Clinical impact of genetic testing for lipid disorders.

PURPOSE OF REVIEW: Genetic testing is increasingly becoming a common consideration in the clinical approach of dyslipidemia patients. Advances in research in last decade and increased recognition of genetics in biological pathways modulating blood lipid levels created a gap between theoretical knowledge and its applicability in clinical practice. Therefore, it is very important to define the clinical justification of genetic testing in dyslipidemia patients. RECENT FINDINGS: Clinical indications for genetic testing for most dyslipidemias are not precisely defined and there are no clearly established guideline recommendations. In patients with severe low-density lipoprotein cholesterol (LDL-C) levels, the genetic analysis can be used to guide diagnostic and therapeutic approach, while in severe hypertriglyceridemia (HTG), clinicians can rely on triglyceride level rather than a genotype along the treatment pathway. Genetic testing increases diagnostic accuracy and risk stratification, access and adherence to specialty therapies, and cost-effectiveness of cascade testing. A shared decision-making model between the provider and the patient is essential as patient values, preferences and clinical characteristics play a very strong role. SUMMARY: Genetic testing for lipid disorders is currently underutilized in clinical practice. However, it should be selectively used, according to the type of dyslipidemia and when the benefits overcome costs.

The Complex Connection between Obesity and Cancer: Signaling Pathways and Therapeutic Implications.

Obesity has emerged as an important global health challenge, significantly influencing the incidence and progression of various cancers. This comprehensive review elucidates the complex relationship between obesity and oncogenesis, focusing particularly on the role of dysregulated signaling pathways as central mediators of this association. We delve into the contributions of obesity-induced alterations in key signaling cascades, including PI3K/AKT/mTOR, JAK/STAT, NF-κB, and Wnt/ß-catenin to carcinogenesis. These alterations facilitate unchecked cellular proliferation, chronic inflammation and apoptosis resistance. Epidemiological evidence links obesity with increased cancer susceptibility and adverse prognostic outcomes, with pronounced risks for specific cancers such as breast, colorectal, endometrial and hepatic malignancies. This review synthesizes data from both animal and clinical studies to underscore the pivotal role of disrupted signaling pathways in shaping innovative therapeutic strategies. We highlight the critical importance of lifestyle modifications in obesity management and cancer risk mitigation, stressing the benefits of dietary changes, physical activity, and behavioral interventions. Moreover, we examine targeted pharmacological strategies addressing aberrant pathways in obesity-related tumors and discuss the integration of cutting-edge treatments, including immunotherapy and precision medicine, into clinical practice.

Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis.

AIM: The present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three-level mixed-effects meta-analysis. RESULTS: In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin-to-creatinine ratio compared with controls [mean difference (MD) -26.9%; 95% confidence interval (CI) (-34.76, -19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio ≥30 mg/g [MD -41.42%; 95% CI (-54.38, -28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose-response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m2 ; 95% CI (-0.64, 1.42); p = .46; LoE moderate]. CONCLUSION: Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.

Neurological Consequences, Mental Health, Physical Care, and Appropriate Nutrition in Long-COVID-19.

SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data collected indicated that in the next future the disease will affect an increasing number of individuals and that interdisciplinary action is needed to counteract it.

The effect of Spirulina supplementation on lipid profile: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials.

BACKGROUND: Cardiovascular diseases (CVD) are one of the most important causes of death worldwide. Dyslipidemia is one of the main causal risk factors for CVD that can be controlled by modifying lifestyle, which entails the use of healthy diets containing functional foods. The present study was conducted to summarize the effects of Spirulina on the lipid profile in previous randomized controlled trials. METHODS: MEDLINE, Scopus, Clarivate Analytics Web of Science, and the Cochrane Library databases were searched systematically until January 2023, for clinical interventions that investigated the effect of Spirulina supplementation on plasma lipid profile concentrations. RESULTS: ooled results of 20 studies (with 23 arms and 1076 participants) indicated that Spirulina intervention significantly reduced LDL-C (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05), TC (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05) and TG (SMD: -0.6, 95% CI: -0.9, -0.2, P<0.05) levels while HDL-C levels were significantly increased (SMD: 0.3, 95% CI: 0.0, 0.6, P<0.05). CONCLUSIONS: The findings of the present meta-analysis and review show the usefulness of supplementing with Spirulina in improving serum levels of TC, TG, LDL-C, and HDL-C.

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP).

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Efficacy and safety of once-weekly versus once-daily basal insulin analogues in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues. METHODS: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis. RESULTS: A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups. CONCLUSION: The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.

A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy-A Systematic Review and Meta-Analysis.

The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI -0.54 [-1.1, 0.01], p = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI -0.2 [-0.87, 0.47], p = 0.55; and for tofogliflozin 95% CI 3.13 [-12.02, 18.28], p = 0.69, while for tirzepatide it was 0.15, 95% CI [-0.50, 0.80] (p = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients' age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles.

Does Iodine Influence the Metabolism of Glucose?

Thyroid function and glucose status are linked; experimental, clinical, and epidemiological studies have shown this. Iodine is a vital trace element that is inextricably linked to thyroid hormone synthesis. The latter is also associated with glucose metabolism and diabetes. Recently, some-but not all-studies have shown that iodine is linked to glucose metabolism, glucose intolerance, impaired fasting glucose, prediabetes, diabetes mellitus, or gestational diabetes. In this concise review, we review these studies, focusing on iodine and glucose metabolism and prediabetic conditions or type 2 diabetes mellitus. The potential beneficial effect of iodine on glucose metabolism may be attributed to its antioxidant properties.

The Effects of Sodium-Glucose Cotransporter 2-Inhibitors on Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease or Steatohepatitis and Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials.

Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are part of metabolic syndrome and share multiple causal associations. Both conditions have an alarmingly increasing incidence and lead to multiple complications, which have an impact on a variety of organs and systems, such as the kidneys, eyes, and nervous and cardiovascular systems, or may cause metabolic disruptions. Sodium-glucose cotransporter 2-inhibitors (SGLT2-i), as an antidiabetic class with well-established cardiovascular benefits, and its class members have also been studied for their presumed effects on steatosis and fibrosis improvement in patients with NAFLD or non-alcoholic steatohepatitis (NASH). The MEDLINE and Cochrane databases were searched for randomized controlled trials examining the efficacy of SGLT2-i on the treatment of NAFLD/NASH in patients with T2DM. Of the originally identified 179 articles, 21 articles were included for final data analysis. Dapagliflozin, empagliflozin, and canagliflozin are some of the most used and studied SGLT2-i agents which have proven efficacy in treating patients with NAFLD/NASH by addressing/targeting different pathophysiological targets/mechanisms: insulin sensitivity improvement, weight loss, especially visceral fat loss, glucotoxicity, and lipotoxicity improvement or even improvement of chronic inflammation. Despite the considerable variability in study duration, sample size, and diagnostic method, the SGLT2-i agents used resulted in improvements in non-invasive markers of steatosis or even fibrosis in patients with T2DM. This systematic review offers encouraging results that place the SGLT2-i class at the top of the therapeutic arsenal for patients diagnosed with T2DM and NAFLD/NASH.

Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach (2022).

Dyslipidemia in patients with type 2 diabetes (DMT2) is one of the worst controlled worldwide, with only about 1/4 of patients being on the low-density lipoprotein cholesterol (LDL-C) target. There are many reasons of this, including physicians' inertia, including diabetologists and cardiologists, therapy nonadherence, but also underusage and underdosing of lipid lowering drugs due to unsuitable cardiovascular (CV) risk stratification. In the last several years there is a big debate on the risk stratification of DMT2 patients, with the strong indications that all patients with diabetes should be at least at high cardiovascular disease (CVD) risk. Moreover, we have finally lipid lowering drugs, that not only allow for the effective reduction of LDL-C and do not increase the risk of new onset diabetes (NOD), and/or glucose impairment; in the opposite, some of them might effectively improve glucose control. One of the most interesting is pitavastatin, which is now available in Europe, with the best metabolic profile within statins (no risk of NOD, improvement of fasting blood glucose, HOMA-IR, HbA1c), bempedoic acid (with the potential for the reduction of NOD risk), innovative therapies-PCSK9 inhibitors and inclisiran with no DMT2 risk increase, and new forthcoming therapies, including apabetalone and obicetrapib-for the latter one with the possibility of even decreasing the number of patients diagnosed with prediabetes and DMT2. Altogether, nowadays we have possibility to individualize lipid lowering therapy in DMT2 patients and increase the number of patients on LDL-C goal without any risk of new onset diabetes and/or diabetes control worsening, and in consequence to reduce the risk of CVD complications due to progression of atherosclerosis in this patients' group.

The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO International Expert Panel.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic-pituitary-adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

The effect of statin therapy in combination with ezetimibe on circulating C-reactive protein levels: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Previous studies have reported that statin or ezetimibe therapy has an anti-inflammatory effect. However, the results of individual studies on the effect of statin therapy in combination with ezetimibe on C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels have not been clear. Therefore, the present systematic review and meta-analysis were conducted on randomized clinical trials (RCTs) to evaluate the effect of statin therapy in combination with ezetimibe on CRP and hs-CRP levels. METHODS: A literature search was carried out on the MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases up to February 2022 to find eligible studies. The pooled effect sizes were considered for weighted mean difference (WMD) and 95% confidence intervals (CI) for CRP and hs-CRP, and it was also determined as standardized weighted mean difference (SMD) for overall CRP. For all variables, a random-effects model was used. RESULTS: Of the 57 studies included in the systematic review, 53 were used for meta-analysis. Statin therapy in combination with ezetimibe significantly reduced the serum levels of hs-CRP (WMD - 0.2 mg/l; 95% CI - 0.4, - 0.1, P ˂ 0.001) and overall CRP (SMD - 0.16 mg/l; 95% CI - 0.2, - 0.07, P ˂ 0.001). Nevertheless, CRP levels were not significantly changed by combination therapy. A significant association was observed between the serum low-density lipoprotein cholesterol (LDL-C) changes and hs-CRP levels, which can justify the source of heterogeneity. CONCLUSIONS: The current study showed that statin therapy in combination with ezetimibe could be effective in reducing the levels of hs-CRP and overall CRP.

Metformin: Sex/Gender Differences in Its Uses and Effects-Narrative Review.

Metformin (MTF) occupies a major and fundamental position in the therapeutic management of type 2 diabetes mellitus (T2DM). Gender differences in some effects and actions of MTF have been reported. Women are usually prescribed lower MTF doses compared to men and report more gastrointestinal side effects. The incidence of cardiovascular events in women on MTF has been found to be lower to that of men on MTF. Despite some promising results with MTF regarding pregnancy rates in women with PCOS, the management of gestational diabetes, cancer prevention or adjunctive cancer treatment and COVID-19, most robust meta-analyses have yet to confirm such beneficial effects.

The Role of Physicians' Digital Tools in Pharmacological Management of Type 2 Diabetes Mellitus.

Background and Objectives: The constantly increasing prevalence of type 2 diabetes mellitus (T2DM) and the advent of new treatment options have made management of T2DM patients more demanding. We aimed to (a) estimate the familiarity of general practitioners with novel T2DM treatment options, (b) determine whether a digital tool can aid in their treatment decisions and (c) demonstrate that an evidence-based digital clinical support tool can be made using an existing digital platform. Materials and methods: This proof-of-concept study consisted of two parts: We first conducted a simple online survey among general practitioners of three European countries to estimate their familiarity with novel T2DM treatment options and to determine whether they believe that a digital tool can aid in their T2DM treatment decisions. We then proceeded to develop a new digital tool that provides quick, evidence-based support for treatment of patients with T2DM using an existing digital platform. Results: The online survey was completed by 129/5278 physicians (94 from Italy, 22 from Czech Republic and 13 from Slovenia). Only 30.7% of all general practitioners reported to be either very or extremely familiar with novel T2DM treatments; the vast majority of participating general practitioners (82.8%) reported that they would find a digital clinical decision support tool for treating T2DM patients either very or extremely useful. A digital tool which features the characteristics deemed most important by the polled physicians was subsequently developed. Conclusions: The results of the online survey showed that familiarity of general practitioners with novel T2DM treatment options is relatively low and that there is a need for digital clinical decision support tools intended to facilitate treatment decisions in T2DM patients. We demonstrated that such a tool can easily be developed using an existing digital platform.

Managing the Systemic Impact of Periodontitis.

Periodontitis is a microbially driven host-mediated disease that leads to loss of periodontal attachment and bone. It is associated with elevation of systemic inflammatory markers and with the presence of systemic co-morbidities. Furthermore, periodontal treatment leads to a 24-48 h-long acute local and systemic inflammatory response. This systemic response might increase the burden of patients with compromised medical history and/or uncontrolled systemic diseases. The correlation between periodontitis and systemic diseases, the impact of periodontitis on the quality of life and public health, the effects of periodontal treatment on systemic health and disease, and the available methods to manage systemic inflammation after periodontal therapy are discussed. The main focus then shifts to a description of the existing evidence regarding the impact of periodontitis and periodontal treatment on systemic health and to the identification of approaches aiming to reduce the effect of periodontitis on systemic inflammation.

Impact of COVID-19 Pandemic on Disease Control Status and Quality of Life of Patients with Acromegaly.

Background and Objectives: Despite the best efforts of healthcare workers and the deployment of alternative healthcare delivery solutions through telemedicine, the pandemic has disrupted standard care for patients with chronic conditions. The long-lasting pandemic has also had a profound impact on the quality of life (QoL) of the majority of patients with chronic illnesses. The management of rare diseases has been particularly challenging. We aimed to evaluate the impacts that the long-lasting pandemic had on the disease control status and QoL in patients with acromegaly. Materials and Methods: Our prospective study included 34 patients from a national referral centre. The baseline SAGIT and AcroQoL results were obtained in October 2020 during the lockdown period of the SARS-CoV2 pandemic. The follow-up results were assessed during the summer of 2022 in a period without any public health restrictions. All the patients were additionally evaluated for their attitude towards preventative public health measures against SARS-CoV2 spread and required mask wearing during the pandemic. Results: By comparing assessments in 2020 during the lockdown period and 2022 post-lockdown, we observed some improvement in SAGIT subscores T and I, most likely reflecting treatment changes in a small number of patients. The global SAGIT score remained stable. QoL measurement by AcroQoL did not demonstrate any changes. There was a negative correlation between SAGIT subscore S and the AcroQoL results. We also noted that the group of patients with the most negative attitude toward public health measurements for preventing SARS-CoV2 spread had higher AcroQoL results than others. Conclusion: Our results showcase that the SARS-CoV2 pandemic, lasting over two years, did not impact the disease control status and QoL in patients with acromegaly. The cohort continued to be well controlled and without changes in QoL. We measured a relatively favourable attitude towards the public health measures to prevent the spread of SARS-CoV2; in particular, patients who had a lower QoL had more positive attitudes towards these measures.

Atherosclerosis Development and Progression: The Role of Atherogenic Small, Dense LDL.

Atherosclerosis is responsible for large cardiovascular mortality in many countries globally. It has been shown over the last decades that the reduction of atherosclerotic progression is a critical factor for preventing future cardiovascular events. Low-density lipoproteins (LDL) have been successfully targeted, and their reduction is one of the key preventing measures in patients with atherosclerotic disease. LDL particles are pivotal for the formation and progression of atherosclerotic plaques; yet, they are quite heterogeneous, and smaller, denser LDL species are the most atherogenic. These particles have greater arterial entry and retention, higher susceptibility to oxidation, as well as reduced affinity for the LDL receptor. Increased proportion of small, dense LDL particles is an integral part of the atherogenic lipoprotein phenotype, the most common form of dyslipidemia associated with insulin resistance. Recent data suggest that both genetic and epigenetic factors might induce expression of this specific lipid pattern. In addition, a typical finding of increased small, dense LDL particles was confirmed in different categories of patients with elevated cardiovascular risk. Small, dense LDL is an independent risk factor for cardiovascular diseases, which emphasizes the clinical importance of both the quality and the quantity of LDL. An effective management of atherosclerotic disease should take into account the presence of small, dense LDL in order to prevent cardiovascular complications.

A New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer.

There is very recent and strong evidence relating Fusobacterium nucleatum to colorectal cancer. In this narrative review, we update the knowledge about gingival dysbiosis and the characteristics of Fusobacterium nucleatum as one of the main bacteria related to periodontitis. We provide data on microbiome, epidemiology, risk factors, prognosis, and treatment of colorectal cancer, one of the most frequent tumours diagnosed and whose incidence increases every year. We describe, from its recent origin, the relationship between this bacterium and this type of cancer and the knowledge and emerging mechanisms that scientific evidence reveals in an updated way. A diagram provided synthesizes the pathogenic mechanisms of this relationship in a comprehensive manner. Finally, the main questions and further research perspectives are presented.

Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes.

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic.