with WFS1 mutations, and the high consanguinity rate in Lebanon, we aimed to evaluate the contribution of WFS1 mutations as monogenic determinants to JOD in Lebanon. We performed a family-based genetic study, with linkage analysis followed by systematic mutation screening of WFS1 exons in all JOD probands. The study population consisted of an unbiased recruitment of all juvenile-onset insulin-dependent diabetic patients from a specialized diabetes pediatric clinic in Beirut, Lebanon. Homozygous or compound heterozygous WFS1 mutations were found in 22 of the 399 JOD probands (5.5%), resulting in WFS (17 probands) or in non-syndromic non-autoimmune diabetes mellitus (DM, five probands). These accounted for 12.1% (21/174) of probands in consanguineous families, compared with 0.4% (1/225) in non-consanguineous families. Of the 38 patients identified with homozygous or compound heterozygous WFS1 mutations, 11 (29%) had non-syndromic DM, all of whom carried a particular WFS1 mutation, WFS1(LIB), encoding a protein with an extended C-terminal domain. This mutation resulted in a delayed onset or absence of extrapancreatic features. These results underscore the major impact of population-specific factors, such as population-specific mutations and founder effects, and family structure in the genetic determinism of JOD.

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.

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.